Dissociations and Cognitive Distortions: True, True, and Possibly Related

Cognitive Behavioural Therapy for Adults With Dissociative Seizures (CODES): A Pragmatic, Multicentre, Randomized Controlled Trial. Goldstein LH, Robinson EJ, Mellers JDC, et al Lancet Psych. 2020;7(6):491-505. doi:10.1016/S2215-0366(20)30128-0. Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioral therapy (CBT) plus standardized medical care with standardized medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicenter, randomized controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardized medical care or CBT plus standardized medical care, using a web-based system. Randomization was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomization. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. P values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between January 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardized medical care (n = 186) or standardized medical care alone (n = 182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardized medical care group and 157 [86%] of 182 patients in the standardized medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median: 4 seizures [interquartile range: 0–-0] in the CBT plus standardized medical care group vs 7 seizures [1-35] in the standardized medical care group; estimated incidence rate ratio [IRR]: 0.78 [95% CI: 0·56-1.09]; P =.144). Dissociative seizures were rated as less bothersome in the CBT plus standardized medical care group than the standardized medical care group (estimated mean difference: −0.53 [95% CI: −0.97 to −0.08]; P =.020). The CBT plus standardized medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR: 1.64 [95% CI: 1.22-2.20]; P =.001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analog scale (estimated mean difference: 6.16 [95% CI: 1.48-10.84]; P =.010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference: −4.12 [95% CI: −6·35 to −1.89]; P <.001), less overall psychological distress than the standardized medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference: −1.65 [95% CI: −2.96 to −0.35]; P =.013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference: −1.67 [95% CI: −2.90 to −0.44]; P =.008). Clinical improvement at 12 months was greater in the CBT plus standardized medical care group than the standardized medical care alone group as reported by patients (estimated mean difference: 0.66 [95% CI: 0.26-1.04]; P =.001) and by clinicians (estimated mean difference: 0·47 [95% CI: 0.21-0.73]; P <.001), and the CBT plus standardized medical care group had greater satisfaction with treatment than did the standardized medical care group (estimated mean difference: 0.90 [95% CI: 0.48-1.31]; P <.001). No significant differences in patient-reported seizure severity (estimated mean difference: −0·11 [95% CI: −0.50 to 0.29]; P =.593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR]: 1.77 [95% CI: 0.93-3.37]; P =.083) were identified between the groups. Furthermore, there were no significant differences in dissociative seizure frequency reduction compared with baseline (OR: 1.27 [95% CI: 0.80-2.02]; P =.313). Additionally, the 12-item Short Form survey–version 2 scores (estimated mean difference for the Physical Component Summary score: 1.78 [95% CI: −0.37 to 3.92]; P =.105; estimated mean difference for the Mental Component Summary score: 2.22 [95% CI: −0.30 to 4.75]; P =.084), the Generalized Anxiety Disorder-7 Scale score (estimated mean difference: −1·09 [95% CI: −2.27 to 0.09]; P =.069), and the Patient Health Questionnaire-9 Scale depression score (estimated mean difference: −1.10 [95% CI: −2.41 to 0.21]; P =.099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardized medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardized medical care group reported 79 adverse events. Interpretation: Cognitive behavioral therapy plus standardized medical care had no statistically significant advantage compared with standardized medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardized medical care when compared with standardized medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach.