Two studies evaluated the selective serotonin reuptake inhibitor (SSRI) anti-depressant medication fluoxetine in this population. A post hoc analysis of 13 cannabis-using patients among a larger sample of alcohol-abusing, depressed adolescents treated with fluoxetine (20–40 mg daily) showed reduction in cannabis and alcohol dependence and depressive symptoms [86]. Five-year follow-up of 10 patients showed that cannabis and alcohol dependence were reduced and academic ability improved, but clinical depression remained problematic. A later 12-week, controlled clinical trial in 70 adolescents and young adults with comorbid major depression and cannabis use disorder found fluoxetine (20 mg daily) no better than placebo in treating either the depressive symptoms or the cannabis- related symptoms [87]. The lack of a significant between-group difference in symptoms may reflect limited medication efficacy, a ceiling effect because of the efficacy of the concurrent psychosocial treatment (cognitive behavioral/motivational enhancement psychotherapy), or low statistical power from small sample size.
