BOSTON— Fluoxetine is not an effective treatment for depression in adolescents with comorbid substance-related disorders, suggest results of a placebo-controlled trial presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Previous studies have suggested that—in adolescents with comorbid major depression and alcohol use disorder in particular—fluoxetine may minimize depressive symptoms and drinking.
In the current study, designed to assess the efficacy and tolerability of fluoxetine in adolescents aged 12–17 years who were diagnosed with depression and a substance use disorder, Dr. Robert L. Findling and his colleagues at University Hospitals Case Medical Center, Cleveland, showed that the effect of treatment with the selective serotonin reuptake inhibitor was comparable with placebo in alleviating depressive symptoms. Additionally, patients treated with fluoxetine did not show a significantly greater decrease in their substance use, compared with patients who received placebo.
The 34 adolescents (mean age 16.46 years) who were enrolled in the trial met DSM-IV-R (revised) criteria for major depressive disorder or dysthymic disorder, and all had depressive symptoms of at least moderate severity, Dr. Findling reported in a poster presentation.
In addition, all the patients had a comorbid substance use disorder, including cannabis use disorder (in 56%), polysubstance use disorder (39%), and alcohol use disorder (11%).
For the study, 18 patients were randomized to receive 10-mg fluoxetine for 4 weeks, after which the dose could be increased to 20 mg, and 16 patients were randomized to placebo with a matching increase after 4 weeks.
The primary study outcome was mean change from baseline to end point in depressive symptoms and psychosocial functioning, based on Children's Depression Rating Scale-Revised (CDRS-R) scores. Additional measures included the Clinical Global Impressions-Severity (CGI-S) scale, the CGI-improvement (CGI-I) scale, the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), and the Children's Global Assessment of Functioning (CGAS). Rates of positive urine drug screens were calculated.
Comparison of the primary outcome via mixture model analysis demonstrated no treatment difference in mean change in CDRS-R total score, said Dr. Findling, who also noted that no significant treatment-by-visit interaction was observed in the random effects regression model, “suggesting there was no difference between treatment groups [in mean CDRS-R] change over time.”
No statistically significant differences in mean change from baseline were observed in any of the measures of depressive symptoms and psychosocial functioning, and an analysis of urine drug-screen results showed no difference in the rates of positive screens between treatment groups, he said.
Treatment was discontinued before 8 weeks by three patients in the placebo arm and six in the fluoxetine arm because of lack of efficacy, Dr. Findling said. Enrollment in the trial was stopped after the 8-week analysis based on the prespecified futility stopping rule.
Funding was provided by the American Foundation for Suicide Prevention and St. Luke's Foundation of Cleveland; medications were provided, in part, by Eli Lilly & Co.
The data suggest that there was no difference between the groups in terms of change in depression scores. DR. FINDLING