The paper expands on analyses first made available by the US Food and Drug Administration (FDA) two years ago. It includes different methods, additional explorations of the data, and an expanded discussion of the implications of the findings.
Previous studies have shown that antidepressant drugs are linked with an increased risk of suicidal behaviour and thoughts in children and adolescents, particularly in the early stages of treatment. This led the FDA to add a black box warning to antidepressants in 2005 and to examine trials of antidepressants in adults to look for similar effects.
Dr Marc Stone and colleagues from the FDA asked eight manufacturers of antidepressant products to provide data on suicidal thinking and behaviour from published and unpublished randomised trials on antidepressants in adults. They reviewed data from 372 placebo controlled trials involving nearly 100,000 patients.
Findings showed eight completed suicides, 134 suicide attempts, 10 patients who had made preparations without attempting suicide, and 378 patients who had thoughts about suicide but had not acted on them.
Overall, drug type and diagnostic category made little difference to risk of suicidal behaviour, with the exception of some differences among selective serotonin reuptake inhibitors (SSRIs).
However, an increased risk was noted among adults under 25 years of age, similar to that reported in children and adults - this increased risk was greatest in those with psychiatric disorders other than depression.
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, say the authors.
The findings also support the idea that antidepressant drugs can have two separate effects: an undesirable effect in some patients that promotes suicidal thoughts or behaviour, with a risk that appears to diminish with age, and a protective effect in others that alleviates depression and reduces any suicidal risk, they add. This should be the subject of further research, particularly in terms of possible mechanisms for age related differences.
In the meantime, the FDA has expanded the suicide warning on antidepressant drugs with this new information, including the strong age relatedness of the findings.
But in an accompanying editorial Professor John Geddes from the University of Oxford and colleagues warn that "fundamental uncertainty" remains. They point to important limitations in the analysis, such as the very low numbers of completed suicides in the primary trials and a lack of transparency in some of the methods used. They also discuss some important differences in risk between individual drugs.
It is becoming apparent that antidepressants vary in both their efficacy and adverse effects, they say. The increased risk of suicidal behaviour in adults taking antidepressants is probably restricted to younger people and varies greatly between individual drugs, they conclude.