Low-dose mirtazapine: a new option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranolol-controlled trial.

Abstract

BACKGROUND:

Preliminary evidence indicates a beneficial effect of serotonin 2A (5-HT(2A)) receptor antagonists in antipsychotic-induced akathisia (AIA). We investigated the antiakathisia effect, safety, and tolerability of low-dose mirtazapine, an agent with marked 5-HT(2A) antagonism.

METHODS:

In a 7-day double-blind trial, 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were randomly assigned to mirtazapine (n = 30; 15 mg), propranolol (n = 30; 80 mg), or placebo (n = 30). Primary outcome measures were between-group differences in Barnes Akathisia Scale (BAS) global scores and in the proportion of responders (reduction of > or = 2 points on BAS). Analysis was by intention to treat.

RESULTS:

Twenty-four patients (26.6%) who were assigned treatment did not complete the study (7 mirtazapine, 8 propranolol, 9 placebo), due to lack of response (n = 19) and adverse events (n = 5). Both mirtazapine and propranolol significantly reduced AIA severity (BAS: -34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023, respectively). Thirteen (43.3%) mirtazapine and 9 (30.0%) propranolol-treated patients versus 2 (6.7%) placebo-treated patients responded (the corresponding odds ratios 10.7 [95% confidence interval (CI), 2.1-53.3] and 6.0 [95% CI, 1.1-30.7]). Five (16.7%) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups (p = .0195 for both) prematurely discontinued the study due to clinically significant hypotension or bradycardia.

CONCLUSIONS:

The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol, the current first-line treatment for AIA, position mirtazapine as a favorable candidate for the treatment of acute AIA and may improve current therapeutic practices.

• Authors: Michael Poyurovsky, Artashes Pashinian, Ronit Weizman, Camil Fuchs, Abraham Weizman
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 59 Issue 11 Pg. 1071-7 (Jun 01 2006) ISSN: 0006-3223 [Print] United States
• PMID: 16497273 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Anxiety Agents
• Antidepressive Agents, Tricyclic
• Antipsychotic Agents
• Placebos
• Mianserin
• Propranolol
• Mirtazapine

Topics

• Adult
• Akathisia, Drug-Induced (drug therapy)
• Analysis of Variance
• Anti-Anxiety Agents (administration & dosage)
• Antidepressive Agents, Tricyclic (adverse effects, therapeutic use)
• Antipsychotic Agents (adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Mental Disorders (drug therapy)
• Mianserin (adverse effects, analogs & derivatives, therapeutic use)
• Middle Aged
• Mirtazapine
• Placebos
• Propranolol (administration & dosage)
• Prospective Studies
• Treatment Outcome