Pharmacologic Treatment of Tardive Dyskinesia: A Meta-Analysis and Systematic Review.

OBJECTIVE

To examine the efficacy of pharmacologic treatments for tardive dyskinesia (TD).

DATA SOURCES

PubMed was searched on December 12, 2017, for randomized, placebo-controlled trials examining the treatment of TD using the search terms (drug-induced dyskinesia OR tardive dyskinesia) AND (psychotic disorders OR schizophrenia).

STUDY SELECTION

Studies were included if they examined tardive dyskinesia treatment as the primary outcome and were randomized and placebo-controlled trials.

DATA EXTRACTION

The effect size (standard mean difference) of improvement (compared to placebo) stratified by medication class is reported for each of the trials included in this systematic review. A meta-analysis was conducted utilizing a fixed-effects model.

RESULTS

Vitamin E was associated with significantly greater reduction in TD symptoms compared to placebo (standardized mean difference [SMD] = 0.31 ± 0.08; 95% CI, 0.16 to 0.46; z = 4.1; P < .001). There was significant evidence of publication bias in vitamin E studies (Egger test: P = .02). Shorter duration of treatment and lower dose of vitamin E were significantly associated with greater measured treatment benefit. Vitamin B₆ was associated with significantly greater reduction in TD symptoms compared to placebo (SMD = 1.41 ± 0.22; 95% CI, 0.98 to 1.85; z = 6.4; P < .001) in 2 trials conducted by the same research group. Vesicular monoamine transporter 2 (VMAT2) inhibitors demonstrated significant benefit on tardive dyskinesia symptoms compared to placebo (SMD = 0.63 ± 0.11; 95% CI, 0.41 to 0.85; z = 5.58; P < .005). Amantadine was associated with significantly greater score reduction compared to placebo (SMD = 0.46 ± 0.21; 95% CI, 0.05 to 0.87; z = 2.20; P < .05). Calcium channel blockers were not associated with significantly greater score reduction compared to placebo (SMD = 0.31 ± 0.33; 95% CI, -0.34 to 0.96; z = 0.93; P = .35).

CONCLUSIONS

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 suggest 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.

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