Cognitive Behavioural Therapy in Adults with Psychogenic Non-Epileptic Seizures: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background Randomised controlled clinical trials (RCTs) investigating cognitive-behavioural therapy (CBT) among adults with psychogenic non-epileptic seizures (PNES) has become increasingly available, prompting the opportunity to critically appraise the efficacy and safety of CBT in this population. Methods We conducted a systematic review and meta-analysis including RCTs comparing CBT in addition to standardised medical treatment (SMT) versus SMT alone for adults with PNES. The primary outcome was seizure freedom at the end of treatment. Secondary outcomes included measures of quality of life, anxiety and depression assessed via standardised clinical questionnaires. Results Three RCTs were included comprising 228 participants treated with CBT and 222 with SMT. The intervention was significantly associated with seizure freedom (Odds Ratio [OR] 1.98; 95% confidence interval [CI] 1.14, 3.46; p = 0.02; I2 = 0%), reductions in anxiety (standardised mean difference [SMD] −0.21; 95% CI −0.41, −0.003; p = 0.047; I2 = 0%) and improvements in quality of life (SMD 0.34; 95% CI 0.12, 0.57; p = 0.003; I2 = 0%) at the end of treatment. Conversely, no significant differences between groups were observed regarding depression symptoms (SMD −0.19; 95% CI −0.39, 0.02; p = 0.08; I2 = 0%). There was no statistically significant increase in the risk of suicidal ideation and self-harm with CBT (OR 2.11; 95% CI 0.81, 5.48; p = 0.13; I2 = 0%) nor were there differences in terms of discontinuation rates during follow-up (OR 0.92; 95% CI 0.49, 1.72; p = 0.79; I2 = 7%). Conclusions There is high-quality evidence supporting the efficacy and safety of CBT in treating PNES. Future research should investigate whether combining CBT with other therapeutic methods could potentially enhance treatment efficacy. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This systematic review and meta-analysis was registered a priori in the International Prospective Register of Systematic Reviews database (PROSPERO registration number: CRD42024512943). This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines [26]. We conducted a comprehensive literature search using the MEDLINE, Cochrane, and Scopus databases electronic databases on November 28, 2023. (See method section) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data relevant to the study are included in the article or uploaded as supplementary information. * CBT : Cognitive-Behavioural Therapy CI : Confidence Interval EEG : Electroencephalography EQ-5D-5L : EuroQol Five-Dimensional Questionnaire GAD-7 : Generalised Anxiety Disorder seven-item scale HADS : Hospital Anxiety and Depression Scale OR : Odds Ratio PHQ-9 : Patient Health Questionnaire nine-item scale PNES : Psychogenic Non-Epileptic Seizures PRISMA : Preferred Reporting Items for Systematic Reviews and Meta-analyses PROSPERO : International Prospective Register of Systematic Reviews QOLIE-31 : Quality of Life in Epilepsy Inventory 31 RCTs : Randomised Controlled Trials RoB 2 : Cochrane risk-of-bias tool for randomised trials SD : Standard Deviation SMD : Standardised Mean Difference SMT : Standardised Medical Treatment