SSRIs and Suicide

By Neuroskeptic | June 1, 2010 5:40 pm

Prozac and suicide: what’s going on?

Many people think that SSRI antidepressants do indeed cause suicide, and in recent years this idea has gained a huge amount of attention. My opinion is that, well, it’s all rather complicated…

At first glance, it seems as though it should be easy to discover the truth. SSRIs are some of the most studied drugs in the world. We have data from several hundred randomized placebo-controlled trials, totaling tens of thousands of patients. Let’s just look and see whether people given SSRIs are more likely to die by suicide than people given placebo.

Unfortunately, that doesn’t really work. Actual suicides are extremely rare in antidepressant trials. This is partly because most trials only last 4 to 6 weeks, but also because anyone showing evidence of suicidal tendencies is excluded from the studies at the outset. There just aren’t enough suicides to be able to study.

What you can do is to look at attempted suicide, and at “suicidality”, meaning suicidal thoughts and self-harming behaviours. Suicidality is more common than actual suicide, so it’s easier to research. Here’s the bad news: the evidence from a huge number of trials is that compared to placebo, antidepressants do raise the risk of suffering suicidality(1) and of suicide attempts(1) (from 1.1 per 1000 to 2.7 per 1000), when given to people with psychiatric disorders.

There’s no good evidence that SSRIs are any worse or any better than other antidepressants, or that any one SSRI stands out as particularly bad(1,2). The risk seems to be worst in younger people: compared to placebo, SSRIs raised suicidality in people below age 25, had no effect in most adults, and lowered it in the oldest age groups(1). This is why SSRIs (and all other antidepressants) now carry a “black box” in the USA, warning about the risk of suicide in young people.

*

This is very troubling. Hang on though. I mentioned that suicidality is an exclusion criterion from pretty much all antidepressant trials. This is for ethical as well as practical reasons: it’s considered unethical to give a suicidal person an experimental drug, and it’s really impractical to have patients dying during your trial.

Indeed the recorded rate of suicidality in these trials is incredibly tiny: only 0.5% of the psychiatric patients experienced any suicidal ideation or behaviour at all(1). The other 99.5% never so much as thought about it, apparently. If that were representative of the real world it would be great; unfortunately it isn’t. Yet what this all means is that antidepressants could not possibly reduce suicidality in these trials, because there’s just nothing there to reduce. Even if, in the real world, they prevent loads of suicides, these trials wouldn’t show it.

How do you investigate the effects of drugs “in the real world”? By observational studies – instead of recruiting people for a trial, you just look to see what happens to people who are prescribed a certain drug by their doctor. Observational studies have strengths and weaknesses. They’re not placebo controlled, but they can be much larger than trials, and they can study the full spectrum of patients.

Observational studies have found very little evidence suggesting that antidepressants cause suicide. Most strikingly, since 1990 when SSRIs were introduced, antidepressant sales have increased enormously, and the suicide rate has fallen steadily; this is true of all Western countries.

More detailed analyses of antidepressant sales vs. suicide rates across time and location have generally either found either no effect, or a small protective effect, of antidepressant sales(1,2,3, many others). In the past few years, concern over suicidality has led to a fall in antidepressant use in adolescents in many countries: but there is no evidence that this reduced the adolescent suicide rate(1,2).

Another observational approach is to see whether people who have actually died by suicide were taking SSRIs at the time of death. Australian psychiatrists Dudley et al have just published a review of the evidence on this question, and they found that out of a total of 574 adolescent suicide victims from the USA, Britain, and Scandinavia, only 9 (1.5%) were taking an SSRI when they died. In other words, the vast majority of youth suicides occur in non-SSRI users. This sets a very low upper limit on the number of suicides that could be caused by SSRIs.


*

So what does all this mean? As I said, it’s very controversial, but here’s my take, with the standard caveat that I’m just some guy on the internet.

The evidence from randomized controlled trials is clear: SSRIs can cause suicidality, including suicide attempts, in some people, especially people below age 25. The chance of this happening is below 1% according to the trials, but this is still worrying given that lots of people take antidepressants. However, the use of antidepressants on a truly massive scale has not led to any rise in the suicide rate in any age group. This implies that overall, antidepressants prevent at least as many suicides as they cause.

My conclusion is that the clinical trials are not much use when it comes to knowing what will happen to any individual patient. The evidence is that antidepressants could worsen suicidality, or they could reduce it. This is hardly a satisfactory conclusion for people who want neat and tidy answers, but there aren’t many of those in psychiatry. For patients, the implication is, boringly, that we should follow the instructions on the packet – be vigilant for suicidality, but don’t stop taking them except on a doctor’s orders.

ResearchBlogging.orgDudley, M., Goldney, R., & Hadzi-Pavlovic, D. (2010). Are adolescents dying by suicide taking SSRI antidepressants? A review of observational studies Australasian Psychiatry, 18 (3), 242-245 DOI: 10.3109/10398561003681319

  • dearieme

    There's a feature of trials of statins that struck me when I read about it; do SSRI trials share it? In statin trials, if patients suffered serious side-effects in the first couple of weeks they were withdrawn from the trials, I read, and all subsequent statistics reported for the trials ignored their existence. You'll see that this means that all the reported figures for side effects are systematically biased to the low side. In my field of science, we'd probably call that “lying”.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    I've never heard of that happening in antidepressant trials. People suffering side effects tend to withdraw from the trials (dropout rates are routinely 30% or higher) but their adverse events will be recorded.

    However there was other dodginess over the SSRI / suicide data, as David Healy worked out: basically, suicides occurring before the main phase of the study were counted as “suicides in the placebo group”; this masked the fact that there were more suicides in the drug group, by wrongly inflating the # in the placebo arm.

  • dearieme

    Thank you. I think we'd call that “lying” too.

  • http://www.blogger.com/profile/16203083806436919715 Bernard Carroll

    Neuroskeptic wrote: This implies that overall, antidepressants prevent at least as many suicides as they cause. That is consistent with calculations I published after the JAMA report of the TADS trial of fluoxetine and behavior therapy in depressed adolescents. Here is the citation: JAMA 2004;292:2578

  • http://www.blogger.com/profile/07429793255785560043 Dirk Hanson

    Two thoughts: Teasing out suicide rates due to medication side effects is terribly difficult in a population that is marked by high rates of suicide to begin with, i.e. clinical depressives.

    Also, let us not forget the originators of the “Prozac Kills” campaign: Scientology.

  • Anonymous

    I am so glad you mentioned this because I have been thinking about this very topic. As a 13 year old, I was depressed but not suicidal. I only became suicidal after being on SSRIs. Obviously I am only one anecdote but the whole controversy made me wonder if it was a factor. Why would it make people suicidal if it's supposed to make them less depressed? I wonder if it gives them just enough “get up and go” to act on their impulses.

    Also, have you heard of Robert Whitaker's book Anatomy of an Epidemic? I am not sure if he is a quack confusing correlation with causation or not. His thesis is that SSRIs increase relapse rates making depression more chronic.
    I wish you'd review that book. I find your blog very interesting, Thanks!

  • http://www.blogger.com/profile/08461338194309128443 Paul

    I find much of Robert Whitaker's work very interesting, especially his book 'Mad in America'. However, Anonymous, you may be interested to read The Macguffin's views on the book:

    http://chekhovsgun.blogspot.com/2010/05/anatomy-of-epidemic-or-story-told-over.html

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Time for a back of the envelope calculation…

    The US suicide rate is about 11 per 100,000 per year, which comes out as about 33,000 per year.

    10% of the US population take antidepressants each year, i.e. 30 million people. Up from 15 million 10 years ago.

    According to Table 2 in David Healy's 2005 BMJ paper, SSRIs raise the risk of suicide attempts from 1.1 per 1000 to 2.7 per 1000, i.e. they cause 1.6 per 1000 people to attempt suicide. relative to placebo.

    Now, if you take those numbers literally, the 15 million “extra” people taking antidepressants means 24,000 additional suicide attempts per year.

    How many extra suicides is that? It depends how lethal the attempts are…the NIMH say that there are 12 to 25 attempts for each death. So it's 1000 to 2000 extra suicides.

    In other words, if antidepressants were as bad as the clinical trial data suggest, they would be causing 1000 to 2000 suicides in the US compared to 10 years ago. (And 2000 to 4000 in total.)

    Whether this is credible I'll leave to you.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    P.S. but that's assuming that the NIMH are right about 12 to 25 attempts per death, with strikes me as a very low fatality rate.

    In the antidepressant trials, there were 7 deaths and 29 non-fatal attempts, i.e. a 20% fatality rate,

    If you apply that to the American population you get: antidepressants cause 10,000 fatal suicides in total, 5,000 more than ten years ago. Which seems implausible.

  • Anonymous

    No. I read your posts as follows: SSRI's don't cause suicide, nor do they prevent suicide. So why the hell would one take them, anyway? I mean research indicates the SSRI's are largely placebo in effect, no?

  • http://www.blogger.com/profile/08673665063857901577 skornblith

    Anonymous: from clinical trials of antidepressants, we know that, due to the placebo effect, giving any old pill will help to relieve depression. But:

    1) You can't exactly prescribe a patient a placebo.
    2) If you had a choice between prescribing a true placebo, which has some measurable effect, and a pill that is statistically significantly better than placebo (even if the difference is small), why wouldn't you give the latter pill?

  • http://www.blogger.com/profile/01127763374693792450 FunPsych

    In the past few years, concern over suicidality has led to a fall in antidepressant use in adolescents in many countries: but there is no evidence that this reduced the adolescent suicide rate(1,2).

    I'm wondering why you didn't mention that in the U.S., suicide rates among 10-24 year-olds have actually increased since 2003 (to 7.32 per 100,000), after falling from 1990 to 2003 (from 9.48 to 6.78 per 100,000 people). I know this was mentioned in one of the articles you linked to, but you didn't point it out. And in the U.S. at least, it seems as though suicide rates have continued to climb.

    According to this NIMH site, in 2006 the suicide rate among adolescents age 15 to 19 was 8.2 per 100,000, and among young adults ages 20 to 24 it was 12.5 per 100,000. This clearly seems to coincide with decreased prescribing of SSRIs. Thoughts?

    -Funpsych

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    It's a good point, however I don't think the same increase has been observed in other countries… although maybe the decline in antidepressant prescribing was less in other countries too.

    Overall I think it's reading too much into the data to say that because suicides rose in one country after antidepressant use fell, that's a causal link. Whereas the fact that across all countries and ages there is no positive correlation of harm, does strongly suggest there is no causal link…

  • http://www.blogger.com/profile/12380121045241425522 Richard

    All useful stuff about suicides while taking SSRIs.
    Are similar data available for suicides, suicidal ideation, etc. on withdrawal from SSRIs or other psychiatric medication?

  • Anonymous

    What's the reason for the overall decline in suicide rate? Could it be possible that an increase in suicides due to SSRIs [at the levels you calculated or lower] could be masked by a decline due to other reasons?

    I'm thinking it's probably not very plausible given your calculations, but then FunPsych's note about suicides in adolescents and young adults… Is there a large decline in suicide in older populations? If so, this would be the trend [but not the exact numbers] you'd expect given the supposed suicidality effects of SSRIs.

    Also, what's the age breakdown on SSRI use? Is one age population more likely to be taking SSRIs? If so, that would be something to take into account.

  • Alex

    Having dated an adolescent (when I was also an adolescent) on antidepressants, I would argue that, if the study is true (and more research may be needed), one cause they might want to look into is intermittent use of the drug. It's well known that stopping an anti-depressant, especially cold turkey, leads to suicidal ideation and high levels of depression. Adults are probably less likely than kids to discontinue their treatment because they think it's a good idea or because their friends tell them that anti-depressants are a scam.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    True. Unfortunately we know little about discontinuation because there's not much money in researching people who stop taking drugs.

  • http://www.blogger.com/profile/16240719198048604115 esistvollbracht

    I'm sorry that this comment is both late and unscientific. Speaking as someone who is depressed, thinks about suicide, and has taken a variety of anti-depressants, I wonder if any correlation there may be between anti-depressants and suicide is the result of… disappointment? My experience has been that they all cause unpleasant side-effects but that none of them cure depression. (The most they did for me was take the worst edge off anxiety.) I was depressed for a long time before I first took an anti-depressant; it felt like a last resort, taken out of desperation, and I suspect that many others feel the same way. The side-effects developed within hours, but the alleviation of depression never happened. The feeling of disappointment, that the last resort had failed, made me feel far more suicidal than ever.

  • FlawedArgument

    You have made a common error in establishing your argument. You are using a statistic that has many other variables; therefore, can neither prove nor disprove your presumption. According to you, if SSRIs caused a increase in suicidal attempts/fatalities, this would be evident by an increase in the national suicide rate. However, you are ignoring the fact that the national/global suicide rates are dependent upon many other factors, conditions and variables. (Can you prove that the suicide rate is not falling for other reasons and would not fall even further if it weren't for SSRIs? Can you prove that the previous rates were not elevated for other socioeconomic reasons? Can you prove that all suicides had a toxicology report accompanying their autopsies?) There are too many variables, so a logical chain cannot be definitely established. The only way to determine validity of this claim is to test the drug against placebo or record the reactions in a context that is specific to SSRIs alone. Unfortunately, as you've noted, these studies do not reflect real-world conditions (exclude currently suicidal candidates). Additionally, these studies are not performed by the FDA, but are conducted by an “independent” party. The manufacturer of the medication pays for these studies during the patent process; therefore, the issue of conflict of interest cannot be entirely excluded. There needs to be an independent study performed; one not funded by anyone with an interest in the outcome. Lastly, these studies only pertain to a 4-6 week trial period and exclude suicides that occur after the trial has concluded. Even though manufacturers have admitted a link between withdrawal and elevated suicidal ideation, attempts and fatalities, these late occurring suicides (those within the weeks immediately following the study)are still not recorded or factored into the statistics. Sadly, there are no currently available statistics which prove/disprove the link between SSRIs and suicide. There are only the thousands of families that are filing complaint against the FDA and taking legislative action against pharmaceutical companies. Hopefully, someone will heed their call and perform a truly independent study.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    FlawedArgument: You're right that none of the existing data allow us to definitively say whether or not SSRIs cause more suicides than they prevent.

    However many observational studies of suicide rates (some of which have attempted to control for other factors) suggest that antidepressants either don't change, or reduce, suicide risk. But then again you can never control for everything.

    My point is, we can't know for sure – i.e. we shouldn't take the placebo controlled trials as showing for sure that there is a link.

  • http://www.blogger.com/profile/01033119473291087413 julietta

    Interesting to read all these comments. Some of the studies that are cited are probably not that reliable if you looked into the methodology etc as Healy does in his writings, but I would like to say that my 22 year old son recently attempted suicide on an SSRI – sertraline to be precise. A friend's husband committed suicide on Seroxat a few years ago and another friend had a work colleague who committed suicide on an SSRI a few years ago. In the case of my son, yes he was depressed before he took the SSRI but the drugs sent him into a whole different level of stuff – he started acting out – that is the difference I noticed – the drug made him ACT OUT, and as David Healy says it is the time going on and coming off the drug that is most dangerous. On his last day weaning off Sertraline, as directed by his psychiatrist, he felt so bad he told me he didn't feel safe in himself and then went off and took an overdose.Interestingly David Healy talks in Let Them Eat Prozac of how SSRI's were firstly tested as a remedy for high blood pressure, but there were problems found in that they caused suicidality in the patients taking it. This proves that the suicidality caused by SSRIs is not just down to the prediposition of the patient being depressed.

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About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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