Antidepressants may slightly raise risk of suicidality in children

Last Updated: 2006-03-07 8:57:57 -0400 (Reuters Health)

NEW YORK (Reuters Health) - During the early phase of antidepressant treatment of pediatric patients, there is a slightly increased risk of suicidal thoughts and behaviors, results of a meta-analysis suggest.

However, the US Food and Drug Administration research team that conducted the study does not discourage the use of antidepressant drugs for pediatric use. Instead, they advise "close monitoring of patients as a way of managing the risk of suicidality," according to their report in the Archives of General Psychiatry for March.

Dr. Thomas Laughren and his colleagues in Rockville, Maryland, analyzed data from 24 placebo-controlled trials ranging from 4 to 16 weeks in length that included 4582 patients. The drugs tested were fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, bupropion, venlafaxine, nefazodone and mirtazapine. Indications included major depression, obsessive-compulsive disorder and generalized anxiety disorder.

There were 209 suicide-related adverse events but no completed suicides. Eighty-nine events were classified as the primary outcome of suicidal behavior or ideation, and 120 as the secondary outcome, possible suicidal behavior or ideation.

The overall risk ratio for suicidality for all drugs across all indications was 1.95. The risk ratio for selective serotonin reuptake inhibitors -- fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram -- in depression trials was 1.66. The authors note that risk estimates often varied between trials of the same drugs.

The overall risk difference between active treatment and placebo arms, the authors report, was 0.01 for the primary outcome and 0.02 (confidence interval 0.01 - 0.03) for the secondary outcome. "This can be interpreted as indicating that when considering 100 treated patients, we might expect 1 to 3 patients to have an increase in suicidality beyond the risk that occurs with depression itself owing to short-term treatment with an antidepressant."

The investigators suggest that the apparent increased risk of drug-induced suicidality may be related to a greater likelihood of the patients to report suicidality rather an increased rate of the events themselves. They explain that several of the drugs reduce social anxiety and increase communication with others.

This theory is supported by the decline in adolescent suicide in recent years, Dr. Laughren and his team point out. For example, there has been a documented 31% reduction in suicide risk among males aged 15 to 19 years between 1992 and 2002.

Moreover, the FDA has not contraindicated antidepressant drugs for pediatric use, opting instead for new labeling warning of the risk and recommending the clinicians balance the risk with clinical need, because "depression and psychiatric disorders in pediatric patients can have significant consequences if not appropriately treated."

In a related editorial, Dr. Ross J. Baldessarini from McLean Hospital in Belmont, Massachusetts, and colleagues suggest that "potential adverse effects of antidepressant treatment, such as worsening insomnia, agitation, restlessness, irritability, and anger, or their adverse impact on unrecognized bipolar disorders contributes to increased risk of suicidal acts in occasional patients."

They suggest that discontinuing the antidepressant medication or adding agents to reduce agitation and aggression, such as antipsychotic, antimanic, or anxiolytic drugs, may reverse suicidal ideation or behavior.

Arch Gen Psychiatry 2006;63:246-248,332-339.