BLACK BOX WARNING TO BE REQUIRED ON ALL ANTIDEPRESSANTS RE: SUICIDE RISK IN CHILDREN AND ADOLESCENTS

October 21, 2004

BLACK BOX WARNING TO BE REQUIRED ON ALL ANTIDEPRESSANTS CONCERNING SUICIDE RISK IN CHILDREN AND ADOLESCENTS

Belatedly, the Food and Drug Administration (FDA) announced on October 15, 2004 that it is taking steps to inform parents and physicians about the risks of antidepressants when these drugs are used to treat major depressive disorder in children and adolescents.

This announcement came more than a year after investigators first learned of concerns over the selective serotonin reuptake inhibitor (SSRI) antidepressant Paxil (paroxetine), ten months after British regulators warned physicians not to use the drugs for children, and eight months after an FDA scientist recommended warning the public about the drugs.

The FDA has directed manufacturers of antidepressant drugs to add black box warnings to the professional product labeling, or package inserts, about the increased risk of suicidal thinking and behavior in children and adolescents being treated with these agents.  A black box warning is the strongest type of warning that the FDA can require.

Unfortunately, patients rarely know of the existence of black box warnings unless they ask their pharmacist for the drug’s professional product labeling. Furthermore, research has shown that black box warnings do little to prevent physicians from prescribing drugs inappropriately.

The drugs involved in the new labeling requirements appear at the end of this article.

The FDA’s recommended text for the black box warning reads:

Suicidality in Children and Adolescents

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Antidepressant’s Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Antidepressant’s Name] is not approved for use in pediatric patients except for patients with [Any approved pediatric claims here].

Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine antidepressant drugs (SSRIs and others) in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.

There is a second element of the FDA’s plan that is perhaps even more important.  Namely, providing patients-and the parents of patients-with objective risk information, written in non-technical language, based on a drugs professional product labeling. These Medication Guides, or MedGuides, for short, place the risk in a meaningful context.  MedGuides will be given to patients when the prescription is filled.  The FDA has the authority to require this type of information for drugs which present unique public health risks.  MedGuides should be provided as soon as possible.

The FDA says that it will work with manufacturers to implement "Unit of Use" packaging for all antidepressants as a means of ensuring that patients and parents receive a MedGuide with every prescription or refill.  Unit of use packaging is a method of preparing a medication in an original container, sealed and pre-labeled by the manufacturer, and containing sufficient medication for one normal course of therapy.

What You Can Do

If your child is taking one of the drugs listed below to treat major depressive disorder, do not stop him or her without consulting the prescribing physician.

Drugs Involved in the New Labeling Requirements

Anafranil (clomipramine)
Paxil (paroxetine)
Aventyl (nortriptyline)
Pexeva (paroxetine)
Celexa (citalopram)
Prozac (fluoxetine)
Cymbalta (duloxetine)
Remeron (mirtazapine)
Desyrel (trazodone)
Sarafem (fluoxetine)
Effexor (venlafaxine)
Serzone (nefazodone)
Elavil (amitriptyline)
Sinequan (doxepin)
Lexapro (escitalopram)
Surmontil (trimipramine)
Limbitrol (chlordiazepoxide/amitriptyline)
Symbyax (olanzapine/fluoxetine)
Ludiomil (maprotiline)
Tofranil (imipramine HCl)
Luvox (fluvoxamine)
Tofranil-PM (impiramine)
Marplan (isocarboxazid)
Triavil (perphenaine/amitriptyline)
Nardil (phenelzine)
Vivactil (protriptyline)
Norpramin (desipramine)
Wellbutrin (bupropion)
Pamelor (nortriptyline)
Zoloft (sertraline)
Parnate (tranylcypromine)           
Zyban (bupropion)