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Cognitive behavioural therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT

Research output: Contribution to journalArticlepeer-review

Laura Goldstein, Emily J. Robinson, Izabela Pilecka, Iain Perdue, Iris Mosweu, Julie Read, Harriet Jordan, Matthew Wilkinson, Gregg Rawlings, Sarah Feehan, Hannah Callaghan, Elana Day, James Purnell, Maria Baldellou Lopez, Alice Brockington, Christine Burness, Norman Poole, Carole Eastwood, Michele Moore, John DC Mellers & 9 more Jon Stone, Alan Carson, Nick Medford, Markus Reuber, Paul McCrone, Joanna Murray, Mark Richardson, Sabine Landau, Trudie Chalder

Original languageEnglish
Pages (from-to)vii-144
Number of pages144
JournalHealth Technology Assessment
Issue number43
Accepted/In press28 Aug 2020
Published1 Jun 2021

Bibliographical note

Funding Information: Declared competing interests of authors: Alan Carson reports being a paid editor of the Journal of Neurology, Neurosurgery and Psychiatry, and is the director of a research programme on functional neurological disorders; he gives independent testimony in court on a range of neuropsychiatric topics (50% pursuer, 50% defender). Sabine Landau is a paid editor of the Journal of Child Psychology and Psychiatry. Markus Reuber is the paid editor-in-chief of Seizure – European Journal of Epilepsy and receives authorship fees from Oxford University Press (Oxford, UK) in relation to a number of books about dissociative seizures. Markus Reuber benefited from the support of the National Institute for Health Research (NIHR) Sheffield Biomedical Research Centre (Translational Neuroscience). Mark P Richardson reports funding from Xenon Pharma (Burnaby, BC, Canada). Jon Stone reports independent expert testimony work for personal injury and medical negligence claims, royalties from UpToDate for articles on functional neurological disorders and runs a free non-profit self-help website, Jon Stone is also supported by an NHS Scotland NHS Research Scotland (NRS) Career Fellowship. Jon Stone and Alan Carson also acknowledge the financial support of NHS Research Scotland through the Edinburgh Clinical Research Facility. Laura Goldstein, Trudie Chalder and Sabine Landau report support from the NIHR Maudsley Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London. Emily J Robinson received salary support from the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Gregg Rawlings is entitled to authorship fees from Oxford University Press for several books on dissociative seizures. Funding Information: Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 43. See the NIHR Journals Library website for further project information. Funding Information: The research reported in this issue of the journal was funded by the HTA programme as project number 12/26/01. The contractual start date was in June 2014. The draft report began editorial review in April 2020 and was accepted for publication in August 2020. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Publisher Copyright: © 2021 Goldstein et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.


King's Authors


BACKGROUND: Dissociative (non-epileptic) seizures are potentially treatable by psychotherapeutic interventions; however, the evidence for this is limited. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of dissociative seizure-specific cognitive-behavioural therapy for adults with dissociative seizures. DESIGN: This was a pragmatic, multicentre, parallel-arm, mixed-methods randomised controlled trial. SETTING: This took place in 27 UK-based neurology/epilepsy services, 17 liaison psychiatry/neuropsychiatry services and 18 cognitive-behavioural therapy services. PARTICIPANTS: Adults with dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous year and meeting other eligibility criteria were recruited to a screening phase from neurology/epilepsy services between October 2014 and February 2017. After psychiatric assessment around 3 months later, eligible and interested participants were randomised between January 2015 and May 2017. INTERVENTIONS: Standardised medical care consisted of input from neurologists and psychiatrists who were given guidance regarding diagnosis delivery and management; they provided patients with information booklets. The intervention consisted of 12 dissociative seizure-specific cognitive-behavioural therapy 1-hour sessions (plus one booster session) that were delivered by trained therapists, in addition to standardised medical care. MAIN OUTCOME MEASURES: The primary outcome was monthly seizure frequency at 12 months post randomisation. The secondary outcomes were aspects of seizure occurrence, quality of life, mood, anxiety, distress, symptoms, psychosocial functioning, clinical global change, satisfaction with treatment, quality-adjusted life-years, costs and cost-effectiveness. RESULTS: In total, 698 patients were screened and 368 were randomised (standardised medical care alone, n = 182; and cognitive-behavioural therapy plus standardised medical care, n = 186). Primary outcome data were obtained for 85% of participants. An intention-to-treat analysis with multivariate imputation by chained equations revealed no significant between-group difference in dissociative seizure frequency at 12 months [standardised medical care: median of seven dissociative seizures (interquartile range 1-35 dissociative seizures); cognitive-behavioural therapy and standardised medical care: median of four dissociative seizures (interquartile range 0-20 dissociative seizures); incidence rate ratio 0.78, 95% confidence interval 0.56 to 1.09; p = 0.144]. Of the 16 secondary outcomes analysed, nine were significantly better in the arm receiving cognitive-behavioural therapy at a p-value < 0.05, including the following at a p-value ≤ 0.001: the longest dissociative seizure-free period in months 7-12 inclusive post randomisation (incidence rate ratio 1.64, 95% confidence interval 1.22 to 2.20; p = 0.001); better psychosocial functioning (Work and Social Adjustment Scale, standardised treatment effect -0.39, 95% confidence interval -0.61 to -0.18; p < 0.001); greater self-rated and clinician-rated clinical improvement (self-rated: standardised treatment effect 0.39, 95% confidence interval 0.16 to 0.62; p = 0.001; clinician rated: standardised treatment effect 0.37, 95% confidence interval 0.17 to 0.57; p < 0.001); and satisfaction with treatment (standardised treatment effect 0.50, 95% confidence interval 0.27 to 0.73; p < 0.001). Rates of adverse events were similar across arms. Cognitive-behavioural therapy plus standardised medical care produced 0.0152 more quality-adjusted life-years (95% confidence interval -0.0106 to 0.0392 quality-adjusted life-years) than standardised medical care alone. The incremental cost-effectiveness ratio (cost per quality-adjusted life-year) for cognitive-behavioural therapy plus standardised medical care versus standardised medical care alone based on the EuroQol-5 Dimensions, five-level version, and imputed data was £120,658. In sensitivity analyses, incremental cost-effectiveness ratios ranged between £85,724 and £206,067. Qualitative and quantitative process evaluations highlighted useful study components, the importance of clinical experience in treating patients with dissociative seizures and potential benefits of our multidisciplinary care pathway. LIMITATIONS: Unlike outcome assessors, participants and clinicians were not blinded to the interventions. CONCLUSIONS: There was no significant additional benefit of dissociative seizure-specific cognitive-behavioural therapy in reducing dissociative seizure frequency, and cost-effectiveness over standardised medical care was low. However, this large, adequately powered, multicentre randomised controlled trial highlights benefits of adjunctive dissociative seizure-specific cognitive-behavioural therapy for several clinical outcomes, with no evidence of greater harm from dissociative seizure-specific cognitive-behavioural therapy. FUTURE WORK: Examination of moderators and mediators of outcome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05681227 and NCT02325544. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 43. See the NIHR Journals Library website for further project information.

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