Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis

The primary aim of this systematic review and meta-analysis was to assess the proportion of patients with Treatment Resistant Schizophrenia (TRS) that respond to ECT augmentation of clozapine (C + ECT). We searched major electronic databases from 1980 to July 2015. We conducted a random effects meta-analysis reporting the proportion of responders to C + ECT in RCTs and open-label trials. Five clinical trials met our eligibility criteria, allowing us to pool data from 71 people with TRS who underwent C+ ECT across 4 open label trials (n = 32) and 1 RCT (n = 39). The overall pooled proportion of response to C + ECT was 54%, (95% CI: 21.8-83.6%) with some heterogeneity evident (I-2 = 69%). With data from retrospective chart reviews, case series and case reports, 192 people treated with C + ECT were included. All studies together demonstrated an overall response to C+ ECT of 66% (95% CI: 57.5-74.3%) (83 out of 126 patients responded to C+ ECT). The mean number of ECT treatments used to augment clozapine was 11.3. 32% of cases (20 out of 62 patients) with follow up data (range of follow up: 3-468 weeks) relapsed following cessation of ECT. Adverse events were reported in 14% of identified cases (24 out of 166 patients). There is a paucity of controlled studies in the literature, with only one single blinded randomised controlled study located, and the predominance of open label trials used in the meta-analysis is a limitation. The data suggests that ECT may be an effective and safe clozapine augmentation strategy in TRS. A higher number of ECT treatments may be required than is standard for other clinical indications. Further research is needed before ECT can be included in standard TRS treatment algorithms. (C) 2016 Elsevier B. V. All rights reserved.