Published October 19, 2004
Federal health officials are ordering makers of antidepressants to use stark new warnings alerting doctors and consumers that the medications increase the risk of suicidal thoughts and behaviors in children and adolescents who take them.
The move affects a host of popular antidepressants including Prozac, Paxil, Zoloft, and many others (see below for complete list). Antidepressants have faced glaring public scrutiny because of a government scientific review in September showing that they increase the risk of suicidal behavior in children by as much as 3 percent.
Black Box Antidepressant Warning
The FDA announced Friday that all antidepressant drugs must now carry so-called "black-box" warnings, alerting doctors and consumers that the antidepressants increase suicidal behavior in children with depression and that the risk of using antidepressants must be carefully balanced with the need.
"In other words, these drugs should not be used casually," says Sandra Kweeder, MD, the acting director of FDA's Office of New Drugs. The box also carries warnings that patients who use antidepressants must be closely monitored for "clinical worsening, suicidality, or unusual changes in behavior."
The black box is the strongest warning the FDA can place on drugs. Manufacturers must include the box in any print advertisements for their antidepressant drugs, and radio and TV ads must include information read from the box.
Antidepressant Warning Changes Immediate
The changes are set to take effect immediately, though lag times for printing and shipping mean that most consumers won't see the labeling changes in antidepressant packaging for one to two months, Kweder says.
Officials announced that they would also require drug companies and pharmacies to distribute a medication guide along with all new antidepressant medications. The guide lays out warnings from the black box in everyday language, though the agency is still negotiating with drug companies on its final form, officials say.
The action comes several weeks after an FDA advisory panel recommended stricter warnings about safety concerns with antidepressants and also called for actions to alert the public that most antidepressants have not been shown to have any benefit in children with depression.
Only Prozac has FDA approval for use in children and adolescents with depression, though other similar antidepressants are routinely prescribed to children. The antidepressants Prozac, Zoloft, Luvox, and Anafranil are approved for obsessive-compulsive disorder in children.
"We continue to believe, however, that these drugs provide significant benefit when used as directed in pediatric patients," says acting FDA Commissioner Lester M. Crawford.
The agency was criticized in recent weeks by consumer groups and on Capitol Hill because of reports that for months they delayed releasing data on the increased risk of suicidal behavior in users of antidepressants.
FDA scientists conducting reviews of more than 20 studies found that overall, the antidepressants could be expected to raise suicidal behavior in two to three out of every 100 children who took them. No cases of completed suicide were reported in any of the industry-sponsored trials, however.
Regulators say they will move to disallow bulk packaging of antidepressant drugs, instead requiring companies to ship them in the same units that are delivered to patients. The action makes it easier to bundle warnings with the drugs to ensure they always reach patients, Kweeder says.
Full List of Antidepressants in Warning
Anafranil (clomipramine HCl); Aventyl (nortriptyline HCl); Celexa (citalopram HBr); Cymbalta (duloxetine HCl); Desyrel (trazodone HCl); Effexor (venlafaxine HCl); Elavil (amitriptyline HCl); Lexapro (escitalopram oxalate); Limbitrol (chlordiazepoxide/amitriptyline); Ludiomil (Maprotiline HCl); Luvox (fluvoxamine maleate); Marplan (isocarboxazid); Nardil (phenelzine sulfate); Norpramin (desipramine HCl); Pamelor (nortriptyline HCl); Parnate (tranylcypromine sulfate); Paxil (paroxetine HCl); Pexeva (paroxetine mesylate); Prozac (fluoxetine HCl); Remeron (mirtazapine); Sarafem (fluoxetine HCl); Serzone (nefazodone HCl); Sinequan (doxepin HCl); Surmontil (trimipramine); Symbyax (olanzapine/fluoxetine); Tofranil (imipramine HCl); Tofranil-PM (imipramine pamoate); Triavil (perphenaine/amitriptyline); Vivactil (protriptyline HCl); Wellbutrin (bupropion HCl); Zoloft (sertraline HCl); Zyban (bupropion HCl)
SOURCES: Sandra Kweeder, MD, acting director, FDA Office of New Drugs. Lester M. Crawford, acting director, FDA. News release, FDA.
Reviewed by Michael W. Smith, MD