Meta-analysis and systematic review of vesicular monoamine transporter (VMAT-2) inhibitors in schizophrenia and psychosis

Rationale Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia. Methods We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population : adults diagnosed with psychosis or schizophrenia; Intervention : treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison : comparison with placebo or/and antipsychotic drug; Outcomes : with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies : in randomised controlled trials and non-randomised studies. Results We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome ‘slight improvement’ (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for ‘moderate improvement’ (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for—‘slight improvement’ (RR 1.05 (95% CI 0.6, 1.81)) and ‘moderate improvement’ (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis. Conclusions VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.