Do Antidepressants Increase Suicide Risk?

I want to present a single paper on the topic for the moment.  It’s a meta-review:  it reviews the existing reviews/summaries of what is known, and it’s perfect for someone like me who really needs the high-level view of the topic.  There are some newer reviews on the topic, but none so thorough as this.  I’m only focusing on a single comparison, but the paper goes into several other topics.

Here’s the paper, full text, not behind a paywall:

BMJ. 2005 February 19; 330(7488): 396. “Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials”

This figure really tells the story.  It breaks down whether the literature supports an increased risk for suicide attempts in people taking placebo or SSRI antidepressants.  The effect is rather weak, but multiple studies support this slight increase.

What I look for in data like this are error bars that don’t overlap the midline… in other words we can be reasonably confident that there’s a reproducible “real” difference between these two groups, and that difference supports an increased risk in people taking the drug.

I always need to caution people who read these types of epidemiological data with the standard warning:

“WARNING: The risk assessments here are STATISTICAL ONLY.  Being 5% more likely to make a suicide attempt does not mean SSRI’s will cause you to attempt suicide!  It may have an effect on a susceptible proportion of the population, but all we can say for sure is that SSRI users are slightly higher risk than placebo users with depressive conditions”

Scientists have to be very careful communicating these risks, because we’re so used to minor statistical differences between very large groups that we forget that patients don’t see themselves as statistics or group members… they translate stochastic risk into deterministic outcomes.

I’m not sure if I follow why the sex differences are significant.  I gather from the literature that depression in women can be related to PMDD, possibly using a mechanism different than non sex hormone specific depression pathways in the brain?

It’s also interesting to me that pharma-funded research is actually more likely to find increase suicide attempt risk than non-pharma funded.

The paper contains a nice summary of findings, which I will briefly quote here:

“We documented a more than twofold increase in the rate of suicide attempts in patients receiving SSRIs compared with placebo or therapeutic interventions other than tricyclic antidepressants. Although many trials have documented the benefits of SSRIs in many forms of depression and other clinical indications, it has been difficult to document the relatively rare but very serious risk of suicide. We documented a difference in absolute risk of 5.6 suicide attempts per 1000 patient years of SSRI exposure compared with placebo. Although small, the incremental risk remains a very important population health issue because of the widespread use of SSRIs. In the United Kingdom, 1 million person years of SSRI treatment are provided annually by general practitioners.13 For the United States, the number of visits by patients for depression was 24.5 million in 2001, a 70% increase since 1987.1 In 2001, 69% of patient visits for depression resulted in prescriptions for SSRIs.1 Thus, a large number of patients were at risk for treatment induced suicidality.”

One comment on “Do Antidepressants Increase Suicide Risk?

  1. The article you review compare the incidence of suicide in a groups of patients on antidepressants with groups of patients on placebo.

    However, this does not seem to control for the outcome of “getting better”. What if a similar increase in incidence of suicide in patients exposed to drug-free psychotherapy was observed?

    Bridge et. al. (2005) investigated precisely this possibility. They concluded that psychotherapy alone increased the incidence of suicide and the strongest predicator of emergent suicidality was baseline level suicidal thoughts and that this increase in incidence is similar to that observed in antidepressant trials.

    This suggests that, perhaps, severely depressed individuals lack even the motivation for suicide to a certain degree, that returns when the patient gets slightly better, no matter if the treatment are drugs or drug-free psychotherapy.

    This can also explain the increase in incidence of suicide in antidepressant trials compared with placebo with a similar mechanism and/or because the baseline level of suicidal thoughts may not have been controlled for in the trails investigating the association between suicide and antidepressants.

    Other studies, such as Hamilton et. al. (2007), have shown an increase in incidence of suicide with 18% after prescription rates fell due to the black box scare, which is the first increase in over a decade. Chronological association does not entail causation, but it is difficult to explain if antidepressants clearly increase the risk of suicide (compared with placebo or alternative, effective, treatments).

    References:

    Bridge JA, Barbe RP, Birmaher B, Kolko DJ, Brent DA (2005). Emergent suicidality in a clinical psychotherapy trial for adolescent depression. Am J Psychiatry 162: 2173-2175

    Hamilton BE, Miniño AM, Martin JA, Kochanek KD, Strobino DM, Guyer B (2007). Annual summary of vital statistics: 2005. Pediatrics 119:345-360.

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