Small suicidal behavior risk linked to drug therapy

During the early phase of antidepressant treatment of pediatric patients, there is a slight increased risk of suicidal thoughts and behavior, the results of several studies suggest.

However, the US Food and Drug Administration research team that conducted the study review does not discourage the use of antidepressant drugs for children. 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 studies ranging from 4 to 16 weeks in length that included 4,582 patients. The drugs tested were Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Luvox (fluvoxamine), Celexa (citalopram), Wellbutrin (bupropion), Effexor (venlafaxine), Serzone (nefazodone) and Remeron (mirtazapine).

The children’s diagnoses included major depression, obsessive-compulsive disorder and generalized anxiety disorder.

There were 209 suicide-related events but no completed suicides. Eighty-nine episodes were attributed to suicidal behavior or thoughts, and 120 were associated with possible suicidal behavior or thoughts.

The overall risk for suicidal behavior that accompanied all of the drugs and diagnoses was increased by 95 percent. The increased risk associated with selective serotonin reuptake inhibitors—Prozac, Zoloft, Paxil, Luvox and Celexa—in depression trials was 66 percent. The authors note that risk estimates often varied between trials of the same drug.

When considering 100 patients on drug therapy, we might expect one to three patients to have an increase in suicidal behavior—beyond the risk that occurs with depression itself, Laughren noted.

The investigators suggest that the apparent increased risk of drug-induced suicidal behavior may be related to a greater likelihood of the patients to report the symptoms rather an actual increase risk. They point out 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, Laughren and his team point out. For example, there has been a documented 31 percent reduction in suicide risk among males aged 15 to 19 years between 1992 and 2002.

Moreover, the FDA has not banned antidepressant drugs for pediatric use, opting instead for new labeling warning of the risk and recommending that physicians balance the risk with the 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 or antimanic drugs, may reverse suicidal thoughts or behavior.

SOURCE: Archives of General Psychiatry, March 2006.

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