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Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial

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ABSTRACT

Objective

To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression.

Method

After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20–40 mg), imipramine (gradual upward titration to 200–300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score ≤8 or ≥50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores.

Results

Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score ≤8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent-or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects.

Conclusions

Paroxetine is generally well tolerated and effective for major depression in adolescents.

Section snippets

Study Design

This was an 8-week, multicenter, double-blind, randomized, parallel-design comparison of paroxetine with placebo and imipramine with placebo in adolescents with major depression. The trial was conducted at 10 centers in the United States and 2 in Canada. Four hundred twenty-five subjects were screened for eligibility, and 275 subjects were randomly assigned to experimental treatment. The trial was conducted in accordance with good clinical practices and the Helsinki Declaration. All subjects

RESULTS

Treatment groups were similar with regard to demographic characteristics and psychiatric profile (Table 1). Most subjects had a first-degree relative with major depression and were experiencing their first episode of major depression. The mean duration of the current depressive episode was more than 1 year, with a mean baseline HAM-D total score between 18 and 19. Features of melancholic or endogenous depression were exhibited by 35% to 40% of patients, and 20% had features of atypical

DISCUSSION

This is the first study to compare efficacy of an SSRI and a tricyclic antidepressant with placebo in the treatment of major depression in adolescents. Paroxetine was significantly more effective than placebo with regard to achievement of both HAM-D total score ≤8, CGI score of 1 (very much improved) or 2 (much improved), and improvements in the depressed mood items of the HAM-D and the K-SADS-L. Paroxetine did not separate statistically from placebo for K-SADS-L depression subscore, mean CGI

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    This study was supported by a grant from GlaxoSmithKline, Collegeville, PA. The authors acknowledge the contributions of the following individuals: Jill M. Abbott, Ellen Basian, Ph.D., Carolyn Boulos, M.D., Elyse Dubo, M.D., Mary A. Fristad, Ph.D., Joan Hebeler, M.D., Kevin Kelly, Ph.D., Sharon Reiter, M.D., and Ronald A. Weller, M.D. Editorial assistance was provided by Sally K. Laden, M.S.

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