DUR: FDA Warnings of Suicidal Behavior in Children Taking Antidepressants or Atomoxetine
In September 2005, the Food and Drug Administration (FDA) released a public health advisory warning (similar to the warning released in 2004 regarding all antidepressant medications) of suicidal thinking and behavior in children and adolescents. This article summarizes the clinical trial data and information released by the FDA on atomoxetine and antidepressants, and provides utilization data on the use of these agents in the Medi-Cal pediatric population.
I. Suicidality with Atomoxetine
The FDA and its Pediatric Advisory Committee recently requested an analysis of adverse event data from Eli Lilly’s atomoxetine database and clinical trials. The FDA’s request for this review was prompted by prior findings that antidepressants pose an increased risk of suicidal thoughts and behavior in children taking them. The analysis of atomoxetine data identified a statistically significant increased risk of suicidal thoughts among atomoxetine-treated children and adolescents as compared to placebo groups (4 per 1,000 patients in the atomoxetine group compared to none in the placebo group). There was one suicide attempt observed in among a total of 2,200 patients, and this patient was in the atomoxetine-treated group.
On September 29, 2005, the FDA issued a Public Health Advisory to alert patients and medical professionals of reports of suicidal thinking in children and adolescents taking atomoxetine. The FDA directed Eli Lilly to add a “boxed” warning on the labeling, and to create a medication guide for pharmacists to distribute with all new and refill prescriptions of atomoxetine for children/adolescents.
The FDA advised that upon starting treatment with atomoxetine or changing dose of the drug, pediatric patients must be closely monitored for a few months for the advent of the following signs/symptoms:
- Clinical worsening
- Unusual changes in behavior
- Agitation, irritability
- Suicidal thinking or behavior
It is not yet known if the suicidality in children/adolescents is a phenomenon that extends to the traditional ADHD medications. In early 2006, the FDA plans to complete an ongoing review of side effect data for all ADHD medications.
II. In 2004 the FDA Issued a Black Box Warning Regarding Suicidality in Children and Adolescents with All Antidepressants
On September 16, 2004, the FDA released the following recommendations made by the Psychopharmacologic Drugs and Pediatric Advisory Committees:
- Concluded that increased risk of suicidality in pediatric patients applied to all the drugs studied (fluoxetine, sertraline, mirtazapine, paroxetine, venlafaxine, citalopram, bupropion, fluvoxamine, nefazodone) in controlled clinical trials.
- Recommended that warnings of increased risk of suicidality in pediatric patients be applied to all antidepressant drugs.
- Recommended a "black-box" warning and endorsed a Medication Guide with every prescription for this class of drugs.
- Recommended that the products not be contraindicated because access to these therapies is important.
On October 15, 2004, the FDA announced its decision to require a “Black Box Warning and Medication Guide” for the use of all antidepressants in children and adolescents under 18 years of age. New warning language did not prohibit the use of antidepressants in children and adolescents. It only warned of the risk of suicidality and encouraged providers to balance this risk versus benefit. The Medication Guide About Using Antidepressants in Children and Teenagers is an approved medication guide Medi-Cal providers can review.
III. How Are Medi-Cal Providers Impacted?
The FDA has issued two warnings to alert medical professionals of reports of suicidal thinking and behavior in children and adolescents taking antidepressants and atomoxetine. Between September 2004 and September 2005, a large number of Medi-Cal recipients were being treated with these agents. Therefore, it is important to properly counsel and closely monitor all pediatric patients who are starting new therapy with these agents, those who are titrating dosage, and those with a predisposition/history of bipolar disorder.
Medi-Cal is actively monitoring the impact that the label changes have made to antidepressants and atomoxetine on the utilization of these drugs and clinical outcomes.
To report any unexpected adverse events associated with these agents, contact the FDA Medwatch program at 1-800-FDA-1088; by fax at 1-800-FDA-0178; by mail to MedWatch; Food and Drug Administration; HFD-410; 5600 Fishers Lane; Rockville, MD 20857-9787.
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