A pilot randomized controlled trial of prolonged exposure therapy vs. psychoeducation for psychogenic nonepileptic seizures and comorbid post-traumatic stress disorder

OBJECTIVE: To evaluate two treatments (Prolonged Exposure [PE] and Psychoeducation) for patients diagnosed with psychogenic nonepileptic seizures (PNES) and post-traumatic stress disorder (PTSD). TRIAL DESIGN, SETTING, AND PARTICIPANTS: An outpatient pilot randomized controlled clinical trial was conducted at the Northeast Regional Epilepsy Group's (NEREG) PNES program. Between 2020 and 2025, 44 subjects with video EEG-confirmed PNES and PTSD were enrolled; 35 were randomized into a virtually administered treatment modality. Thirty participants completed treatment; 3- and 12-months follow-ups were included in the final analysis. METHODS: Seizure frequency was the primary outcome measure. Secondary outcome measures were depression and PTSD symptoms. Data were collected prospectively, including at baseline, last session, and follow-up intervals of 3- and 12 months. Within-group change and between-group differences of primary/secondary measures over time were evaluated using mixed-effects models. RESULTS: Compared to baseline, the PE group showed 76% within-group seizure reduction at 12 months; between-group interaction favored PE (b = 0.299, p = 0.014) while Psychoeducation did not result in within-group seizure reduction at 12 months (p = 0.147). Both treatment groups showed improvement on PTSD measures by 12 months; Psychoeducation had an advantage on depression (interaction b = - 0.130, p < 0.001). CONCLUSIONS AND RELEVANCE: This pilot trial demonstrated benefits of both treatment modalities. At final follow-up, the PE group retained reduced seizure frequency and posttraumatic symptoms. At final follow-up, the Psychoeducation sample sustained improved depression and PTSD symptoms but not seizure frequency. Results suggest PE can reduce seizures and PTSD symptoms, while Psychoeducation can improve depression symptoms and PTSD; larger trials will be needed.