FDA To Study Potential Link Between Antidepressants, Suicidal Thoughts in Adults
FDA officials plan to study antidepressants' risks in adults following the release of clinical trial data showing that the drugs increase the risk of suicidal tendencies in children, the Wall Street Journal reports (Wilde Mathews, Wall Street Journal, 9/28).
An FDA advisory panel on Sept. 14 voted 15-8 to recommend that all antidepressants carry a black box warning -- the strongest warning issued by the government -- to inform consumers that the medications can cause suicidal thoughts and behavior in patients under age 18. A black box warning is a black section with white writing that appears at the top of drug inserts distributed to physicians and patients. On Sept. 13, FDA officials said that an analysis of 15 clinical trials -- some of which were not made public for years -- found that there is a "consistent link" between the use of any kind of antidepressant and suicidal tendencies in children (California Healthline, 9/24).
The analysis found that 2% to 3% of the time, antidepressants appeared to raise the risk of suicidal thoughts or actions in children. According to the Journal, the findings "pu[t] a new spotlight on the old questions."
FDA officials will "comb through the existing data on adult clinical trials" of antidepressants "in the same detailed fashion" as they did for children and adolescents, according to the Journal. As with the pediatric clinical trials, the agency will examine existing adult data to find and characterize incidents that could indicate suicidal tendencies.
FDA is trying to determine an exact approach for the study. For example, it is undecided whether the data should be sent to researchers outside the agency to examine. The agency plans to study a database of 234 randomized trials for 20 drugs. For the pediatric patient study, FDA analyzed 23 pediatric drug-industry trials and one result from an NIH study.
FDA has previously examined the issue in adults and found no increased risk of suicide. British regulators also are studying adult data for evidence of suicidality risk.
According to the Journal, it is "unclear" why antidepressants could increase suicidal tendencies in some adolescents and not in adults. Many doctors believe "there is something different in depression in children and adolescents versus adults," according to John Mann, a professor of psychiatry at Columbia University.
Younger people may have less control over their impulses or less ability to cope with or understand an unexpected drug effect. Children -- who are "are already a bit disinhibited" because their brains are not fully developed -- could be prone to a disinhibiting effect, according to Wayne Goodman, chair of the FDA panel that examined the issue in adolescents. Children's serotonin systems also are more active than those in adults. Antidepressants such as Prozac, Paxil and Zoloft function by increasing the amount of serotonin in the brain, although it is not clear whether that factor would make the drugs ineffective or create side effects, according to Mann.
According to the Journal, "Why medications that are supposed to alleviate depression could, in rare cases, actually have the opposite effect remains a mystery." Theories include that the drugs give patients more energy before affecting their depression, enabling a person to act on a suicidal impulse. Another theory is that the antidepressants could somehow exacerbate depression in a small subset of patients. A third theory is that the drugs could cause a state of agitation and restlessness, according to Martin Teicher, a laboratory chief at McLean Hospital who published a paper on antidepressants' effect in six adults (Wall Street Journal, 9/28).