Open trial of bupropion SR in adolescent major depression

Journal of Child and Adolescent Psychiatric Nursing, Jul-Sep 2003 by Glod, Carol A, Lynch, Arlene, Flynn, Elizabeth, Berkowitz, Cynthia, Baldessarini, Ross J

Subjects had mean or - SD total SIGH-SAD scores of 31.3 or - 7.8 at baseline, compared with 8.2 or - 6.6 at the end of 8 weeks-a highly significant overall improvement of 73.7% (paired-t [10 df] = 5.26, p or =50% decrease of total SIGH-SAD scores to ratings

Overall clinical improvement also was assessed with CGI-I ratings provided independently by the rating clinician as well as by each subject (see Table 1). Patient and clinician ratings of improvement were in good agreement. All but 1 of the 8 adolescents completing the 8-week trial reported being "much" (n = 6) or "very much" (n = 1) improved at the end of the trial, and the clinician-raters considered all 8 trial completers as "much" (n = 7) or "very much" improved (n = 1). These ratings indicate an overall response rate of 8 of 11 treated subjects (72.7%) when using clinician ratings vs. a rate of 7 of 11 (63.6%) based on subject-ratings.

Finally, additional SIGH-SAD and clinician-CGI-I ratings were obtained for 7 subjects who continued open treatment with bupropion SR from weeks 8 through 12. At 12 weeks, the improvements attained within the first 8 weeks were sustained in 6 of 7 subjects.

Bupropion SR was well tolerated by the 11 treated subjects (Table 2). Only insomnia and weight loss were commonly experienced (each in 6 of 11, or 54.6%, of the treated subjects). Most subjects and their parents saw the weight loss as beneficial, since 3 of 11 treated subjects had gained weight during their illness in association with increased appetite and decreased physical activity. Other adverse effects noted in a minority of treated subjects included dry mouth (5 of 11), headache (2 of 11), agitation (1 of 11), lightheadedness (1 of 11), diarrhea (1 of 11) or rash (1 of 11). The adverse effects encountered were more prominent at doses of 300 mg/day or more. Insomnia was particularly likely with higher doses, however, in all but one case, sleep normalized with continued drug exposure at the same dose. Notably, there were no instances of switching into manic or mixed affective states in any of the 11 treated subjects.

Discussion

Bupropion SR given at doses up to 400 mg/day for 8 weeks, and extended to 12 weeks, appeared to be effective for moderately severe major depression in adolescents, in both typical and atypical depressive symptoms, in this small, open trial involving 11 treated subjects. These preliminary findings are among the first to indicate antidepressant efficacy of bupropion SR in this age group. They are consistent with a recent preliminary, open study of this agent in 16 adolescents (10 males, 6 females, ages 12.8 1.8 years) with co-morbid DSM-IV ADHD and major depression (Daviss et al. 2001). In that trial, responses of "much" or "very much" improved on the psychiatrist-rated CGI scale were found in 14 of 16 subjects (87.5%) for depression, and 10 of 16 (62.5%) for ADHD symptoms.

The present study, even without including a placebo arm, reflected a number of difficulties commonly encountered in experimental and even clinical treatment trials in juveniles. Notably, only 11 of 21 (52%) of appropriate candidates accepted enrollment in the trial, and only 8 of 21 (38%) completed 8 weeks of treatment. Many patients denied the presence of depression, blamed it on their parents or external circumstances, and resisted any treatment, despite significant deterioration of academic and social performance and pleas by their parents to accept treatment. Acceptance of treatment for juvenile depression was only 20% in a recent study (Lewinsohn, Rohde, Seeley, Klein, & Gotlib, 2000).