Mental Health: A Report by the Surgeon General

Pharmacological Treatment
Prior to 1996, the medications of choice for major depression in children and adolescents were the tricyclic antidepressants, a choice based on numerous studies in adults. However, 13 distinct trials in children and adolescents failed to demonstrate the efficacy of tricyclic antidepressants for younger ages. Tricyclic antidepressants also have a higher risk of toxicity than selective serotonin reuptake inhibitors (SSRIs) (Walsh et al., 1994; Kutcher, 1998). The current consensus is that tricyclic medications are not the medication of choice for depressed children and adolescents (Eisenberg, 1996; Fisher & Fisher, 1996).

Recent research indicates that young people with depressive disorders may respond more favorably to SSRIs than to tricyclic antidepressants. The first SSRI tested in children and adolescents was fluoxetine. In a study of 96 outpatients over 8 weeks, 56 percent receiving fluoxetine and 33 percent receiving placebo were “much” or“very much” improved on the Clinical Global Improvement Scale. Benefits were comparable across age groups. Complete symptom remission occurred for 31 percent of fluoxetine-treated patients compared with 23 percent of placebo-treated patients (Emslie et al., 1997). A recent open trial of fluoxetine for adolescents hospitalized for treatment of major depression found it to decrease depression scores more effectively than imipramine, a tricyclic antidepressant (Strober et al., 1999), with the further advantage that fluoxetine was well tolerated.

The safety of a second SSRI, paroxetine, was demonstrated in a multicenter double-blind placebo-controlled trial. Paroxetine was compared with imipramine and placebo in 275 adolescents who met the DSM-IV criteria for major depression. Preliminary results indicate that, mostly because of side effects, one-third of imipramine patients withdrew from the study, a proportion significantly higher than that for paroxetine (10 percent) and placebo (7 percent) (Wagner et al., 1998). One of the co-investigators of this study noted that paroxetine’s efficacy was superior to that of imipramine and placebo on the Clinical Global Improvement Scale (Graham Emslie, personal communication, October 1998). However, final conclusions about the benefit of this second SSRI must await publication of the outcomes of this multicenter study.

In summary, psychosocial interventions for depressed children and adolescents indicate great promise, with several types of cognitive-behavioral therapy for the child or adolescent leading the way. With respect to pharmacotherapy, new studies attest to the safety and efficacy of two SSRIs. These promising findings are being extended in the recently begun NIMH-funded Treatment of Adolescents with Depression study.

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