Objectives To determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect.
Methods Systematic searches of all published studies through March 2017 were identified from PubMed, Cochrane library, Embase, Web of Science and Scopus. Only randomised controlled trials of patients receiving dopamine D2 antagonist antiemetic therapy for acute migraine in which an anticholinergic or placebo was compared were included. Pooled ORs were calculated for incidence of extrapyramidal symptoms and sedation.
Results Four placebo-controlled randomised controlled trials consisting of 737 patients met the inclusion criteria for our meta-analysis. The effect of diphenhydramine differed depending on the method of administration of the antiemetic. When the antiemetic was delivered as a 2 min antiemetic bolus, the odds of extrapyramidal symptoms were significantly reduced in the diphenhydramine group compared with placebo (OR 0.42; 95% CI 0.22 to 0.81; P=0.01). However, when the antiemetic was given as a 15 min infusion, there was no significant difference in extrapyramidal symptoms with or without diphenhydramine (OR 1.06; 95% CI 0.58 to 1.91; P=0.85). The lowest incidence of extrapyramidal symptoms was observed in patients receiving a 15 min antiemetic infusion without diphenhydramine prophylaxis (9.8%). In two trials including 351 patients that dichotomously reported sedation scales, diphenhydramine had significantly higher rates of sedation (31.6%vs19.2%, OR 2.01, 95% CI 1.21 to 3.33; P=0.007).
Conclusion Prophylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis.
- clincial management
- emergency care system
- admission avoidance
- emergency care systems
- emergency departments
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Contributors RSD performed the conception and background of research, designed and performed the analysis and interpretation of data, drafted the manuscript and created all figures. CM performed the design, analysis and interpretation of data, revised the manuscript critically for intellectual content and gave final approval of the manuscript. EO performed the analysis and interpretation of data, revised the manuscript critically for intellectual content, validated the bias methods performed and gave final approval of the manuscript. SD performed background search and drafted the introduction section, performed the analysis and interpretation of data, revised the manuscript critically for intellectual content and gave final approval of the manuscript. AS performed background searches, partially drafted the introduction section, helped with bias assessment and revised the manuscript critically for intellectual content. JM performed background searches, helped with bias assessment and revised the manuscript critically for intellectual content. AS helped with formulating search strategies, performed background searches and revised the manuscript critically for intellectual content. AD performed the conception, design and interpretation of data, performed the study selection and bias assessment, revised the manuscript critically for intellectual content and gave final approval of the manuscript.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.