February 2016 - Electroconvulsive Therapy Augmentation in Clozapine-Resistant Schizophrenia: A Prospective, Randomized Study

Association of Medicine & Psychiatry
On-line Journal Club
Scholarship & Research Committee
Editors: Glen L. Xiong, MD; Kelly Clearo, MD
Resident Editor: Sabrina Silva-McKinzie, MD
February, 2016

[ If you would like to submit a review, please contact glen.xiong@ucdmc.ucdavis.edu ]

Electroconvulsive Therapy Augmentation in Clozapine-Resistant Schizophrenia: A Prospective, Randomized Study

Reviewed by Gregory Brown, PGY-5, Internal Medicine-Psychiatry, Duke University

Question:
In treatment-resistant schizophrenia, does ECT as augmentation to clozapine lead to a greater response rate?

Methods:
The study was a single-center, randomized, single-blinded, 8-week controlled study. Patients had to have failed at least 2 antipsychotic trials of 400 mg of chlorpromazine equivalents for at least 4 weeks and had persistent psychotic symptoms after at least 12 weeks on clozapine at a blood level ≥ 350 ng/mL. Patients were randomized to treatment as usual (clozapine) or bilateral ECT (in addition to clozapine). Non-responders from the treatment as usual group received an open 8-week trial of ECT. Response was defined as ≥ 40% improvement on Brief Psychiatric Rating Scale psychotic symptom subscale, CGI-severity rating of < 3, and CGI-improvement rating of ≤ 2. Raters were blinded to clinical assignment. ECT was conducted with bilateral lead placement, administered 3 times per week for 4 weeks then 2 times per week for next 4 weeks. If patients met remission criteria before 8 weeks, ECT was continued once weekly through the remainder of the 8 weeks.

Main Results:
10 of 20 patients in the ECT augmentation group and 0 of 19 patients in the clozapine-alone group met response criteria at the end of 8 weeks. At a lower response criterion of 20% reduction in the psychotic symptom subscale, still 0 patients in the clozapine-alone group would meet response criteria. At a higher response criterion of 50%, 60% or 70%, still 9, 6, or 3 patients respectively in the ECT augmentation group would have met response. In the crossover phase, 9 of 19 patients met response criteria as well.

Comments:
This study of 39 patients with persistent psychotic symptoms on clozapine demonstrated the effectiveness of bilateral ECT in augmentation to target psychotic symptoms of schizophrenia. Prior open label studies have demonstrated effectiveness for the addition of ECT to clozapine-resistant patients with schizophrenia or schizoaffective disorder. This is the first randomized study for ECT augmentation in this patient population. In sum, the study demonstrated a 50% response rate for a 40% reduction in symptoms based on the BPRS psychotic symptom subscale. The study excluded patients with schizoaffective disorder, bipolar disorder, a current affective episode or a score > 18 on the 24-itm Hamilton Depression Rating Scale to minimize confounding given the known effectiveness for ECT in treating affective disorders. It further sought to enhance rating objectivity by having an independent masked rater also review the baseline and final BPRS rating interviews. The tapes were edited to remove evidence of treatment groups. The average score between the two ratings was used in data analysis. Post hoc analysis showed statistically significant differences in psychotic symptoms between groups by 3 weeks. Further studies would be needed to demonstrate if effects persisted after ECT concluded, if maintenance ECT treatments led to further persistence of response, if response could also be achieved with unilateral standard or brief-pulse ECT, and with all of the above, the optimal ECT treatment schedule. Given the limited augmentation strategies in schizophrenia for patients who have failed or had incomplete response to an adequate trial of clozapine, ECT should be considered as a standard of care augmentation option.