Internet Intervention for Functional Seizures: A Randomized Clinical Trial

Why clinicians should know about it

• Picked for Neurology (clinical) (top studies of the week, 1 November 2026): Randomized trial evaluates accessible treatment for functional seizures

Abstract

IMPORTANCE: Functional seizures (FS) are a common and disabling presentation in neurology clinics, but evidence-based treatments are difficult to access in Australia and in many regions globally. A brief, scalable, internet-delivered intervention could narrow this treatment gap. OBJECTIVE: To compare a self-guided and a therapist-guided internet-based intervention for FS, each delivered alongside standard care, with standard care alone. DESIGN, SETTING, AND PARTICIPANTS: This was a 3-arm, parallel, randomized clinical trial conducted between February 2022 and April 2024, with follow-up through to 12 months after randomization. The location was a specialist outpatient clinic in Melbourne, Australia. Included were adults (≥18 years) with a documented diagnosis of FS confirmed by video electroencephalogram monitoring and at least 4 seizures per month, excluding comorbid active epilepsy. INTERVENTIONS: Participants were randomized 1:1:1 to a self-guided internet-based intervention plus standard care, therapist-guided internet-based intervention plus standard care, or standard care alone. Re-PROGRAM is an internet-based intervention developed for FS, comprising 5 structured sessions integrating lifestyle factors, seizure management techniques, and elements of cognitive behavioral, acceptance and commitment, and dialectical behavior therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was monthly seizure frequency at 6 weeks, 6 months, and 12 months after randomization, recorded by daily prospective seizure diary, with retrospective estimates used for incomplete records. Secondary outcomes included depression, anxiety, quality of life, psychosocial functioning, and somatic symptoms. RESULTS: Of 220 individuals screened for eligibility, 107 (mean [SD] age 36.0 [12.4] years; 89 female [83%]) were randomized. Of these participants, 96 contributed to the full analysis set (29 self-guided, 34 therapist-guided, 33 standard care). The self-guided arm produced significantly greater overall reductions in monthly seizure frequency than standard care (rate ratio [RR], 0.35; 95% CI, 0.18-0.69; Holm-Bonferroni [HB] method P = .006), with sustained between-group effects at 6 weeks (RR, 0.37; 95% CI, 0.18-0.76; HB P = .02), 6 months (RR, 0.31; 95% CI, 0.12-0.78; HB P = .04), and 12 months (RR, 0.35; 95% CI, 0.16-0.78; HB P = .03). The self-guided arm also showed greater improvements in anxiety than standard care at all 3 time points and in depression and mental quality of life at 1 or more time points. The therapist-guided arm showed greater improvement in anxiety at 6 months, but reductions in seizure frequency did not reach statistical significance. Direct comparison between the 2 active arms showed no significant difference in seizure reduction (RR, 0.67; 95% CI, 0.33-1.36). Sensitivity analyses confirmed robustness of the primary findings. No adverse events occurred in any arm. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial show that in adults with FS, a self-guided internet-based intervention reduced seizure frequency and improved anxiety relative to standard care, offering a scalable option for patients unable to access specialist psychological care. TRIAL REGISTRATION: Identifier: ACTRN12622000262707.

Abstract as published, via PubMed.