{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:16:18Z","timestamp":1791000978389,"version":"4.1.0"},"reference-count":174,"publisher":"National Institute for Health and Care Research","issue":"43","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["12\/26\/01"],"award-info":[{"award-number":["12\/26\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dissociative (non-epileptic) seizures are potentially treatable by psychotherapeutic interventions; however, the evidence for this is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-2\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the clinical effectiveness and cost-effectiveness of dissociative seizure-specific cognitive\u2013behavioural therapy for adults with dissociative seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-3\">\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This was a pragmatic, multicentre, parallel-arm, mixed-methods randomised controlled trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-4\">\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>This took place in 27 UK-based neurology\/epilepsy services, 17 liaison psychiatry\/neuropsychiatry services and 18 cognitive\u2013behavioural therapy services.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-5\">\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-6\">\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>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\u2013behavioural therapy 1-hour sessions (plus one booster session) that were delivered by trained therapists, in addition to standardised medical care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-7\">\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 698 patients were screened and 368 were randomised (standardised medical care alone,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009182; and cognitive\u2013behavioural therapy plus standardised medical care,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009186). 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\u201335 dissociative seizures); cognitive\u2013behavioural therapy and standardised medical care: median of four dissociative seizures (interquartile range 0\u201320 dissociative seizures); incidence rate ratio 0.78, 95% confidence interval 0.56 to 1.09;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.144]. Of the 16 secondary outcomes analysed, nine were significantly better in the arm receiving cognitive\u2013behavioural therapy at a\n                      <jats:italic>p<\/jats:italic>\n                      -value\u2009&lt;\u20090.05, including the following at a\n                      <jats:italic>p<\/jats:italic>\n                      -value\u2009\u2264\u20090.001: the longest dissociative seizure-free period in months 7\u201312 inclusive post randomisation (incidence rate ratio\u20091.64, 95% confidence interval 1.22 to 2.20;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001); better psychosocial functioning (Work and Social Adjustment Scale, standardised treatment effect \u20130.39, 95% confidence interval \u20130.61 to \u20130.18;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); greater self-rated and clinician-rated clinical improvement (self-rated: standardised treatment effect 0.39, 95% confidence interval 0.16 to 0.62;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001; clinician rated: standardised treatment effect 0.37, 95% confidence interval 0.17 to 0.57;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); and satisfaction with treatment (standardised treatment effect 0.50, 95% confidence interval 0.27 to 0.73;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Rates of adverse events were similar across arms. Cognitive\u2013behavioural therapy plus standardised medical care produced 0.0152 more quality-adjusted life-years (95% confidence interval \u20130.0106 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\u2013behavioural therapy plus standardised medical care versus standardised medical care alone based on the EuroQol-5 Dimensions, five-level version, and imputed data was \u00a3120,658. In sensitivity analyses, incremental cost-effectiveness ratios ranged between \u00a385,724 and \u00a3206,067. 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-9\">\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>Unlike outcome assessors, participants and clinicians were not blinded to the interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-10\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There was no significant additional benefit of dissociative seizure-specific cognitive\u2013behavioural 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\u2013behavioural therapy for several clinical outcomes, with no evidence of greater harm from dissociative seizure-specific cognitive\u2013behavioural therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-11\">\n                    <jats:title>Future work<\/jats:title>\n                    <jats:p>Examination of moderators and mediators of outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-12\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Current Controlled Trials ISRCTN05681227 and ClinicalTrials.gov NCT02325544.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs1-13\">\n                    <jats:title>Funding<\/jats:title>\n                    <jats:p>\n                      This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in\n                      <jats:italic>Health Technology Assessment<\/jats:italic>\n                      ; Vol. 25, No. 43. See the NIHR Journals Library website for further project information.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3310\/hta25430","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T07:03:13Z","timestamp":1625122993000},"page":"1-144","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Cognitive\u2013behavioural therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT"],"prefix":"10.3310","volume":"25","clinical-trial-number":[{"clinical-trial-number":"isrctn05681227","registry":"10.18810\/isrctn","type":"results"},{"clinical-trial-number":"nct02325544","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9387-3035","authenticated-orcid":true,"given":"Laura H","family":"Goldstein","sequence":"first","affiliation":[{"name":"Department of 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