Trazodone for the treatment of neuroleptic-induced acute akathisia: a placebo-controlled, double-blind, crossover study.
BACKGROUND
Neuroleptic-induced acute akathisia (NIA) is a common and distressing extrapyramidal symptom usually resulting from the use of antipsychotic medication.Despite its high incidence (20%-45%), the underlying mechanism of NIA has not yet been adequately explained. Although treatment strategies for NIA have traditionally included anticholinergic agents, γ-aminobutyric acid agents, dopamine enhancers, and the β-adrenergic antagonists, many patients fail to respond. Trazodone (Trz) is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. In a recent pilot open-label trial, Trz demonstrated to be strongly effective in the treatment of NIA in 9 female schizophrenic patients.


OBJECTIVE
On the basis of the results of this pilot study, we investigate further the efficacy of Trz in the treatment of NIA in a double-blind, placebo (Pla)-controlled, crossover design.


METHODS
Thirteen inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia or schizo-affective disorder and with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition NIA with a severity of at least mild akathisia according to the Barnes Akathisia Rating Scale participated in the study. Patients were randomly assigned to either the order Trz-Pla or the order Pla-Trz in the treatment periods. Each period lasted for 3 consecutive days (days 1-3 and 4-6). Eight patients were treated with the Trz-Pla order (100 mg/d before bedtime); and 5, with the opposite order (Pla-Trz).


RESULTS
Statistically significant improvement in most symptoms of NIA, as measured by the Barnes Akathisia Rating Scale, was detected with Trz compared with Pla treatment.


CONCLUSIONS
The findings of this double-blind, placebo-controlled, crossover study indicate the efficacy of Trz in the management of NIA, corroborating the results of a preliminary pilot study. We suggest that Trz's property of serotonin 2A postsynaptic receptor antagonism may be its principal mechanism for the improvement of NIA.
Stryjer
Rafael
R
Beer Yaakov-Ness Ziona Mental Health Center, Beer Yaakov, Israel. Stryjer@gmail.com
Rosenzcwaig
Silvio
S
Bar
Faina
F
Ulman
Ann Marie
AM
Weizman
Abraham
A
Spivak
Baruch
B
D000328:Adult; D017109:Akathisia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014196:Trazodone / Q000627:therapeutic use*; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D017367:Selective Serotonin Reuptake Inhibitors; D014196:Trazodone