An Overview of the Systematic Reviews About the Efficacy of Fluvoxamine on Depression

Background: Depression is one of the leading causes of disability worldwide. Among pharmacological treatments, fluvoxamine—an early SSRI with a distinct pharmacological profile—has been recently reappraised for its broader clinical relevance. Objective: To assess the efficacy of fluvoxamine in the treatment of depression compared to placebo and other antidepressants through a comprehensive overview of systematic reviews and meta-analyses. Methods: A systematic search was conducted in MEDLINE and the Cochrane Central Register of Controlled Trials, including systematic reviews and meta-analyses of randomized controlled trials evaluating fluvoxamine’s efficacy. Reviews were eligible if they included adults diagnosed with depressive disorders based on the DSM or ICD criteria. Reviews focusing on other psychiatric disorders, comorbidities, tolerability, or economic evaluations were excluded. Data extraction included effect size measures and methodological quality assessments using the AMSTAR-2 tool. Results were synthesized by comparing fluvoxamine to placebo, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and other antidepressants. Results: A total of 74 reviews were identified, of which 14 systematic reviews met the inclusion criteria after screening and full-text analysis. These reviews, published between 1994 and 2021, predominantly involved nine pairwise meta-analyses and five network meta-analyses, comparing fluvoxamine with placebo and various antidepressants. Fluvoxamine demonstrated consistent superiority over placebo in achieving treatment response and remission outcomes. Comparisons with imipramine, clomipramine, amitriptyline, dothiepin, paroxetine, fluoxetine, citalopram, mianserin, nortriptyline, and moclobemide generally revealed no significant differences in efficacy. However, some reviews indicated that venlafaxine and mirtazapine were superior to fluvoxamine in certain outcomes, while fluvoxamine demonstrated greater efficacy than desipramine in one review. Sertraline and milnacipran showed mixed or review-quality-dependent results, with one low-quality review favoring milnacipran. Most reviews assessed outcomes over a median follow-up of six weeks using standardized depression rating scales. Conclusions: Fluvoxamine is a robust and effective antidepressant, demonstrating consistent efficacy comparable to other antidepressants and superior to placebo. While no single antidepressant was universally superior, fluvoxamine’s unique pharmacological profile and favourable safety characteristics support its clinical utility. Further research is needed to explore its role in personalized treatment strategies and emerging therapeutic contexts, such as comorbid anxiety and post-traumatic stress disorder.