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Tardive dyskinesia (TD) is a movement disorder that arises as a side effect of prolonged exposure to dopamine receptor antagonists (DRAs), commonly prescribed for schizophrenia and mood disorders. Its management remains a significant clinical challenge, necessitating the identification of effective pharmacological interventions. Two recent systematic reviews and network meta-analyses sought to evaluate and rank available treatments for TD, offering insights into their efficacy and safety.
In one study1, researchers conducted a comprehensive systematic review and network meta-analysis (NMA) of 46 randomized controlled trials (RCTs) encompassing 2,844 participants. The study aimed to assess the effectiveness of various pharmacological and brain stimulation interventions in improving TD symptoms. Among the 22 treatments tested against placebo, only a few demonstrated statistically significant benefits. When restricting the analysis to higher-quality trials (i.e., those with more than 20 participants and multiple RCTs), valbenazine (SMD = -0.69) and vitamin E (SMD = -0.49) emerged as the most effective treatments. Deutetrabenazine showed moderate efficacy (SMD = -0.57 to -0.60), particularly when analyzing trials with a low risk of bias. However, the confidence in these findings remained low, and most treatments lacked robust supporting evidence. Additionally, the study found that switching to molindone or implementing an antipsychotic washout strategy worsened TD symptoms, highlighting approaches to avoid in clinical practice.
A second study2, another NMA based on 33 RCTs and 1,817 participants, aimed to indirectly compare and rank different pharmacological treatments for TD. This study similarly identified valbenazine (at both 80 mg and 40 mg doses) and vitamin E as significantly effective in reducing TD symptoms. The standardized mean difference for valbenazine 80 mg was notably high (-1.66), followed by valbenazine 40 mg (-1.00) and vitamin E (-0.77). In contrast, deutetrabenazine (SMD = -1.00) and reserpine (SMD = -0.54) did not show statistically significant improvements. Importantly, the study also highlighted potential safety concerns with valbenazine and deutetrabenazine, which were associated with psychiatric adverse events, including depression, worsening schizophrenia, and suicidal ideation.
Both studies reinforced the efficacy of valbenazine and vitamin E as primary treatment options for TD, with valbenazine demonstrating the strongest effect size. However, concerns over valbenazine’s psychiatric side effects underscore the need for further research into alternative treatment options with better safety profiles, according to both studies. Deutetrabenazine showed moderate efficacy but did not achieve statistical significance in one of the analyses.
Furthermore, the limited quality and small sample sizes of many studies emphasize the necessity for higher-quality clinical trials to strengthen the evidence base for TD management.
In conclusion, while valbenazine and vitamin E appear to be the most promising pharmacological treatments for TD, clinicians must weigh their benefits against potential risks. The findings suggest that valbenazine is the most effective option, albeit with notable psychiatric side effects, whereas vitamin E may serve as a safer, albeit less potent, alternative.
Future research should focus on expanding treatment options and conducting larger, high-quality RCTs to provide more definitive guidance on the optimal management of TD.
