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Do antidepressants increase or decrease suicide risk? The answer is clearly both, as you’ll hear in this Quick Take. But the crucial question is: If your 16-year-old patient has severe depression and psychotherapy has not led to sufficient improvement, how much risk does he face if you start an antidepressant?
Hi! Jim Phelps here for the Psychopharmacology Institute. Here’s a study from Denmark that looks at rates of suicidal ideation and nonsuicidal self-harm in young people before and after they start an antidepressant. What do you think we’ll see?
Well, it’s a signal-to-noise ratio problem. Remember how that concept works: If the background rate of the phenomenon you’re looking for is low, then when a new event occurs, you’ll be able to see it. It will stand out above the noise because the noise level is low. Conversely, if the background rate of the phenomenon you’re looking at is high, you’ll have a much harder time detecting new events. The signal you’re looking for will not easily be recognized against the noisy skyline. That’s the problem with this Danish study.
If you want to quantify the risk that your patient will face when you start an antidepressant, you’re looking for the risk posed by the antidepressant, not the risk they face from simply being severely depressed in the first place. If they already have suicidal ideations, you wouldn’t easily recognize a new contribution to that suicidal thinking from an antidepressant.
On the other hand, what if they start the antidepressant and suicidal ideation just stops? That would look like a clear benefit, a reduction in overall risk. Indeed, that’s what the Danish team saw. They looked at charts for 365 young people with a mean age of 14 who were treated with an antidepressant for depression or anxiety. They used a standard measure of suicidality, the Columbia Classification Algorithm, and compared rates before and after the initiation of the antidepressant. Seventy-five percent got sertraline, and 25% got fluoxetine. A reduction in suicidal ideation from 54% of patients to 34% was found, and the p-value for that change was 0.001. As the authors made clear, regression toward the mean and other treatments likely accounted for some of that improvement. Without a control group, the amount contributed by the antidepressant can’t be determined. But here’s the signal-to-noise problem: The authors don’t offer us a separate analysis for the children who didn’t have suicidal ideation before starting the antidepressant. Is it possible that while depression improved overall and thus suicidal ideation rates went down overall, antidepressants might have caused suicidal ideation for a small minority of patients? We wouldn’t be able to see that signal because suicidal ideation was already present in over half of these young patients.
A previous study, which the authors cited in their Introduction, has suggested that antidepressants do cause suicidal ideation in a small percentage of patients, particularly younger patients. As you know, those data led to the controversial FDA warnings required for antidepressants in 2004 and a similar warning from the European Medicines Agency in 2005. Those warnings were associated with an increase in completed suicide rates according to some, although even that finding is debated. Yet even amongst those who criticize the warnings, most acknowledge that a small number of patients do experience new-onset suicidal ideation. They just think it’s a small number, especially relative to the overall reduction in suicidal ideation that was found again in this new study.
Interestingly, the study found an increase in suicide attempts after the initiation of an antidepressant, from 22 events before prescription to 33 in the following 6 months. This was not statistically significant, thus the “both” answer. Per prior literature, antidepressants can cause suicidal ideation in a small number of young people. And per the prior literature plus this current study, starting an antidepressant is associated with a decrease in suicidal ideations in the entire group of patients who take them.
For a thoughtful appraisal of the FDA warning controversy 10 years after it began, see the New England Journal essay by Marc Stone in the references of this Quick Take. This essay is also linked here in the Psychopharmacology Institute.
Abstract
Objective:
Meta-analyses have established a heightened risk of suicidality for youth treated with selective serotonin reuptake inhibitors (SSRIs). The present study investigates the risk and possible predictors of suicidality and non-suicidal self-injury (NSSI) associated with SSRI treatment in a clinical sample of children and adolescents.
Methods:
An observational, longitudinal, retrospective study using a within-subject study design including in- and outpatients aged 0–17 years treated with SSRIs. Data were obtained from digital medical records and prescription software.
Results:
N = 365 patients were included (64.1% female), mean (SD) age 14.5 (2.04) years, with primary depression, anxiety or obsessive-compulsive disorder. No suicides occurred. When comparing the 6-week period immediately prior to versus following SSRI initiation, the patient proportion with broadly defined suicidality decreased (38.5% vs. 24.2%, p < 0.001) while the proportion with suicide attempts was stable (2.8% vs. 2.8%, p = 1.000). The proportion with NSSI decreased statistically non-significantly (12.4% vs. 8.4%, p = 0.067). Results from individually standardized observation periods were similar; however, the proportion with suicide attempts decreased statistically non-significantly and the proportion with NSSI decreased significantly. Suicidality during SSRI treatment was associated with previous suicidality (OR[CI] = 6.0 [2.4–14.8], p < 0.001), depression as indication for SSRI treatment (OR[CI] = 2.1 [1.2–3.7], p = 0.01), female sex (OR[CI] = 2.1 [1.1– 4.1], p = 0.02) and previous NSSI (OR[CI] = 2.0 [1.2–3.5], p = 0.01).
Conclusion:
Suicidality was common in youth treated with SSRIs. The patient proportion with overall suicidality decreased, and the proportion with attempted suicide was stable in the weeks following SSRI initiation. Previous suicidality, depression, female sex and previous NSSI are important predictors for suicidality during SSRI treatment in youth.
Keywords
adolescents, children, non-suicidal self-injury, serotonin reuptake inhibitors, suicidality
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Reference
Sørensen, J. Ø., Rasmussen, A., Roesbjerg, T., Verhulst, F. C., & Pagsberg, A. K. (2021). Suicidality and self‐injury with selective serotonin reuptake inhibitors in youth: Occurrence, predictors and timing. Acta Psychiatrica Scandinavica, 00:1–14.
Related References
Stone, M. B. (2014). The FDA warning on antidepressants and suicidality—why the controversy?. New England Journal of Medicine, 371(18), 1668-1671.
