Increased Risk of Suicide and Aggressive Behavior in Adolescents Prescribed Antidepressant

Research Highlights

     Some of the most frequently prescribed and profitable drugs in the pharmaceutical market are antidepressants. Antidepressants can include selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).  The first ideas that SSRIs may induce suicidal tendencies occurred in 1990, but didn’t grow to be widely recognized until the 2000s. By 2004, a UK review revealed that adolescents were more at risk for suicidal behavior, and that discrepancies between unpublished and published trials were apparent. This led to a general warning against using these drugs for people under 18 years old. Although antidepressants were still safe for adults, it was unclear how much dangerous they remain for children.

            In January 2016, a comprehensive review and analysis observing the harms connected with SSRIs and SNRIs was published from Denmark. The study used data from clinical study reports done for fluoxetine, duloxetine, sertraline, paroxetine, and venlafaxine. The reports came from drug regulators in Europe and the UK, as well as pharmaceutical company websites. Overall, reports from 70 trials including 18,526 patients were utilized in the analysis. Any studies included had to be double blind controlled trials with placebos. The studies also had to include individual patient reports and narratives. The harms were divided into primary and secondary outcomes. Primary outcomes included suicidality and mortality. Suicidality included suicides, suicide attempts or preparation, self harm, and suicidal thoughts. Secondary outcomes only included aggressive behavior and akathisia, a state of distress that has been noted as a side-effect of antidepressants.

            Because the study reports came from many different sources, the quality of the reports varied greatly. Overall, only sixteen deaths occurred, and all of them were adults, while only six suicides were reported. Suicidality, however, had a greater prevalence, with 155 patients reporting some degree of suicidality.  73 events of suicide attempts were counted, including intentional severe self harm, intentional overdoses, and preparatory events that were stopped before harm. 75 patients reported suicidal ideation. 62 patients showed aggressive behavior, and only 30 akathisia events were reported.

            Though the systematic review faced a lot of difficulty and a degree of uncertainty due to the lack of standardization among the reports, the trial did manage to show certain results. There no were significant mortality or suicidality differences found. However, in adolescents, there was a confirmed increased suicide risk. There was also a significantly increased risk of aggressive behavior that was only apparent in adolescents as well. Finally, akathisia seemed to be very under-reported. Akathisia occurred more frequently in participants taking antidepressants as opposed to those taking a placebo. This prevalence was noted in adults as well as adolescents, but there was not a statistically significant difference.

            Ultimately, this study was only a review that tried to meta-analyze reports coming from a variety of sources. Although the reports were not published under the same rules and formats, and did not always include the same information, there was still a clear pattern that proved to be true when statistically tested. The risk of suicide risk and aggressive behavior is apparent in adolescents given antidepressants.

 

BMJ 2016;352:i65

Lena Chatterjee is the 2015-2016 Research Highlights Editor.