Akathisia is a movement disorder that consists of increased motor activity and inner restlessness. Drug-induced akathisia is a common side of antipsychotics and varies by antipsychotic. A recent study investigated the relationship between akathisia and the doses of various antipsychotic medications. The researchers conducted a comprehensive dose-response meta-analysis using 16 second-generation antipsychotics and haloperidol. The study included randomized controlled trials (RCTs; 98 studies with 343 arms; n=34,225) examining adults with schizophrenia or related disorders. The median study duration was 6 weeks (range: 3–26 weeks), and most participants were inpatients with a mean age of 39 years and a mean duration of illness of 14 years. Approximately two-thirds of participants were male. Data were available for all antipsychotics except clozapine and zotepine. The results showed that the propensity for akathisia varied significantly among the antipsychotics. Most medications exhibited either monotonic or hyperbolic dose-response curves, meaning that higher doses were associated with a greater or equal risk of akathisia (Table 1).

Good treatment options to avoid akathisia include sertindole and quetiapine, as well as risperidone and paliperidone because their dose-response curves did not show rapid increases in akathisia. Aripiprazole, iloperidone, and ziprasidone also had relatively low risk of akathisia across doses; however, certainty of evidence was low to very low. The dose-response curves of olanzapine, brexpiprazole, asenapine, and lumateperone were initially flat, but started to rise around the midpoint of their dose ranges, so akathisia should certainly be monitored when doses are increased for these medications. Lurasidone demonstrated the most steeply rising dose-response curve with a large risk of akathisia, suggesting that this medication might be avoided in people with risk for akathisia. Haloperidol, amisulpride, and cariprazine also reached high levels of akathisia risk and perhaps should be avoided in certain patients. Overall, the study provides valuable information for clinicians to make informed decisions about antipsychotic dosages based on their patients' susceptibility to akathisia. However, the findings are limited by the nature of RCTs and may not fully represent real-world populations.

Reference:

Wu H et al. Eur Neuropsychopharmacol 2023;72:40-9. Abstract