Adjunctive Fluvoxamine for Schizophrenia: A Meta-analysis of Randomized Double-Blind, Placebo-Controlled Trials

Abstract

Background This was a meta-analysis of double-blind, randomized controlled trials that examined the therapeutic effects and tolerability of adjunctive fluvoxamine versus placebo for schizophrenia. Methods The Review Manager, Version 5.3, was used to analyze data. Results Five double-blind randomized controlled trials (N = 284) covering 145 patients on adjunctive fluvoxamine and 139 patients on placebo were included in the analyses. Meta-analyses of total psychopathology, and negative, positive, and depressive symptoms did not show significant differences between the fluvoxamine and placebo groups. Two studies examined the effects of adjunctive fluvoxamine on cognitive functioning with mixed findings. Fluvoxamine was superior over placebo in lessening weight gain and metabolic abnormalities. Although fluvoxamine led to more discontinuation, no significant group differences were found regarding adverse drug reactions. Conclusions There was inconsistent evidence for the therapeutic effect of adjunctive fluvoxamine on cognitive functions and preliminary evidence for alleviating metabolic syndrome caused by clozapine. More studies are needed to explore further the effectiveness of adjunctive fluvoxamine for schizophrenia.

European Psychiatric Association guidance on treatment of cognitive impairment in schizophrenia

“…Regarding antidepressants, a recent meta-analysis [ 82 ] considering the effects of adjunctive fluvoxamine, included five randomized controlled trials (284 participants), two of which also evaluated cognitive outcomes, and observed no significant pro-cognitive effect of the antidepressant drug. A Cochrane Collaboration meta-analysis [ 83 ] focused on adjunctive mirtazapine and included nine randomized controlled trials (310 participants): four studies reported data on cognitive outcomes, three of which were included in the systematic evaluation of cognition, and, although minimal positive effects were reported in one trial, no substantial improvement in cognition was observed.…”

Acid sphingomyelinase/ceramide system in schizophrenia: implications for therapeutic intervention as a potential novel target

“…We suggest that the FIASMA-antidepressants may thus be expected to benefit patients with schizophrenia. Considering the inconsistent results among previous clinical trials and investigations on the FIASMA antidepressant fluvoxamine adjunctive therapy for patients with schizophrenia [60][61][62], it is worthy investigating whether FIASMAs may have therapeutic effect on a group of patients with schizophrenia or combined depressive disorders who present abnormal ASM/ceramide system. We also propose future directions from the biological landscape for the development of new treatments for schizophrenia.…”

“…FIASMAs induce the detachment of ASM from inner lysosomal membranes and thereby cause its consecutive inactivation [59]. However, clinical trials of adjunctive therapy using the FIASMA-antidepressant fluvoxamine to treat schizophrenia have given inconsistent results [60][61][62]. Because the activated ASM/ceramide system may be inhibited by approved FIASMAs and particularly by the antidepressants in this drug class, FIASMAs may be expected to benefit patients with schizophrenia or combined depressive disorders who have ASM/ceramide system dysfunction and abnormal ceramide levels.…”