Research published today on bmj.com reports that adults taking antidepressants are not at greater risk of suicidal thoughts or behavior. On the other hand, young adults less than 25 years of age are at an increased risk, comparable to that seen in children and adolescents.

The article elaborates on data previously made available by the US Food and Drug Administration (FDA) two years ago. It incorporates different methods, supplementary examinations of the data, and discusses at length the implications of the findings.

There is confirmation in earlier studies that antidepressant drugs are associated with an increased risk of suicidal behavior and feelings in children and adolescents. This is mostly evident in the early stages of treatment. This prompted the FDA to include a black box warning to antidepressants in 2005 and to examine trials of antidepressants in adults to search for comparable effects.

Dr Marc Stone and his collaborators from the FDA studied data on suicidal thinking and behavior from published and unpublished randomized trials on antidepressants in adults. The information was provided by eight manufacturers of antidepressant products. Records from 372 placebo controlled trials involving nearly 100,000 patients were reviewed.

The results revealed eight committed suicides, 134 suicide attempts, 10 patients who had made planning without attempting suicide, and 378 patients who had thoughts about suicide but had not acted on them.

In general, there was no distinction in drug type and diagnostic category and the effect on risk of suicidal behavior. However, there were some differences among selective serotonin reuptake inhibitors (SSRIs).

On the other hand, an increased risk was noted among adults under 25 years of age, comparable to that reported in children and adults. This amplified risk was highest in young patients with psychiatric disorders other than depression.

The authors explain: “These results suggest that, compared with placebo, the risks of suicidality associated with antidepressants are strongly age dependent – the risk is raised in people under 25, not affected in those aged 25-64, and reduced in those aged 65 and older.”

The findings also sustain the suggestion that antidepressant drugs can have two different effects:

• Adverse effect in some patients that promotes suicidal thoughts or behavior, with a risk that appears to weaken with age.
• Protective effect in others that alleviates depression and reduces any suicidal risk.

The authors call for further research, particularly in terms of possible mechanisms for age related differences.

Meanwhile, the FDA has extended the suicide warning on antidepressant drugs with this new information, including the significant relation of the findings with age.

In an associated editorial Professor John Geddes from the University of Oxford and collaborators caution that “fundamental uncertainty” persists. They call attention to essential restrictions in the analysis, such as the very low numbers of completed suicides in the primary trials and a lack of precision in some of the methods used. In addition, they consider some significant differences in risk between individual drugs.

They add: “It is becoming apparent that antidepressants vary in both their efficacy and adverse effects.” In closing they say: “The increased risk of suicidal behavior in adults taking antidepressants is probably restricted to younger people and varies greatly between individual drugs.”

“Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration”
Marc Stone, medical officer, Thomas Laughren, director, division of psychiatry products, M Lisa Jones, medical officer, Mark Levenson, mathematical statistician, P Chris Holland, mathematical statistician, Alice Hughes, associate director for safety, division of neurology products, Tarek A Hammad, associate director, division of epidemiology, Robert Temple, associate director for medical policy, George Rochester, mathematical statistics team leader
BMJ 2009; 339:b2880

“Risk of suicidal behaviour in adults taking antidepressants”
John Richard Geddes,professor of epidemiological psychiatry, Corrado Barbui, lecturer in psychiatry, Andrea Cipriani, lecturer in psychiatry
doi=10.1136/bmj.b3066
bmj.com

Written by Stephanie Brunner (B.A.)