Major depressive disorder, which affects 3 percent of children and 8 percent of adolescents, is associated with high social and economic costs and may linger into adulthood. Selective serotonin reuptake inhibitors (SSRIs) are considered the best available treatment option for depression in children and adolescents, based on their efficacy and safety profile in adults; however, the recommendation for use in children and adolescents is based on limited evidence. Wagner and colleagues report the results of two identically designed, concurrently conducted, 10-week, international, randomized, double-blinded, placebo-controlled, multicenter trials comparing the SSRI sertraline with placebo in children and adolescents with major depressive disorder.
Participants were children and teens six to 17 years of age who met the diagnostic criteria for major depressive disorder. A variety of concomitant psychiatric disorders (such as attention-deficit/hyperactivity disorder and bipolar disorder) served as exclusion criteria. Patients were randomized to receive sertraline or matching placebo for 10 weeks in a 1:1 ratio. Improvement in depression was measured by their performance on the Children’s Depression Rating Scale–Revised (CDRS–R), which includes parent and observer input. The other scales used in the studies included the Clinical Global Impression of Severity of Illness (CGI–S) scale and the Clinical Global Impression of Improvement (CGI–I) scale.
Of the 376 randomized patients, 189 received sertraline, and 187 received placebo. Forty-six patients receiving sertraline (24 percent) and 31 patients receiving placebo (17 percent) discontinued the study early because of adverse events, withdrawal of consent, or loss to follow-up. Most of those who left the study because of adverse events were receiving sertraline.
Patients receiving sertraline demonstrated significantly greater improvement over the course of the study than those receiving placebo, as measured by CDRS–R, CGI–S, and CGI–I scores. Statistically significant greater improvement from baseline to the end of the study was noted in patients receiving sertraline on items of the CDRS–R scale, including irritability, low self-esteem, listless speech, excessive weeping, and hypoactivity. No significant change was found between treatment groups in suicidal ideation, and borderline change was found for depressed feelings and difficulty having fun. Adolescents appeared to have a slightly greater improvement than children.
At study end point, 69 percent of patients treated with sertraline and 59 percent of patients receiving placebo met the CDRS–R criteria for being responders. A similar pro portion met responder criteria for the CGI–I scale. The number of persons needed to treat to expect a difference in response between sertraline and placebo would be 10 according to the criteria of either scale. The differences between groups on either scale favored sertraline but did not reach statistical significance. Sertraline was generally well tolerated but had an increased incidence of diarrhea, vomiting, agitation, and anorexia.
Sertraline was found to be more effective than placebo in these trials, with improvement occurring as early as week 3. The authors note that the differences between sertraline and placebo in this study are numerically small, but important, particularly when compared with trials using tricyclic antidepressants, which showed no pharmacologic benefit. Sertraline was well tolerated up to a maximum dosage of 200 mg per day. A major limitation of the study was its short duration. As with trials in adults, this study showed a high response rate in the placebo group.