Nefarious Nefazodone And Flashy Rare Side Effects

[Epistemic status: I am still in training. I am not an expert on drugs. This is poorly-informed speculation about drugs and it should not be taken seriously without further research. Nothing in this post is medical advice.]


Which is worse – ruining ten million people’s sex lives for one year, or making one hundred people’s livers explode?

I admit I sometimes use this blog to speculate about silly moral dilemmas for no reason, but that’s not what’s happening here. This is a real question that I deal with on a daily basis.

SSRIs, the class which includes most currently used antidepressants, are very safe in the traditional sense of “unlikely to kill you”. Suicidal people take massive overdoses of SSRIs all the time, and usually end up with little more than a stomachache for their troubles. On the other hand, there’s increasing awareness of very common side effects which, while not disabling, can be pretty unpleasant. About 50% of users report decreased sexual abilities, sometimes to the point of total loss of libido or anorgasmia. And something like 25% of users experience “emotional blunting” and the loss of ability to feel feelings normally.

Nefazodone (brand name Serzone®, which would also be a good brand name for a BDSM nightclub) is an equally good (and maybe better) antidepressant that does not have these side effects. On the other hand, every year, one in every 300,000 people using nefazodone will go into “fulminant hepatic failure”, which means their liver suddenly and spectacularly stops working and they need a liver transplant or else they die.

There are a lot of drug rating sites, but the biggest is 467 users have given Celexa, a very typical SSRI, an average rating of 7.8/10. 14 users have given nefazodone an average rating of 9.1/10.

CrazyMeds might not be as dignified as, but they have a big and well-educated user base and they’re psych-specific. Their numbers are 3.3/5 (n = 253) for Celexa and 4.1/5 (n = 47) for nefazodone.

So both sites’ users seem to agree that nefazodone is notably better than Celexa, in terms of a combined measure of effectiveness and side effects.

But nefazodone is practically never used. It’s actually illegal in most countries. In the United States, parent company Bristol-Myers Squibb (which differs from normal Bristol-Myers in that it was born without innate magical ability) withdrew it from the market, and the only way you can find it nowadays is to get it is from an Israeli company that grabbed the molecule after it went off-patent. In several years working in psychiatry, I have never seen a patient on nefazodone, although I’m sure they exist somewhere. I would estimate its prescription numbers are about 1% of Celexa’s, if that.

The problem is the hepatic side effects. Nobody wants to have their liver explode.

But. There are something like thirty million people in the US on antidepressants. If we put them all on nefazodone, that’s about a hundred cooked livers per year. If we put them all on SSRIs, at least ten million of them will get sexual side effects, plus some emotional blunting.

My life vastly improved when I learned there was a searchable database of QALYs for different conditions. It doesn’t have SSRI-induced sexual dysfunction, but it does have sexual dysfunction due to prostate cancer treatment, and I assume that sexual dysfunction is about equally bad regardless of what causes it. Their sexual dysfunction has some QALY weights averaging about 0.85. Hm.

Assume everyone with fulminant liver failure dies. That’s not true; some get liver transplants, maybe some even get a miracle and recover. But assume everyone dies – and further, they die at age 30, cutting their lives short by fifty years.

In that case, putting all depressed people on nefazodone for a year costs 5,000 QALYs, but putting all depressed people on SSRIs for a year costs 1,500,000 QALYs. The liver failures may be flashier, but the 3^^^3 dust specks worth of poor sex lives add up to more disutility in the end.

I don’t want to overemphasize this particular calculation for a couple of reasons. First, SSRIs and nefazodone both have other side effects besides the major ones I’ve focused on here. Second, I don’t know if the level of SSRI-induced sexual dysfunction is as bad as the prostate-surgery-induced sexual dysfunction on the database. Third, there are a whole bunch of antidepressants that are neither SSRIs nor nefazodone and which might be safer than either.

But I do want to emphasize this pattern, because it recurs again and again.


In that spirit, which would you rather have – something like a million people addicted to amphetamines, or something like ten people have their skin eat itself from the inside?

I can’t get good numbers on how many adults abuse Adderall, but a quick glance at the roster for my hospital’s rehab unit suggests “a lot”. Huffington Post calls it the most abused prescription drug in America, which sounds about right to me. Honestly there are worse things to be addicted to than Adderall, but it’s not completely without side effects. The obvious ones are anxiety, irritability, occasionally frank psychosis, and sometimes heart problems – but a lot of the doctors I work with go beyond what the research can really prove and suggest it can produce lasting negative personality change and predispose people to other forms of addictive and impulsive behavior.

If you’ve got to give adults a stimulant, I would much prefer modafinil. It’s not addictive, it lacks most of Adderall’s side effects, and it works pretty well. I’ve known many people on modafinil and they give it pretty universally positive reviews.

On the other hand, modafinil may or may not cause a skin reaction called Stevens Johnson Syndrome/Toxic Epidermal Necrolysis, which like most things with both “toxic” and “necro” in the name is really really bad. The original data suggesting a connection came from kids, who get all sorts of weird drug effects that adults don’t, but since then some people have claimed to have found a connection with adults. Some people get SJS anyway just by bad luck, or because they’re taking other drugs, so it’s really hard to attribute cases specifically to modafinil.

Gwern’s Modafinil FAQ mentions an FDA publication which argues that the background rate of SJS/TEN is 1-2 per million people per year, but the modafinil rate is about 6 per million people per year. However, there are only three known cases of a person above age 18 on modafinil getting SJS/TEN, and this might not be different from background rates after all. Overall the evidence that modafinil increases the rate of SJS/TEN in adults at all is pretty thin, and if it does, it’s as rare as hen’s teeth (in fact, very close to the same rate as liver failure from nefazodone).

(also: consider that like half of Silicon Valley is on modafinil, yet San Francisco Bay is not yet running red with blood.)

(also: ibuprofen is linked to SJS/TEN, with about the same odds ratio as modafinil, but nobody cares, and they are correct not to care.)

I said I’ve never seen a doctor prescribe nefazodone in real life; I can’t say that about modafinil. I have seen one doctor prescribe modafinil. It happened like this: a doctor I was working with was very upset, because she had an elderly patient with very low energy for some reason, I can’t remember, maybe a stroke, and wanted to give him Adderall, but he had a heart arrythmia and Adderall probably wouldn’t be safe for him.

I asked “What about modafinil?”

She said, “Modafinil? Really? But doesn’t that sometimes cause Stevens Johnson Syndrome?”

And then I glared at her until she gave in and prescribed it.

But this is very, very typical. Doctors who give out Adderall like candy have no associations with modafinil except “that thing that sometimes causes Stevens-Johnson Syndrome” and are afraid to give it to people.


Nefazodone and modafinil are far from the only examples of this pattern. MAOIs are like this too. So is clozapine. If I knew more about things other than psychiatry, I bet I could think of examples from other fields of medicine.

And partially this is natural and understandable. Doctors swear an oath to “first do no harm”, and toxic epidermal necrolysis is pretty much the epitome of harm. Thought experiments like torture vs dust specks suggest that most people’s moral intuitions say that no amount of aggregated lesser harms like sexual side effects and amphetamine addictions can equal the importance of avoiding even a tiny chance of some great harm like liver failure or SJS/TEN. Maybe your doctor, if you asked her directly, would endorse a principled stance of “I am happy to give any number of people anxiety and irritability in order to avoid even the smallest chance of one case of toxic epidermal necrolysis.”

And yet.

The same doctors who would never dare give nefazodone, consider Seroquel a perfectly acceptable second-line treatment for depression. Along with other atypical antipsychotics, Seroquel raises the risk of sudden cardiac death by about 50%. The normal risk of cardiac sudden death in young people is about 10 in 100,000 per year, so if my calculations are right, low-dose Seroquel causes an extra cardiac death once per every 20,000 patient-years. That’s ten times as often as nefazodone causes an extra liver death.

Yet nefazodone was taken off of the market by its creators and consigned to the dustbin of pharmacological history, and Seroquel is the sixth-best-selling drug in the United States, commonly given for depression, simple anxiety, and sometimes even to help people sleep.

Why the disconnect? Here’s a theory: sudden cardiac death happens all the time; sometimes God just has it in for you and your heart stops working and you die. Antipsychotics can increase the chances of that happening, but it’s a purely statistical increase, such that we can detect it aggregated over large groups but never be sure that it played a role in any particular case. The average person who dies of Seroquel never knows they died of Seroquel, but the average person who dies from nefazodone is easily identified as a nefazodone-related death. So nefazodone gets these big stories in the media about this young person who died by taking this exotic psychiatric drug, and it becomes a big deal and scares the heck out of everybody. When someone dies of Seroquel, it’s just an “oh, so sad, I guess his time has come.”

But the end result is this. When treatment with an SSRI fails, nefazodone and Seroquel naively seem to be equally good alternatives. Except nefazodone has a death rate of 1/300,000 patient years, and Seroquel 1/20,000 patient years. And yet everyone stays the hell away from the nefazodone because it’s known to be unsafe, and chooses the Seroquel.

I conclude either doctors are terrible at thinking about risk, or else maybe a little too good at thinking about risk.

I bring up the latter option because there’s a principal-agent problem going on here. Doctors want to do what’s best for their patients. But they also want to do what’s best for themselves, which means not getting sued. No one has ever sued their doctor because they got a sexual side effect from SSRIs, but if somebody dies because they’re the lucky 1/300,000 who gets liver failure from nefazodone, you can bet their family’s going to sue. Suddenly it’s not a matter of comparing QALYs, it’s a matter of comparing zero percent chance of lawsuit with non-zero percent chance of lawsuit.

(Fermi calculation: if a doctor has 100 patients at a time on antidepressants, and works for 30 years, then if she uses Serzone as her go-to antidepressant, she’s risking a 1% chance of getting the liver failure side effect once in her career. That’s small, but since a single bad lawsuit can bankrupt a doctor, it’s worth taking seriously.)

And that would be a tough lawsuit to fight. “Yes, Your Honor, I knew when I prescribed this drug that it sometimes makes people’s livers explode, but the alternative often gives people a bad sex life, and according to the theory of utilitarianism as propounded by 18th century philosopher Jeremy Bentham – ” … “Bailiff, club this man”.

And the same facet of nefazodone that makes it exciting for the media makes it exciting for lawsuits. When someone dies of nefazodone toxicity, everyone knows. When someone dies of Seroquel, “oh, so sad, I guess his time has come”.

That makes Seroquel a lot safer than nefazodone. Safer for the doctor, I mean. The important kind of safer.

This is why, as I mentioned before, I hate lawsuits as a de facto regulatory mechanism. Our de jure regulatory mechanism, the FDA, is pretty terrible, but to its credit it hasn’t banned nefazodone. One time it banned clozapine because of a flashy rare side effect, but everyone yelled at them and they apologized and changed their mind. With lawsuits there’s nobody to yell at, so we just end up with people very quietly adjusting their decisions in the shadows and nobody else being any the wiser.

I don’t want to overemphasize this, because I think it’s only one small part of the problem. After all, a lot of countries withdrew nefazodone entirely and didn’t even give lawsuits a chance to enter the picture.

But whatever the cause, the end result is that drugs with rare but spectacular side effects get consistently underprescribed relative to drugs with common but merely annoying side effects, or drugs that have more side effects but manage to hide them better.

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331 Responses to Nefarious Nefazodone And Flashy Rare Side Effects

  1. AlexanderRM says:

    I feel like comparing medical effects is an excellent case to introduce Rawls-Style calculations: Instead of asking “Which is worse – ruining ten million people’s sex lives for one year, or making one hundred people’s livers explode?”, ask “would you rather have a 50% chance of these sexual dysfunction symptoms for one year, or a 1 in 300,000 chance of death per year?”.

    Better yet, rather than having the doctor or the regulatory agency ask this question, you can ask the actual patients this question. Admittedly, they aren’t likely to be hyper-rational about tiny chances of spectacular things either, but I’m not sure it’ll be any worse than the voting public or a regulatory agency; in fact, they’ll probably be significantly more rational overall.
    That also has an obvious advantage of allowing customization for the individual patient- a patient who has little to no sex anyway might weight sexual dysfunction much lower, for instance, a patient in their 80s might weight a chance of death a bit lower (again not likely to be fully rational, but moreso than a voting public talking about someone else’s life), etc.

    Furthermore, and most importantly, you could potentially use this method and then ask patients to sign off saying that they chose this chance over the other, which seems far more defensible in a lawsuit (“my client decided that a 1 in 300,000 chance of death was small enough to be worth it” rather than “I decided a 1 in 300,000 chance was small enough to be worth it”) and might help with regulation as well.

    • Douglas Knight says:

      ask “would you rather have a 50% chance of these sexual dysfunction symptoms for one year, or a 1 in 300,000 chance of death per year?”

      That is exactly what Scott did in this post. More specifically, he consulted a QALY database that was built by asking patients lots of questions like this and trying to smooth out their answers into coherence.

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  3. grendelkhan says:

    I’d like to nominate this Wikipedia article (“List of SJS-inducing substances”) for possibly the worst, most useless thing I’ve ever damned well seen. It’s a table of chemicals with a “certainty of implication” column, each of which says “Certain”. Not a word about relative risk, not a word about the base rate, just… aargh. I’m not even a doctor and I know this is a goddamned awful table.

  4. Winfried says:

    I’m a bit late to the party, but I am narcoleptic and have taken Provigil (modafinil) for years. Now I take Nuvigil (armodafinil). It’s much better for the already mild side effects I was having.

    On very rare occasions, I would have days where I felt strongly compelled towards gambling, smoking, and drinking, activities that I seldom take part in. I played a friendly game of Poker with friends every week and had to quit taking it those evenings because I could not keep from incorrectly estimating odds and going broke (or winning quickly on a streak).

    In addition, if I took it every day for more than a week or so, I would get headaches that felt like a caltrop behind my right eye. These headaches were untouchable by common OTC headache medications.

    Nuvigil has yet to give me any of these headaches and I haven’t really gambled much on it, but from occasional forays I seem to do about as well as can be expected for basic strategy in games of chance.

    I highly recommend Nuvigil over Provigil.

    • Douglas Knight says:

      had to quit taking it those evenings

      Did you take it in the evenings? Or do you mean take it in the mornings of those days?

  5. Taylor says:

    This kind of speculation is part of the problem with modern medicine (and society): generally, the removal of personal responsibility.

    If you have two options to prescribe a patient: A) this one works but has a tiny chance of horrible consequences; and B) this one doesn’t work and will possibly make you less likable as a human, however, there is a near zero risk of sudden death.

    If a patient is briefed of the relative risks and rewards of options A and B, they can still choose option C (do nothing). Just because humans have a slavish tendency to look at well-educated people with Pharaohic longing, if the human race ever expects to reach another plateau of existence, people have to start receiving the feedback from the consequences of risk and reward. Physicians who prefer to stand on a pedestal and say, “Well, they just don’t have the benefit of my perspective and expertise,” are just enabling the arrested development of man.

    I realize that professional liability has arisen to this leviathan level of nonsense and “the system” just “is how it is”; but, seriously, is it impossible to give full disclosure to patients and let them make up their mind?

    The thought just occurred to me that the leviathan-level of nonsense is probably the culprit behind arresting the common man’s tenuous understanding of the link between cause and effect, thereby reducing his ability to choose between options without the assurance that somebody somewhere will pay should his judgment get the better of him.

    New question: What causes society’s decline into nonsense and can the process be reversed or is it strictly entropic? Did the US hit event horizon when bell-bottomed teen-agers protested war while wearing Che t-shirts and celebrating Soviet efficiency thus imploding 250 years of popular, liberal politics into the singularity of stupidity that continues today?

    Rant ended.

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  8. Ann T says:

    Great analysis…one comment, I don’t think calculating QALYs from data on sexual dysfunction on prostate surgery and using it for SSRIs is apt, because the sexual dysfunction from prostate surgery will last until the end of that patient’s life (I assume), whereas that from putting the pt on an SSRI can be stopped by stopping the SSRI. So it’s not a full .85 QALY as in prostate cancer surgery. In addition, a patient on an SSRI may have sexual side effects and not care (maybe they don’t have or want a partner, maybe they’ve just had their 19th kid and the lack of a libido is welcomed, etc.). In which case there is really no reduction in quality of life.

    • Douglas Knight says:

      Scott took that into account. The Y in QALY stands for Year. He counted a year of SSRI as costing 0.15 QALY, compared to a year of nefazodone having a chance of killing and costing 50 QALY, ie, 50 years of life.

      Yes, patients on SSRIs might not care about sexual side effects, but neither might patients with prostate cancer. That should already be accounted for in the 0.85 (although it might not be). If you think the cost of sexual side effects is only 1%, redo the calculation and see that the cost of SSRIs is now only twenty times the cost of nefazodone.

  9. Jon H says:

    “but a lot of the doctors I work with go beyond what the research can really prove and suggest it can produce lasting negative personality change and predispose people to other forms of addictive and impulsive behavior.”

    I’ve wondered if doing things with addictive potential (gambling, internet surfing?, etc) while on a dopaminergic drug like ritalin or adderall might boost the addictiveness of those activities.

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  12. Michael Dubriwny MD says:

    I must be one of the very few that prescribes nefazodone and after 30 plus years I still have a few patients on it. I worry more about Seroquel than nefazodone, not because of sudden cardiac eath, but by concern about weight gain (which may play a role in sudden cardiac death). Seroquel more often than not causes weight gain which is a prelude to the “metabolic syndrome” which leads to other problems such as diabetes and heart disease. Weight gain occurs easily and rapidly which is contrary to the difficutly with losing weight. It takes may years for the “harm” related to a medication to emerge, a fact often neglected by the newly emerging physician.

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  14. Nat Kuhn says:

    Hi Scott, I still prescribe nefazodone, and you can, too! I prescribe it usually after trying an SSRI and bupropion (Wellbutrin, which also has a favorable profile in terms of sexual side-effects). I say something like this: “My understanding is that if you give a million people nefazodone for a year, 3 or 4 will get liver failure and either die or need a transplant, and if you have a million people and you DON’T give them nefazodone for a year only one of them will get liver failure. Now you might look at that and say ‘Wow, that triples or quadruples my chance of liver failure, forget it!’ or you might say ‘Wow, my odds of dying in a car wreck on Route 128 [I’m in the Boston area] are way worse than that.'” Some people decide not to take it, but most people at that point decide to take it. It is also weight-neutral unlike mirtazapine (Remeron, which causes agranulocytosis in is it 1 in 20,000? but nobody seems to get freaked out about that). If the person chooses to take it, I document that that’s what they decided “after usual discussion of risks and benefits, including the risk of liver failure.”

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  16. Peter Gerdes says:

    You’ve seen the meta-analysis that suggests SSRIs are no better than a placebo (it left the small category of the most extremely depressed patients as possibly being benefited).

    When you combine these results with the issues of unblinding (over 80% of the time the *doctors* administering the double blind trials could guess who was getting the placebo and who was getting the active drug) the disturbingly high placebo response (placebo seemed to work in 50% of cases or so) and the lack of any underlying mechanism for these drugs to work on depression (looking at serotonin levels in treated animals brains undermines the standard theories) casts serious doubt on their efficacy at all.

    At best it seems like SSRIs are a random disruption to brain function which, by regression to the mean, might help those with the most extreme form of depression slightly more often than it is harmful.

  17. Linde says:

    I am commenting as a rank amateur that reads a bit. I would guess that most cases of SJS (Stevens-Johnson syndrome) is related to antibiotics, specifically those similar to Bactrim or Septra. I just did a search and Merck says “Drugs, especially sulfa drugs, antiepileptics, and antibiotics, are the most common causes.” Wonder how many of the people on modafinil also had an infection (real or presumed) and were prescribed broad spectrum antibiotics “just in case” and then ended up with SJS.

  18. Tim Sanders says:

    WOW!! A doc who can think rationally. Congratulations to your parents and educational institutions and of course your own interpretive constitution. I agree with you; we are a nation of sensationalists, whether individually or as a group, such as journalists or politicians. In ending, for your information, there are quite a few doctors who prescribe modafinil. I live in the sticks with few close friends but of the say ten that I do have, 4 are on modafinil and all live in different cities or small towns. One even in Tennessee! You will find a higher percentage of air traffic controllers on modafinil (vs. the general public) or people who do shift work, also people with chronic fatigue. Give me the nefazodone…I’m tired of living in a world that gives me chronic fatigue. To be able to orgasm again would be priceless and what a way to go out. We’ve all seen it…the over 50 guy, out of shape, climaxing with his mistress or prostitute and then dying of a heart attack. Always a smile on his face…well most of the time. LOL. Thanks for an insightful take on this subject.

  19. cynthia vautier says:

    How important is sexual activity to quality of life? Different answers would come from different people. For some people, this aspect of life is critical. Life without sex would be half a life. Other, more asexual people don’t care. To assign one value to the absence of the ability to have an active sex life is scientifically and statistically unsound. New metrics need to be developed if such metrics concerning quality-of-life are to have credibility. Hopefully, those who have the brains to complete medical school will recognize this basic logic. Also, doctors are human and cannot help but worry about their own vulnerability. As in, vulnerability to career-destroying lawsuits. Responsibility should be shifted, with the proviso that there be FULL, INFORMED CONSESNT once the comparative and possible side-effects of a proposed medication are known. That responsibility should be shouldered by the patient, who is a thinking, decision-making individual. Patients who are thinking, decision-making individuals go to Las Vegas and lose fortunes, screwing up their lives to no end; yet, no one sues the casinos for gamblers’ poor decisions. Such facts point up a double standard. Individuals who choose a particular medication, who are FULLY-INFORMED of its possible side effects, should be precluded from suing their prescribing physicians. Such a change in policy would allow doctors to think more about what is available for their patients as an anodyne, and less about their own survival as physicians. With added responsibility for the patient comes great benefit: the patient is no longer treated as a child by his or her doctor, power is taken away from those who, living with the idea that they know what is best, inevitably come to abuse their power, and play God. Patients and doctors both deserve better than this current deplorable state of affairs. Tell the patient EVERYTHING. Tell the patient all his options. Let the patient make the choice about what real quality of life means for the individual who has to live, day-in, day-out, with the decision. Relieve doctors of both fear and the slippery slope of the abuse of power.

  20. aek says:

    I can speak to this as a provider and as a patient. I have taken several antidepressants from several classes, and none provided any apparent benefit. However, one week after stopping agomelatine (in a US trial as a sublingual form), I developed acute hepatotoxicity. The clinical site and the emergency department shared my labs (I had given prior permission at the start of the trial during the consent process), and then nobody wanted to report it – anywhere. I contacted the for-profit IRB, and they dismissed my concern. The FDA doesn’t take reports from clinical trials. And whaddya know – the study never reported results.

    That’s about the time I began to search for drug trial results, and discovered the horror that is pharma drug trials and biological psychiatry.

    So you can be flippant about NNH and NNT and livers exploding, but I consider myself very lucky that I was able to extract myself more or less intact after having LFT values generally incompatible with life. If there were more ethical prescribers of psychotropics, there wouldn’t be patients solely blamed for their misery (supposed faulty thoughts and expressions of distress that are pharmacologically or electrically suppressed lest they make the observers of them uncomfortable), but instead we’d have a hella more robust public health system, supports and physicians who actually advocated for social determinants of health on an individual patient (precision medicine, my friend) and community/population basis.

    • Douglas Knight says:

      The FDA doesn’t take reports from clinical trials.

      Maybe that’s what they told you, but it was a bald-faced lie. The FDA wants to know about every last headache experienced by a subject in a clinical trial.

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  22. Murphy says:

    It does appear that others are taking QALY’s into account when judging cost effectiveness but I don’t know if these QALY numbers take into account sexual function.

    QALYs were greatest for nefazodone (14.64) compared with 14.32 for imipramine, 14.40 for the step approach, and 14.58 for fluoxetine.

    Remember that in communities a particular treatment can become popular simply because it’s been talked up by the right people so the non-blind ratings/reviews may not be great evidence in of themselves.

    It appears that the NHS does proscribe it but as scott notes, at a very low rate:

  23. Shenpen says:

    Stupid question, but why not let the patient decide? This was figured out so long ago… have them sign a paper “yes I was informed and I made my choice and I absolve my doctor of all responsibility”

    Is the legislation of the United States so fucked up that this cannot be done? Why would the doctor “give” a medication instead of the doctor just informing the patient and the patient _choosing_ one? Why is the doctor considered by US legislation having the patient basically his ward, instead of just being his advice giver?

    • Murphy says:

      Because then it would become almost impossible to sue even when the doctor made a really stupid call or made a bad call for all the wrong reasons.

      Your doctor is getting kickbacks for every prescription of some medicine or just failed to keep their knowledge up to date and proscribed it even though there was a safer/better or one they could have given you? well it was in the small print of what you sign away all right to sue no matter what so sucks to be you.

  24. Dennis Ochei says:

    One solution is to have an algorithmic system that determines the right course of action. A large body of doctors determine the assumptions of the system and rely on the output. This will likely resuly in better than the national medical performance. If any doctor thinks the system makes a repugnant conclusion in a specific case they can suggest modifications to the system. Any doctor can choose in any specific case to follow the system or deviate from it. If they deviate and get sued, they and their personal malpractice insurance covers the case. If they followed the system and get sued, the cost is distributed across all doctors who are a part of the system. This could be implemented by the system as a whole having it’s own malpractice insurance. Personal malpractice insurance rates are adjusted, as joining lowers the chance that you will be personally sued. If qaly juggling is built into the system, then interventions that have rare but spectacular side effects will be used. Of course, this doesn’t solve the incentive problem, but hopefully we can assume doctors care more about helping people than a marginal increase in distributed legal costs. Lastly, given what we know, what we can do, and how much it costs, there is presumbly a right answer (as in most justifiable) to a given medical case. If so, we want more doctors to do it. There could even be built in A/B testing in cases where that answer is suitably murky. Lastly, any time the system gets sued, they can point to there data on national performance and spend ungodly amounts on any given legal case if they so choose, laying the smackdown on malpractice suits. Hmmm… I’m gonna go implement this…

    • Anthony says:

      Hmmm… I’m gonna go implement this…

      Do you work for Kaiser?

      • Dennis Ochei says:

        I guess it does sound a lot like a HMO, but you see it’s better, because I thought of it.

        I was thinking that 1) you stick in your notes and out comes a diagnosis and course of action. 2) the system wouldn’t actively try to push lawsuits on its doctors that followed it’s prescriptions. 3) The doctors have more say than I imagine a HMO gives. 4) Patients wouldn’t sign up with it.

    • Murphy says:

      This sounds a lot like NICE in the UK.

      They publish recommended treatments based on QALY’s and doctors are fairly well legally protected if they can show they were following best practice guidelines like that.

  25. Lurker654dot1 says:

    Yay! A topic I can finally add something to (maybe)

    Fun fact:

    Doctors routinely prescribe mood stabilising drugs that have horrible side effects, including SJS/TEN — they just usually prescribe them to treat epilepsy. Case in point: I have a fun type of (thankfully treatable) seizure disorder. Pretty much every drug I’ve ever been on ( has a similarly low risk of causing SJS/TEN and probably liver explosions. Still, I have yet to have a neuro dissuade me from taking any of these drugs.

    Now, I’m not saying that your theory of lawsuit-as-deterrent doesn’t hold water, just that it might be worthwhile to game out the analysis looking outside the purely psychiatric lens.

  26. namae nanka says:

    I would much prefer modafinil

    Didn’t affect me much, but then I was on such a cocktail that it probably couldn’t anyway. Left with a loud ringing tinnitus and headaches, and my head can’t get still.
    Had some cognitive effects as well, worse reaction times and working memory, besides what headaches would do to your normal self. The former seems to have recovered, the latter is still having problems considering the increased number of mistakes I am making while typing out posts like these.

  27. Faradn says:

    I can’t find the comment policy anywhere (hint to SA).

    The filters are Kind, Necessary, and what else again?

  28. busboy says:

    Shades of The Last Psychiatrist here … tysm for this post

  29. thisspaceavailable says:

    I would like to say something that may sound flippant, but I am quite serious. Due to verbally abusive behavior on his part, I find mention of gwern to be somewhat triggering, and I would appreciate Scott taking that into account.

      • Murphy says:

        huh, using trigger-politics to try to suppress even the mention of an opponent.

        I haven’t seen this tactic before.

        I was half expecting some typically really personal topic but apparently abstract geopolitics is enough.

        • thisspaceavailable says:

          I am not trying to “suppress en the mention of an opponent”. I have reported your comment for being both dishonest and antagonistic.

          “I was half expecting some typically really personal topic but apparently abstract geopolitics is enough.”

          While geopolitics was what led to the discussion, the central issue is that gwern thinks that the appropriate response to someone being confused by one’s statement is not to consider whether it was unclearly stated, but rather to immediately jump to personal insults. There is the further issue that there has, to a large degree, been the impression from other people that this sort of behavior is not deserving of any sanction. Gwern, in fact, cited his large amount of Karma as a counterargument to the assertion that his behavior was inappropriate. I.e. “I’m one of the popular kids, you’re not, so shut the fuck up.” Given that gwern has cited his prominent position as refuting complaints about his behavior, I think that it is legitimate to point out that Scott’s continued choice to speak of him favorably gives the impression of implicitly endorsing this line of thinking.

      • thisspaceavailable says:

        It is interesting that you have enough time to track down links and post them, but you don’t have enough time to explain how “the USSR would have no reason to think this serves a useful purpose, and would be therefore justified in concluding it was a bluff” is not, in fact, a reasonable reading of “the USSR had no reason to think and be correct in thinking it served a useful role for the USA which meant the threats were bluffs that were best ridden out”.

        If you simply were not allocating effort to responding to me, that would be one thing. But you have plenty of time to spend posting responses insulting me, but none actually making any effort to clarify your confusing comments for which you, in your narcissism, refuse to even entertain the possibility that they may be anything less than the paragon of clarity.

        I will also note that one of those links is you being an asshole to me after I attempted to engage in active listening and make sure that I understood your statement, and thus would fall under the category of things you did to earn my animus (although I did not start taking particular note of you until, rather than continuing the discussion in the original thread, dragged the discussion into another thread and presented my alleged obtuseness as some sort of rhetorical point). The other link you provide is simply disagreeing with the characterization of you as a rationalist, and therefore is a bit odd to be described as a cause of my “vendetta”.

  30. Albatross says:

    I know doctors hate this idea, but at some point patients need to make educated decisions and then sign a waiver in case their liver explodes.

    I think the most mainstream example is medical marijuana. Lots of people think given marijuana pills to kids is terrible, just terrible, until you explain morphine to them and then they understand aren’t choosing between tynenol and pot but against pot and other last resort pain killers.

    The patient or their designated decision maker is in the best position to decide if high sexual side effects risk, medium heart attack risk, or low risk of liver explosion or deadly skin diseases.

    These are clearly different decisions for a recently married person or someone already at high risk for heart attack or someone who already has a low sex drive.

    We let people elect to suck the fat out of their bodies at huge risk, we ought to let patients decide which suite of risks and side effects they prefer. A patient who doesn’t know about the other drugs doesn’t actually understand the risks.

  31. CThomas says:

    “of Seroquel, it’s just an ‘oh, so sad, I guess his time has come.'”

    I tend to think that the lawsuit risk cuts the other way in this situation. If you have a bad outcome taking a drug that doubles a small risk, everyone assumes the drug is responsible, and you get blame in all the cases. Take cigarettes as an analogy. Non-smokers get lung cancer at a certain rate. Smokers get it at a significantly elevated rate, but not astronomically elevated. Yet every single lung cancer victim who smokes is positive that the smoking is responsible. The result in these cases is usually a greater lawsuit risk, not less. The estate of everyone whose heart stops looks at the drugs the decedent was taking and immediately fixates on the fact they were on Seroquel, which doubled the risk. Problem solved! You get the risk of lawsuits in every one of those cases, not just the number reflecting the marginal increase in adverse outcomes. So this is the one part of the analysis that rang false to me.


    P.S. Let me edit this in advance to mention that the particular numbers in the smoking case are irrelevant. There are all sorts of different smoking-related risks and they involve elevations of ordinary risks by different factors. No matter what the condition and no matter what the statistical increase from smoking people almost always assume causality if it is a condition that has been shown to be associated with smoking. I’m sure the same is true of all sorts of other conditions associated with things besides cigarettes.

    • Anonymous says:

      You’re full of shit. The numbers do matter.

      • CThomas says:

        Thank you! That’s why I come here — for the articulate and well-reasoned thoughts like yours.

      • Murphy says:

        CThomas is factually wrong in respect to this statement:

        “but not astronomically elevated”

        but otherwise the actual argument is coherent and reasonable without the need for actual numbers in any particular case.

        • CThomas says:

          Thanks. I’m not sure it’s fair to call me wrong on that point given that I anticipated it and added a disclaimer about it. But as a complete aside, I wonder how much smoking does elevate the risk of lung cancer.

          • Anonymous says:

            Thomas, you’re a sheep-fucker.

            Disclaimer: made-up claim.

          • Murphy says:


            “Smoking, a main cause of small cell and non-small cell lung cancer, contributes to 80 percent and 90 percent of lung cancer deaths in women and men, respectively. Men who smoke are 23 times more likely to develop lung cancer. Women are 13 times more likely, compared to never smokers.”

            it’s actually one of those rare cases where “astronomically elevated” is a good description.

            But your argument in no way hinges on the specific numbers in any specific case, it’s just that in the case of lung cancer they’re right something like 90% to 95% of the time.

          • Jiro says:

            If the truth of the example didn’t matter, he could have used a hypothetical of, for instance, people who try using faith healing on their children being blamed for causing the death of their children even though in some cases the faith healing actually makes the children better. But we all know that he wouldn’t use this as an example, and we all know why (pretty much all, anyway).

          • CThomas says:

            Jiro, I have no idea what sinister motives you are ascribing to me, or why you think you “all know” why I wouldn’t use your hypothetical rather than the one I selected. Back here on planet Earth, I would be more than happy to use your example (although I wouldn’t have selected it ab initio because it isn’t really analytically akin to the case of a drug taken for purpose x that has the incidental effect of producing bad effect y). I’m sitting here wondering if you have confused me with someone else or if you are just one of these people like anonymous who just seem kind of deranged. I’m hoping it’s the former, or that there’s something else going on here that I’m just not following.

          • CThomas says:

            Murphy — thanks. That’s very good to know and a fair point.

          • CThomas says:

            Jiro, I don’t know if you’re still reading this but it would be a shame if this just sort of drifted away without any clarification. I’m honestly baffled about what you think everyone knows about my dark motives. Not looking to argue with you, just really curious what you’re thinking here and what your basis is for it. It’s up to you, obviously, but having made such a personal charge against me I would hope you would explain.


          • Jiro says:

            The cigarette smoking example uses a falsehood that 1) many people would really like to believe is true and 2) is actively being spread by evil people. Those factors will make the example more convincing than a random example. But they will make the example convincing for the wrong reasons.

            I wasn’t personally accusing you of anything but choosing an example because it’s more convincing while disregarding why it’s more convincing.

            Furthermore, it’s a bad example because it contributes incrementally to people having bad beliefs–someone’s going to read this and two years later only vaguely remember that cigarette smoking isn’t all that dangerous.

  32. Steve Sailer says:


    What you are seeing is that most smart people can’t really reason statistically. Most of the world isn’t like baseball where Bill James can actually change things in one lifetime just by persuading other people who can reason statistically just by correctness of argument that they should try a few things his way.

    Medicine is pretty bad, but there are even worse fields. If you were made Dictator of the Public Schools and every grown-up in the school system had to do what you said, you could probably raise test scores (and their underlying performance) by half a standard deviation in a decade.

    • HeelBearCub says:

      If you were made Dictator of the Public Schools and every grown-up in the school system had to do what you said, you could probably raise test scores (and their underlying performance) by half a standard deviation in a decade.

      This is the kind of statement that is so hyperbolic, that I don’t know whether it is actually intended to be taken seriously. And yet, it isn’t the type of hyperbole that could employed in some other way.

      Do you mean this statement seriously?

      • Anthony says:

        Considering the well-documented dysfunctions of the public schools which are caused by failures of rationality, I would agree with Steve Sailer that if somehow, Scott could impose his will on the public schools, and chose to do so by requiring people in the system to evaluate policies and proposals somewhat more rationally than they do now, that the results would be very significant.

        Hell, if we could get the public schools to stick to one not-completely-stupid fad for ten years, we’d see a pretty good improvement.

        • HeelBearCub says:

          which are caused by failures of rationality

          And making someone (anyone, I don’t care who) dictator somehow magically creates rationality among all actors? Hardly.

          Hell, if we could get the public schools to stick to one not-completely-stupid fad for ten years, we’d see a pretty good improvement.

          Which is caused by the fact that the problem is hard to solve, and everyone wants it solved. So people keep trying different solutions.

          This is especially true given the constraints around how funds can be raised and allocated. Unless we are contemplating making Scott “Dictator of All” and not just public schools.

          Is Scott going to solve the problems of using property taxes to fund schools? The problem of white-flight from public schools? The problems of entrenched poverty affecting educational outcomes?

          Is Scott going to clone himself and replace every board of education member, administrator, and parent?

          Just because Dictator Scott says jump doesn’t mean very many people will actually ask “how high”.

          • FacelessCraven says:

            @HeelBearCub – “Just because Dictator Scott says jump doesn’t mean very many people will actually ask “how high”.”

            …Isn’t part of being Dictator the ability to fire people who don’t cooperate?

            “Which is caused by the fact that the problem is hard to solve, and everyone wants it solved.”

            It might be uncharitable to say so, but I don’t think everyone involved does want this. At least, it isn’t the main priority. It seems obvious to me that preservation of the status quo and ideological partisanship are major drivers in the educational debate.

          • HeelBearCub says:


            Thus may be a dead thread, but I’ll hope you see this.

            Scott becoming dictator doesn’t make him magically able to assess the hundreds of thousands teachers, administrators, etc.

            And even he could identify those who need to go, he is even less able to assess everyone in the pool of possible replacements.

            At the end of the day it has to be about convincing, far more than dictating.

          • FacelessCraven says:

            @HeelBearCub – no thread truly dies.

            I contend that a large part of why “fixing education” is such an intractable problem is that the current political climate heavily penalizes any change to the status quo that isn’t a no-strings-attached increase in funding.

            I do not think it is a defensible position that we cannot define or measure education or the efficacy of specific educational methods. The fact that the current system is incapable of doing so is an indictment of that system, and the reasons for that failure do not seem mysterious to me.

            “Scott becoming dictator doesn’t make him magically able to assess the hundreds of thousands teachers, administrators, etc.”

            Schools can teach according to any method they like. Their students are tested quarterly or yearly. On a yearly scale, schools that fall below a certain threshold have their staff cleared out and replaced by new staff. Schools that hit the high threshold receive bonuses, and their methods are studied to examine why they work better. Obviously you would need to rigorously randomize student populations to prevent segregation by student quality.

            “And even he could identify those who need to go, he is even less able to assess everyone in the pool of possible replacements.”

            Cut off funding for the existing system, use that funding to build a new, better system. Hire people to do the assessment, develop metrics to gauge their performance. Again, I do not believe that this is impossible to do; it seems to me that the people currently tasked with doing it have a much bigger interest in protecting the status quo.

            …The above probably has practical problems. I’m pretty sure they aren’t unsolvable. The current system, where there appears to have been zero accountability for a half-century or more, seems obviously worse. The causes of the current system seem almost entirely political to me: an educational bureaucracy that has successfully escaped meaningful oversight, protected by a powerful halo effect and deep cultural biases, together with the selfish interests of parents trying to get their children into “good schools”. A dictator, being unconstrained by political concerns, could cut the Gordian knot relatively easily. Lacking a dictator, we can still cut the knot with some difficulty.

            Maybe the above is terribly naive and simplistic. Do you think effective oversight exists in the current educational system? Do you think meaningful definition and measurement of education are unsolved problems? Do you think the current system gives good incentives?

          • HeelBearCub says:

            ” Obviously you would need to rigorously randomize student populations to prevent segregation by student quality.”

            Well, now you are making Scott dictator of all, and not just education. This takes funding, funding that the education system is not in direct control of.

            In addition, it takes the cooperation of the parents. Post Brown v. Board and the Civil Rights Act of 1968, white flight was (and continues to be) a real actual thing. If you push to hard on this “rigorous randomization” the result will be to make the average school population poorer, and then it will result in enclaves of the well off who opt-out of the public system all together.

            As an example of the kinds of pressures here, in NC the Wake County School system has been in a back and forth brawl over the last 5 to 10 years or so. In the aftermath of the civil rights act, Wake County joined two the two districts and had a very successful busing program that had made Wake schools perform very well overall (especially in serving the lowest income students) “According to U.S. News and World Report, in 2005, 63.8% of low-income students in Wake County passed the state’s end of high school exams, which was significantly higher than surrounding counties that do not have similar integration policies.”

            Wake County also has a nice fat tax base and decent property tax rates (although not nearly as sizable as Orange County).

            But still, parents near rioted that kids were being bussed. They wanted neighborhood schools. Good luck trying to change by dictate what parents want.

            Look at what has happened in Atlanta, where they keep chopping everything up into new municipalities. Does Scott as education dictator get to decide municipal and county boundaries?

            The net effect of simply taking poorly performing schools and squishing them will simply be to churn the poorest schools. Good luck getting results out of that approach.

      • Murphy says:

        I believe that claim would involve increasing the mean SAT scores by 50 points.

        looking at graphs of historical averages it looks like there was a drop of about that size in a decade so a similar rise wouldn’t be that absurd unless the drop is due to changes in how it was scored.

  33. Doug S. says:

    If you’ve got to give adults a stimulant, I would much prefer modafinil. It’s not addictive, it lacks most of Adderall’s side effects, and it works pretty well. I’ve known many people on modafinil and they give it pretty universally positive reviews.

    I wouldn’t be surprised to find that modafinil works pretty well for energy levels, but I don’t have any particular reason to believe it would help ADD symptoms the way dopamine-affecting stimulants such as Ritalin, amphetamines, and cocaine do.

    • Scott Alexander says:

      It’s used as an ADD drug in Europe, and I think was going to be marketed as one here too, but it actually does cause SJS at a higher rate in kids, and since kids are such a big part of the ADD market it was withdrawn..

      • Deiseach says:

        since kids are such a big part of the ADD market

        That is such a horribly depressing statement 🙁

        • houseboatonstyx says:

          “since kids are such a big part of the ADD market”

          That is such a horribly depressing statement

          As to “the ADD market”. Kids are not the buyers. The buyers are parents, partly at the advice of schoolteachers and other adults who are inconvenienced by some behaviors of some kids.

          Perhaps some partial solutions might correlate with Woo. Homeschooling, so there are no outside teachers to complain. If schooling outside, then a Woo influenced school that does not require much sitting still and quiet. Woo avoidance of substances that former generations were not exposed to. Etc.

          • Deiseach says:

            The only child I knew with ADHD was the son of a co-worker, and it wasn’t simply “fidgety in class”, he had the involuntary vocalisations (he’d make ‘barking’ noises or loud ‘hah!’ noises), spasmodic movements (jerks and facial tics) as well as the impulsiveness, restlessness, and the rest of it.

            I don’t know what he was prescribed, but it genuinely was a problem that his parents tried several doctors to get sorted. I don’t know if any of the kids with behavioural problems in the school were diagnosed ADHD, some of them could certainly have been classed like that, but (at least five to ten years ago) the idea of stimulants being a common prescription for kids certainly wasn’t present in Ireland.

            I don’t know what current practice is here. But the idea that there’s a huge market for these drugs, and that the majority of it is for young people, makes my heart sink. Maybe it is genuinely necessary in all the cases, but it’s still not very heartening to think that so many children have this condition and need to be medicated for it.

  34. Jane says:

    Oh, hey, an actual American patient prescribed nefazodone, here! I got on it about the only way anyone gets on it these days: I (1) had depression, (2) had had a particular bad side effects on multiple other antidepressants of various classes, and (3) was a mental health professional with unfettered access to PsycINFO who did her own damn homework.

    Your fine post isn’t actually about nefazodone, specifically; it’s using it as an example of poor risk evaluation. Appreciating that, I still want to mention some things about nefazodone and prescribers to you, because, hey, my favorite antidepressant.

    It’s not just risks that prescribers remember in half-assed ways, like in your example about the psychiatrist who wasn’t going to proscribe modafinil: it’s also indications. Everybody remembers that nefazodone is That Antidepressant For People With Libido Problems on SSRIs. Nobody remembers the other big problematic SSRI (and antidepressant) side effect nefazodone doesn’t have.

    The reason I wound up on nefazodone is that all the other antidepressants I tried caused me profound insomnia. They made it impossible for me to sleep at all without chemical intervention, and even with some complimentary sleep medication (btw, thanks for the heads up about anticholinergics), my sleep efficacy was dreadfully poor, such that I was sleeping 10hrs a day but being exhausted all the time. So I hit the lit, and discovered Armitage, R. (2000) The effects of antidepressants on sleep in patients with depression Can J Psychiatry 2000;45:803-809, and Brunello, N, Armitage, R, et al. (2000) Depression and sleep disorders: Clinical relevance, economic burden and pharmacological treatment Neuropsychobiology 2000;42:107-119. Obviously this information is now pretty dated, and I’d be pleased to hear from anyone with more recent info, but the upshot was that nefazodone singular in reducing sleep latency, improving sleep efficiency, and not merely not suppressing REM sleep, but increasing it.

    Now, myself, I found that nefazodone did impair my sleep, though not as much as escitalopram, and certainly not as much as any other antidepressant. I found having an antidepressant I could tolerate was worth the risk of liver explosion.

    Talking with my prescriber, I get the impression that, contra above, it wasn’t the doctors who rejected it. I had been concerned that she would not feel comfortable prescribing me a medication associated with exploding livers, but she was cool with it. No, I get the impression that the people who freaked out about the remote possibility of exploding livers were the patients, who were panicked by the media coverage.

    That would fit my experience as a clinician, discussing with my patients the meds they’re on. It’s not uncommon for someone to come into my office and suddenly want to d/c a medication because, “My buddy Joey just told me he saw on TV that it can cause strokes in left-handed Inuit redheads! Is there something else I could take?” In my experience, it’s the patients who are risk-averse and easily discouraged from a medication, while the psychiatrists and other psychiatric providers are mostly pretty phlegmatic about risks. Admittedly, that may have something to do with the small N of psychiatric providers I’ve worked with; I can think of one exception, and it could be that he’s the typical one.

    I get the impression that prescribers don’t bother offering it to patients because, well, why bother? There’s so many other medications, and maybe one of those won’t kill the patient’s libido. And they expect the patient to freak out at the liver-exploding thing.

    • Steve Sailer says:


      Sleep is a huge deal.

      As a full-time blogger with fairly stable quality control standards, I can measure my productivity in a straightforward fashion: the number of blog-worthy ideas I have per day is closely correlated with the number of hours of sleep I have. The Y-intercept is around five and the slope is about 1.5 decent blog posts per hour of sleep above that. For example, 9 hours of sleep equals about six quality posts.

    • Anonymous says:

      And do the patients freak out about death, or about the specific problem of livers exploding?

      I was just hearing about an FDA approval process where there was (a suspicion of) a small chance that the drug would cause cancer. It was a very simple cost-benefit analysis, not mobidity vs mortality, no QALYs, just 100 heart attacks vs 1 cancer. Yet the belief in the drug company was that patients were terrified of cancer in a way that they were not worried about heart attacks.

      • Jane says:

        I wouldn’t know about livers exploding, specifically, since I’ve never seen a patient offered nefazodone. But, yes, I think some illnesses are much scarier than others to patients.

        Which is not to say they shouldn’t be. There is a joke among medical people: “Cardiologists see how heart patients die, so they’re all diet-conscious, regularly-exercising, clean-living freaks. Oncologists see how cancer patients die, so they’re all why-yes-I’ll-have-a-second-serving-of-pie bon vivants.”

        So I don’t think it’s even wrong to be more afraid of dying of cancer than afraid of dying of heart attacks. The destination may be the same, but the trips sure are different.

        When I was discussing my choice of nefazodone with my prescriber, I pointed out that most of the other meds we were discussing had a risk of extrapyramidal side effects. Maybe that doesn’t sound like a big deal to anybody else, but I’m pretty sure Tardive’s Dyskinesia would be the end of my professional career, while I could practice just fine with somebody else’s liver in my middle. Patient tolerance of side effects can be pretty idiosyncratic, highly dependent on personal circumstances.

  35. Anthony says:

    Aren’t MAOIs that way because the potential really bad reactions to certain foods, etc., are actually pretty common?

    • onyomi says:

      I have a friend who found relief on an MAOI after many years of suffering with severe depression seemingly non-amenable to SSRI treatment. It was only after years of going to psychiatrists that one of them even mentioned it as an option, basically because they’re all afraid of the bad possible interactions. And that’s understandable, but for some they seem to be the only thing that works.

    • Scott Alexander says:

      I’ve been told very uncommon – so much so that they were out on the market without any warning for about a decade before someone noticed them, and that was only because it was a psychiatrist’s wife who had the reaction and he managed to put two and two together.

  36. emily says:

    Maybe Serzone could be made safe if it were handled the way Clozaril is- to refill your prescription ever couple of weeks or month or whatever the studies show, you have to get a test of liver function first. The would make it less economical and a real bother to be on- but I know a lot of people who can’t tolerate the SSRI’s because of the SSRI’s emotional blunting and sexual side effect, don’t respond to wellbutrin, and their doctor won’t give them an MAOI.

    • Scott Alexander says:

      There’s a recommendation for regular liver monitoring on Serzone, but I can’t find any statistics about whether it helps or not.

      • Murphy says:

        “As of December 2002, there were 51 Canadian reports of hepatotoxicity, ranging from no symptoms to transplantation, suspected to be associated with nefazodone use. One of two transplant recipients subsequently died. Cases of liver injury have occurred as early as a few weeks after initiation of therapy or after continuous use for up to 3 years. To date, no risk factor to predict patients who will develop irreversible liver failure with nefazodone has been identified. Also, no clinical strategy, such as routine liver function tests, could be identified to reduce the risk of liver failure.”

  37. Alsadius says:

    > And something like 25% of users experience “emotional blunting” and the loss of ability to feel feelings normally.

    Isn’t that exactly the same as depression, which is the thing the SSRI is trying to cure?

  38. US says:

    “If you take this drug, there’s a one in 300.000 risk of you dying from liver failure within the next year,” said the doctor to the patient before he started treatment (assuming a worst case scenario where all patients with the side effect die). “This is roughly ten times less likely than you getting a royal flush during one hand of Texas hold’em.”

    If the doctor communicates the risk to the patient and even makes an effort of making the level of risk apparent/conceivable to the patient, how is he ever liable? If the risk is communicated to the patient, how is the liver failure ever the doctor’s fault? If the side effect is known and the risk of the adverse event communicated openly to the patient, it seems insane to me to fault the doctor, yet the assumption seems to be that the doctor wouldn’t have a leg to stand on. I don’t understand this? Do people making the decisions in medical trials assume that health care consumers are children who can’t read or understand simple words? What happened to the concept of informed consent?

    • Scott Alexander says:

      That’s a good question and I don’t know the answer. Which is itself sort of an answer, because people like me who don’t know the answer are the ones who have to prescribe this drug.

      Certainly if I ever prescribe nefazodone it will be after making the patient sign a form saying that I have explained the side effects to them, and the alternatives, and so on, and they have agreed.

      Will that be enough? It’ll help. But I think a lot of malpractice cases basically depend on how the jury is feeling that day. If the jury thinks “Well, yes, he signed a consent form, but then he died horribly, and his family is so devastated, and the doctor is probably rich anyway…” well, so it goes.

      It doesn’t help that the standard by which malpractice cases are judged is “Is there a reasonable body of medical opinion supporting what the doctor did?”. Right now I’m not sure I could say with a straight face that there’s a reasonable body of medical opinion supporting giving nefazodone instead of Seroquel. “The reasonable body of medical opinion is wrong and I’m right” is not necessarily a defense.

      Overall I think that if you really cover your bases you can be pretty safe. But for a lot of doctors that’s a trivial inconvenience they’re not willing to take when appointments are only supposed to last like fifteen minutes.

      • US says:

        Thanks for the reply.

        “It doesn’t help that the standard by which malpractice cases are judged is “Is there a reasonable body of medical opinion supporting what the doctor did?”.”

        I was not aware of this. This thought immediately occurred to me:
        “Well, we’ve been using mercury to treat hysteria in women for decades, and it is the opinion of most medical men that this is a good treatment option.”

        Oh, well.

        I was assuming you were going to have to discuss benefits and risks associated with the treatment options at hand either way and so I had not considered this aspect, but it makes perfect sense that if there’s a minor additional cost associated with doing things ‘right’, choosing the (from the patient’s perspective) optimal solution may well be a dominated strategy.

        • Devilbunny says:

          I was assuming you were going to have to discuss benefits and risks associated with the treatment options at hand either way

          Even setting aside the issues Deiseach raises, the problem is that there is very little evidence, period, in most medical matters. And the granularity of the decisions that are made is such that it is essentially impossible to gather such evidence – for example, is side effect X more common in obese white men over the age of forty with type 2 diabetes? Given that setup, is it more or less likely if they also have obstructive sleep apnea (and how do you define that? Do they need a formal, sleep-study-based diagnosis, or will history alone suffice? For that matter, how many apnea-hypopnea episodes per hour define someone who has OSA?)? Multiplied by the thousands.

          Best to run with the herd. When I don’t, I make sure I have a reason that I could explain to a child and plenty of safeguards for predictable bad outcomes.

      • Deiseach says:

        The trouble is, anything to do with mental illnesses, and the standard rejoinder to “But he signed a consent form” is going to be “But he wasn’t capable of informed/meaningful consent because his mental faculties were affected”.

        It won’t matter in court if “But the chances of my patient developing liver failure were very, very small”, the question the lawyer for the patient (if they got a liver transplant and are still alive) or the family (if the patient died) will be asking is “Did you know there was a risk of this, yes or no? Are there alternative drugs for the condition that don’t have the associated side effect of liver failure, yes or no? So why did you prescribe this one?”

        I don’t know enough about insurance companies to know if the life insurance of the deceased would be paid out unless the family agree to sue for malpractice – anyone know about that? All I know about insurance is seeing grant applications to my place of work for repairs to roofs, because the insurance company refuse to pay for such work on the grounds that it’s natural wear and tear and not covered by the house insurance policy. Really, insurance seems not so much like “In case something happens” but “Any excuse not to pay when it does happen”.

        • RCF says:

          My completely non-expert understanding is that once an insurance company pays a claim, it receives all the rights and privileges associated with whatever was insured. So, for instance, if you claim that someone crash into your car and it’s been totaled, and accept a check from the insurance company for it, the insurance has the right to take possession of the car, and the right to sue the person who crashed into the car. If an insurance company has to pay out a claim because of someone’s death, the insurance company has standing to sue for wrongful death.

      • Steve Sailer says:

        Eventually what needs to happen is that some law school (e.g., U. of Chicago) gets a big grant to make Scott a lecturer on using statistics to think about health care and a generation from now, federal judges who took a law school class from him write the decisions.

      • I suppose it would be tacky to ask a patient “Do you tend to bear grudges? Do members of your family tend to bear grudges?”

        Seriously, I think the malpractice system rewards the angriest people at least as much as it rewards the people who’ve been hurt the most. Am I right about this?

        • Deiseach says:

          What I’ve tended to notice in Irish malpractice cases is that a lot of the families say “We didn’t want to go to court but…

          … we couldn’t get an explanation any other way/the hospital kept fobbing us off and treated us like a nuisance/if they had answered our questions at the time we never would have gone down this path/we want to make sure this doesn’t happen to anyone else”.

          Now, maybe it’s not wanting to sound greedy, but hardly anyone ever says “We wanted financial compensation” (in those cases, it’s usually for children who suffered brain damage during delivery and need expensive care for the rest of their lives).

          I wonder if the tendency of hospitals/doctors to try and avoid blame by stonewalling and not saying from the start “yeah, we screwed up” for fear of “admission of blame means you’ll be skinned in court” actually makes things worse, because the survivors/families get so angry about being jerked about, they do go to lawyers and do look for punitive damages?

          • Anthony says:

            I’ve read somewhere that most (smaller?) malpractice cases start as billing disputes.

            I have used the credible threat of a malpractice lawsuit to get a hospital to back off from collecting a $50 ER co-pay.

            Credible, because yes, they did screw up. I explained what happened, and that I was completely unwilling to pay any of my money for that failure to provide service, and that if they insisted, I would instead collect money from them. Their reply was to send me a letter apologizing and waiving my co-payment.

          • Douglas Knight says:

            Gawande agrees that accepting blame is a good way of heading off malpractice suits.

        • RCF says:

          I’ve heard of studies that find that the biggest predictor of whether a doctor will be sued for malpractice is how the patient feels about the doctor, rather than the actual facts about the case. So malpractice laws punish doctors with poor people skills.

  39. Princess Stargirl says:

    This post is too depressing :(. I should not have read it.

  40. onyomi says:

    I think it is a dynamic which plays out more broadly at all levels in society. In hiring, for example, I notice people often hire the “safe,” “experienced” candidate over the dynamic candidate who may or may not have a lot of potential. This is because they will never be blamed that the safe candidate didn’t become a superstar, but they will be blamed if the more high-risk-high-reward candidate is a disaster (and will probably not receive corresponding credit if he/she does become a superstar).

  41. Protagoras says:

    On your modafinil vs. amphetamines comparison, I tried modafinil, and in my experience I seemed to build up a tolerance to it relatively quickly. I had no similar problem with amphetamines. I’ve also read that my experience with modafinil is not unique in that respect, so that might be a better reason for not preferring it to amphetamines. Of course you admit that there are other issues besides those you mention, but this just didn’t seem as clear a case as your main nefazodone vs. SSRI comparison.

    • Not That Scott says:

      Possibly the improved wakefulness effect attenuates, but not the improvement in executive function? Pharmacist-friend tells me they see patients on daily modafinil for years with no expectation of tolerance developing.

      • Protagoras says:

        No, it was the improvement in executive function that seemed to fade (and not be as good as amphetamines to begin with, for that matter). But of course effects on different people differ.

    • Anon256 says:

      Yeah, I was quite surprised to read “I’ve known many people on modafinil and they give it pretty universally positive reviews.” The reviews on LessWrong are negative on average. When I took modafanil I noticed zero improvement in executive function, all I got was delayed sleep by 12-18 hours (and sleep when it came was fairly long, so I only barely came out ahead on total waking hours). I’ve talked to a lot of people with similarly underwhelming experiences. Whereas the consensus on adderall seems to be that it’s scary (too scary for me to try) but get’s the job done.

      • nydwracu says:

        Modafinil is hitting the gas. Adderall is strapping a jet engine to your car. Both of them will get your car someplace in a hurry, but only one of them will reliably let you drive it.

        • Protagoras says:

          That metaphor could hardly be less accurate for my experience of the two drugs.

        • HeelBearCub says:

          I barely notice when I take adderal XR. When I don’t take it I am moody and irritable and tired.

          Definitely no jet-pack for me.

      • Squirrel of Doom says:

        Sounds like the people who it works for keep taking it for a long time, and those who don’t quit soon.

  42. B Willman says:

    Punt the QALY guessing and think about the “how does society function?” question.

    People who are unhappy because they can’t have sex still generally can raise their children, help raise their grandchildren, go to work, and pay taxes. Therefore, by natural selection upon societies as a whole, they are favored over people who are dead.

    People who die because their liver explodes don’t raise children or grandchildren nor work nor pay taxes.

    • Creutzer says:

      Therefore, by natural selection upon societies as a whole, they are favored over people who are dead.

      How many societies has history seen perished because doctors prescribed medication with better effects, but rare lethal side effects?

    • If people who are unhappy because they can’t have sex do just a little worse in your list of “useful to society” functions, a large number of them “cost society” more than one person who dies.

      Or in other words, you are treating a continuous variable as if it was a binary variable—as if people are or are not useful to society rather than being more or less useful to society.

    • Anthony says:

      David Friedman makes an excellent point.

      Also, on the margin, the number of people whose medication-induced sexual dysfunction is what pushes them over the edge to suicide might be higher than the number whose liver explodes.

    • RCF says:

      Why in the world would I give a fuck about how well “society” is doing, apart from how it’s affecting people’s quality of life? And then to top it off you muddle the waters even more by adding in natural selection.

  43. Keratin says:

    So, question. I’m 21, I take Seroquel for anxiety, and I occasionally get fairly light chest pains that don’t seem to be a result of my diet or exercise. Should I be worrying?

    • Not That Scott says:

      (I am not a doctor nor do I have any qualifications that lend credence to my speculations)

      No, because worrying will make your life worse. It’s not like if you worry about it, your heart actually will stop; your heart will be fine either way but you’ll be less happy and less comfortable.

      When you read something like ‘seroquel raises the risk of heart failure by 50%’, remember that it raises the risk of heart failure by 50% the way buying a third lottery ticket raises your chance of winning by 50%.

      “In the US, an estimated 5 million patients per year present to the Emergency Department with chest pain” gives us 1 per 80 people for the incidence of ’emergency’-level chest pain, which yours is significantly less extreme than.

      I’d suggest thinking about this as something like the “I take daily low-dose aspirin and I have a pain in my head, is it stroke or headache?” question.

      • Keratin says:

        Yeah, I am aware of relative risks and the “flashy rare side effects” given in the title. I guess I mostly made this post because I was surprised that something actually matched up with my experience.

    • Scott Alexander says:


      Since you’re 21 and healthy, you probably have an even lower risk than the 1/20,000 year average. Chest pains are very common including as a result of anxiety (panic attacks). I would say don’t worry – but if you insist on worrying, ask for an EKG, which is a very basic test and would rule out a lot of the problems and which isn’t a terrible idea anyway for antipsychotic monitoring.

  44. yli says:

    Scott, you’re always complaining about how people don’t get the real point of the torture vs. dust specks problem. They aren’t able to see the difference between “millions” and 3^^^3. They can’t see how none of the arguments they cook up about stuff not aggregating linearly and whatever can stand up to how big 3^^^3 is.

    And then you go and muddy the waters and compare this situation with antidepressants to dust specks vs. torture! Are you trying to undermine your own work here!? 🙂

    • Rowan says:

      That characterisation sounds a lot like the way people opposed to the dust specks argument characterise it when they’re trying to strawman it to death: “you can’t even understand how big a number 3^^^3 is, therefore you should torture people to prevent dust specks in people’s eyes”.

      What sort of arguments against utility aggregation even exist that make sense for “millions” but not for 3^^^3? The very concept they’re arguing against is the idea that you can change things just by making the numbers on one side of the equation bigger, why would your strategy to defeat such arguments be “let’s make the numbers even bigger!”

      The dust specks argument isn’t even really an argument for utility aggregation at all. It’s a thought experiment directed at those who already believe utility aggregates, to test that fact and maybe get their aliefs in line with it.

      • yli says:

        I don’t think it’s a strawman at all. I think being unable to make a distinction between 3^^^3 and merely astronomical numbers is common and makes smart people say transparently stupid things all the time. Here’s a couple of examples:

        * A million dust specks is obviously less bad than torture. A million dust specks is probably less bad than one painfully stubbed toe. Everyone would agree with this, I think. But when you’re being pro-dust specks you have a hard time getting this. You expect the an anti dust speck person to also tremble at a million dust specks. That’s because you don’t see a difference between 3^^^3 and a million.

        * People keep trying to come up with concrete examples of “nonlinear aggregation”, like “having a toothache for an hour is not 60 times as bad as having it for one minute, it’s… lemme see… at least a THOUSAND times worse. There you go, that’s nonlinear, so therefore 3^^^3 dust specks is less bad than torture.” As if these meant anything about dust specks vs. torture. They work for comparisons on the scale of a million, but 3^^^3 swamps any nonlinearity that you can come up with. This isn’t obvious to people – again because they don’t get the difference between a million and 3^^^3.

        Of course none of this means specks is the wrong choice. The world’s stupidest man may say the sun is shining, etc.

        • Janos says:

          I think a million dust specks is definitely worse than a stubbed toe. I also think a million stubbed toes are worse than 1 decades-long sexual dysfunction (in a person who experiences it as such, rather than as a different orientation or something), and a million of those is worse than a second of torture, and a trillion of those is worse than a typical human lifespan of torture.

          So I think one person getting a lifespan of torture is better than a nonillion people getting dustspecked. A large number is required, but it doesn’t have to be unfathomably large, like 3^^^3.

          And a nonillion is fairly loose also – a second of torture might not actually be worse than, say, a million dust specks. (imagine getting a dust speck every twenty seconds during every waking hour, for a year! Seems awful to me, and at least half the harm seems to be of the linear sort such that it’d be just as bad if each dust speck went to a new person.)

        • Zykrom says:


          “A million dust specks is probably less bad than one painfully stubbed toe”

          If each second causes one second of irritation, a million of them would be the equivalent of over ten day of irritation.

          • HeelBearCub says:

            No, it wouldn’t.

            Each of these 1 seconds is occurring in an individual person, not in aggregate.

            If I make a million plain m&m’s, and instead of the aggregate 10 peanuts that are in the the 1M pieces, we change it to 11 peanuts, no change has happened, except perhaps for those with a fatal peanut allergy, who already shouldn’t be eating candy processed in a facility that handles peanuts.

            This does not change if we add 10 peanuts to a trillion m&m’s, or 100 peanuts to a Quintillion m&m’s. It doesn’t change the fact that that number of peanuts is just statistical noise.

            No one here would accept the possibility that homeopathy was doing anything for the individual, nor should we accept that the next speck is going to do anyone any harm (especially when any actual harm is explicitly ruled out by the framing of the problem).

            And even better, the dust speck problem is actually adding 1 extra dust-second to hundreds of those events in a lifetime of 2.2 billion seconds.

          • Zykrom says:

            How does the m&m metaphor not apply to the stubbed toes as well? Over a lifetime, they will both be insignificant.

          • HeelBearCub says:


            I would argue that adding one stubbed toe to an individual life is equivalent, especially since we can artificially constrain the outcome to only the temporary pain involved in stubbing the toe and we can rule out stubbed toes in people with bleeding disorders or bone disorders, stubbed toes at a particularly bad time such that it leads to other negative outcomes, etc.

            The only way the really large number starts to have an actual impact is if you start taking into account the probability that dust speck(s) or stubbed toe(s) lead to other negative outcomes, then the bad outcomes really start piling up and you will have an untold number of deaths, maiming, lifetime comas, etc.

            But the actual dust speck or stubbed toe is trivial noise.

            To really illustrate this, don’t use a dust speck, use “catching a glimpse of a room painted in a color you find unappealing”. Not even one you have a visceral “ewww” reaction to, just one you don’t like.

            So if 3^^^3 people catch one extra glimpse of a room they don’t like, does that trade vs. a lifetime of torture? Or make it 3^^^^3. Heck, throw as many carets on as needed to find the number to be “large enough”. It still won’t change the impact you had on each individual life.

          • Zykrom says:

            I think I agree with you.

      • Anon256 says:

        I think many people respond to statistics about suffering in a roughly logarithmic way, where a million people dying of famine is worse than 100,000 dying of famine, but only by about the same margin that 100,000 is worse than 10,000. If you generalise this to logarithmic utility aggregation then mere “*illions” of dust specks are hardly bad at all, but 3^^^3 is so big that even after taking logs it’s still far worse than torture.

        • Jiro says:

          I don’t think that’s correct. Maybe “many people respond to statistics about suffering in a way which is roughly logarithmic over the ranges of suffering for which they are typically expected to respond”, which isn’t the same thing. Responding roughly logarithmically to 1000, 10000, and 100000 doesn’t imply that the logarithmic response goes all the way to 3^^^^3, and if it didn’t, you’d never notice it because nobody gets confronted with dilemmas that go to 3^^^^3. except in thought experiments.

          • Anon256 says:

            People don’t really have any intuition at all about 3^^^3. The only way to reason numbers that big is by attempting to draw consistent generalisations from your intuitions about smaller numbers.

      • Doug S. says:

        The size of the Nearly Infinite number is something of a red herring. The fundamental question of the “torture vs. dust specks” dilemma is this:

        Is an infinite number of trivial harms finitely bad or infinitely bad?

        It’s “intuitively obvious” that one person getting tortured for fifty years is finitely bad. Similarly, it’s “intuitively obvious” that inflicting a trivial harm on N + 1 people is worse than inflicting it on N people, regardless of the value of N. What’s not intuitively obvious to me is whether the amount of badness approaches infinity as N gets larger and larger. If I try to ask my moral intuitions if the badness of trivial harms is bounded or unbounded – if it eventually becomes worse than any single finite harm if you just keep piling enough of them on – my moral intuitions just get confused and refuse to answer.

  45. Tinfoil Hat Wearer says:

    If antidepressants cause sexual dysfunction, and depression is largely genetic, then this is a very impressive eugenics program.

    • Zykrom says:

      iirc depression is positively correlated with iq, I predict that most mental illnesses are probably correlated with something somewhat good in general.

      • Anonymous says:

        Seems reasonable, after all, otherwise these types of illnesses would have been long since removed from the gene pool.

        Kind of like how heterozygous sickle cell protects against malaria.

        • A mental illness could also be caused by harmful recent mutations (mutational load) or by a disconnect between our ancestral and current environment.

          • Zykrom says:

            Isn’t it pretty unlikly that mutational load would regularly reproduce the same illness?

          • switchnode says:

            Isn’t it pretty unlikly that mutational load would regularly reproduce the same illness?

            Not really; why should it be? There are some loci more prone to mutation than others, there are some important genes that we have fewer copies of than others, and there are some long metabolic pathways that have pretty much the same failure modes regardless of what step is interfered with.

          • Douglas Knight says:

            Zykrom, it is observed that multiple infections produce a side effect of permanent narcolepsy. If that is true, then surely many different mutations can lead to the same place. But this is merely evidence that it is true, without addressing how it could be true. (switchnode’s third point is rather better than his first two)

    • Scott Alexander says:

      Depression is less genetic than most things, surprisingly. This might be part of the territory, or it might be a sign that we’re not defining it very well.

      • Lambert says:

        What would a more genetically-correlated definition look like?

        • Douglas Knight says:

          The idea is that we have lumped together two unrelated diseases and called them both “depression.” If Scott actually knew how to properly divide them, that would be a very big deal, the heritability being the least significant consequence. But it’s easy to imagine that there are two diseases without being able to identify them.

          For example, “diabetes” consists of the totally unrelated type 1 and type 2. The heritabilities of the individual diseases are higher than the lumped disease (in particular, the two diseases are negatively correlated across races — type 1 is almost exclusive a disease of whites, while type 2 is relatively rare among whites, at least controlling for BMI).

          For another example, maybe people used to lump manic depression and straight depression together. Surely the heritability figures are higher now than if they had been computed back then.

    • Edward Scizorhands says:

      Without SSRIs I wouldn’t have been social enough to meet my wife and reproduce.

  46. Richard Metzler says:

    I’ve had some thoughts about why a gazillion specks of dust probably ARE worse than one guy getting tortured, and maybe they apply here as well.
    Basically, life isn’t linear. You can’t assume that people just accept non-fatal suffering, and then go on with their lives. For every 1000 people who learn to live with a diminished sex life, and then just live on with a little less fun, you may have a few (or more than a few) where you can draw a straight causal chain: diminished sex life -> unhappy wife -> costly divorce -> loss of apartment, loss of job -> homelessness, alcohol, drugs, death. As Scott points out, no one can say with certainty, “oh, that poor bum died of the side effects of his anti-depression medication”, so the doctor is on the safe side, but in a utilitarian calculation, these cases should still be taken into account.
    Things get even worse if nefazodone is in fact superior as an anti-depressant. For every poor fellow who has his liver explode, you might have dozens, or hundreds, who don’t commit suicide because their depression was treated more effectively. (I’m pulling these numbers out of thin air – just arguing a possibility.) Of course, depressed people who don’t die of suicide are unlikely to show up in any statistic…
    Generally, what I’m saying is that negative events can’t be assigned a single predictable cost on some utilitarian scale. They may have a typical cost, and around that a distribution with a tail that may be very wide, and if the event is frequent enough, the tail may make a significant contribution to the overall calculation.

    • LRS says:

      Great comment.

    • Alexander Stanislaw says:

      This is absolutely relevant in the real world but I don’t think that captures the essence of the dust vs torture thought experiment. Under utilitarianism, it is the sheer discomfort of the dust speck itself multiplied over an unimaginably large number of people that is supposed to be greater than the suffering of one person who is being tortured, not the consequences of it.

      To make this explicit, suppose those dust specks would all go into the eyes of people on their death bed about to die. Is there any number of dust specks that it would be worth preventing more than one person being tortured?

      • “Is there any number of dust specks that it would be worth preventing more than one person being tortured?”

        The logical answer is yes. The intuitive answer is no.

        I take that as evidence that human intuition is bad at handling very large numbers or very small probabilities.

        • TeslaCoil says:

          I don’t see any logical reason why dusts specks have to be commensurable with torture.

      • Richard Metzler says:

        Yes, I get it that the dust speck thought experiment is supposed to illustrate some pathological limits of comparing suffering. If you assign a very small, but non-zero, cost c_d to a speck of dust (as you should), and a very large, but not infinite, cost c_t to lifelong torture (as you should), their ratio c_d/c_t will be very very very small, but still not zero. If you multiply that with a number that is, for all intents and purposes, infinity, you end up with a number larger than 1. Big whoop. The applicability of that to real life is, of course, limited by the availability of a practically-infinite number of occurrences.
        That shouldn’t keep you from asking if assigning a single cost to the chosen nuisance (the dust speck) is a reasonable step, or has hidden assumptions that could spoil the argument.

        • HeelBearCub says:

          I think the dust speck problem actually has bigger issues.

          Everyone gets dust specks in their eyes during their life. Adding 1 more to the many won’t change a persons life in any way. Note, I don’t mean “any meaningful way”. I mean “in any way at all.”

          Much like adding or subtracting a single grain of salt when making 10 gallons of a 1% salt solution makes no difference in the end result, so adding or subtracting a dust speck in the eye from a persons life makes no difference whatever to their life.

          Note, I am not considering people who have eye conditions that make this intensely painful or possibly impairing, and I am also not considering poorly timed dust specks that cause car crashes, as these are all explicitly ruled out by the way the problem is framed.

          • Jiro says:

            By this reasoning, adding a ton of salt to the solution doesn’t affect it either. Proof: One grain doesn’t affect it. Another grain doesn’t affect it. Continue until you added a ton.

          • HeelBearCub says:


            Only if you take seriously the philosophers argument that you can never get anywhere because first you have to go half-way there.

            You have to look at the integrated whole, not each individual delta.

          • Jiro says:

            That philosopher’s argument is wrong because the distances are decreasing each time you take another half. If the distances are decreasing, an infinite number of steps can have a finite sum. The additional grains of salt here are not decreasing, and the sum is infinite.

          • HeelBearCub says:

            Dead thread, I know, but maybe you will see this.

            In both cases (going half way to a destination, adding grains of salt to a pile of salt), you are isolating the effect of a single instance in a series and trying to draw a conclusion about the series.

            Whereas, in my example, you have no series at all. There is merely a single instance of adding 1 grain of salt.

          • Jiro says:

            Although you are adding a grain of salt, your claim applies to all situations–including situations that already have one grain of salt in them, or two, or more. So even though you didn’t say anything about a series of grains of salt, a belief about a series of grains of salt is logically implied by what you did say.

        • RCF says:

          Once we’ve established that there exists a theoretical situation in which a small annoyance is more important that a huge negative effect, that forecloses any argument regarding a real-world situation that the mere fact that a terrible result exists, that that is sufficient to settle the matter. That is, the existence of a terrible result can be part of an argument, but it can’t be the totality of the argument..

  47. Lancelot Gobbo says:

    I used to prescribe nefazodone and had a lot of luck with it. The only serious S/E I ever came across was one chap who developed vasculitis which reversed on stopping it. It’s gone from the market here in Canada now. I always assumed trazodone was a relative that would work in the same way and for patients who had responded to nefazodone. However, no one wants to take the large doses needed for an antidepressant effect, as it is too sedating. I don’t think I have seen it prescribed as anything other than a non-addicting night sedation for twenty years.
    Here’s a quiz: without looking it up, who knows what side-effect trazodone was famous for when prescribed above 450mg per day? Hint—it’s of a sexual nature too.

    • Scott Alexander says:

      Oh, thank God, an actual psychiatrist here to double-check if anything I’m saying makes sense.

      I’ve wondered too whether trazodone is similar enough to nefazodone to be a useful substitute. I guess if its main action is supposed to be 5-HT2A antagonism + 5-HT1A agonism it might work, though they’ve always seemed so different in every other way before that I haven’t been optimistic. I’ve also practically never seen someone get on an antidepressant dose of trazodone. The priapism is way more common than the liver failure on Serzone, but I don’t know how dangerous it is in general.

      Vilazodone has the 5-HT1A agonism but not the 5HT-2A antagonism. I haven’t had great luck with it in practice, but it does rhyme with trazodone and nefazodone, so that’s got to mean something.

      • speedwell says:

        So much for bright ideas. I was wondering if the priapism side effect affected women, but apparently it really does (since the clitoris is analogous) and is definitely associated with trazodone use.

  48. DiscoveredJoys says:

    It seems to me that wherever bureaucratic processes are at work (medicine, government, large corporations) you can explain actions and decisions much more clearly if you assume ‘blame management’ rather then ‘risk management’ is the default. In a bureaucratic organisation blame is easy to allocate…

    • pneumatik says:

      Everyone responds to incentives. The challenge of any bureaucracy is to set up the proper incentives for the bureaucrats so that they produce the actual results that leadership wants. One common problem is getting people who interact with customers, which would be the public for a government bureaucracy or students for a school bureaucracy, to actually treat the customers as their priority. If your job is to collect fees or revenue from customers, you may be punished by your organization for not collecting sufficient fees, or for forgiving too many fees, making you work extremely hard to get the money you need. Or you may not be punished at all when you fail to record the fees collected correctly, even though that could cause problems for the customer.

  49. I agree, of course, with the commenters who think such decisions should ultimately be up to the patients.

    One way of trying to intuit the comparison of X deaths vs a much larger number of bad results well short of death is by going back to probabilities. If you imagine choosing between a certainty of impotence for a year and a 1/300,000 chance of death, which would you choose? People routinely make choices along those general lines, trading off very small risks of death against other things of value—for instance every time they drive.

    The driving mortality rate in the U.S. is 7.6 per billion vehicle kilometers. So the annual risk from using Nefazodone is about the same as from a 200 mile drive. That’s not quite right, since I’m treating the figure as if it were per person mile rather than per vehicle mile, but it’s the right order of magnitude.

    You mention the case of prostate cancer. The drugs used to treat the much more common problem of BPH have a possible side effect of “reduced libido,” aka impotence. One of those drugs is also used to treat baldness.

    • Andrew Hunter says:

      Your suggestion (the world’s worst game of Would You Rather) is in fact, aiui, how QALYs are generally determined, so we’ve already got the data you want. We just need to listen to it.

      • RCF says:

        The thing about QALYs, though, is that discussing them in any but the most limited of contexts gets you labelled a sociopath. Any public discussion of QALYs must be couched in the most careful of framings.

        • grendelkhan says:

          The heuristic is that anyone who wants you to turn off your intuitions and do math with suffering and death is probably trying to get away with something. You can kind of see where that comes from, y’know?

    • onyomi says:

      For me, at least, the question of whether or not I took what I perceive to be an “undue” risk is key, especially because self-flagellation about poor decisions is one of the most unpleasant psychological qualia I experience.

      If I am horribly injured in a car accident which occurs on a routine drive to work and which was not at all my fault, I will certainly be unhappy about it, but I will not blame myself on top of that because it was something I “had” to do (for work) and there was no way I could know it was any more dangerous than any other drive (I have already accepted the general danger of driving as a reasonable trade-off for the convenience).

      The foreknowledge that I am acting in a way for which I cannot reasonably blame myself in the future is very important to me in making decisions.

      By contrast, if I take an exotic drug which has the same probability of a catastrophic side effect as the drive to work, but there were other reasonable options besides the drug, such as a safer drug or a long walk on the beach, I will blame myself much more. Of course, it helps when a doctor has prescribed it. I blame myself far more for harms incurred due to my own ideas, such as taking over-the-counter dietary supplements.

      Thus, it is not only doctors who “play it safe” as a means to avoid potential blame. It is a dynamic which can play out even within one’s own head. (Or at least one person’s head). If this psychology of mine is common, it could result in a net disutility even if everyone is making well-informed, individual decisions (though I still think informing patients of all options and their risk-reward ratios is the best choice).

      • Noumenon72 says:

        Interesting and well stated!

      • Svejk says:

        Excellent point, onyomi. Additionally, I suspect that for many people the frank anxiety attached to even an infinitesimally small possibility of liver explosion is much higher than that attached to the expectation of sexual dysfunction. That should probably be entered into the Qualys equation.

      • shemtealeaf says:

        I’m not really clear on the distinction you’re making between driving and taking a drug with potentially catastrophic side effects. You say that you’ve ‘accepted the general danger of driving as a reasonable trade-off’, but aren’t you still choosing a risk of catastrophic failure instead of a less risky but more inconvenient/unpleasant option? I can understand why you wouldn’t blame yourself for that particular drive, but why wouldn’t you blame yourself for choosing to drive in general?

        • onyomi says:

          It’s all about what I subjectively deem to be an “undue” risk. Driving (relatively carefully) seems to be a risk almost everyone in our society is expected to accept as the price for functioning (I am including riding in cars driven by others). Therefore, driving does not subjectively feel like an undue risk, because I lump it in with “leaving the house” and, indeed, “using my kitchen” as part of the risk of just being alive and functioning.

          Most people do not take unusual drugs with exotic side effects, nor does taking drugs seem to be a precondition for being a functioning member of society (obvious exceptions like using insulin if you’re type 1 diabetic would not strike me as “undue”). The frequency with which others in my society take a given risk definitely factors in; I understand this is problematic, logically speaking, but my self-flagellation over poor decisions in the past is not logic-based.

          I understand, of course, that for some people with severe psychiatric and other disorders, it is precisely the ability to function in society that is at stake, but the solution to crippling depression and anxiety is far less clear-cut than the solution to “it sure is hard get anywhere walking all the time,” though, as I said, I’d be less likely to blame myself for side effects of a drug prescribed by a doctor (assuming I didn’t heavily prompt him/her), than for one I chose to take on my own.

    • Deiseach says:

      But there’s not a certainty of impotence; there’s 25% will get side effects of sexual dysfunction or emotional blunting, which means most of the people won’t have that particular effect. Granted, it’s a much bigger risk than the risk of having your liver explode, but again – if you find one drug makes you impotent, you can stop taking that one and wait for normal functioning to resume. If you find you’ve borked your liver, stopping the drug is no damn good to you.

      The trap here, I imagine, is that once the medication has worked to alleviate your depression sufficiently that now you care about having sex again, it may reduce or take away the ability altogether.

  50. Chris Billington says:

    Is it possible that there is a selection bias in the user ratings of the drugs? Dead people can’t leave ratings on websites.

    • Rowan says:

      Possible, but I don’t see how that would change much of anything unless it’s so torturous it adds an appreciable amount to the QALY cost of the chance of the side effects that kill people. Scott’s just using the ratings there to sketch the idea of the one drug being possibly better than the other, and they’re not actually going into the calculation that forms the main argument on that point.

    • Surlie says:

      But the risk of catastrophic side effects is so low that, given the small number of people rating these drugs, we wouldn’t statistically expect a single person suffering from them to participate (even if they could).

    • RCF says:

      There’s also the fact that people can’t rate the drug less than zero. Suppose you have Drug A that in 96% of cases completely cures the condition with no side effects, and in 4% of cases results in agonizing death. Drug B mostly cures the condition with some symptoms remaining and mild side effects. So everyone on Drug B rates it, say, 8/10. 96% of the people on Drug A rate it 10, while 4% make time between dealing with their agonizing death to rate it 0. Then when you average the scores for Drug A, it will round to 10 and appear to be better than Drug B. A rating system isn’t a very good way of measuring tail risks; a drug that’s absolutely horrible 1% of time isn’t going to get any lower of a score than one that’s really bad 1% of the time.

  51. speedwell says:

    I apologize for the thread derailment (feel free to ignore this if it’s too much of a stretch), but I have been told I am being sent to see a bariatric specialist. The man is a good scientist by all appearances and may be open to a number of treatment methods, but he and his clinic do bariatric surgery, which despite me being judged a candidate for, I am opposed to. In short, I am not convinced, after a review of as much reasonable-looking evidence as I can find on the Internet without an academic subscription, that the claimed benefits of the surgery are actually due to the surgery itself, and I AM convinced that permanently mutilating the bodies and metabolisms of fat people is primarily acceptable to the medical profession because it is motivated by punitive disgust of fatness.

    Now, I don’t want to be fat (and I have a few alternative proposals for the doctor when I meet him). But I also don’t want to engage in self-harming behaviors like agreeing to the removal of parts of my internal organs. These surgeries, even the comparatively mild gastric banding, are not as effective as people seem to think they are, and frequently leave the person as bad off as before the surgery, with additional complications. Many die. My husband didn’t do the research I did, but he knew someone who had bariatric surgery in a top hospital as a private patient with a reputable, experienced doctor, who died of complications, and who told her family that she felt better off dead than fat and medically compromised.

    If bariatric surgery was a pill, and the pill had the same, or even some of, the side effects of the surgery, common or rare, I firmly believe most doctors would prefer to not prescribe it, even when balanced against the known effects of obesity (which not every obese person suffers from, either).

    • suntzuanime says:

      There does seem to be a disparity between the potential risks people will accept from a pill vs. the potential risks people will accept from surgery. Possibly it has to do with the horror of being poisoned compared to the relative acceptability of being cut? That said, it’s not clear that people should be accepting less risk from their surgeries rather than more risk from their pills, and referring to undergoing surgery as “engaging in self-harming behaviors” is absurd, an example of the Worst Argument In The World.

      • speedwell says:

        I think you need to reconsider. I am not equating getting surgery, on the whole, with self-harming behaviors. I am equating THIS type of surgery, for me and for many other people, as being a self-inflicted punishment for being unattractive, as a result of institutionalized societal bullying. If your child came home with a shaved head because she was bullied at school for her hair, you would consider that self-harming behavior, I bet, and that’s not even permanent.

        • suntzuanime says:

          I certainly wouldn’t flip out at a well-meaning barber who suggested a haircut.

          • speedwell says:

            Of course not. Nobody would. My point is exactly that fat people are bullied into “voluntarily” accepting surgery, when there may be a competent professional out there who could compassionately provide a reasonable alternative. I hope my bariatric doctor will turn out to be such a compassionate provider.

          • Gbdub says:

            I think the issue with bariatric surgery is that there really aren’t better more compassionate alternatives that are actually any more effective. Persistent obesity just seems to be a really tough thing to fix, and I think most people come to surgery as a last resort after trying other things anyway. So yes, it’s drastic, but desparate times and all that…

            As someone who has been fat enough to be bullied about it most of his life (although never enough to be a candidate for surgery) I think I feel (some of) your pain. So don’t take this the wrong way – but some of your language worries me. Specifically, your focus on fat-shaming, and villifying/ascribing nefarious motives to a doctor you’ve yet to meet, generally sounding like you consider this forced on you, makes me think you’ve not really accepted obesity as an issue except for the reactions other people have to it.

            But if you’ve reached a point where gastric bypass is a legitimate option, then your obesity probably really is a problem, in terms of being a big impact on your physical wellbeing. Yes, fat-shaming can be cruel, but obesity is not the only disease that faces stigma – the fact that schizophrenia is stigmatized does not mean sufferers should refuse to seek treatment.

            And regardless of what method you choose (and you should get to choose it), I honestly don’t think you can be successful in controlling your weight unless you accept that you have a problem that you want to fix for your own wellbeing, and damn anyone else’s opinion. So don’t let surgery be forced on you, but at the same time don’t assume anyone who suggests it is out to intentionally mutilate you just for jollies. I’d say the best way to not get it suggested, if you really don’t want to be, is to commit and follow through on another alternative (unfortunately, it does seem like pretty much every option requires a ton of dedicating mental effort from the patient and long term success for every method is low).

        • Anthony says:

          So the latest thing seems to be that fecal transplants have all sorts of effects, and might actually be significantly useful for obesity. It’s still completely experimental, but it sounds like a reasonable alternative to major surgery or heavy drugs for handling it. Probably at least worth asking the doctor about, even if he tells you ten reasons it’s a bad idea.

    • pneumatik says:

      Often before performing bariatric surgery the doctor will want their patient to demonstrate an ability to lose weight through a restricted calorie diet first, to demonstrate that the patient will be able to stick to that diet after the surgery. Assuming your doctor wants you to do that, assuming the diet works you could try asking to just stay on that diet. Staying on a diet to lose weight is certainly prone to way fewer complications than having bariatric surgery.

      I know someone who lost somewhere between 150 and 200 pounds (I’m guessing from looking at him). It took him several different diets before he found one that worked for him (which ended up being Weight Watchers). IMHO losing weight is largely a mental challenge, and it can take some time to find the weight loss method that works for you. I think it’s really no different than trying to quit a more standard addiction, where there are lots of different ways to, say, quit smoking, and sometimes you need to keep trying until you find one that works for you.

      • speedwell says:

        Thank you, Pneumatik. Everything you say is true and sound in theory, and for most people. I’ve been trying everything I can think of and afford for 35 years now, ever since I was a young teenager. I tried Weight Watcher when it was a three-step program, monitored by my fanatical mother, and though I stayed on the first “break-in” week for months, I did not lose a single pound despite doing the recommended exercise. Slimming World here in Ireland made me gain weight. I failed to lose weight when I was in intensive care recovering from surgery and not given anything by mouth. I failed to gain weight on a three-week business trip to Dubai where I went nuts on an expense account and ate everything in sight. I am baffled. But I do know I just don’t want to be hacked up.

        • Devilbunny says:

          I suspect you have already considered or even attempted it, but on the off chance you have not: eliminating sugars and refined carbohydrates from my diet resulted in eighty pounds of weight loss and a reversal of low-grade hypertension. I’m not skinny, but I’m no longer obese, and I’ve been able to sustain it for over three years.

    • Alexander Stanislaw says:

      I’m surprised you think bariatric surgery is not effective. Whatever the side effects (I’m not knowledgeable about them), bariatric surgery seems to have pretty spectacular effect sizes, with respect weight loss. As far as epidemiology goes, that is a very long, and large study. You won’t find effects close to that at 10 years out for diet.

      Are you in principle opposed to surgery of any kind?

      • speedwell says:

        No, I am not in principle opposed to surgery. I will forever tell people the story of the surgeon who saved my life by removing my badly infected kidney (when he wiggled his fingers in the air and said “THESE are better than any laproscopic method”, I fell in love). I do know that bariatric surgery has certain effects. I am not convinced that the effects are not due to the drastic change in eating habits and other, possibly psychological, changes attendant to recovery. I am convinced that the doctors do not yet know enough about why it works, and I am not volunteering to be part of an ongoing experiment that costs me part of my body and has a high failure rate. It seems rational to avoid the sort of surgery that has a higher failure rate and often more severe health consequences than the condition it treats.

        In my experience, “fat doctors” are usually disgusted with their patients. I do not want a physician whose basic mindset is that I am unworthy of his full care and consideration. I do hope very sincerely that this new doctor will be different and we can discuss other methods.

        • Alexander Stanislaw says:

          To be clear, I am not recommending bariatric surgery – I think it is appropriate for some obese people, and not others.

          I am not convinced that the effects are not due to the drastic change in eating habits and other, possibly psychological, changes attendant to recovery

          Isn’t the point that it causes you to eat less? How else would it work? I don’t know what you mean by psychological effects.

          But if you agree that it causes substantial weight loss, then why does the mechanism matter to you? This isn’t a rhetorical question, I’m interested in why you are okay with weight loss by some mechanisms but not others.

          and has a high failure rate

          What do you mean? The success rate is much higher than other weight loss methods. As with everything, there are tradeoffs (more risk in this case).

          • speedwell says:

            If eating less would inevitably cause significant and meaningful weight loss, Alexander, then I wouldn’t be obese. Truly.

            WLS has a high failure rate when you follow up on people a year or more after their surgery. They regain the weight, despite the drastic reduction in internal organs. No, not everyone does. But a large fraction of people do. It’s easy to dismiss the frustration of people who try hard to keep themselves on track, and hard to say “hey, maybe the theory has holes in it”. The simple-minded equation of “removing half your stomach means you can’t eat enough to be obese” simply doesn’t hold true for a lot of people. I would like to know more about why, and how I can manage to avoid the effect, before I agree to the surgery. But nobody seems to know.

          • Alexander Stanislaw says:

            WLS has a high failure rate when you follow up on people a year or more after their surgery.

            The study I cited has a 10 – 15 year follow up, did you read it?

            Yes, some of the weight is regained, but unlike other methods (like diets) where all of the weight it is often regained, bariatric surgery is able to keep off 20 – 30% of bodyweight in the long term .

          • speedwell says:

            Well, perhaps the new doctor will have some information for me that I haven’t been able to access on my own. When permanent alteration of a functioning bodily system is in question, I don’t think it’s going too far to ask, “What is the mechanism of action of this treatment”, “What exactly is my underlying issue and how exactly will this treatment directly address it”, “What steps do we take to ensure, as far as possible, the right outcome, permanently and without morbidities caused by the treatment”, and, in the case of inevitable side effects (such as yards of loose skin), “will I be able to access further treatments”.

          • Alexander Stanislaw says:


            If you are merely voicing a concern that neither obesity or bariatric surgery are well understood and therefore you have reasons to be concerned, then I empathize with that concern. Surgery is a decision not be taken lightly and I have never stated otherwise.

            However, that’s not what you started off arguing. You said that bariatric surgery doesn’t work well, and that doctors perform it so they can mutilate and take advantage fat people. I think I’ve provided strong evidence that that isn’t the case – bariatric surgery does indeed work, whatever its drawbacks and mechanism of action might be*. Do you stand by your original claim?

            *Hundreds of studies have shown similar effects, not just statistically significant effects, but very large amounts of weight loss, about 38kg. Studies with longer follow up times (greater than 2 years) show similar effects.

          • Deiseach says:

            Isn’t the point that it causes you to eat less? How else would it work?

            Going by the linked article down below, this is not the case and indeed, doctors are now trying to find out “How the heck does it work?”

            The fact that they tried surgeries in the past which caused liver damage surely is reasonable grounds for speedwell to be cautious?

            Known as a jejunoileal bypass, it caused remarkable weight loss but also an array of unpleasant side effects, including bloating, diarrhoea, anal burning and dehydration. Bacterial populations in the bypassed intestine continually rose and the liver became inflamed. “Everybody realized that five years after you have this, you lose your liver,” says David Cummings, a endocrinologist at the University of Washington in Seattle.

            …Patients said that they were not as hungry as before the surgery, and that they ate fewer meals and snacked less. Over time, their food preferences seemed to change, too; anecdotal reports suggested that they often chose salads over desserts and fatty foods. These shifts could not be explained by reduced stomach size alone, Cummings notes — if the reason was mechanical, patients would simply eat lots of small meals. “That got the field wondering, what’s going on with hunger, here?”

          • Alexander Stanislaw says:

            Deiseach, if it causes you to eat less calorie dense foods, then it is still causing you to lose weight by eating less. (eating less calories).

            I never said that speedwell shouldn’t be cautious! I said that he/she made false claims, and I’d like to know if and why he still stands by them.

    • Anatoly says:

      I applaud your efforts to research the effects of surgery, but your words about the lack of academic subscription give me pause. You should be vigilant about what you accept as “reasonable-looking evidence”, and try to avoid the failure scenario of being too much influenced by anti-surgery rants fueled by motivated reasoning.

      I’m morbidly obese, and am working on losing weight through diet and exercise. I have considered and rejected the option of surgery so far for reasons similar to yours. However, I’m aware that my extreme aversion to and rejection of surgery is at least partially irrational and due to personal biases. Based on my (cursory) survey of effects and risks, bariatric surgery is with a very high probability remarkably effective, and the risks are (to me, in principle, given the payoff) acceptable. If I’m not able to lose weight “naturally” within a few more years, I will likely overcome my aversion and undergo surgery.

      • speedwell says:

        Fair enough, Anatoly. I know it does work for many people, and some of those people are in medical situations that constitute an emergency. Fortunately that is not true of me at the moment. If you were my best friend, and you decided bariatric surgery was right for you, I hope I would have the understanding and courage to keep my bloody mouth shut, hold your hand in the recovery room, drive you home, and be your buddy to help you have the best possible outcome.

    • Glen Raphael says:

      For a similar effect as bariatric surgery that doesn’t require reconfiguring your organs or otherwise permanently altering your anatomy, look up “gastric balloon”. It’s not FDA-approved yet for use in the US but the treatment could be gotten in Europe or Tijuana.

      • speedwell says:

        It’s an interesting technique. It is at least not irreversible! Thanks for linking.

        (I had to laugh though… from the first linked article: “The Obalon balloon is designed for patients with a body mass index (BMI) of at least 27 kg per square meter…” That’s “fat”, folks, not “flat”. :D)

    • Scott Alexander says:

      Sorry, I don’t know much about bariatrics – can you explain what you mean when you say you don’t think the benefits of the surgery are due to the surgery itself?

    • Deiseach says:

      I know; the medical profession is happy about major surgery that involves long-term alteration of organs, but they don’t seem to have any idea about drugs that will act to reduce appetite.

      “Oh no, that might increase your blood pressure, here, go for the surgery that will probably cause you to become malnourished and in need of high volumes of supplements!”

      • Alexander Stanislaw says:

        Which drugs do you have in mind?

        • bartlebyshop says:

          I know several people who “acquired” topiramate or various amphetamine derivatives with the express intention of using them to lose weight.

          • Given the topiramate cognitive side effects (Google autocomplete for “cognitive side effects of” has Topamax as the top result before ECT and chemotherapy!) and the amphetamine cognitive benefits, why would these people ever choose the former over the latter?

          • bartlebyshop says:

            Because people would rather lose 10-20 years of their life than become obese. Not everyone values their cognitive abilities above everything else – otherwise why would so many college students binge drink every weekend (something everyone knows is bad for your health)? Why do people take 2,4-dinitrophenol to lose weight, when it might cook you from the inside out? People will do almost anything for effective weight loss in a pill. People deliberately get addicted to nicotine to lose weight. This doesn’t really address why people chose the anticonvulsant over amphetamine, but I think the fact that the spotlight of the DEA is on amphetamine might go a ways to explaining it. Topamax isn’t thought of as a drug of abuse. Ampethamine also retains some stigma from the 50s and 60s as an addictive diet drug that drove people permanently insane (see also Requiem for a Dream) and more currently from the meth epidemic, whereas Topamax is a seemingly-innocuous seizure drug you don’t get hooked on.

          • Devilbunny says:

            othercriteria – prescribing Topamax will not get the state medical board to knock on your doctor’s door, ask why they are prescribing so many amphetamines, and possibly take away their license to practice medicine. Even if your doctor has dotted all their i’s and crossed all their t’s, it’s a risky thing for them to do.

          • @Devilbunny: Sure, the cost/benefit situation is different for the prescriber, but bartlebyshop’s scenario mentioned “people who ‘acquired'” the drugs.

            Sure, getting topiramate without a prescription is closer to grey market versus a black market for amphetamine. But I’d imagine that the latter market is more robust, reflecting the likelihood that there are more teens willing to part with their meds after finals are over than there are people with epilepsy who are okay risking seizures for a little cash.

            What surprised me was not that medical systems led to perverse outcomes, but that people acting outside of these systems would pick the same bad outcomes.

          • Devilbunny says:

            Othercriteria, true, but the incentives are similar for those acquiring them extralegally – amphetamines are more likely to get you in trouble with the cops. And Topamax is probably diverted from those who take it for migraines or mood stabilization more than epilepsy.

          • bartlebyshop says:

            What I had heard was that at one time you could get it from various sketchy internet pharmacies which make you swear that you really do have a prescription but don’t actually check. I don’t know if that’s still true. Also, Topamax has been legally off-label prescribed for weight loss.

          • grendelkhan says:

            Why do people take 2,4-dinitrophenol to lose weight, when it might cook you from the inside out?

            Wow. I did not know about that. It’s kind of poetic, in a way. For all the supermarket-checkout blather about “burn fat now”, we really, really can do that; it’s just horribly literal.

            I’m surprised you can’t go to a sketchy offshore weight-loss clinic where they put you under general anesthesia and administer DNP along with dantrolene or whatnot under close observation; you wake up a few days later however many pounds lighter. Kind of like rapid detox, though apparently that’s a bad idea?

          • drethelin says:

            here’s a good article on DNP . apparently what people do is take ice baths to mitigate the heating

    • I’ve read that about 30% of bariatric patients develop alcoholism, and this is matched by the anecdotes I’ve heard.

      To be fair, they got over the alcoholism and didn’t wreck their lives, but it’s still quite a side effect.

      • estelendur says:

        Interesting! My mother is a recovering alcoholic, and just got bariatric surgery last year. Hopefully she stays recovering…

  52. eqdw says:

    I don’t know if the level of SSRI-induced sexual dysfunction is as bad as the prostate-surgery-induced sexual dysfunction on the database.

    Speaking from personal experience: unless the “prostate surgery” in question involves removing the penis entirely, it’s not possible for it to be worse than the SSRI dysfunction.

    Especially on the wrong SSRIs, especially for the wrong people, especially at higher doses, it’s not ‘dysfunction’. It just stops working entirely

    • Anonymaus says:

      I don’t know the nature of the side effects of either. I can imagine there is a difference between wanting sex and not being able to have / enjoy it, and not caring about sex at all anymore (asexuality).
      To me it sound like at least the SSRI side effects are of the second kind(?). Since I lack the social skills for having sex very often, naively this sounds like it would actually improve my life (i.e. I would just spend less time watching porn). Question: Are the sexual side effects of SSRIs only bad for people who are in relationships or otherwise sexually active, or am I missing something and they are universally bad (or does the degree of badness depend on something orthogonal to these considerations)?

      • Protagoras says:

        Different people experience different side effects. In my own case, I wasn’t particularly less interested in sex, but on some SSRIs I had great difficulty achieving orgasm. Which really didn’t bother me all that much. But it would have bothered me if I’d had difficulty getting an erection (which some people get), and I don’t know how I’d have felt about having less interest in sex.

        • Robin says:

          They can decrease libido, but they can also make orgasm and physical arousal (like erection and vaginal lubrication) more difficult or impossible. All of the above are pretty common. There are also other possible effects, like decreased genital sensation or pleasure, but those seem to be either rarer or less discussed/researched for other reasons. I tried for a bit to find out how much these tend to go together, or how often people experience other sexual side effects without decreased desire, but didn’t find anything (can’t read paywalled studies though); I’d love to know that if anyone has data.

          (Edit: I thought I was replying to the comment above yours, but at least it’s not totally out of place here.)

    • Scott Alexander says:

      I think your case might be extreme.

    • onyomi says:

      On the other hand, there may be cases where (a milder) change is even welcome. I took SSRIs for a few years in my late teens/early twenties and I recall enjoying the fact that it gave me more “staying power.” (Making orgasm slightly more difficult to achieve can be a boon to a young man in particular).

  53. Leif says:

    What about all the stuff people do with their lives, that impacts the quality of other peoples’ lives, that they won’t get to do if they die?

    Like, maybe it’s true that sexual dysfunction lowers your personal happiness by 15%. But that doesn’t necessarily mean you’re 15% less likely to cure cancer or become president or whatever. Or more realistically, some people with depression have families who depend on them, and death will remove 100% of their ability to be there for their family, but sexual dysfunction will not remove 15%.

    • DanielLC says:

      I’m not sure having a depressed family member makes people happy.

      • Janos says:

        I wonder if anyone has put together a QALY database that includes average effects on other people.

    • Anon256 says:

      If sexual dysfunction makes them unable to have sex with their spouse (or partners generally) then that’s a substantial negative externality; for a faithful monogamous spouse it might be as bad or worse as actually having sexual dysfunction themselves (claimed to cost 15%). Sex is a more positive-sum activity than most things people do.

      • Deiseach says:

        I suppose one consideration is that non-interference still doesn’t guarantee a good sex life; a patient may or may not have a satisfying sex life (or any kind of sex life) before they come in to the doctor with depression.

        But pretty much everyone already has a functioning liver, so even if the chances of inducing liver failure are a lot lower, the danger seems greater. You can’t have sex anymore? Okay, stop taking that particular drug and see if the situation improves. Your liver is exploded? Okay, you’re toast (unless you get a transplant, and then that’s only if it takes, and then you’ll be on anti-rejection drugs for the rest of your life, and there’s a whole raft of problems associated with this which may include that, on top of everything else, you’re not having sex anyway).

        • Anon256 says:

          “stop taking that particular drug and see if the situation improves” A big part of the issue is that for many people SSRI-caused sexual dysfunction ends up being permanent; if it were temporary/reversible that would be a much smaller cost.

    • Anthony says:

      Reduced sexual function also has the effect of making the drug absolutely ineffective. If you’re taking a drug for anything, and the major side effect is to make you less sexually functional, that’s pretty depressing.

      • Anon256 says:

        It’s moderately depressing (varying by person) but very likely less depressing than actually being clinically depressed (to the extent that these are even comparable kinds of thing).

  54. Schmendrick says:

    Also, it can’t be helping that “nefazodone” sounds like someone wanted to see how fast people would run away from a drug with “nefarious” right there in the name. I know, I know, that’s not how drug-naming really works, but still. Most of us jes’ ain’t t’at smart.

    • Scott Alexander says:

      The newer generation drug most like nefazodone is vilazodone, which sounds too much like “villain”. But the brand name is Viibryd, which sounds vibrant (and I’m sure that was intentional)

      • Deiseach says:

        I’d tend to pronounce that name as “vibe-ered” (along the lines of “phasered”, “lasered” and indeed “tasered”).

        Does something that sounds like “tasered” really sound like something you’d want to take? 🙂

        An alternate pronunciation would be “vibe-rid” to rhyme with “hybrid” and again, not sounding particularly thrilling to my ears.

        • Who wouldn't want to be anonymous says:

          Yes, but will the vibe ride cure your sexual dysfunction?

          • Deiseach says:

            will the vibe ride cure your sexual dysfunction?

            If the drug does indeed lack the side effect of causing sexual dysfunction, and this is one of its selling points, then I won’t dismiss the possibility that indeed part of the reasoning behind the marketing team’s choice of name was to make people think of “vibrator” 🙂

  55. Alyssa Vance says:

    “Suddenly it’s not a matter of comparing QALYs, it’s a matter of comparing zero percent chance of lawsuit with non-zero percent chance of lawsuit.”

    I think the main problem here is that everyone is really bad at thinking about legal risks. Pretty much everyone accepts “that’s illegal!” [1] or “you’ll get sued!” as a knockdown argument, without ever thinking quantitatively about how likely legal consequences are, or how bad they would be. In this case, even assuming that the chance of getting sued is 100% and that being sued costs a million dollars out-of-pocket – both pretty extreme assumptions – the expected cost to the doctor is $3.33, about the price of a coffee. Realistically, lawsuits are rarely brought even when they’re fully justified, because they’re slow and annoying and painful and expensive (I have experience on both sides).

    To pick one random example: Suppose you get audited by the IRS. I imagine most people who get audited worry that they’re in trouble. Given that you’re being audited, what is the chance that the IRS will decide to prosecute you for tax fraud? The answer is about 0.1%, and that’s given several generous assumptions, so the real number is almost certainly lower.

    The number of people prosecuted for violating the vast body of federal regulations is even smaller. In 2012, across the entire United States, there were just two federal prosecutions for violating agricultural regulations; 30 for violations of all food and drug regulations; 37 for all violations of environmental rules (excluding killing/selling/etc. endangered species); 72 for killing/selling/etc. endangered species; 49 for gambling violations; 48 for violating antitrust laws; and 65 (!!!) for drug possession and all other drug offenses except trafficking, combined (source:, table 4.2). That’s for a country of 320 million people. (Note to non-Americans: lots of people do get arrested for drug possession here, but it’s almost always by state governments rather than the federal government, and state law is sometimes much less harsh.)

    [1] A lot of people also use “that’s illegal” as a moral argument; the problem there is that, on paper, you’re violating laws every time you tie your shoelaces, e.g. 18 USC 1001.

    • Creutzer says:

      In this case, even assuming that the chance of getting sued is 100% and that being sued costs a million dollars out-of-pocket – both pretty extreme assumptions – the expected cost to the doctor is $3.33, about the price of a coffee.

      The doctor still has no incentive to incur even this minor expected cost. And apart from that, expected value in money isn’t all that counts, since a million dollars is pretty economically catastrophic.

    • Douglas Knight says:

      65 (!!!) for drug possession

      65 for a highest charge of felony drug possession but 1552 for misdemeanor drug possession. Your point about state prosecution is a bigger deal.

    • Fnord says:

      That’s slightly deceptive, especially as to drug offenses. According to table 4.3 of the same document, you see that federal MAGISTRATE judges disposed of ~1400 drug possession cases, with convictions in ~1,100 of them. The labeling is horrible, but it appears that table 4.2 excludes those cases, including only cases that are prosecuted before an actual Article 3 tribunal.

      Now, that’s still not all that many in a country of, as you note, 300 million people, but it’s a lot more than 65.

    • Ano says:

      “I think the main problem here is that everyone is really bad at thinking about legal risks.”

      People are bad at thinking about risks and probability in general.

    • Irrelevant says:

      The number of people prosecuted for violating the vast body of federal regulations is even smaller.

      Therein lies the problem. Selective prosecution is the essence of injustice.

    • Jiro says:

      In this case, even assuming that the chance of getting sued is 100% and that being sued costs a million dollars out-of-pocket – both pretty extreme assumptions – the expected cost to the doctor is $3.33, about the price of a coffee.

      By your reasoning, nobody should ever buy insurance, since the cost of the insurance is greater than the expected cost of what it mightpay for.

      Risk aversion is legitimate.

      • Loquat says:

        As an insurance agent, I’ll second that. To most people, a tiny chance to suffer a catastrophic loss is not at all the same as a 50% chance to lose the price of a McDonald’s combo meal, even if they do work out to the same expected cost when you do the math. I’d estimate most of the people who take out accidental death policies from my company never wind up filing a claim, but nobody wants to be the guy that dies unexpectedly and leaves the family in the financial lurch.

    • Sewing-Machine says:

      I don’t understand your joke about 18 USC 1001.

      • Nornagest says:

        My spider-sense tingles when I read that. On first glance, it seems to indicate that you’re liable for five years in federal prison whenever you say “no, honey, those jeans don’t make you look fat”, but a close reading of the language over jurisdiction makes me think we’re probably looking at a law of much narrower scope than is immediately apparent.

        (IANAL, though.)

        • Jordan D. says:

          The general joke is a lot more narrow, although still a bit horrifying. 18 USC 1001 wouldn’t generally apply to a lie to your girlfriend because that’s not a matter within the jurisdiction of a branch of the government. It gets brought up because what’ll happen is that federal agents will visit you in the course of an investigation and ask you questions they already know the answers to in the hope that you’ll lie to them, thus allowing them to charge you under that section for free.

    • Scott Alexander says:

      I’m not sure we can reduce lawsuits to a million dollars out of pocket. For example, some lawsuits force doctors to go out of practice entirely, which probably costs more than $1 million in future income and which is getting to the point where the risks are too big to be easily modeled by money (eg how if I have $1 million, losing all $1 million and ending up a pauper is much more than twice as bad as losing $500,000).

      • Deiseach says:

        And of course, there’s the hit to your reputation when you get known as “that doctor who prescribes medication that makes his patients’ livers explode”, even if that’s an unfair characterisation, which will probably cause your practice to dwindle even if the lawsuit doesn’t wipe you out.

    • The problem with the coffee comparison is two-fold: first, utility is not linear with respect to dollars. The amount of money/work years lost is the sort of thing that will change your entire way of living, not just set you back a little bit.

      The bigger problem is that there are presumably a lot of different drugs for which doctors are making these decisions, and you run into a slippery slope. Even if one prescription is both justified and low-risk, the cumulative effect of a bunch of independent low-risk decisions can very quickly become high risk. If a doctor used this reasoning for every prescription, as opposed to just a few special cases, then they would basically be guaranteed to be sued at some point. I think the logic is a bit like why it’s not a good idea to steal- in the vast majority of circumstances, the expected cost of stealing say, a candy bar from a convenience store is lower than the cost of the candy, but if you do that every time you want candy you will get caught eventually.

    • Edward Scizorhands says:

      The damage to the doctor isn’t just the payout. Having a lawsuit hanging over your professional head is very depressing.

      I’m sure I’ve read an article in the NYT about how bad the fear is but I totally cannot find it now.

      If you could make it like the vaccine courts, where the patient simply needs to verify “yes, this bad side effect happened to me”, and then gets a payout funded by a trifle added to each patient receiving the drug, it works out very well, because the doctor doesn’t have to get sued for the patient to be made whole.

    • CatCube says:

      Your comments on conviction rates glaze over the fact that the investigation itself can be bad, even if the DA doesn’t decide to charge you.

      It’s similar to people pounding the table about how nobody has been prosecuted for violations of, say, the Anti-Deficiency Act. While it is true that nobody gets jailed for it, being found liable by an internal USG investigation can have career repercussions, and even an investigation that clears you can be soul-eating.

      (NB: I see plenty of stupid ways that money gets wasted, but most of them are done to *avoid* running afoul of laws and regulations than outright corruption or theft. Corruption does happen, but it’s not the major driver of wasted money.)

  56. Douglas Knight says:

    Malpractice is handled very differently across countries. If it were driving these decisions, they would vary between countries. I don’t think that they do, but it’s worth checking. So it’s probably more that doctors don’t want to be personally blamed for flashy side effects, and not the legal consequence of that blame.

    • Richard says:

      It seems which drugs are prescribed varies rather a lot by countries, my first hit on google was:

      I don’t know if this is related to malpractice or other factors.

    • Scott Alexander says:

      That’s a good point. In many countries, nefazodone is just outright banned by whatever their FDA-equivalent is.

      There are major differences in what drugs are used per country, even among drugs on the market in all countries, but it’s hard to say what causes them and usually has more to do with which drug company had a better advertising campaign where.

  57. Salem says:

    As soon as I read the first line, I knew this was about SSRIs.

    But I question the premise. You don’t have to choose between torture and dust specks. Let the customer choose the risk he would happier take.

    Unfortunately that runs headlong into the problem that medicine is not about solving problems. Even the word customer will have jarred many people. I am sure that principal – agent problems are part of the issue, but the larger factor is that we have a deeply paternalistic notion of healthcare, in which things like sexual function barely register, because they’re not the kind of problems that “we” are interested in solving, even though they can matter hugely to the sufferer (see eg Viagra). And hence also why someone lacking health insurance is seen as a political crisis rather than a consumer choice.

    Personally I view doctors as highly pretentious sales assistants with a very effective guild.

    • Artemium says:

      I second this. I dont understand why this isn’t considered as a simple consumer choice where person accepts responsibillity for his decision. In society where every nutcase can buy a high-powered rifle in nearby store, and 50% of people are addicted to horrible food which is destroying their health in every concivable way it really seems weerd to obsess over this kind of risk while the benefits are so glaringly obvious.

      • Richard says:

        With psychiatric meds, the reason you need to make the choice at all is the fact that you are ill equipped to make the choice. Requiring people to take responsibility for a choice they can’t make well seems a bit unfair.

        • Lambert says:

          Well it seems doctors can’t make that choice well either.

        • Surlie says:

          I don’t see why a person can’t make the choice better than a doctor, if the ramifications are fully explained to them.

          Surely people have varying individual tolerances for risking very low chance of death vs. not-very-low chance of sexual dysfunction, such that there isn’t simply a one-size-fits-all solution that can be handed down from on high by doctors.

      • Jiro says:

        In society where every nutcase can buy a high-powered rifle in nearby store

        Federal law prohibits buying guns by anyone who “has been adjudicated as a mental defective or has been committed to any mental institution.”

        I’m not sure what society you’re referring to, but it’s not the USA.

        • Squirrel of Doom says:

          There are many nutcases who have not been so adjudicated.

        • psychorecycled says:

          I think that when Artemium says ‘nutcase’, they might mean something more along the lines of ‘far-right individual’, or ‘individual with an undiagnosed mental health disorder’, or even ‘individual who is purchasing expensive lethal weapons without any clear need to own devices which are basically exclusively intended to kill things’.

          Because, really: how many people can actually justify owning handguns? Long rifles, you want to hunt, okay. But generally, you don’t hunt with handguns. If you aren’t a regular recreational shooter it makes a reasonable amount of sense to use a gun at the range (or keep it there) and I don’t know how many people are concerned for their safety but I think there are more handguns than concealed-carry permits.

          America lets people do stupid things all the time: there is evidence of this. Why not let people decide whether their unimpeded sex lives are worth a small chance of death?

          • Jiro says:

            Because, really: how many people can actually justify owning handguns? Long rifles, you want to hunt, okay.

            You do realize the statement to which I was objecting was about rifles?

          • Mary says:

            “Because, really: how many people can actually justify owning handguns?”

            Justify to whom?

          • John Schilling says:

            Because, really: how many people can actually justify owning handguns? …
            America lets people do stupid things all the time

            Really? You and artemium really want to go there? I’d have thought it polite to at least wait for an open thread, and I’d hope you know better than to assume this is a blue-tribe stronghold where you can post such assertions and/or rhetorical questions without being called on them. But we can do this if you want.

          • suntzuanime says:

            Just because a choice turns out justifiable in retrospect doesn’t mean it was justifiable in prospect.

          • FacelessCraven says:

            @psychorecycled – “Because, really: how many people can actually justify owning handguns? Long rifles, you want to hunt, okay. But generally, you don’t hunt with handguns.”

            1. The right to self-defense is inalienable, and is subject neither to moral coercion nor legal force. As a matter of well-established case law, you and you alone are personally responsible for your own safety. Neither the police nor any other agency or individual are responsible for your safety.
            CW for rape and general horror:

            2. Handguns are the most effective tool for personal defense because they are the only class of firearm portable enough to be with you wherever you are. They are also cheaper, fire lower-price ammo, and are generally more convenient in a variety of ways than long guns. Concealment is an obvious advantage as well, but not the decisive one.

            3. handgun hunting is reasonably common, enough so to drive a market for several whole classes of handguns. If you see a handgun that seems like an obvious phallic substitute, it is probably a hunting/animal-defense gun.

            4. Long guns are either “assault rifles”, “street sweepers”, or “sniper rifles”, and therefore all universally unfit for civilian ownership, so there’s not much point in arguing that handguns are unusually pernicious.

            …And then there’s the half-a-million-to-two-million crimes prevented per year. Please use something else for your example of “stupid things America lets people do every year”

          • grendelkhan says:

            Some back-of-the-envelope checking here.

            The National Crime Victimization Survey reported 6.1M violent victimizations in 2013, of which about a third (~2M) were due to strangers. (The category here faintly maps to the FBI’s UCR category for violent crime: “rape or sexual assault, robbery, aggravated assault, and simple assault”.)

            The estimates for the prevalence of defensive gun use are high enough to, as this research brief says, make crime a “very risky business indeed”; see the graph on page 9. (More defensive gun uses against rape were reported than rapes, which means that prospective rapists are running worse than fifty-fifty odds of being possibly shot.) I know very little about this subject, but something is weird here.

          • Anonymous says:

            Oh, come on. You know enough to say that the rape numbers are false. Here’s the chart.

          • grendelkhan says:

            Anonymous: yes, those rape numbers are far too low (they’re the ‘NCVS’ tier, not the ‘Koss et al.’ tier), but I think the numbers they’re being compared to are… comparable, e.g., from the same tier? In any case, I don’t think the problem you cite exists for robbery, and that seems to come with a one-in-four-ish chance of risking being shot by your intended victim.

          • Anonymous says:

            No, I did not cite any particular problem. I really don’t think it is necessary to explain the cause of the numbers to assert that they are false (as opposed to “weird”). The problem you mention did not even cross my mind.

            And even if you don’t like the common use of rape, that doesn’t make NCVS false.

        • Anthony says:

          To be somewhat contrarian about that, most “nutcases” haven’t been “adjudicated as a mental defective or has been committed to any mental institution.”

          I’m not remembering the particular cases right now, but several high-profile mass shootings were committed by people whom other people were trying to get sent to a mental hospital, but The System wouldn’t do it.

          • “To be somewhat contrarian about that, most “nutcases” haven’t been “adjudicated as a mental defective or has been committed to any mental institution.””

            To be someone picky about this, the quote referred to “every nut case.” As long as some nut cases have been so adjudicated or committed, the quote is wrong.

            And, without being picky, the point is wrong. The fact that a nut case is permitted to do something is a lot less interesting if you make it “someone who is a nut case but not known to be.”

        • vV_Vv says:

          Some nutcases manage to slip through.

          Anyway, I think the point is that society allows people to do far more dangerous things than taking nefazodone, which looks like an inconsistency.

          • John Schilling says:

            You are equating things society allows, with things society fails to completely prohibit.

      • Julie K says:

        Doctors are afraid that they might be sued even if the patient was the one who decided which drug they prefer.

    • eqdw says:

      Personally I view doctors as highly pretentious sales assistants with a very effective guild.

      I’ve reluctantly accepted this, after a few bad experiences with doctors where it became painfully obvious that I know more about mental health and mental health medication than they do.

    • Alexander Stanislaw says:

      Because if his liver explodes, he will still sue you (unless you want patients to sign a long waiver form after accepting prescription, that might not even hold up in a lawsuit).

      There is a also the issue that consent is not informed consent. There are people (many many people), who can’t read a graph, don’t understand probability and don’t understand percentages. Giving them the choice without them understanding is worse than the current system.

      • Edward Scizorhands says:

        The specific problem is that court case are extremely expensive, well beyond their stated risks.

        If everyone taking the drug put $1 into a pot, and the 1:300,000 got to take $300,000 from the pool in exchange for settling the case quickly and easily, we’d all be better off.

        edit: $1 is just for example. Adding $10 per use would still be peanuts.

        • Deiseach says:

          The trouble there is, suppose the patient is married with children? $300,000 is not going to be enough to compensate for the loss of earnings if his liver explodes when he’s 30 or 40 and leaves a dependent family behind.

          Even for a single person, $300,000 might be wiped out in the costs of paying for a liver transplant (does that sound like a reasonable cost in America? I have no idea).

          That’s partly why the damages are so high where death or permanent harm has been caused.

    • Metus says:

      That medicine is not about health will be painfully obvious by noting that physicians – the mere fact that we should all call all of them doctors is testament to their pretentiousness – spend years and years studying disease and how to treat it, but spend only a fraction of their time studying how disease comes about and how to prevent it. Ask a hundred physicians what to do once you get depressed and they all have an answer. Ask a hundred physicians what to do when you’re healthy so you don’t get depressed, they won’t have a good answer.

      In an ideal world, your annual checkup wouldn’t consinst of your physician checking if he can find any symptoms of disease but examining if your lifestyle is conductive to your physical and mental well-being, both in terms of living a happy life and preventing disease. This could and should include reacting in case of sub-clinical cases of hormonal imbalances and depression, which I am sure are cause of millions and millions of lost QALYs.

      • Alexander Stanislaw says:

        In an ideal world, your annual checkup wouldn’t consinst of your physician checking if he can find any symptoms of disease but examining if your lifestyle is conductive to your physical and mental well-being, both in terms of living a happy life and preventing disease

        I think you vastly underestimate how difficult it is to get patients to want to change their lifestyle. And even moreso, getting them to change their lifestyle given that they want to. How do you even get them in the door? The people most in need of change, won’t go to see a doctor. People come to the doctor after their problems have developed, desiring a solution.

        • Metus says:

          And here it is again: “get patients to want to change their lifestyle”, “get them in the door”. Plenty of people change their lifestyle to get a happier life: They change careers, leave their place of birth behind, change their diets and change their exercise regimens. However, when I go to the doctor and complain “my back hurts” that will be covered by insurance. If I go and ask “how do I make that my back will not be hurting, even though it does not hurt now” I’ll have to pay out of pocket.

          • Scott Alexander says:

            This is true for some insurance types but not others.

            My father used to be a big advocate for having more people switch to HMO insurance. HMOs pay doctors a certain amount of money per patient, no matter what, and then the doctor has to hope the patients don’t actually need any care that costs money. So the doctor’s incentive becomes to give the patient as much prevention as possible so that they don’t get an illness that eats into their bottom lines.

            That incentive was great. As you can imagine, there were other incentives from that system that were less great.

          • Alexander Stanislaw says:

            And here it is again: “get patients to want to change their lifestyle”, “get them in the door”. Plenty of people change their lifestyle to get a happier life

            I don’t understand what your objection is. Do you disagree that changing a lifestyle is difficult on the basis that some people do it? Or that many people have no interest in changing?

          • Deiseach says:

            What is your query re: you want to avoid having your back hurt?

            (a) You injured your back previously and want advice on exercises, braces, physiotherapy, etc. to avoid a flare-up

            (b) You’re in a manual job or a job that puts strain on your muscles and joints

            (c) You want to hang new wallpaper in the bedroom and this means you’ll have to move wardrobes and chests of drawers

            The first is medical; the second and third are manual handling courses, how to prevent Repetitive Strain Injury, and don’t move heavy weights on your own, empty out the wardrobe first (there you go, free tip courtesy of how I managed to throw my own back out).

      • Deiseach says:

        Ask a hundred physicians what to do when you’re healthy so you don’t get depressed, they won’t have a good answer.

        Oh, but that’s so simple! Never get sick, never have an unhappy love affair, never have the people you love or care about suffer any ills physical, mental or emotional; never get old or poor or permit yourself to care about the pain in the world; don’t get yourself stuck in a dead-end job or a stagnant career, live in a desirable residence in a desirable location where you can enjoy the amenities of First World life; above all, before you get yourself born, be sure to pick the very most excellent genetic pattern that will not result in whatever biochemical processes cause depression when there is no simple external triggering event.

        Yeah, those doctors and their snooty refusal to tell people how not to be depressed!

        • Metus says:

          That’s like looking at car accidents and concluding that it is impossible to prevent them because there is more than one cause that could lead to car accidents including a genetic disposition to drift off. Yes, how could I dare to ask a physician what factors in my control could lead to major illness, half a million worth of treatment is better than one hundred in prevention.

          • Deiseach says:

            If you have a family history of depression, it makes sense to ask “How can I prevent this or be on the lookout for it happening?”

            But there may be no simple, one-size-fits-all answer. One doctor may recommend you go to counselling to help with any issues you think might trigger a bout of depression. Another might recommend “diet (these foods or supplements seem to have a good effect) and exercise”. A third might say they’ll put you on a regime of such-and-such as a preventative.

            And if you don’t have a family history that makes you anxious about possible genetic depression, then what can anyone tell you? Some people spiral into depression triggered by a bereavement or being made redundant, other people can weather these with no long-term ill affects.

      • “but examining if your lifestyle is conductive to your physical and mental well-being”

        You don’t believe in the division of labor, or don’t think it is relevant here? I expect my doctor knows more than I do about symptoms of disease. I expect he knows less than I do about what choices will make my life happier.

      • HeelBearCub says:

        Is their a name for the fallacy that is being committed here? The argument seems to be, “that which is sub-optimal is evil.”

        Heck, for all I know, many people won’t think that is a fallacy. But hoo-boy, good luck getting any closer to optimal if you are only willing to get there immediately and in one step.

        • Doug S. says:

          The saying you’re looking for is “The perfect is the enemy of the good” – meaning that if you won’t accept anything less than perfect, you’ll end up with nothing instead of the merely good thing you actually could have had.

          • HeelBearCub says:

            I know that statement and considered stating it that way.

            But the question is, is that a fallacy?

            Turns out, using what I should have used to begin with, google and wikipedia tell me this is The Nrivana Fallacy

            But is the sub-case of the The Nrivana Fallacy, The Perfect Solution fallacy.

            It strikes me that the rationalist community falls victim to this quite a bit. Or, maybe that is confirmation bias, as Perfect Solution fallacy (now that I have a label to apply to it) is one of my pet peeves.

    • Jiro says:

      Most people who don’t come from LW or here don’t understand statistics and probabilities. Letting patients decide for themselves that X risk of Y treatment is worth it will lead them to do things whose results are, overall, bad for themselves by their own standards.

      Saying “no paternalism” fails in the absence of competence.

      Of course, we do allow patients to decide between *some* alternatives, but not all of them in all cases.

      Also, of course, this has its own risks. It’s tempting for the doctors to make decisions that are good for the patients by the doctors’ standards, rather than by the patients’ standards, which is a problem with paternalism. You don’t want to let the patient to choose X over Y because he can’t calculate, but you do want to let the patient choose X over Y if his utility function is different from the doctor’s.

      • Hyzenthlay says:

        I think most people can grasp, on a basic level, the difference between “something which is generally more effective but has a very small risk of a horrible side effect” verses “something which is generally a bit less effective and has a high risk of a non-life-threatening but highly unpleasant side effect.”

        Physicians will necessarily have to make some preliminary choices about which options they present, because there are so many that time-constraints wouldn’t permit them to explain them all, but there are ways to present the existing options in language that the average person can understand.

      • “Most people who don’t come from LW or here don’t understand statistics and probabilities.”

        Including most doctors.

    • Scott Alexander says:

      In theory, yes, let the customer decide. But two problems:

      First, you don’t have the right to waive your rights, so a doctor who lets their patient decide to take the nefazodone might still end up on the hook.

      Second, in order to really understand the costs and benefits of all the options you’d probably have to be a psychiatrist yourself (and even then…). I can think of about ten reasonable first-choice antidepressants, and if we expand the definition to include things like nefazodone which aren’t currently considered reasonable first-choice antidepressants but which some people might decide they preferred, then it’s at least twenty-five. So doctors have a role in pruning down the overabundance of choices and deciding which risks and benefits to focus on. And right now the nefazodone choice is pruned before it makes it to a patient.

      • Creutzer says:

        First, you don’t have the right to waive your rights, so a doctor who lets their patient decide to take the nefazodone might still end up on the hook.

        What right would you be waiving by telling a doctor to prescribe you nefazodone?

        • Anonymous says:

          The right to sue him if it explodes your liver.

        • Loquat says:

          Also your family’s right to sue the doctor if your liver explodes and you die. You might be willing to accept the consequences if your choice, but once you’re dead you can’t control what your next of kin do.

      • Deiseach says:

        Yes, really the only way a patient can make an informed choice in these situations is if they’re going to a new doctor, the doctor recommends “I’ll put you on drug A” and the patient reels off “Sorry doc, tried that: doesn’t work for me; tried drug B, makes me throw up all the time; tried drug C which does nothing either way so I’m stuck with drug D which works but which may explode my liver”.

        Otherwise the patient needs to rely on the expertise of the doctor who has tried drug A on a lot of patients over the years and generally it works for most people.

      • HeelBearCub says:

        So doctors have a role in pruning down the overabundance of choices and deciding which risks and benefits to focus on.

        This is known in most professional circles as “doing your job”.

        Hire a plumber: I want the sink not to leak. If there are 20 options for that I do not want to be presented with them all. My head will explode.

        Hire a roofer: I want two choices, fix the existing shingle leak or re-roof. Re-roof has a few sub-choices. Most of those sub-choices should be aesthetic in nature, not qualitative.

        Hire a programmer: You don’t really want to know what algorithm I am going to use to solve the problem. You just want it fixed. If they are is a whole system to design, we will talk about some options, but not nearly every option.

        You CAN go to a plumber, roofer or programmer with a very detailed thought in mind, but you wouldn’t EXPECT them to provide every option on the front end.

    • Paul Torek says:

      Thanks for writing this, so I don’t have to. Let the patient determine the relative importance of a 50% chance of sexual problems vs a tiny tiny chance of death.

    • Robin says:

      I don’t disagree, but you’ll probably get the same distorted perception of risks: how much do you think psychiatrists warn patients about the risk that Seroquel will make their hearts explode?

  58. DanielLC says:

    > Their sexual dysfunction has some QALY weights averaging about 0.85.

    So, 15% of your happiness is from having sex? I know sex is supposed to be fun, but is it really that much?

    • suntzuanime says:

      To some extent yes, to some extent it’s not so much about fun as it is about doing things together with a serious romantic partner to cause bonding and it works a heck of a lot better than like taking yoga classes together, and to some extent it’s a matter of personal pride/dignity.

      Honestly I was surprised it was as high as 0.85.

      • Murphy says:

        Personally I’d rate sex itself I’d rate as a small hit to QALY if I still had semi/non sexual intimacy but it’s the knock on effects. It would make holding a relationship together much harder. Losing my relationship with my SO and thus the intimacy as well would be a massive hit to my personal life quality.

    • gattsuru says:

      I’m increasingly skeptical of disability QALY adjustments as inter-comparisons. Would /expect/ it to be off for things like diseases that cause risk taking or conditions that cause undervaluation of your own life, but even outside of that, diseases that require one to handle medical interactions seem to give odd results. Crohn’s Disease ranges from 0.4 to 0.89 QALY depending on severity and response to medication, trending around 0.8 for typical. Gastric bleeding, on the other hand, runs around 0.68 QALY and severe diarrhoea around 0.73, despite being one of the most common and constant symptoms of even treated Crohn’s.

      Migraine headaches (0.57) end up looking worse than the combination of HIV and tuberculosis (0.6), despite being perhaps one of the least likely medical trades, both of which seem worse than losing both arms without treatment (0.64).

      And other stuff is just weird. I’m not sure what definition of cannibis dependence they’re using to get 0.67, but that must be a hell of a lot of pot.

      If you have no other numbers, they’re better than nothing, but the more varied the conditions effects the more worried I’d be.

      ((They /also/ lead to highly counter-intuitive results, though this may be a feature rather than a bug.))

      (Prostate surgery also has a number of non-sexual side effects, as well as public stigma, though this is a secondary concern and I doubt covers more than half of the QALY metric.)

      • Rowan says:

        Wow, so according to those numbers if I self-medicated my Crohn’s disease with marijuana, and I guess a Magic Medical Marijuana Magician came from /r/trees to vanish away my Crohn’s Disease to replace it with marijuana dependence, I’d be about a decade of life worse off? Maybe if I smoked so many blunts the lung cancer killed me at 50.

      • moridinamael says:

        I dunno man, chronic migraines are pretty bad. It’s basically “you can’t do anything” + “you can’t enjoy anything” + “you’re experiencing level 7-10 pain virtually all the time”. Treated HIV, for example,doesn’t have the pain component or the generalized disability component.

      • Losing your arms is temporarily awful, but people tend to return to their hedonic set point. Chronic pain is one of the few things people seem unable to adapt to. The fact that QALYs capture that makes me like them more.

      • RCF says:

        “than the combination of HIV and tuberculosis”

        Was a number given specifically for that combination, or are you extrapolating from the given numbers?

    • randy m says:

      Something being a big frustration when it goes wrong is not necessarily v the same as being a big satisfaction when it’s working right.
      Also part of the problem is probably the reduced self esteem at being able to satisfy your partner, which is noticeable often when absent but only briefly when present.

      • Edward Scizorhands says:

        As someone on an SSRI, and having sexual side effects, the pleasing of my partner has not been an issue.

        I’m often not in the mood for sex at all. Still, I frequently verbally attempt to start it, because 90% of the time the answer will be “no,” and it makes her happy for me to attempt.

    • onyomi says:

      That doesn’t seem especially high to me, at least not for younger people.

    • Deiseach says:

      It’s easy for me to pooh-pooh worries about sexual side-effects: I’m asexual, so I’d be a lot more worried about “will my liver explode” (particularly given that an aunt of mine died from liver failure) rather than “will I stop wanting to jump my partner’s bones”.

      Yesterday was not a good day; I got home from work and the next thing I knew, out of the blue for no reason, I was walking around the house crying and mumbling “I am very, very unhappy” (feeling rather better today, before anyone thinks I’m sympathy-whoring!). Give me something that will help me not do this and I’ll happily take the chances of “Yeah, but you probably won’t want to bone anyone while you’re on this”.

      Maybe this is one of those “Elderly Hispanic woman” cases, where the risks of sexual dysfunction will be much lower down on the list of concerns about side-effects for certain people so they’ll be happy to take what doesn’t cause their liver to explode.

    • Scott Alexander says:

      Well, I’m asexual, so I don’t have a good intuitive feel, but it doesn’t seem so unlikely that people would be indifferent between living an extra 8.5 years able to have sex vs. living an extra 10 years unable to have sex.

      • onyomi says:

        I would definitely take 8.5 years with sex over 10 years without sex, and I think my libido is average at best.

        • John Schilling says:

          It would have to be really, amazingly good sex, and frequent, with highly desirable partners, for me to make that trade. And if I’m suffering the sort of mental illness that requires SSRI for treatment, that’s probably not a realistic proposition even if the treatment turns out to be successful.

          However, if we amend that to, “along with the sort of personal relationships that people who have regular sex tend to enjoy and people who do not have regular sex tend to not”, that would probably push it over the edge even for average sex. But there are some unstated assumptions going into that correlation.

          • onyomi says:

            For me, the pleasure of sexual activity alone, be it with a partner and/or on my own is enough to trade 1.5 years. I could probably also gain several years by eliminating all fat, salt, sugar, and dairy from my diet, but I enjoy eating those things enough that I still won’t do it.

            If you said “no sexual activity and no intimate, loving relationships” I would give up even more than 1.5 years out of 10 to avoid that.

            That said, overly frequent orgasms make me anxious and depressed in a very noticeable way, and for that reason I am willing to practice a more “tantric” style of sexuality (not having an orgasm every time I have sex).

            I might also note here that I think psychiatry should look into this connection more. The idea of having fewer orgasms than you might desire in an effort to “preserve vital energy,” etc. is generally dismissed as Yogic/Daoist woo, but there is absolutely an unmistakable correlation in my case with frequent orgasm and worsening of psychiatric problems.

          • Pete says:


            Interesting. I find that less frequent orgasms leads to higher energy levels. I get so much more done. I just can’t find any scientific reason why this should be so and most explanations seem to be somehow spiritual in nature (which I dismiss out of hand).

          • onyomi says:

            Well it doesn’t have to be spiritual. Orgasms are known to have all kinds of neurochemical effects, like increasing prolactin, etc. The annoying this is that they are, in my experience, only ever described in positive terms in popular science reporting, probably as part of an effort to appear “sex positive.”

      • Deiseach says:

        Not to be laughing at anyone, but this is increasingly sounding like “Cake or death?”

      • HeelBearCub says:

        “8.5 years able to have sex vs. living an extra 10 years unable to have sex.”

        This seems like a very poor way to attempt to understand it.

        Much like your “increase lawsuit risk from zero” insight, the person who is hearing about this risk is perceiving that the risk of death from medication is increasing from zero as well.

        It is not the case that the drug makes you age faster/removes 1.5 years from your life expectancy. That you take this drug and die at 72 instead of 74.

        The drug increases your risk of dieing at 30. And that isn’t playing around with numbers, that really is a qualitative difference.

        You might say that the persons risk of dieing from medication wasn’t actually zero, but neither was the doctors risk of lawsuit actually zero. If you prescribe SSRIs, you run the risk of your patient committing suicide and then being sued for that. In both cases, it’s more about perceived risk, than actual risk.

      • Limi says:

        Reading this article, my thoughts were constantly ‘I would happily roll those dice’. In fact, it would have to be more like 5 years vs 10 years before I gave it any thought, and even then I think (and other things I have done suggest I am correct) I would still go ahead with it.

        Of course, I have major depressive disorder, or whatever they call it these days, so I can’t remember a time when I didn’t feel, at best, apathetic about living, let alone actively wishing for death. I would try a lot of much more life threatening treatments if they could potentially make me feel more like life was worth living, which would ironically then I guess make me less likely to try life threatening treatments.

        I am also acutely aware that my lack of libido disappoints my partner, and I would try anything to change that.

    • pku says:

      My personal experience with SSRI sexual side effects was that they were a lot more bothersome than I expected, even though I wasn’t dating anyone. It’s really frustrating to see a pretty girl, know you should feel attracted, but just feel nothing. (And also, it’s pretty frustrating when it suddenly becomes much harder to relieve your anxiety with masturbation). (Note: my doctor said those were probably placebo side effects, and they went away eventually).

      • Deiseach says:

        It’s really frustrating to see a pretty girl, know you should feel attracted, but just feel nothing.

        That’s the part that, as an asexual, I don’t understand so I should emulate Job here:

        Behold, I am vile; what shall I answer thee? I will lay mine hand upon my mouth.

        If it is any comfort to anyone, from the other side of the Embarrassing Confessions street, about five or six years ago I went through some kind of hormonal surge (possibly to do with menopause) that left me constantly aroused, in a way I’d not experienced since I was fourteen or fifteen, and it was horribly inconvenient and frustrating; “Hell’s sake, I just had an orgasm a little while ago, I can’t still be horny!” type of thing. I was so glad when it all calmed down again 🙂

        • Who wouldn't want to be anonymous says:

          Oh, well, apparently we’re going down that road. When I was taking an SSRI, it had no impact on my ability to find people attractive or become aroused. I could even orgasm if I was… persistent. This is certainly frustrating as heck when you’re trying to bang out a quick one, but I was, I believe the phrase is “marginally employed,” so I had plently of time to fit it into my schedule the customary number of times. Moreover, because the whole process was telescoped from a few minutes to few dozen minutes it was usually trivial to prolong the sweet spot indefinitely. Or at least to the “if you experience an erection lasting more than…” limit.

          I am pretty sure the sexual side effects did more to improve my quality of life than the antidepressant effect. Now this certainly wouldn’t have been the case if I didn’t have the time to accommodate it, in addition to a social life and hobbies (and a job, such as it was); or if I was obliged to try matching the time investment with that of another person—-a libedo mismatch can be very trying on a relationship.

          Everything I have heard tells me that my experience was… unusual.

          • Doug S. says:

            My experience is oddly similar; to the extent that taking antidepressants delayed my orgasms, I liked it because it let me have longer masturbation sessions. Apparently, some people even take SSRIs to treat “premature ejaculation”. I did have a bit of an issue though once I started trying to have sex with an actual partner, though; I think my medication may be made it more difficult to get a completely firm erection, which wasn’t a problem at all when masturbating but made intercourse more difficult.

      • Careless says:

        my doctor said those were probably placebo side effects, and they went away eventually

        Sounds like a placebo cure.

        I’ve done a bit of yoyoing with my SSRI dose without thinking of the sexual side effects beforehand, and the changes were pretty dramatic. Also the changes in weight gain/loss between different dosages

    • Desertopa says:

      It could be significantly more or less for different people, but I’d note that .85 quality adjustment for ruined sex life doesn’t necessarily mean 15% of your happiness is from sex. It could also mean, say, you worry about whether your partner is still happy with you, maybe your relationship starts to deteriorate, and the whole thing ends in tears.

      A person’s libido can be a vital component to their relationship health, and since a single person’s sex drive can be a resource of shared value to multiple people, the .85 QUALY reduction may even understate the impact.

    • Surlie says:

      “Sexual dysfunction” isn’t simply the opposite of having sex, though.

      It’s the partial or complete *inability* to have sex. That creates all kinds of quality of life ripple effects that impact relationships, etc.

    • Short term, it’s no big deal. But if one half of a typical married couple has sexual dysfunction *long term*, then both halves will likely grow very noticeably unhappier in their relationship.

    • Shenpen says:

      Probably even more. I have recently heard that our habit – about twice a month in good times, and none at all in bad ones – unusual for married couples, even every day is not unheard of. Any 30 minutes long activity that requires a shower both before and after should contribute more than 15% if you would do it every day or else you would not do it every day. Basically like an exercise. Sure if you are willing to do 200 pushups every day and showever before and after, it would be more than 15%.