OBJECTIVES: Tardive dyskinesia (TD) is a persistent and often disabling movement disorder associated with antipsychotic therapy for which there is no approved treatment. Tetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, has been studied for the treatment of TD and is listed in TD treatment guidelines. Two novel VMAT2 inhibitors have shown promising efficacy in recent clinical trials. The objective of this analysis was to assess the feasibility of conducting a meta-analysis comparing tetrabenazine versus the VMAT2 inhibitors in development. METHODS: A systematic literature search of clinical trials for use of selective VMAT2 inhibitors in TD was undertaken in the databases Pubmed, Embase and OVID (1980-August 2016). Data were collected for the study design, duration, size, sites, comparators, outcomes, efficacy and safety. Feasibility assessment for meta-analysis was conducted based on the potential for developing an evidence network for all selective VMAT2 inhibitors. RESULTS: Out of 479 references, 11 studies were relevant in 893 patients with movement disorders, including TD, for three VMAT2 inhibitors valbenazine, deutetrabenazine and tetrabenazine. Two TD randomized controlled trials (RCTs) were identified for valbenazine (N=325) and one for deutetrabenazine (N=117). No RCTs were identified for tetrabenazine. All studies for tetrabenazine (n=8) were case series or open-label trials, with a median sample size of 20 TD patients. 7 of 8 studies defined efficacy by a subjective assessment of “improvement”. One (single-arm) study used the AIMS. Valbenazine’s KINECT2 and KINECT3, and deutetrabenazine’s ARM-TD were multi-site, randomized, placebo-controlled studies. Efficacy was evaluated by centralized, blinded raters using the standardized assessment (AIMS). Safety and tolerability were evaluated at every study visit. CONCLUSIONS: Due to a lack of controlled and blinded studies with validated primary endpoints, published evidence supporting the efficacy and safety of tetrabenazine as a treatment for TD cannot be compared to novel VMAT2 inhibitors in a meta-analysis.