Regarding antipsychotics, risk factors for akathisia include drug potency, dose, and rapidity of titration.20 All of these factors were relevant in our patient’s case. Risk across antipsychotic classes is not well understood; few head-to-head studies have comparing antipsychotics. However, general estimates suggest a 15% to 40% prevalence in patients exposed to typical antipsychotics, as compared with 0% to 12% exposed to atypical antipsychotics.8 The literature-reported difference in risk, as well as our patient’s comparative difference in exposure to large doses of haloperidol (50 mg) as compared with 1 dose of olanzapine (5 mg), led us to believe his akathisia developed primarily due to his exposure to haloperidol. Conclusively linking his symptoms to haloperidol alone, however, is not possible, and we did consider that olanzapine may in fact have had some effect in worsening Mr. B’s akathisia.
The authors’ observations
While there are reports on the efficacy of various agents in the treatment of akathisia, the most commonly evaluated agents are propranolol, anticholinergics, and benzodiazepines.17, 21
Propranolol is a nonselective beta-adrenergic blocker with numerous indications.17 Despite a 2004 Cochrane Review indicating that there is no evidence in support of central acting beta-blockers for treating akathisia,22 propranolol is not yet recognized as an appropriate treatment.17 The reason for this discrepancy is likely due to the Cochrane Review’s restrictive inclusion criteria, which prevented the analysis of much of the literature.22 In fact, several reports cite evidence for the treatment efficacy of propranolol17 and, to date, some reports continue to advocate for its use as a first-line agent in the treatment of akathisia. Admittedly, besides the Cochrane Review,22 other reports have found propranolol to be ineffective for treating akathisia,23 although these tend to be limited by their population size and generalizability.
As with propranolol, a 2006 Cochrane Review found “no reliable evidence to support or refute” using anticholinergic agents in the treatment of akathisia.24 We suspect that the review’s findings were likely secondary to its strict inclusion criteria.24 In fact, several reports support using anticholinergic agents for treating akathisia.25 Here we focus on benztropine and diphenhydramine.
Two reviews—Blaisdell26 (1994) and Poyurovsky27 (2010)—suggest modest benefits from benztropine, primarily in patients with comorbid Parkinson’s disease. Despite these benefits, head-to-head trials seem to either point to the superiority of propranolol or to no difference between these agents for treating akathisia.28,29 In a review, we only found 1 trial demonstrating benztropine’s superiority over propranolol,23 but this trial was constrained by its small population (6 patients). Therefore, the data suggest that, when indicated, clinicians should lean towards using propranolol for treating akathisia.
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