Title:The Incidence of Akathisia in the Treatment of Schizophrenia with Aripiprazole, Asenapine and Lurasidone: A Meta-Analysis
Volume: 13
Issue: 5
Author(s): Jennifer E. Thomas, Joshua Caballero and Catherine A. Harrington
Affiliation:
Keywords:
Akathisia, aripiprazole, asenapine, lurasidone.
Abstract: Akathisia is a troubling side effect that leads to non-adherence with antipsychotic
regimens. Second generation antipsychotics (SGAs) tend to cause less akathisia than older agents but
the risk still exists and rates vary between agents. Little is known about the incidence of akathisia
among the newer SGAs. The purpose of this study was to conduct a meta-analysis of akathisia
incidence rates for three of the newer SGAs: aripiprazole, asenapine, and lurasidone. Data were
drawn from published and unpublished clinical trials comparing the drug of interest to either placebo
or another SGA in adults with schizophrenia. Twenty-four studies (11 aripiprazole, 5 asenapine, and 8 lurasidone)
provided incidence rates for akathisia and related nervous system events. Data showed that the relative risk (RR) of
akathisia was double that of controls, with lurasidone having the highest individual RR at 2.7 [CI: 2-3.6]. Sensitivity
analysis changed the RR of akathisia to less than 10%. The RR of akathisia was still elevated (1.75 [1.4-2.1]) when these
drugs were compared only to actives (older SGAs). Agitation and anxiety RRs were also higher with the newer SGAs as
compared to the older SGAs. Previous theory suggests antagonism of serotonin (5-HT)2A receptors may decrease akathisia
risk. Expectations were that aripiprazole, asenapine and lurasidone would have a low incidence of akathisia, as all display
strong antagonism at 5-HT2A. However, in this study all three had a significantly higher risk of akathisia compared to
placebo or other SGAs. This suggests the pathophysiology of akathisia involves other receptors and is multifactorial.