Antidepressants May Double Risk of Suicide, Aggression In Adolescents

In children and adolescents taking antidepressants, the risk of suicide and aggression may be doubled compared with those taking placebo, according to research published in The BMJ.

However, the researchers noted that these risks may actually be even higher, due to limitations in the data that may have led to under-reporting of these harms.

To study potential serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI), Peter Gøtzsche, MD, of the Nordic Cochrane Centre and University of Copenhagen in Denmark and colleagues conducted a meta-analysis of 70 trials that included 64 381 pages of clinical study reports and 18 526 patients.

“These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms,” the authors wrote. “For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials.”

The researchers found that for adults, the odds ratios were not significant: the risks were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were much higher, at 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65).

However, “because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately,” the authors wrote.

In a corresponding editorial, Joanna Moncrieff, MD, from the University College London, described some glaring discrepancies between the results listed in the clinical study reports and data from individual patient listings and narratives, as well as inconsistencies between summary trial reports and clinical study reports. 

“More than half of the suicide attempts and instances of suicidal ideation were coded as ‘emotional liability’ or ‘worsening of depression,’ for example,” Dr Moncrieff wrote. “Summary [trial] reports published on Eli Lilly’s website were even more incomplete, listing only 10% of the suicide attempts revealed in the corresponding clinical study reports, and no instances of suicidal ideation.” 

In order to accurately estimate the SSRI-associated harms in patients, the researchers noted that they would need “access to anonymised individual patient data.”

Despite the discrepancies in the data they were analyzing, the researchers “suggest minimal use of antidepressants in children, adolescents, and young adults, as the serious harms seem to be greater [than what was reported], and as [the effects of selective serotonin and SSRIs seem] to be below what is clinically relevant.”

“Alternative treatments such as exercise or psychotherapy may have some benefit and could be considered, although psychotherapy trials also suffer from publication bias,” they concluded. 


Sharma T, Cuski LS, Freund N, Gøtzsche PC. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ. 2016; doi:10.1136/bmj.i65.