Dr. Boazak is a PGY-3 psychiatry resident, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. Dr. Schwartz is Associate Professor of Psychiatry and Behavioral Sciences, Director, Psychiatry Residency Education, and Director, Consultation-Liaison Service at Grady Memorial Hospital, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. Dr. Young is Associate Professor of Psychiatry and Behavioral Sciences, Division Chief, Consultation-Liaison Services at Emory Healthcare, and Director, Psychosomatic Medicine Fellowship, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. Dr. F. Boyer is Assistant Professor of Psychiatry and Behavioral Sciences, and Emergency Department Psychiatry Attending Physician, Grady Memorial Hospital, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. Dr. A. Boyer is a PGY-2 psychiatry resident, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. Dr. Greenspan is Assistant Professor of Psychiatry and Behavioral Sciences, and Consultation-Liaison Psychiatry Attending Physician, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
Disclosures The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Diphenhydramine, a first-generation antihistamine with antimuscarinic properties, has been studied for its efficacy in treating metoclopramide-induced akathisia in the emergency setting.30 There are several reports on the efficacy of this agent, including a large randomized study involving 281 patients that found it effective for preventing metoclopramide-induced akathisia.30 Another head-to-head trial reported the benefit of the diphenhydramine vs midazolam.31 Both agents were efficacious for treating akathisia; however, midazolam had a more rapid onset. Despite these positive reports, double-blind trials have found diphenhydramine to be ineffective,17 which suggests propranolol should be the first-line agent, assuming it is not contraindicated.
Benzodiazepines have also been found to be efficacious for treating akathisia. A 1999 Cochrane Review included 2 randomized controlled trials that assessed the efficacy of clonazepam vs placebo for treating akathisia.32 It found evidence of benefit for clonazepam, but questioned the generalizability of these studies.32 This review did not include several other reports that suggest benefits of other benzodiazepines for treating akathisia. Other than clonazepam, reports suggest benefit for diazepam, lorazepam, and midazolam for treating akathisia.17 Despite this evidence and the findings from this Cochrane Review, the literature does not appear to point to clear dominance of these agents over propranolol. Given the safety concerns when prescribing benzodiazepines, it would be prudent to utilize propranolol as a first-line agent for treating akathisia.
Finally, other reports have cited treatment efficacy linked to serotonin 2A receptor (5-HT2A) antagonists (mianserin, mirtazapine, and trazodone), clonidine, gabapentin, amantadine, and other agents.17 If treatment with propranolol is ineffective or contraindicated, clinicians should utilize their clinical judgement in deciding on the use of one agent over another.
OUTCOME Complete resolution
Haloperidol is discontinued and diphenhydramine, 50 mg IV, is administered. (Diphenhydramine was used instead of propranolol due to immediacy of availability.) Most of Mr. B’s signs and symptoms resolve on a repeat interview 3 hours later. He receives another dose of diphenhydramine, 25 mg IV, for persistent mild irritability. By Day 2 of follow-up, his symptoms completely resolve as measured on the Barnes Akathisia Scale33 (Table 2).
