FDA Issues Public Health Advisory On Antidepressants And Suicide Risk In Children

The Food and Drug Administration (FDA) issued a Public Health Advisory on October 27, 2003 about reports of suicidal thinking and suicide attempts in clinical trials of eight drugs in pediatric patients with major depressive disorder (MDD).

This advisory follows earlier warning about the antidepressants paroxetine (PAXIL) and venlafaxine (EFFEXOR, EFFEXOR XR).

On June 19, 2003, the FDA issued a public advisory concerning the safety of paroxetine (PAXIL), a member of the selective serotonin re-uptake inhibitor (SSRI) family of antidepressants, in children or adolescents less than 18 years of age. The advisory is based on reports of a possible increased risk of suicidal thinking and suicide attempts in children and adolescents under the age of 18 taking paroxetine for MDD (see Worst Pills, Best Pills News August 2003).

The FDA’s advisory followed a similar announcement nine days earlier, June 10, 2003, by the Committee on Safety of Medicines, the British counterpart to the FDA.

The manufacturer of the antidepressant venlafaxine (EFFEXOR, EFFEXOR XR), Wyeth Pharmaceuticals, issued a Dear Health Care Professional letter on August 22, 2003 warning of increased reports of suicide-related adverse events such as suicidal ideation and self harm, in addition to hostility, with the use of this drug in children and adolescents (see Worst Pills, Best Pills News October 2003).

The FDA’s October 27th advisory indicated that the agency had completed a preliminary review of clinical trials involving children for eight drugs: citalopram (CELEXA), fluoxetine (PROZAC), fluvoxamine (LUVOX), mirtazapine (REMERON), nefazodone (SERZONE), paroxetine (PAXIL), sertraline (ZOLOFT), and venlafaxine (EFFEXOR). At this time fluvoxamine is not approved for depression in the U.S.

Only fluoxetine was found effective in pediatric MDD patients, and it is approved in the U.S. to treat children ages eight to less than 13 and adolescents 13 to 18 years of age. In the 20 controlled clinical trials reviewed by the FDA for these eight drugs, involving over 4,100 pediatric patients, there have been no reports of completed suicides.

The FDA urged that these drugs be used with caution and reminded prescribers of the following statement that is present in the professional product labeling or package insert for all antidepressant drugs:

Suicide: The possibility of a suicide attempt is inherent in major depressive disorder and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. Prescriptions for Drug X should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

We would add that in addition to close supervision during initial treatment with one of these drugs and only purchasing small prescriptions, that a physician qualified in treating serious mental illness in children make the diagnosis of MDD in pediatric patients. None of these drugs should be used for mild situational depression, they are approved to treat MDD, a serious mental illness.

Nefazodone is of special concern because of its association with the development of liver toxicity that has led to deaths. We have petitioned the FDA on two occasions to remove this dangerous drug from the market. The only two countries in which this drug is still being sold are the U.S. and Australia. See the article about nefazodone in this issue of the newsletter.

What You Can Do

Parents whose children are using any of the drugs mentioned above should consult the prescribing physician immediately.

DO NOT stop treatment with any of these drugs immediately. Discontinuation requires medical supervision.