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Electroconvulsive Therapy Augmentation in Clozapine-Resistant Schizophrenia: A Prospective, Randomized Study
Georgios Petrides, M.D.; Chitra Malur, M.D.; Raphael J. Braga, M.D.; Samuel H. Bailine, M.D.; Nina R. Schooler, Ph.D.; Anil K. Malhotra, M.D.; John M. Kane, M.D.; Sohag Sanghani, M.D.; Terry E. Goldberg, Ph.D.; Majnu John, Ph.D.; Alan Mendelowitz, M.D.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.13060787
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Dr. Petrides has received research support from Amgen, Astra Zeneca, Corcept, Eli Lilly, NIMH, Proteus, St. Jude Medical, and Sunovion, and he has served on an advisory panel for Corcept. Dr. Schooler has received honorarium from Lundbeck, advisory board honoraria from Amgen, Eli Lilly, EnVivo, Janssen Psychiatry, Roche, and Sunovion, and research grant support from Genentech, Neurocrine, and Otsuka. Dr. Malhotra has served as a consultant to Genomind. Dr. Kane has served as a consultant to or on the advisory board or speaker’s bureau of Alkermes, Bristol-Myers Squibb, Eli Lilly, Forest, FORUM, Genentech, H. Lundbeck, Intracellular Therapeutics, Janssen, Johnson and Johnson, Otsuka, Reviva, and Roche, and he is a shareholder with MedAvante. All other authors report no financial relationships with commercial interests.

Supported by an RO1 grant from NIMH to Dr. Petrides (MH-603930).

From the Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, N.Y., and The Feinstein Institute for Medical Research, Manhasset, N.Y.

Address correspondence to Dr. Petrides (Petrides@lij.edu).

Copyright © 2014 by the American Psychiatric Association

Received June 17, 2013; Revised February 25, 2014; Revised May 05, 2014; Accepted June 06, 2014.

Abstract

Objective  Up to 70% of patients with treatment-resistant schizophrenia do not respond to clozapine. Pharmacological augmentation to clozapine has been studied with unimpressive results. The authors examined the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia.

Method  In a randomized single-blind 8-week study, patients with clozapine-resistant schizophrenia were assigned to treatment as usual (clozapine group) or a course of bilateral ECT plus clozapine (ECT plus clozapine group). Nonresponders from the clozapine group received an 8-week open trial of ECT (crossover phase). ECT was performed three times per week for the first 4 weeks and twice weekly for the last 4 weeks. Clozapine dosages remained constant. Response was defined as ≥40% reduction in symptoms based on the psychotic symptom subscale of the Brief Psychiatric Rating Scale, a Clinical Global Impressions (CGI)-severity rating <3, and a CGI-improvement rating ≤2.

Results  The intent-to-treat sample included 39 participants (ECT plus clozapine group, N=20; clozapine group, N=19). All 19 patients from the clozapine group received ECT in the crossover phase. Fifty percent of the ECT plus clozapine patients met response criterion. None of the patients in the clozapine group met response criterion. In the crossover phase, response was 47%. There were no discernible differences between groups on global cognition. Two patients required the postponement of an ECT session because of mild confusion.

Conclusions  The augmentation of clozapine with ECT is a safe and effective treatment option. Further research is required to determine the persistence of the improvement and the potential need for maintenance treatments.

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FIGURE 1. CONSORT Diagram for Patients With Clozapine-Resistant Schizophrenia

FIGURE 2. Changes in Brief Psychiatric Rating Scale (BPRS) Psychosis Subscale Results Over Timea

a The graph shows the changes in psychosis symptoms in the clozapine group (blue line; phase 1) and the ECT plus clozapine group (red line; phase 1). Treatment-by-time interaction: F=5.38, df=8, 238, p<0.0001. The degrees of freedom for mixed-models analysis were obtained using Satterthwaite’s method. Error bars represent standard deviations.

FIGURE 3. Changes in Clinical Global Impressions (CGI)-Severity Scale Ratings Over Timea

a The graph shows the changes in symptom severity in the clozapine group (blue line; phase 1) and the ECT plus clozapine group (red line; phase 1). Treatment-by-time interaction: F=5.00, df=8, 238, p<0.0001. The degrees of freedom for mixed-models analysis were obtained using Satterthwaite’s method. Error bars represent standard deviations.

Anchor for Jump
TABLE 1.ECT Dosing Algorithm
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TABLE 2.Demographic and Clinical Characteristics of Patients With Clozapine-Resistant Schizophrenia
Table Footer Note

a The p value was calculated using Wilcoxon rank-sum test (p=0.03; W=269).

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