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.