Background: Akathisia is among the most common and distressing side effects of antipsychotic medications, adversely affecting treatment adherence and clinical outcomes. This study aimed to evaluate the effectiveness of cyproheptadine compared with placebo in treating acute neuroleptic-induced akathisia. Methods: This double-blind, randomized controlled trial enrolled patients hospitalized in psychiatric units who were diagnosed with neuroleptic-induced akathisia and met the inclusion criteria. Fifty patients (25 per group) were included based on the anticipated effect size a 0.5-point change on the Barnes Akathisia Rating Scale (BARS). The intervention group received cyproheptadine at a dose of 4 mg every 12 hours. Akathisia symptoms were evaluated using the BARS, assessing objective, subjective, distress, and global akathisia scores at baseline and on days 4 and 7 postintervention. The minimum BARS score required for study entry was 2. Data analysis was performed using STATA software version 14. Results: The intervention and control groups were homogeneous regarding sex distribution ( P =1), age ( P =0.393), and antipsychotic medications used ( P =0.493). Repeated-measures ANOVA revealed a significant reduction in BARS scores over time in the intervention group compared with the placebo group on days 4 and 7 postintervention ( P <0.001). Significant reductions were observed in global akathisia scores, distress, and objective and subjective symptoms in the cyproheptadine group compared with placebo on days 4 and 7 postintervention ( P <0.05). The absolute risk reduction (ARR) was 0.52, and the number needed to treat (NNT) was 1.92 (≈2 patients). Although increased appetite did not significantly differ between the groups, drowsiness was significantly higher in the cyproheptadine group ( P <0.05). There were no dropouts among participants during the intervention phase. Conclusions: Cyproheptadine significantly reduces symptoms of antipsychotic-induced akathisia. Based on the evidence of this study, particularly the ARR and the NNT for achieving complete remission, it seems that cyproheptadine could be a potential alternative for managing akathisia induced by antipsychotic medications, especially in comparison to previous studies involving mirtazapine and propranolol.
ُShams-Alizadeh et al. (Wed,) studied this question.