Comparative efficacy and acceptability of treatment strategies for antipsychotic-induced akathisia: a systematic review and network meta-analysis

Abstract

Background: Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear. Design: We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on 24th July 2023. We included randomized clinical trials comparing one or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA. Results: We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7 % [195 of 532] women). No trials examined dose-reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k=6, n=108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k=8, n=105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k=2, n=13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k=3, n=67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights. Conclusions: Our findings suggest that 5-HT2A antagonists, beta blockers, and with a lesser certainty, benzodiazepines and vitamin B6 might improve akathisia. These conclusions are extremely preliminary and further trials are needed.