In a new study, researchers found SSRIs increased the risk of suicide attempts threefold for those younger than 18 and up to twofold for those aged 18-24. They had no preventative effect at any age, even for those at high risk of suicide.
“The present study finds similar results to prior observational research—that is, consistent evidence of an increased risk of suicidality during treatment with SSRIs in children and adolescents,” the researchers write.
The study was led by Tyra Lagerberg at the Karolinska Institutet and was published in Neuropsychopharmacology.
The data came from a Swedish registry, including 162,267 people who received a diagnosis of depression. Of these, 52,917 people began treatment with an SSRI antidepressant within 28 days, while 109,350 did not. The outcome of interest was suicide attempts as recorded in the registry (thus, attempts serious enough to result in an encounter with the medical profession). The researchers analyzed data at a three-month follow-up and at one year (the results were similar at both time points).
The researchers included both the intention-to-treat analysis and the per-protocol analysis, two different ways of handling the outcome data. The gold standard is to include both so that the reader can see all the data.
In this case, both the intention-to-treat analysis and the per-protocol analysis showed that SSRI use was associated with increased suicide attempts in those under 25. The only difference was the magnitude of the effect.
In the intention-to-treat analysis, 6-17-year-olds were 2.9 times more likely to attempt suicide on SSRIs. In the per-protocol analysis, they were 3.34 times more likely.
Those 18-24 were 1.59 times more likely to attempt suicide in the intention-to-treat analysis and 2.01 times as likely in the per-protocol analysis.
Those over 25, however, were not more likely to attempt suicide if they received an antidepressant, based on either analysis.
However, this null finding also means that antidepressants did not have a preventative effect—they did not reduce the likelihood of suicide for those over 25, either.
The main limitation of this study is that the researchers couldn’t account for baseline severity. That is, people who had more severe depression—and thus, increased suicide risk—may have been more likely to take an antidepressant. This is especially true since the researchers note that psychotherapy is the first-line treatment for mild-to-moderate depression in Sweden.
However, the researchers accounted for suicide risk in another way: they were able to account for those who had a history of suicidal behaviour (which is a good proxy for those at the highest risk of future suicide attempts).
Those who had previous attempts were more likely to attempt again—whether or not they took antidepressants. That is, antidepressants seemed to neither worsen the problem nor help at all.
“Those with a history of suicidal behaviour (N = 4221) showed greater absolute risks among both initiators and non-initiators. We found no evidence of a difference between initiators and non-initiators in this group in terms of suicidal behaviour risk,” the researchers write.
Thus, probably the best way to interpret the results of the study is as follows:
For those younger than 25, with no history of suicidal behaviour, taking an antidepressant makes you up to three times more likely to attempt suicide, with that likelihood decreasing as you age. For those 25 or older, taking an antidepressant doesn’t help reduce suicide. Similarly, for those at high risk for suicide, taking an antidepressant doesn’t reduce the risk.
The finding here is consistent with previous studies, which have repeatedly shown that antidepressants increase suicide risk, particularly for children and adolescents, with some studies finding more than doubling the risk of suicide and at least one analysis finding a sixfold increase.
And one study found that those with more severe depression, those with comorbid anxiety, and those who were suicidal were the least likely to benefit from antidepressant drugs.
Lagerberg, T., Matthews, A. A., Zhu, N., Fazel, S., Carrero, J. J., & Chang, Z. (2023). Effect of selective serotonin reuptake inhibitor treatment following diagnosis of depression on suicidal behaviour risk: A target trial emulation. Neuropsychopharmacology. Published online July 28, 2023. https://doi.org/10.1038/s41386-023-01676-3 (Link)
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