• 
• 

Three Part Question

In [patients receiving metoclopramide], should [diphenhydramine] be [routinely administered to prevent akathisia]?

Clinical Scenario

A 52-year-old woman presents to your emergency department with a severe gastroenteritis. She is moderately dehydrated and is nauseated. While you prescribe intravenous rehydration and metoclopramide as antiemetic medication, one of your colleagues comes in and suggests that you add prophylactic diphenhydramine to prevent metoclopramide-induced akathisia. You wonder if this should be done routinely and perform a thorough search of the literature.

Search Strategy

A. No BestBETs or critical appraisal were found on this subject.

B. No Cochrane review was found on this topic.

C. The website clinicaltrials.gov was search for an ongoing trial on this subject. None was found.

D. MEDLINE (PubMed)
1) “Metoclopramide”[MeSH term] = 4424
2) “Diphenhydramine”[MeSH term] = 3708
3) “Akathisia”[MeSH term] OR “Akathisia, drug induced”[MeSH term] OR “Drug induced akathisia” [MeSH term] = 4207
4) 1 AND 2 AND 3 = 6 articles
5) 2 articles were selected after abstract review. The 4 other articles were not relevant to the subject.



E. EMBASE

1) “Metoclopramide” = 20 738
2) “Diphenhydramine” = 17 739
3) “Akathisia” = 5337
4) 1 AND 2 AND 3 = 78
5) 2 articles were selected after abstract review. No new article was found.

Search Outcome

2 studies were found to be relevant to the question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Friedman BW and al. 2009 USA	289 patients randomized, 286 patients included in the final analysis Age: 21-65	randomized, double-blind, factorial design trial	Primary outcome: development of akathisia within 60 minutes of medication administration	OR of akathisia with diphenhydramine relative to placebo 1.0 (95% CI 0.5-2)	Single-site study Difficulties related to the times of measurement of akathisia Low doses of diphenhydramine
Bulent E. and al. 2010 Turkey	920 patients received metoclopramide during the study period 684 (74%) were excluded 236 were eligible and only 225 patients were randomized, all the randomized patients completed the trial Age: 18-65	Randomized, double-blind, controlled trial	Primary outcome : development of akathisia within 60 minutes of medication administration	P = 0,20 diphenhydramine vs placebo	A majority of patients were not randomized during the study period: Are those patients comparable to the ones included in the study Reasons for non-egibility Low dose of diphenhydramine

Comment(s)

Doses of 20 or 25 mg of diphenhydramine did not prevent akathisia and should not be routinely administered in patients receiving metoclopramide. Diphenhydramine may decrease the incidence of subjective restlessness in patients receiving 20 mg of intraveinous metoclopramide. However, this result should not be given high importance because it comes from an ad hoc analysis. Other studies should be done with a higher dose of diphenhydramine to verify that those results are not quantity-related.

Clinical Bottom Line

Diphenhydramine 25mg as prophylaxis did not prevent akathisia and should not be routinely administered in patients receiving metoclopramide.

References

1. Friedman BW and al. A randomized trial of diphenhydramine as prophylaxis against metoclopramide-induced akathisia in nauseated emergency department patients. Ann Emerg Med 2009 Mar;53(3):379-85
2. Bulent E. and al. A trial of midazolam vs diphenhydramine in prophylaxis of metoclopramide-induced akathisia. Am J Emerg Med 2012 Jan;30(1):84-91