title: Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis.
abstract: 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: 3-468weeks) 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.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom; National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, United Kingdom. Electronic address: john.lally@kcl.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Lally
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Tully
authors.affiliation: Clinical Academic Group with South London and Maudsley (SLaM) NHS Foundation Trust, United Kingdom; Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, United Kingdom.
authors.forename: Dene
authors.initials: D
authors.lastname: Robertson
authors.affiliation: Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, United Kingdom; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, United Kingdom.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom; National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, United Kingdom; Institute of Psychiatry, Psychology and Neuroscience, Kings College London, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Gaughran
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom; National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, United Kingdom.
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D004565:Electroconvulsive Therapy / Q000379:methods*; D006801:Humans; D012559:Schizophrenia / Q000628:therapy*
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Clozapine; ECT; Psychosis; Schizoaffective disorder; Treatment resistant schizophrenia