Adolescents with major depressive disorder show improvement after treatment that combines the antidepressant fluoxetine (Prozac®) and cognitive behavioral therapy, according to the results of the Treatment for Adolescents with Depression Study (TADS), published in the August 18 issue of the Journal of the American Medical Association.
The TADS researchers said that major depressive disorder is common, with one in 20 teens affected at varying levels of severity. Like other forms of depression, major depressive disorder has been associated with increased risk of suicidal behavior and with completed suicide.
Major depressive disorder also has been linked to long-term psychosocial impairment in adulthood, said Mark Reinecke, professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, chief of the division of psychology and principal investigator on the TADS study at Northwestern.
In the United States, 500,000 adolescents attempt suicide every year and 2,000 die as the result of their injuries. According to 2001 statistics from the National Center for Injury Prevention and Control, suicide is the third leading cause of death in Americans aged 10 to 24.
Thus, improvements in the treatment of major depressive disorder, which is quite common among adolescents, should positively affect public health, TADS researchers said.
Researchers from the Feinberg School, Duke University Medical Center and 11 other academic and community clinics participating in the TADS study evaluated the effectiveness of four treatments among adolescents with major depressive disorder. The study included 439 patients with a primary diagnosis of major depressive disorder who ranged from 12 to 17 years.
The participants were randomly assigned to 12 weeks of fluoxetine alone; cognitive-behavioral therapy alone; cognitive behavioral therapy with fluoxetine; or placebo (sugar pill).
Compared with fluoxetine alone and cognitive behavioral therapy alone, treatment combining fluoxetine with cognitive behavioral therapy was superior, said Reinecke.
Rates of response for fluoxetine with cognitive behavioral therapy were 71 percent; with fluoxetine alone, 61 percent; with cognitive behavioral therapy alone, 43 percent; and with placebo, 35 percent.
Clinically significant suicidal thinking, which was present in 29 percent of the sample at the beginning of the study, improved significantly in all four treatment groups.
Fluoxetine with cognitive behavioral therapy showed the greatest reduction in suicidal thoughts. A little over 1 percent of 439 patients attempted suicide; there were no completed suicides.
The researchers also found treatment with fluoxetine alone elevated the risk for psychiatric adverse events.
“While fluoxetine did not appear to increase suicidal ideation, harm-related adverse events may occur more frequently in fluoxetine-treated patients and cognitive behavioral therapy may protect against these events,” Reinecke said.
“Given the high prevalence, morbidity, and significant mortality associated with major depressive disorder, the identification of depressed adolescents and provision of evidence-based treatment should be mandatory in health care systems, Reinecke and co-researchers said.
Second, despite calls to restrict access to medications, medical management of major depressive disorder with fluoxetine, including careful monitoring for adverse events, should be made widely available, not discouraged.
Third, given incremental improvement in outcome when cognitive behavioral therapy is combined with medication and, as importantly, increased protection from suicidality, cognitive behavioral therapy also should be readily available as part of comprehensive treatment for depressed adolescents, the authors strongly recommended.
The TADS results raise a mixture of questions and answers regarding the complicated issue of whether antidepressant drug treatment prescribed to treat depression might increase the risk for depression’s most dangerous outcome, suicidal behavior, said an accompanying editorial.
This research was supported by a grant from the National Institute of Mental Health. Lilly Inc. provided fluoxetine and matching placebo under an independent educational grant to Duke University.