Neurology Center

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.



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.

Dudley, 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