Switching From Clozapine to Zotepine in Patients With Schizophrenia A 12-Week Prospective, Randomized, Rater Blind, and Parallel Study
Resource
J. Clin. Psychopharmacol., 33(2), 211-214
Journal
Journal of Clinical Psychopharmacology
Pages
211-214
Date Issued
2013
Date
2013
Author(s)
Lin, Chao-Cheng
Chiu, Hsien-Jane
Chen, Jen-Yeu
Liou, Ying-Jay
Wang, Ying-Chieh
Chen, Tzu-Ting
Bai, Ya-Mei
Abstract
Clozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, but many adverse effects are noted. Clinicians usually hesitate to switch from clozapine to other antipsychotics because of the risk of a re-emergence or worsening of the psychosis, although empirical studies are very limited. Zotepine, an atypical antipsychotic with a pharmacologic profile similar to clozapine, was found to be an effective treatment for patients with treatment-resistant schizophrenia in Japan. This 12-week study is the first prospective, randomized, and rater-blind study to investigate the efficacy and tolerability of switching from clozapine to zotepine. Fifty-nine patients with schizophrenia, who had taken clozapine for at least 6 months with a Clinical Global Impression Severity score of at least 3, were randomly allocated to the zotepine and the clozapine groups. At the end of the study, 52 patients (88%) had completed the trial. The 7 withdrawal cases were all in the zotepine group. The final mean (SD) dose of zotepine and clozapine was 397.1 (75.7) versus 377.1 (62.5) mg/d, respectively. Patients in the zotepine group showed a significant increase in the Brief Psychiatric Rating Scale [mean (SD), 4.7 (8.7) vs -1.3 (6.3); P = 0.005], more general adverse effects as revealed by the Udvalg for Kliniske Undersogelser Rating Scale [mean (SD), 1.74 (3.9) vs -0.2 (2.8); P = 0.039], more extrapyramidal adverse effects as demonstrated by the Simpson and Angus Scale [mean (SD), 1.29 (3.5) vs 0.17 (2.1); P = 0.022], an increased use of propranolol (37.1% vs 0%, P < 0.0001) and anticholinergics (25.7% vs 0%, P = 0.008), and an increased level of prolactin (29.6 vs -3.8 ng/ mL, P < 0.0005), compared with the clozapine group. The results suggested that switching from clozapine to zotepine treatment should be done with caution.
Subjects
clozapine
zotepine
antipsychotics
schizophrenia
switch
SDGs
Other Subjects
cholinergic receptor blocking agent; clozapine; prolactin; propranolol; zotepine; adult; aged; article; Brief Psychiatric Rating Scale; Clinical Global Impression scale; controlled study; drug efficacy; drug substitution; drug tolerability; drug withdrawal; human; Kliniske Undersogelser Rating Scale; major clinical study; priority journal; prospective study; randomized controlled trial; rating scale; schizophrenia; Simpson-Angus Scale; treatment duration; Adult; Aged; Antipsychotic Agents; Clozapine; Dibenzothiepins; Dose-Response Relationship, Drug; Drug Substitution; Humans; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Schizophrenia; Severity of Illness Index; Single-Blind Method; Treatment Outcome; Young Adult
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