Abstract
Background
Neuroleptics are commonly prescribed drugs to treat acute conditions (e.g., migraines)
in the emergency department, but can cause serious adverse effects. Using diphenhydramine
to prevent these adverse effects is very common but remains controversial.
Objective
We performed a systematic review to determine whether prophylactic administration
of diphenhydramine reduces the incidence of neuroleptic adverse effects in patients
with acute conditions.
Methods
Medline, Embase, Cochrane, PsycInfo, and Web of Science were searched for randomized
controlled trials evaluating any neuroleptic with diphenhydramine vs. the same neuroleptic
with any inactive agent. Primary outcome was incidence of any extrapyramidal adverse
effect. Secondary outcomes were akathisia, rescue medication, subjective restlessness,
neuroleptic malignant syndrome, and sedation. Independent reviewers scanned identified
citations, extracted data, and assessed risk of bias. Meta-analysis was performed
using random effect models.
Results
Of 1566 identified citations, nine studies (n = 1648 patients) met eligibility criteria.
Four studies were specifically designed to compare the incidence of neuroleptic adverse
effects with and without co-administration of diphenhydramine. Four studies were at
high risk of bias. In primary analysis, diphenhydramine had no effect on the incidence
of extrapyramidal symptoms (7 studies, n = 1393, risk ratio [RR] 0.75; 95% confidence
interval [CI] 0.44–1.31) or akathisia (5 studies, n = 1094; RR 0.78; 95% CI 0.33–1.82)
or any of the secondary outcomes. In subgroup analysis, diphenhydramine was associated
with a significant decrease in extrapyramidal adverse effects compared with placebo
(4 studies, n = 705; RR 0.61; 95% CI 0.41–0.90). Dosage analysis yielded no further
information.
Conclusions
When compared with placebo, diphenhydramine was associated with a significant reduction
of extrapyramidal adverse effects. Overall quality of evidence is low. Further studies
are warranted.
Keywords
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Article info
Publication history
Published online: October 29, 2020
Accepted:
September 12,
2020
Received in revised form:
August 12,
2020
Received:
May 22,
2020
Identification
Copyright
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