Electroconvulsive therapy (ECT) for depressive illness, schizophrenia, catatonia and mania Report commissioned by: NHS R&D HTA Programme On behalf of: The National Institute for Clinical Excellence Produced by: The School of Health and Related Research (ScHARR), University of Sheffield Nuffield Institute for Health, University of Leeds Authors: Ms Joanne Greenhalgh, Research Officer, Nuffield Institute for Health Mr Chris Knight, Senior Operational Research Analyst, ScHARR Dr D Hind, Research Associate, ScHARR Ms C Beverley, Systematic Reviews Information Officer, ScHARR Mr. Stephen Walters, Medical Statistician, ScHARR Correspondence to: Ms Joanne Greenhalgh, Nuffield Institute for Health, University of Leeds, 71-75 Clarendon Road, Leeds, LS2 9PL Date completed: Expiry Date: Expiry date 1 PUBLICATION INFORMATION Referencing Information. ABOUT THE TRENT INSTITUTE Trent Institute for Health Services Research is a collaborative venture between the Universities of Leicester, Nottingham and Sheffield, with support from NHS Executive Trent. Members of staff in the Sheffield Unit, based in the School of Health and Related Research (ScHARR), have been engaged in reviewing the effectiveness and cost-effectiveness of health care interventions in support of the National Institute for Clinical Excellence. In order to share expertise on this work, we have set up a wider collaboration, InterTASC, with units in other regions. These are The Wessex Institute for Health Research and Development, Southampton University, The University of Birmingham Department of Public Health and Epidemiology, The Centre for Reviews and Dissemination, University of York. CONTRIBUTIONS OF AUTHORS Joanne Greenhalgh and Daniel Hind carried out the review of clinical effectiveness. Chris Knight carried out the review of cost effectiveness. Catherine Beverley carried out the electronic searches. Stephen Walters provided statistical advice. Joanne Greenhalgh is responsible for the report as lead author. CONFLICTS OF INTEREST Source of funding This report was commissioned by the NHS R&D HTA programme. Relationship of reviewer(s) with sponsor None of the authors has any financial interests in the companies producing or marketing ECT machines. ACKNOWLEDGEMENTS Paul Birkett, Clinical lecturer in Psychiatry, Charlie Brooker, Professor of Psychiatry, both in Sheffield and Simon Gilbody, Lecturer in Clinical Psychiatry and David Cottrell, Professor of child and adolescent psychiatry, provided clinical advice and guidance. Clive Adams gave clinical and methodological guidance and provided the group with the raw data from the recently updated Cochrane Group Review of ECT in schizophrenia. The UK ECT group provided the group with a copy of their report prior to publication. Suzy Paisley provided guidance on literature searching, proof reading, and guidance in the production of the report. Suzy Paisley, Ron Akehurst and Jim Chillcott (ScHARR), Dr. Niall Moore, Consultant Psychiatrist, Bristol, Dr. Douglas Gee, Consultant Psychiatrist, Humberside, Sarah Garner and Tina Eberstein (NICE) provided comments on the initial draft of the report. All responsibility for the contents of the report remains with the authors. 2 CONTENTS List of Abbreviations 6 Summary 8 1 Aim of the Review 11 2 Background 12 2.1 Description of the underlying health problem 12 2.1.1 Schizophrenia 12 2.1.2 Depression 12 2.1.3 Mania 13 2.1.4 Catatonia 13 2.1.5 Epidemiology 13 2.2 Current service provision 14 2.2.1 Description of intervention 14 2.2.2 Patient populations 14 2.2.3 Stimulus parameters and administration of ECT 16 2.2.4 Information and consent 17 2.2.5 Current service provision in England and Wales 18 2.2.6 Training and the quality of ECT services 19 2.2.7 Current mental health policy in England and Wales 20 3 Effectiveness 20 3.1 Methods for reviewing effectiveness 20 3.1.1 Search strategy: clinical effectiveness 20 3.1.2 Search strategy: cost effectiveness 21 3.1.3 Inclusion and exclusion criteria 21 3.1.4 Quality assessment and data extraction strategy 22 3.2 Results 24 3.2.1 Quantity of research available 24 3.2.2 Quality of studies identified 30 3.2.3 Depression 36 3.2.4 Mania 46 3.2.5 Schizophrenia 46 3.2.6 Specific outcomes not covered by the randomised evidence 51 3.2.7 The efficacy of ECT in specific subgroups 53 3.2.8 Conclusions and discussion 59 4 Economic Analysis 60 4.1 Introduction 60 4.1.1 Search Strategy 60 4.1.2 Overview of Economic Literature Review and Economic 60 Evidence 4.2 Economic Modelling of ECT for depressive illness, 60 schizophrenia, catatonia and mania 4.2.1 Modelling Depressive Illness 60 4.2.2 Introduction 60 4.2.3 Methodology 61 4.2.4 Assumptions and Probabilities 63 4.2.5 Results 73 4.2.6 Sensitivity Analysis 78 4.2.7 Conclusions 81 4.2.8 Further Areas of Research 81 4.3 Modelling Schizophrenia 81 4.3.1 Introduction 81 3 4.3.2 Methodology 82 4.3.3 Results 86 4.3.4 Sensitivity Analysis 86 4.3.5 Conclusions and Recommendations 87 5 Implications for OTHER Parties 88 6 Factors Relevant to the NHS 88 7 Discussion 89 7.1 Summary of Main results and discussion 89 7.1.1 Depressive illness 89 7.1.2 Schizophrenia 92 7.1.3 Mania 94 7.1.4 Catatonia 94 7.1.5 Children and adolescents 94 7.1.6 Older people 95 7.1.7 Pregnancy 95 7.1.8 Long term efficacy of ECT 95 7.1.9 Adverse events: mortality 95 7.1.10 Adverse events: cognitive functioning 95 7.1.11 Adverse effects: brain damage 95 7.1.12 Patient acceptability in choice 95 7.1.13 Patient information and consent 95 7.2 Assumptions, limitations and uncertainties 96 7.2.1 Comprehensiveness of the review 96 7.3 Need for further research 96 8 Conclusions 98 8.1 Clinical effectivess 98 8.2 Cost effectiveness 98 APPENDICES Appendix 1 Electronic Bibliographic Databases Searched 100 Appendix 2 Other Sources Consulted 101 Appendix 3 Search Strategies Used in the Major Electronic Bibliographic 102 Databases Appendix 4 Methodological Search Filters Used in Ovid Medline 112 Appendix 5: Descriptions of included studies 112 Appendix 6 TABLES Table 1: Overlap between NICE scope and the 6 systematic review 26 identified Table 2: NICE scope and sources of evidence used 27 Table 3: Summary of efficacy of ECT in children and adolescents from 55 Rey and Walters(1) Table 4: Clinical Success for Pharmacological and ECT Interventions in 66 Major Depression Table 5: Failure to complete Treatment Rates 66 Table 6: Maintenance Therapy Relapse Assumptions 67 Table 7: Cost of Acute Treatment for Major Depression 68 4 Table 8: Cost of Continuation/Maintenance Therapy for Major 69 Depression Table 9: QoL Utility assumptions 71 Table 10: Summary of Model Scenarios 72 Table 11: Treatment Scenario Results 73 Table 12: Analysis of the Incremental Net Benefit 75 Table 13: Scenario Results based on Revicki QALYs 79 Table 14: ICER Analysis using scenarios based on Revicki QALYs 79 Table 15: Scenario Results based on reduction of 25% in ECT Cost 80 Table 16: ICER Analysis using scenarios based on a 25% reduction in 80 ECT Cost Table 17: Event Probabilities 84 Table 18: Quality of Life Utility Estimates 85 Table 19: Dosage and Cost Estimates 85 Table 20: Cost-Effectiveness Results 86 Table 21: Threshold Analysis for Treatment-Resistant Schizophrenia 86 Table A 5.1 Systematic reviews of the clinical effectiveness and safety of 115 ECT in depression, schizophrenia and mania Table A5.2 Systematic reviews of non randomised evidence: patient 117 acceptability and choice Table A5.3 Systematic reviews of non-randomised evidence: children and 118 adolescents Table A5.4 Systematic reviews of non-randomised evidence: Catatonia 119 Table A5.5 Systematic review of non randomised evidence: Use of ECT in 120 pregnancy Table A5.6 Randomised controlled trials comparing real vs sham ECT: 121 depression Table A5.7 Randomised controlled trials comparing ECT with 128 phamacotherapy: depression Table A5.8 Randomised controlled trials of ECT compared with rTMS in 142 depression Table A5.9 Randomised controlled trials of ECT plus pharmacotherapy vs 143 ECT plus placebo/pharmacotherapy only 2: Depression Table A5.10 Randomised controlled trials comparing ECT+ 148 pharmacotherapy/placebo + continuation pharmacotherapy: Depression Table A5.11 Randomised controlled trials comparing continuation 152 pharmacotherapy only Table A5.12 RCTS of patient information videos 158 Table A5.13 Non randomised evidence of efficacy of ECT in older people 156 with depression Table A5.14 Non randomised evidence: Children and adolescents 156 Table A5.15 Non randomised evidence: Catatonia 158 Table A5.16 Non randomised evidence: pregnancy 159 160 FIGURES Figure 1 Decision model - depressive illness 62 Figure 2 Treatment success rate 65 Figure 3 Cost-effective acceptability curves 77 5 Figure 4 Cost-effective acceptability curves 78 Figure 5 One-year Treatment Resistant Schizophrenic Treatment Model 83 6 LIST OF ABREVIATIONS APA American Psychiatric Association BBB Blood Brain Barrier BDI Beck Depression Inventory BGT Bender Gestalt Test BPRS Brief Psychiatric Rating Scale C. TCA Continuation Therapy with TCAs C.ATP Continuation Therapy with antipsychotic drugs C.MAOI Continuation Therapy with MAOIs C.placebo Continuation therapy with placebo C.SSRI Continuation Therapy with SSRIS CASP CEAC Cost Efectiveness Acceptabilty Curve CECT Continuation ECT CGI Clinical Global Inpression CIRS Cumulative Illness Rating Scale CODS Cronholme and Ottoson Rating Scale CONSORT recommendations CT Computerised tomography CTCA+LI Continuation therapy with Lithium and TCAs DSM Diagnostic and Statistical Manual EEG GAF Global