Depression is a significant cause of injury and death in children and adolescents. Many children with depression have difficulties in school and sometimes drop out of school altogether. Suicide continues to be a leading cause of death among adolescents. Many adults with depression, especially women, experienced their first episode during the teenage years. Studies to date have shown little, if any, real benefit from prescribed antidepressant medications in patients between six and 18 years of age. Use of selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, has been studied on a rather limited basis. Emslie and colleagues compared the efficacy of treatment with fluoxetine with use of a placebo in children and adolescents with nonpsychotic major depressive disorder.
Children and adolescents between the ages of seven and 17 years who met criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) for nonpsychotic major depressive disorder were enrolled in the study. Patients with histories of bipolar disorder, psychotic depression, alcohol or other substance abuse (within the past year), anorexia nervosa or bulimia, or previous treatment with fluoxetine for more than three weeks were excluded.
A total of 583 patients underwent initial screening, 256 were interviewed, and 106 patients were enrolled in the study. After a one-week placebo run-in period, 96 patients were randomized to the placebo group or the fluoxetine group. Demographic and clinical characteristics were similar in both groups. In each group, 24 patients were younger than 12 years of age, and 24 patients were 13 years of age or older. The treatment group received 20 mg daily of fluoxetine for eight weeks. Outcomes were measured weekly, and a Clinical Global Impressions (CGI) scale improvement rating and a Children's Depression Rating Scale-Revised (CDRS-R) were obtained at each visit.
After eight weeks of treatment, 25 patients (74 percent) in the fluoxetine group showed a clinical response, compared with only 15 (58 percent) in the placebo group. Improvement in the fluoxetine group was first found to be statistically significant after week five of medication. Based on CGI ratings after eight weeks of treatment, 27 patients (56 percent) in the fluoxetine group and 16 patients (33 percent) in the placebo group were rated as “much” or “very much” improved. Age and sex had no effect on patient responsiveness. However, complete remission of depressive symptoms was uncommon in all patients. Side effects from the drug were minimal, with four patients in the fluoxetine group and one patient in the placebo group discontinuing the study because of medication intolerance.
The authors conclude that treatment with 20 mg of fluoxetine daily is superior to placebo in treating nonpsychotic major depressive disorder in children and adolescents. However, they add that the effectiveness of long-term treatment requires more study.