TORONTO – Fluoxetine combined with cognitive-behavioral therapy was more effective in improving functioning, global health, and quality of life in depressed adolescents than was either treatment alone, Dr. Benedetto Vitiello said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.
However, he noted, although symptoms of depression might have improved, many patients remained functionally impaired after 12 weeks of treatment, even with the most effective therapy. “It's not really surprising that function doesn't improve as quickly as symptoms,” he said in an interview. “You would expect symptoms to improve first, and then to see a gradual improvement in function.”
Dr. Vitiello, chief of the child and adolescent treatment and preventive intervention research branch of the National Institute of Mental Health, presented a secondary analysis of the Treatment for Adolescents with Depression Study (TADS). The TADS trial included 439 patients aged 12–17 years with major depressive disorder. Patients were randomized to either 12 weeks of fluoxetine alone (10–40 mg/day), cognitive-behavioral therapy (CBT) alone, CBT with fluoxetine (10–40 mg/day), or placebo.
The study found that combination therapy reduced the symptoms of depression better than did fluoxetine or CBT alone. But when the main outcome measure was function, rather than symptoms of depression, the results were not as robust, he concluded. “The data seem to show that treatment effects on function lag behind those on symptoms.”
In the analysis, functional outcomes were measured with the Children's Global Assessment Scale (CGAS), the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and the Health of the Nation Outcome Scales for Children and Adolescents (HONOSCA). Baseline scores showed moderate impairment, Dr. Vitiello said. Average scores were 50 (ideal score, 100) on the CGAS, 17 (ideal, 0) on the HONOSCA, and 43 (ideal, 75) on the PQ-LES-Q.
After 12 weeks of treatment, the combination therapy was clearly superior to any of the other arms on the basis of these measurements, he said. Average scores on the CGAS improved to 65 in the combination therapy group, 60 in the fluoxetine-only group, and 57 in the CBT-only and placebo groups.
HONOSCA scores declined (showing improvement) in all arms. However, the only statistically significant decline occurred in the combination therapy group. On the PQ-LES-Q, the most improvement occurred in the combination therapy group, with the average score increasing to 55.
“Combination therapy was consistently superior to the other arms in improving function in all three measures,” Dr. Vitiello said.
Even with these improvements, however, most patients didn't regain normal function. Only 35% of those in the combination therapy group attained a CGAS score higher than 70, representing normal function, although 71% of those in this group were classified as responders when assessing their symptoms of depression.
In the fluoxetine-only group, only 20% of patients attained normalization, although 61% were classified as responders. “It's quite a dramatic difference when you take the level of function as the outcome,” Dr. Vitiello said.
The numbers were significantly lower in the other groups–13% of those in the CBT-only arm and 19% of those in the placebo arm attained normalized function.
“It was quite disappointing that CBT had only a 13% recovery rate,” Dr. Vitiello said.