Welcome to my blog, a place to explore and learn about the experience of running a psychiatric practice. I post about things that I find useful to know or think about. So, enjoy, and let me know what you think.

Wednesday, October 23, 2013

Book Review, Sort Of

I just finished reading David Healy's Let Them Eat Prozac.

In it, he takes a passionate position on the adverse effects of SSRI's, particularly with respect to suicidality. While initially convinced that prozac did not induce suicidality, Dr. Healy was subsequently an expert witness on several suicide/homicide lawsuits related to SSRI use. While researching those cases, he had more data made available to him, and was then convinced that SSRIs significantly increase suicidality. The supporting data include:

*Re-evaluations of results from SSRI studies

*Cases in which patients were started on an SSRI, became akathetic and agitated, stopped the SSRI, improved, then were subsequently restarted on the SSRI (or other serotonergic drug) and deteriorated once more (challenge/dechallenge/rechallenge, which is how causality can be established)

*Internal Memos from Lilly, which stated things like, "We know prozac causes a 5.6 times greater risk of suicidality than placebo, so we need to figure out how to deal with it, and specifically, how to figure out which patients will benefit from Prozac."

*His own trial of and SSRI in healthy volunteers, in which suicidality emerged

*Early studies in which subjects who developed akathisia and agitation on Prozac were either removed from the study, or given benzos for those side effects, essentially demonstrating that benefits in the study may have been from benzos, rather than Prozac.

*The fact that the BGA (the German equivalent of the FDA) did not approve fluoxetine, claiming that it was not sufficiently effective, and that it induced akathisia and agitation in patients, and ran the risk of inducing suicidality. Fluoxetine was approved in Germany a number of years later, under what appears to be powerful political pressure.

What I liked about the book is the fact that, despite how strongly Dr. Healy feels about this subject, and despite the fact that he lost a job because of his opinions, he still doesn't assume a conspiracy took place. Rather, he makes a case for a series of bad decisions, bad luck, predictable greed, overall good intentions, and selective blindness.

I also liked the fact that he is not advocating a complete moratorium on SSRI use. He believes, and this confirms my clinical impression, that there are subgroups of patients, some of whom do well on SSRIs, and others who don't. He advocates for research to figure out how to predict which group a given patient will fall into. He also advocates for research to specifically examine suicidality in SSRI use, and points out that, remarkably, no such study has been undertaken.

What I didn't like about the book was that his arguments are sometimes difficult to follow, causing me to question his conclusions, My impression, in general, though, is that the dude knows his stuff.

This is only "sort of" a book review because I'm including a link to his paper, Antidepressants and Suicide: Risk-Benefit Conundrums, as part of the online journal club The link is from his site, and another thing I like about his work is that he encourages open sources, and provides links to publications.

He's written more recent papers on this topic, but this one, in particular, summarizes what he covered in Let Them Eat Prozac, although the paper is for a professional audience, while the book is more for a lay population.

This is a table from the paper:

Note that on Placebo, there were 2 completed suicides, and 21 suicide attempts, on Active Comparators (e.g. TCAs), there were 5 completed suicides, and 24 attempts, and on All SSRIs, there were 23 completed suicides, and 186 attempts.

I'm very curious to hear people's evaluations of his statistical methods, so please comment.


  1. I saw a Healy interview somewhere where he was asked if he personally prescribes SSRIs. He said that he does. I dont't know if he comments on that in his book of not, but it is part of his larger position that antidepressants don't treat depression - psychiatrists do. I think the corollary is that the largest and most important part of prescribing when you are a physician is recognizing and managing side effects.

    I have followed Khan's work for about 2 decades at this point. Do you have the reference for the table in your blogpost? I know that he has written at least one article showing no difference in suicidality with SSRIs.

    I agree with you that when you have treated thousands of patients in your career you appreciate that medications are good for subgroups of people. There are for example people with extreme irritability, anger control problems and PMDD that all benefit from SSRIs. On the other hand there are people who don't tolerate antidepressants from any class.

    1. There were two references for the table (which is from the linked article, so all his references are there):

      Khan A, Warner HA, Brown WA. Symptorn reduction and
      suicide risk in patients treated with placebo in antidepressant
      clinical trials. Arch Gen Psychiatry 2000;57:311-7.

      Khan A, Khan SR, Leventhal RM, Brown WA. Symptom
      reduction and suicide risk in patients treated with placebo in
      antidepressant clinical trials: a replication analysis of the Food
      and Drug Administration database. Inf / Neuropsychopharmacol

      Healy does make it clear in his book that he prescribes SSRIs. In fact, I think one of his main points is that what is needed is a study to try to determine who will and who won't benefit from them.

      What he didn't describe in this book, although maybe he does elsewhere, is how he determines, initially, which antidepressant he'll prescribe. That would have been helpful. I think I have some kind of internal algorithm, of which I'm not consciously aware, that pushes me in the direction of one med or another. Some of it is about the level of anxiety, but I can tell there's more than that. And then it's just trial and error, which I try to make clear to patients. But it would be good to have a more explicit way of determining this. Only, once you go down that road, it's back to checklists, and that's a slippery slope. Do you have some way you go about it?

  2. Even conceding that “science” is better than experienced intuition, everybody would agree that experienced intuition beats pseudoscience – or worse – dishonest science.