We’ve been using them since the ‘50s, yet we are still unravelling the effects of antidepressants. The entire basis for their use – that depression results from a chemical imbalance in the brain – is disputed, and while their consumption has skyrocketed in recent decades, there is little evidence to show that they are much better than a placebo. To add to this, a new study has highlighted the link between these drugs and serious harms.

Reported in the BMJ (British Medical Journal), researchers in Denmark found that two of the most commonly prescribed antidepressants – selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) – are associated with a significantly increased risk of suicide and depression in children and adolescents. In addition, the study identified another worrying issue: Clinical trials often underreport or misidentify adverse side effects, meaning we still don’t know the true risk of serious harm.

This is by no means the first study to draw such an association. Reports of suicidality on SSRIs go back as far as 1990, just three years after the first drug within this class – Prozac – was approved by the FDA. Yet it wasn’t until the early 2000s that this side effect started to gain recognition, prompting researchers to reanalyze trial data and subsequently discover that suicidal behavior in under 18s was less likely to be reported in published data than unpublished.

^{The FDA requires that antidepressants carry warning labels of the suicide risks to young people associated with their use. Photographee.eu/Shutterstock}

But suicide isn’t the only serious harm that’s been linked with these drugs: some reports also noted aggressive behavior with antidepressants, like hostility and violence, however there have been few efforts to pool this data and look for trends. Evidently there are many grey areas when it comes to the possible harmful effects of these drugs, which is where this latest study came in.

The team began by collating data from 70 placebo-controlled SSRI or SNRI trials, which totaled more than 18,500 participants. Because harms are often not included in published trial data, the team used clinical study and summary trial reports that contained patient narratives and listings of harms and are therefore considered more reliable.

While no increase in aggression or suicidality was found in adults taking antidepressants, the risk for these harms was doubled among children and adolescents. In addition, they found that trials would often misidentify harms, such as classifying suicide attempts as “emotional liability,” suggesting that reports likely underestimate the extent of the adverse events linked with these drugs. Furthermore, while almost all deaths were reported, after comparing the data gathered with that available on pharma company Eli Lilly’s website, they found that suicide attempts were missing in 90 percent of instances.

“The evidence for benefit for antidepressants is limited and below what is clinically relevant,” lead researcher Tarang Sharma from the Nordic Cochrane Centre told IFLScience. “Other treatments like psychotherapy appear to work just as well and exercise works even better for this age group, but without these serious harms. Therefore, it seems obvious using evidence-based principles that the other two alternatives should be offered to this age group, while antidepressants should be slowly stopped under good clinical guidance.”

Precisely why these drugs raise the risk of these behaviors, apparently in young people but not adults, remains unclear. Poor reporting and low rates of suicide also means that estimating risks remains problematic. But as evidence stacks up, Sharma points out the need for governments and doctors to use this to inform practice and policy, and weigh up the risks and benefits of these drugs.