Antidepressants may double risk of suicide and aggression in children, study findsBMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i545 (Published 28 January 2016) Cite this as: BMJ 2016;352:i545
Doctors should avoid prescribing antidepressants to children and teenagers wherever possible because they are associated with a doubling in the risk of aggression and suicide, Danish researchers have concluded in The BMJ.1 They recommend considering alternative treatments such as exercise or psychotherapy.
The researchers carried out a systematic review and meta-analysis of 70 trials with 18 526 patients. The trials examined the use of five of the most commonly prescribed antidepressants: duloxetine; fluoxetine; paroxetine; sertraline, and venlafaxine.
They included in their study only double blind placebo controlled trials containing patient narratives or individual patient listings of associated harms. Because harms associated with antidepressants are often not included in published trial reports, the researchers analysed clinical study reports prepared by drug companies for market authorisation. They also looked at summary trial reports on duloxetine and fluoxetine taken from the drug company Eli Lilly’s website. Eleven of the trials (including 12% of the patients) concerned children and adolescents.
The study identified 16 deaths, all in adults. Overall, 155 suicidal events took place, 13 before randomisation. In adults the study found no increase in the risk of suicide, suicidal thoughts, or suicide attempts associated with taking antidepressants (odds ratio 0.81 (95% confidence interval 0.51 to 1.28)). However, in children and adolescents the study found a doubling of the risk of suicide, suicidal thoughts, or suicide attempts associated with antidepressant use (2.39 (1.31 to 4.33)).
In adults antidepressants were not associated with an increased risk of aggression (1.09 (0.55 to 2.14)) but were associated with more than a doubling of this risk in children and adolescents (2.79 (1.62 to 4.81)). The risk of akathisia—a form of restlessness that may increase suicide and violence—doubled, both in adults (2.00 (0.79 to 5.04)) and in children and adolescents (2.15 (0.48 to 9.65)).
The researchers found that clinical study reports often misrepresented adverse events. For example, four deaths were misreported by a drug company, in all cases favouring the antidepressant. More than half of the instances of suicide attempts and suicidal ideation were coded as “emotional lability” or “worsening of depression.” In most of the included clinical study reports the individual patient listings had been withheld, suggesting that not all adverse events were identified.
The researchers concluded, “The true risk for serious harms is still unknown [because] the low incidence of these rare events, and the poor design and reporting of the trials, makes it difficult to get accurate effect estimates.” They also emphasised the need to identify “hidden information in clinical study reports to form a more accurate view of the benefits and harms of drugs.”
Cite this as: BMJ 2016;352:i545