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Artukoglu, et al. J Clin Psychiatry. 2020; 81:19r12798.
Tardive dyskinesia (TD) is a potentially debilitating condition. This study aimed to assess the efficacy of various available pharmacologic treatments for TD using published meta-analysis of clinical trials examining TD treatment.
PubMed was searched on December 12, 2017, for randomized, placebo-controlled trials examining the treatment of TD. Studies were included if they examined TD treatment as the primary outcome and were randomized and placebo-controlled trials. The effect size (standard mean difference) of improvement (compared with placebo) stratified by medication class is reported for each of the trials included in this systematic review. A meta-analysis was subsequently conducted.
Vitamin E was associated with a significantly greater reduction in TD symptoms compared with placebo. There was significant evidence of publication bias in vitamin E studies. A shorter duration of treatment and lower dose of vitamin E was significantly associated with greater measured treatment benefit. Vitamin B6 was associated with a significantly greater reduction in TD symptoms compared with placebo in 2 trials conducted by the same research group. VMAT2 inhibitors demonstrated significant benefit on TD symptoms compared with placebo. Amantadine was associated with a significantly greater score reduction compared with placebo. Calcium channel blockers were not associated with significantly greater score reduction compared with placebo.
Data from multiple trials suggests that VMAT2 inhibitors, vitamin E, vitamin B6, and amantadine may be effective for the treatment of TD. Evidence of publication bias and a significant negative association of dose and duration of treatment with measured efficacy suggests that the benefits of vitamin E in TD may be overstated. Head-to-head trials are needed to compare the efficacy and cost-effectiveness of pharmacologic agents for TD.
Clinical Commentary (Sanjay Gupta, MD)
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies addressing the same scientific question. This method is often used to assess which interventions work. By combining multiple studies, the sample size can be significantly increased. Publication bias occurs in academic research when the outcome of a study determines whether it should be published or distributed.
Clinical Commentary (Joseph P. McEvoy, MD)
Before the availability of the VMAT2 inhibitors, healthcare professionals tried a wide range of medications to reduce the severity of TD. The few studies reported herein documented benefits in some patients from vitamin B6 or amantadine, and many seasoned healthcare professionals believe, from their experiences, that these agents can be helpful.
In my opinion, we should be using valbenazine or deutetrabenazine (FDA approved) for the treatment of TD. The other agents studied do not have similar evidence of efficacy based on randomized, double-blind studies. It is hard to make a case for starting non-FDA–approved agents before FDA-approved agents have been tried.