Fluoxetine in the management of major depressive disorder in children and adolescents: A meta-analysis of randomized controlled trials

Abstract

Fluoxetine is a serotonin specific reuptake inhibitor anti-depressant and is the only approved pharmacological treatment for major depressive disorder (MDD) in children and adolescent. We searched the published randomized controlled-trials (RCT) to review fluoxetine efficacy and tolerability using the databases PubMed, EUDRACT, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials for fluoxetine role in managing MDD in children and adolescents. A meta-analysis was conducted using the identified 7 clinical trials to assess efficacy using the outcomes: Children’s Depression Rating Scale-Revised (CDRS-R), Clinical Global Impressions – Severity of Illness (CGI-S) and Clinical Global Impressions – Improvement (CGI-I) response rate. The risk of discontinuation due to adverse effects and common side effects were examined. The mean difference in change from baseline for CDRS-R was -2.72 [95% Confidence Interval (CI) -3.96, -1.48] favouring fluoxetine treatment (p<0.001). Similarly, mean difference for CGI-S was -0.21 [95% CI -0.36, -0.06]. The risk ratio (RR) of discontinuing due to adverse events was 0.98 [95% CI 0.54, 1.83], with RR for headache side effects 1.34 [95% CI 1.03, 1.74] and rash 2.6 [95% CI 1.32, 5.14]. Fluoxetine demonstrates significant improvements in symptom intensity control in young patients suffering from MDD and is considered well-tolerated with similar rates of trials discontinuation; however, fluoxetine was associated with a higher risk of headache and rash side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting the care of young mental health patients.