January 27, 2010 — Physicians have responded to US Food and Drug Administration (FDA) warnings about a link between antidepressant use in children and suicidality by adjusting their prescribing patterns but have failed to heed specific safety recommendations about follow-up monitoring in their young patients taking these medications.
"Although we found changes in prescribing patterns, the FDA's recommendation regarding increased physician monitoring appears to have been largely ignored," the study authors, led by Susan H. Busch, PhD, Yale School of Public Health, New Haven, Connecticut, write.
This finding, say the study authors, "highlights the limited power of the FDA to directly affect the care received by patients."
The study is published in the January issue of Psychiatric Services.
Between June 2003 and October 2004, the FDA issued 5 warnings about increased risk of suicidality among children and youth taking antidepressants. The first warning focused on paroxetine after GlaxoSmithKline disclosed evidence of an increased risk of suicidality among pediatric patients.
Subsequent warnings incrementally expanded the scope to ultimately include all classes of these agents. In an advisory issued in October 2003, the FDA noted that of the drugs evaluated only fluoxetine showed efficacy in children with major depressive disorder. It also highlighted the importance of close monitoring after initiation of therapy.
In the fifth and final advisory in October 2004, the FDA, in addition to directing all manufacturers of antidepressants to include a black box warning about the increased risk of suicidality among children and adolescents, also laid out monitoring recommendations and specifically called for "weekly, face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment."
The study authors note that the FDA's initial decision to issue these warnings was controversial. Proponents argued that physicians and other health care professionals need to be informed of the risk of suicidality. Detractors were concerned it would cut rates of depression diagnosis and treatment.
In 2005, a year after the final warning, there was a documented 20% to 30% decrease in pediatric antidepressant use. The investigators note that there was also a concurrent increase in the national suicide rate. However, no research has linked the 2 occurrences.
Although previous research has demonstrated an association between the FDA warnings and a decrease in overall use of antidepressants in this patient population, the study authors note that there has been no research examining changes in treatment patterns in the periods after the individual warnings to determine whether specific information contained in these warnings was associated with relevant treatment changes.
The investigators sought to determine whether:
• The use of paroxetine decreased in children after the first FDA warning;
• The use of fluoxetine increased after specific benefits in treating children were mentioned in FDA warnings; and
• Children with major depression who received prescriptions for antidepressants were more likely to have 2 or more outpatient visits in the first 30 days after initiation of drug treatment as recommended by the FDA.
Using 2001 to 2005 claims data for 22,689 episodes of major depressive disorder in a national sample of privately insured children, the investigators found a 19% decrease in antidepressant use, confirming previously documented decreases in antidepressant prescribing.
They also found a 12% decrease in paroxetine use — from 20% to 8% — after the first warning, and the rate of paroxetine use remained low. In 2005, approximately 5% of new episodes of childhood depression were treated with paroxetine.
The study also showed an increase in fluoxetine use — from 13% to 16% — in the period immediately after the October 2003 advisory, which first noted the drug's benefit. Use of the drug continued to increase to 28% at the end of the study period.
However, despite the FDA's recommendation for weekly face-to-face contact during the first month of treatment, the investigators found no evidence of outpatient follow-up visits.
The study authors speculate that the lack of follow-up may be due to the "high cost of office visits, a shortage of providers (particularly child psychiatrists) or out-of-pocket costs associated with mental health visits in many health plans."
The investigators point out that although the FDA is charged with protecting public health by ensuring the safety, efficacy, and security of drugs, it has few direct methods of addressing safety risks beyond issue advisories and pulling products from the market.
The study was supported by that National Institute of Mental Health. Study investigator Robert A. Rosenbeck discloses that he has received research support from Wyeth Pharmaceuticals. The other study authors have disclosed no relevant financial relationships.
Psychiatr Serv. 2010;61:11-16.
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Cite this: FDA Suicide Warnings Change Antidepressant Prescribing Patterns, but Physicians Ignore Monitoring Recommendations - Medscape - Jan 27, 2010.