Healthy adults who are taking certain antidepressants have a higher risk of suicidal thoughts and violent behaviour, according to the results of a systematic review.
The research suggests that selective serotonin and serotonin-norepinephrine reuptake inhibitors may increase the risk of events that can lead to suicide or violent behaviour in adults with no sign of a mental illness.
“While it is now generally accepted that antidepressants increase the risk of suicide and violence in children and adolescents (although many psychiatrists still deny this), most people believe that these drugs are not dangerous for adults. This is a potentially lethal misconception,” warn the researchers, based at the Nordic Cochrane Centre and the University of Copenhagen in Denmark.
Writing in the Journal of the Royal Society of Medicine
, the team says: “We found that antidepressants double the risk of suicidality and violence, and it is particularly interesting that the volunteers in the studies we reviewed were healthy adults with no signs of a mental disorder.”
The researchers say their results suggest that it is likely that antidepressants increase the number of suicides in people of all ages and warn that their risk calculation may be an underestimate because they were unable to access data from 2 of the 13 relevant trials identified.
The findings are based on the results of 13 double-blind, placebo-controlled trials involving the following antidepressants: citalopram, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine.
The researchers say that the analysis reveals that treatment of adult healthy volunteers with antidepressants doubled their risk of harms related to suicidality and violence, including psychotic events and mood disturbances (odds ratio 1.85; 95% confidence interval [CI] 1.11–3.08; P=0.02, I2=18%). The number needed to treat to harm one healthy person was 16 (95% CI 8–100; Mantel-Haenszel risk difference 0.06).
The researchers point out the difficulty in obtaining full data about adverse events with these drugs: “There can be little doubt that we underestimated the harms of antidepressants… it [is] well documented that the drug companies underreport seriously the harms of antidepressants related to suicide and violence, either by simply omitting them from the reports, by calling them something else or by committing scientific misconduct.”
They highlight the case of a healthy 19-year-old student who volunteered in a trial of duloxetine (Cymbalta; Eli Lilly) to help pay her college tuition and later hanged herself in a laboratory run by Eli Lilly.
“It turned out that missing in the FDA’s files was any record of the college student and at least four other volunteers known to have committed suicide, and Lilly admitted that it had never made public at least two of those deaths,” the researchers say.
A spokeswoman for the company says: “Lilly reported all known incidents of suicide in our duloxetine program to the FDA, either as a part of our submission for marketing approval or regular safety monitoring reports. A death during a clinical trial is investigated by both Lilly and the FDA. Lilly remains committed to Cymbalta and its safety and benefits.”
The study was greeted with caution by Steve Bazire, honorary professor of pharmacy at the University of East Anglia, who was consultant pharmacist in medicines management for Norfolk and Suffolk NHS Foundation Trust until October 2014 and chief pharmacist for Norfolk mental health services before that.
“I am concerned that the implications of this [study] is that you would never dispense antidepressants again because they make people kill themselves, which isn’t true,” says Bazire. “The message is suicidal ideation is not the same as completed suicide. Prescribing antidepressants must not be taken lightly but start them slowly and stop them slowly. Remember that overall antidepressants do reduce the overall completed suicide rate, which has been shown in a number of large national studies.”
 Andreas Ã, Bielefeldt A, Ã, Danborg PB et al. Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers. J R Soc Med 2016;109(10):381–392. doi: 10.1177/0141076816666805