Low-dose mirtazapine: a new option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranolol-controlled trial.
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.
Research Unit, Tirat Carmel Mental Health Center, Tirat Carmel, Israel. poyurovs@tx.technion.ac.il
Michael
M
Poyurovsky
Artashes
A
Pashinian
Ronit
R
Weizman
Camil
C
Fuchs
Abraham
A
Weizman
D000328:Adult; D017109:Akathisia, Drug-Induced / Q000188:drug therapy*; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010919:Placebos; D011433:Propranolol / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D010919:Placebos; D008803:Mianserin; D011433:Propranolol; D000078785:Mirtazapine