REVIEW OF: Connolly A et al, Psychopharmacology (Berl) 2024;241(2):225–241

STUDY TYPE: Meta-analysis and systematic review 

Antipsychotic medications can cause tardive dyskinesia (TD) by making dopamine receptors overly sensitive. Drugs like tetrabenazine, deutetrabenazine, and valbenazine treat TD by lowering dopamine levels. Does this also affect psychosis? 

This meta-analysis included five studies of adults with psychosis or schizophrenia. Researchers compared vesicular monoamine transporter 2 (VMAT-2) inhibitors against placebo and both first- and second-generation antipsychotics, including clozapine. Their primary outcomes were the Brief Psychiatric Rating Scale and Clinical Global Impressions Improvement Scale (CGI-I). The researchers predefined two CGI-I tiers, “slight” improvement and “moderate” improvement (defined as everything greater than slight). Authors disclosed funding from pharmaceutical companies, one from the maker of brand-name valbenazine (Ingrezza).

All studies were from Europe or North America. They spanned 50 years and 173 patients, all prescribed tetrabenazine. Tetrabenazine slightly improved psychotic symptoms compared to placebo (relative risk [RR] = 1.77, 95% confidence interval [CI] 1.03–3.04). There was no significant difference between tetrabenazine and antipsychotics for either slight (RR 1.05, 95% CI 0.6–1.81) or moderate (RR 1.11, 95% CI 0.51–2.42) improvement. The most commonly reported adverse effects of tetrabenazine were parkinsonism, hypotension, GI symptoms, and “tetrabenazine malaise” (described as dysphoria, irritability, and fatigue). There was no direct comparison between the side effects of tetrabenazine and other medications. 

CARLAT TAKE

VMAT-2 inhibitors may improve psychotic symptoms, but we’ll wait for confirmation as this was a secondary analysis.