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 Data were drawn from published and unpublished clinical trials comparing the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.