Treatment Trial for Psychogenic Nonepileptic Seizures

Study Overview
=================
Brief Summary
-----------------
The investigators propose that patients who receive targeted pharmacotherapy (sertraline) or focused psychotherapy (cognitive behavioral therapy-informed psychotherapy (CBT-ip) for NES) or combined treatment (CBT-ip + sertraline) will report fewer nonepileptic seizures (NES) compared to patients who receive community care / treatment as usual (TAU). The purpose of this study is to provide pilot testing and data to inform the future multicenter randomized controlled trial based on the hypothesis.

Detailed Description
-----------------
This is a pilot, prospective, multi-center, randomized controlled trial, that assesses the number of NES in patients treated with either flexible dose sertraline (Zoloft), cognitive behavioral therapy-informed psychotherapy (CBT-ip), combined therapy (sertraline + CBT-ip) or community care (treatment as usual TAU). This study will provide outcomes data and the effect size necessary for a future R01, multi-center randomized control trial. Secondary objective variables include reduction in depression, anxiety, impulsivity scores, and improvement in psychosocial functioning. After being diagnosed with NES by video EEG monitoring (vEEG), up to 40 participants will be enrolled and monitored during a two week lead in period for their baseline NES and psychosocial symptoms and functioning. At week 2, they will be randomized to either: flexible dose sertraline (25 to 200mg), CBT, CBT+med, or to the control arm, TAU. Participants randomized to the sertraline arm will be titrated over 6 weeks up to 200mg or to dose limited by side effects. The subjects will stay on their maximum fixed dose for the next 4 weeks. At week 10, the subjects may elect to remain on the sertraline or they can taper off the medication over the final two weeks of the treatment trial. Those randomized to the CBT-ip arm will receive 12 weekly sessions of CBT-ip for NES. Those randomized to the CBT-ip + med arm will receive both treatments. Those randomized to the TAU arm will follow with their treatment providers. After the treatment trial, the subjects will have follow up phone calls at month 4, 8, and 12 after enrollment to assess seizure status, medication usage, and global functioning. Upon enrollment, subjects will be evaluated with a structured psychiatric and neurological exam, and with bi-weekly, 30 to 60 minute appointments where they will complete symptom and function scales. They will keep a seizure diary to evaluate their daily seizure activity.

Official Title
-----------------
Medication and Psychotherapy Treatment Trial for Psychogenic Nonepileptic Seizures

Conditions
-----------------
Convulsion, Non-Epileptic, Conversion Disorder, Depression, Stress Disorders, Post-Traumatic, Dissociative Disorders

Intervention / Treatment
-----------------
* Drug: sertraline
* Behavioral: CBT-ip
* Other: Combined (sertraline + CBT-ip)
* Other: Standard Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Video electroencephalogram (EEG) confirmed diagnosis of NES Have at least one nonepileptic seizure per month Able to complete self report symptom scales Not receiving optimized sertraline Exclusion Criteria: Equivocal EEG findings using monoamine oxidase inhibitors (MAOIs), pimozide, or sumatriptan allergy/sensitivity to sertraline current alcohol/drug dependence serious medical illness requiring current hospitalization

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: sertraline<br>flexible dose sertraline | Drug: sertraline<br>* flexible dose sertraline<br>* Other names: Zoloft;|
| Active Comparator: CBT-ip<br>cognitive behavioral therapy-informed psychotherapy for nonepileptic seizures: 12 individual, 1 hour therapy sessions | Behavioral: CBT-ip<br>* cognitive behavioral therapy-informed psychotherapy for nonepileptic seizures: 12 individual 1 hour therapy sessions<br>|
| Active Comparator: Combined (sertraline + CBT-ip)<br>flexible dose sertraline and cognitive behavioral therapy-informed psychotherapy for nonepileptic seizures: flexible dose sertraline and 12 individual, 1 hour therapy sessions | Other: Combined (sertraline + CBT-ip)<br>* flexible dose sertraline and cognitive behavioral therapy-informed psychotherapy for nonepileptic seizures: flexible dose sertraline and 12, individual 1 hour therapy sessions<br>* Other names: CBT-ip;|
| Active Comparator: Standard care<br>community care / treatment as usual: routine follow up with existing providers | Other: Standard Care<br>* community care, treatment as usual: routine follow up with existing providers<br>* Other names: TAU, standard care;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| seizure frequency |  | weekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify predictors of response from the following 3 groups: clinical diagnoses |  | baseline | 
| psychological symptoms |  | bi-weekly | 
| socio-demographic variables |  | bi-weekly | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Treatment, Cognitive Behavior Therapy, pharmacotherapy, psychogenic nonepileptic seizures, pseudoseizures, dissociative seizures, conversion disorder