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The specific symptom pattern in depressed adolescents was associated with likelihood of improvement with fluoxetine (Prozac), a secondary analysis of the indicated.

Among 426 children with moderate-to-severe depression, those with "cardinal" symptoms such as anhedonia, sleep problems, and social withdrawal had significantly improved scores on the Children's Depression Rating Scale-Revised (CDRS-R) with fluoxetine alone (4.1 points, 95% CI 1.1-7.1) or with added cognitive behavioral therapy (CBT) (5.8 points, 95% CI 2.8-8.9) compared with a placebo arm at 12 weeks, reported Christian Kieling, MD, PhD, of the Hospital de Clínicas de Porto in Porto Alegre, Brazil, and colleagues.

In contrast, teens on fluoxetine with a second cluster of symptoms such as physical complaints, appetite changes, and suicidal ideation showed no significant improvements on the CDRS-R scale, with or without CBT, compared with the placebo arm, the researchers wrote in .

However, among adolescents with this second symptom cluster, those on fluoxetine and CBT had significantly improved scores compared with those on fluoxetine or CBT alone, the researchers added.

"Our results confirm that response to treatment is heterogeneous and suggest the clinical profile for which a given therapeutic modality might be more or less beneficial," Kieling and co-authors wrote, adding that the two clusters selected in the study have previously been as playing an important role in treatment effects.

These findings can inform treatment recommendations depending on symptom presentations, commented Toshi Furukawa, MD, PhD, of the Kyoto University Graduate School of Medicine in Japan, in an .

For example, fluoxetine with or without CBT would appear to work well in children with mainly cardinal depression symptoms, whereas patients with the second cluster of symptoms would need fluoxetine plus CBT, he noted.

However, these two groups of symptom clusters were correlated, and it is thus "quite likely" that individuals with high scores in one cluster would also have high scores in the other, Furukawa wrote.

The lack of treatment effect in the second cluster of patients may be due to the "floor effect," in which fewer participants in the study had these symptoms, Furukawa said.

Overall, these findings question the validity of psychometric scales, showing "once again that different items on an established scale can have differential sensitivity to change ... and differential sensitivity to differences in change," he wrote.

The TADS study involved 439 teens from ages 12 to 17 with depression and a minimum score of 45 on the CDRS-R. Patients were excluded if they had bipolar disorder, thought disorders, or conduct disorders, although those with anxiety, obsessive-compulsive disorder, or attention deficit-hyperactivity disorder were included.

This analysis focused on the acute phase of the trial, in which participants were assigned to receive 10-40 mg daily fluoxetine with or without CBT, CBT alone, or a placebo pill for 12 weeks.

The 426 children with complete CDRS-R data were 54% female and about age 15, on average. Baseline depression scores were similar across the four groups, from 54.3 to 56.6.

Despite the greater treatment effect observed in patients with cardinal symptoms with fluoxetine and CBT and fluoxetine alone, the CBT alone and placebo groups did not significantly differ from each other, researchers reported.

Limitations, the team noted, included that the study involved children residing in a high income country who were treated as outpatients and had never taken fluoxetine, so the findings may not be generalizable to other populations.

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