A Meta-Analysis of the Risk of Acute Extrapyramidal Symptoms With Intramuscular Antipsychotics for the Treatment of Agitation

Abstract

OBJECTIVE We examined the evidence for a decreased risk of extrapyramidal symptoms (EPS) with intramuscular second-generation antipsychotics (SGAs) versus intramuscular haloperidol alone or in combination with an anticholinergic agent. DATA SOURCES We searched MEDLINE, EMBASE, and the Cochrane Registry for studies published in English of intramuscular SGAs and intramuscular haloperidol alone or in combination with an anticholinergic agent. Initially, we included only randomized controlled trials (RCTs). To obtain more data comparing SGAs to the combination of haloperidol and an anticholinergic, we conducted a second analysis including studies of any methodology. STUDY SELECTION Seven RCTs that compared SGAs to haloperidol alone were identified. However, we found only one RCT of haloperidol plus an anticholinergic. In the second analysis, we identified 18 studies, including four using haloperidol combined with promethazine (an antihistamine with anticholinergic properties). DATA EXTRACTION The primary outcome measure was acute dystonia; secondary outcomes included akathisia, parkinsonism, or additional anticholinergic medication. For RCTs, risk ratios (RR) and 95% confidence intervals (CI) were calculated for each outcome. When all studies were included in the second analysis, we calculated the risk of acute dystonia. DATA SYNTHESIS Among RCTs (N=2032), SGAs were associated with a significantly lower risk of acute dystonia (RR 0.19, CI 0.10-0.39), akathisia (RR 0.25, CI 0.14-0.45), and anticholinergic use (RR 0.19, CI 0.09-0.43) compared with haloperidol alone. When all trials were considered (N=3425), rates of acute dystonia were higher for haloperidol alone (4.7%) than SGAs (0.6%) or haloperidol plus promethazine (0%). CONCLUSIONS Intramuscular SGAs have a significantly lower risk of acute EPS compared to haloperidol alone. However, intramuscular haloperidol plus promethazine has a risk of acute dystonia comparable to intramuscular SGAs. The decision to use SGAs should consider other factors in addition to the reduction of EPS, which can be prevented by the use of an anticholinergic agent.

Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone

“…10,37 Moreover, other studies have not consistently demonstrated the superior efficacy of SGA compared to haloperidol alone. 35,[38][39][40] Our results demonstrated that olanzapine required fewer additional medications, which was different from the results of the TREC study. 4 Some clinical trials among patients with acute agitation associated with schizophrenia have demonstrated that the IM formulations of atypical antipsychotics provide similar efficacy to those of conventional antipsychotics, albeit without the associated high incidence of extra-pyramidal side effects (EPS).…”

“…Atypical antipsychotics may be associated with prolongation of the QT interval and sudden cardiac death, and appropriate precautions should be taken when administering the drug. 17,33 Although some trials have provided limited evidence for a superior speed of onset 34,35 or degree of response, 32,34,36 other studies have demonstrated similar results between first-generation and second-generation antipsychotics (SGA). 10,37 Moreover, other studies have not consistently demonstrated the superior efficacy of SGA compared to haloperidol alone.…”

A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in agitated elderly patients with schizophrenia

“…The findings also are consistent with those of previously conducted research [Perrin et al 2012;Satterthwaite et al 2008]. …”

Intramuscular olanzapine for agitated patients: A systematic review and meta-analysis of randomized controlled trials

“…In fact, Satterthwaite and colleagues reported that SGAs-IM (olanzapine and ziprasidone) have a significantly lower risk of acute EPS compared with haloperidol alone (dystonia: RR ¼ 0.19, 7 RCTs, n ¼ 2032, akathisia: RR ¼ 0.25, 5 RCTs, n ¼ 1415, anticholinergic use: RR ¼ 0.19, 2 RCTs, n ¼ 434) (Satterthwaite et al, 2008). Moreover, although Belgamwar and Fenton did not report a comprehensive meta-analysis of ZIP-IM because of insufficient data, OLA-IM produced more responders than placebo (RR ¼ 0.49, ¼ 4, 4 RCTs, n ¼ 769) and there was no significant difference in the discontinuation rate between OLA-IM and placebo (Belgamwar and Fenton, 2005).…”