http://www.medscape.com/viewarticle/491998?src=mp
Combination SSRI and CBT Most Effective for Adolescent Depression
Paula Moyer
Oct. 25, 2004 (Washington) — Adolescents with major depressive disorder are more likely to respond to a combination of the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) and cognitive behavioral therapy (CBT) than to either as monotherapy, according to investigators of a publicly funded study who presented their findings here at the 51st annual meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).
In addition, the researchers found that the combination — and each therapy alone — were more effective than placebo, said principal investigator John S. March, MD. He spearheaded the Teenage Depression Study (TADS), which was funded by the National Institute of Mental Health.
“We still have questions about the low response rate in the CBT and placebo groups,” Dr. March said during his presentation. “It may be that this population was sicker than typically seen in adolescent depression studies, and it may also be that the placebo-controlled phase, at 12 weeks, was shorter than is typically seen in trials of CBT.” Dr. March is director of the Program in Child and Adolescent Anxiety at Duke University Medical Center in Durham, North Carolina.
The investigators recruited 439 adolescents with major depressive disorder and randomly assigned them to one of four groups: medication management with fluoxetine (n = 109), medication management with placebo (n = 112), CBT (n = 111), or a combination of CBT and fluoxetine (n = 107). The placebo-controlled phase of the study lasted 12 weeks.
The investigators used two instruments to measure response to treatment: the Child Depression Rating Scale–Revised (CDRS-R) total score and the Clinical Global Impression–Improvement (CGI-I) score. The participants’ mean baseline CDRS-R score was 60.0 ± 10.4. The severity as assessed by CGI was an average of 4.8 ± 0.8; severity by the Child-Global Assessment Scale averaged 59.6 ± 7.5.
At 12 weeks, 10% of the original subjects dropped out due to lack of efficacy, adverse events, and other study-related issues. Another 10% were prematurely terminated due to unrelated medical problems and other issues that had developed and taken priority over participation in the study. The dropout and premature termination rates did not differ among the groups, Dr. March said.
Assessments at weeks 6 and 12 showed that most of the response to treatment occurred in the first six weeks. By the end of the 12-week period, CBT monotherapy did not differ significantly from placebo, with each group having a CDRS-R averaging approximately 45. At that point, combination therapy produced the greatest reduction on the CDRS-R, with patients in that group having an average score of 30; the fluoxetine monotherapy group had an average CDRS-R score of 35. These results held true even when adjusting for dropouts and premature terminations, Dr. March said, and they were validated when the subjects were evaluated on the Reynolds Adolescent Depression Scale.
The response rates, as defined by CGI-I results of “improved” or “much improved,” were 71% for the combination group, 51% for the fluoxetine monotherapy group, 40% for the CBT monotherapy group, and 34% for the placebo group. According to a number-needed-to-treat analysis, to obtain a statistically significant result it would be necessary to treat two patients with combination therapy, four patients with fluoxetine alone, and 12 patients with CBT alone. The investigators would have expected a 60% response rate for CBT alone, and a 40% placebo response rate, Dr. March said.
The study found a significantly reduced rate of suicidal ideation in the treatment groups compared with the placebo group, writes Steven P. Cuffe, MD, in an AACAP memo related to TADS. “Additionally, suicide attempts were not significantly associated with SSRI use.”
Dr. Cuffe continued, “However, there was a significantly higher rate of ‘harm-related events’ in the adolescents treated with fluoxetine. These events include both suicidal and nonsuicidal (for example, cutting oneself without suicidal intent) self-harm, increase in suicidal ideas, or thoughts or acts of harm to others or property.”
When the investigators used this broader definition (harm-related events), they found a significant difference between the fluoxetine groups and the others, according to Dr. Cuffe. He is the director of child and adolescent psychiatry at the University of South Carolina School of Medicine in Columbia.
Eli Lilly, the manufacturer of Prozac, provided the medication used in the study.
AACAP 51st Annual Meeting: Abstract 49b. Presented Oct. 23, 2004.
Reviewed by Gary D. Vogin, MD