266 The Relative Frequency of Akathisia from Parenteral Antidopaminergics: A Systematic Review and Meta-Analysis

Abstract

Parenteral antidopaminergic medications are frequently administered in the acute setting for nausea, vomiting, and headache. Extrapyramidal symptoms, which are extremely distressing to patients, may develop in the near term after parenteral administration of these medications. In this study, we performed a systematic review and meta-analysis to determine how frequently these symptoms arise in the aftermath of antidopaminergic medication use. PubMed, EmBase, Web of Science, and the Cochrane Library were searched in January 2017 for randomized controlled trials and prospective cohort studies in which a parenteral antidopaminergic drug was administered for headache, migraine, nausea, or vomiting. Articles were selected based on independent determinations of two investigators. Data was abstracted into a standardized form. Evidence was graded using the Cochrane risk of bias tool. Weighted mean frequencies were calculated for each type of extrapyramidal symptom. Meta-analysis, using random effects models, was performed, when appropriate—results are reported as OR (95% CI). A total of 36 studies with 4643 participants were included (median number of participants=98). Most were set in the emergency department. Baseline demographics were generally comparable amongst the included studies. In general, the quality of the studies was good with low risk of bias. Akathisia was the only consistently reported extrapyramidal side effect. The overall rate of acute drug-induced akathisia was 16.3% (642/3942). Prochlorperazine induced the highest rates of akathisia at 27.3% (95% CI [24.8%, 30.0%]), followed by haloperidol at 19.6% (95% CI [10.8%, 32.7%]), droperidol at 13.1% (95% CI [10.4%, 16.4%]), promethazine at 11.6% (95% CI [6.4, 19.7%]), and metoclopramide at 11.0% (95% CI [9.5%, 12.2%]). Overall, dystonic reactions occurred in 2.9% (6/206) of antidopaminergic administrations. For metoclopramide the frequency of dystonic reactions was 3.9% (95% CI [1.2%, 10.0%]) and for droperidol 1.9% (95% CI [0.1%, 7.2%]). There were no reported cases of tardive dyskinesia. Metoclopramide was more likely to cause akathisia than non-antidopaminergic standard therapy (OR 15.5 95% CI [2.1, 117.1]). Similarly, prochlorperazine was more likely to cause akathisia than non-antidopaminergic therapy (OR 4.7 95% CI [1.2, 18.8]). Slow infusion was less likely to cause akathisia than bolus administration for both metoclopramide (OR 3.0 95% CI [2.0, 4.6]) and prochlorperazine (OR 1.3 95% CI [0.8, 2.2]). Antidopaminergics other than metoclopramide were more likely to cause akathisia than metoclopramide itself (OR 2.2 95% CI [1.0, 5.1]), while antidopaminergics other than prochlorperazine were less likely than prochlorperazine to cause akathisia (OR 0.6 95% CI [0.4, 1.0]). Overall, akathisia occurs in 16.3% of patients administered a parenteral antidopaminergic. Other extrapyramidal side effects were much less common. Akathisia is much more common after administration of antidopaminergics than when non-antidopaminergic therapy is given. Metoclopramide is less likely to cause akathisia than other antidopaminergics while prochlorperazine is more likely to cause akathisia.