Clinical trial NCT00159965: Treatments for Psychogenic Nonepileptic Seizures (NES)
Official title: Treatment for Psychogenic Nonepileptic Seizures: A Pilot, 12 Week, Prospective, Randomized, Placebo-controlled, Double-blind, Clinical Trial of Sertraline in the Treatment of Comorbid Psychiatric Disorders in NES
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Convulsion, Non-Epileptic
Conversion Disorder
Depression
Stress Disorders, Post-Traumatic
Keywords: nonepileptic seizure
pseudoseizure
conversion disorder
psychogenic
Depression
Anxiety
Abuse
post-traumatic stress disorder
sertraline
serotonin
randomized controlled trial
Lead sponsor: Rhode Island Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2005-09-12
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators propose that treatment of the comorbid disorders (depression, anxiety, and impulsivity) with sertraline in patients with lone psychogenic nonepileptic seizures (NES), will result in a decreased number of NES. The purpose of this study is to provide pilot testing and data to inform the future randomized controlled trial based on the hypothesis.

Detailed description: This is a pilot, prospective, single center, randomized, placebo-controlled, double-blind trial, that assesses the number of NES in patients treated with flexible dose sertraline (Zoloft). 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 electroencephalogram monitoring (vEEG), up to 50 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 blindly randomized to the treatment arm with flexible dose sertraline (25 to 200mg) or to the placebo control arm. The dose will be titrated over 4 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.

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 prospectively, to evaluate their daily seizure activity. They will be given two weeks of the medication at each visit.

In the first phase of the study 12 patients were screened and 8 enrolled in an open label trial of flexible dose sertraline. In the second phase of the study, 38 patients enrolled in the pilot, randomized, placebo-controlled trial.

Eligibility criteria: Inclusion Criteria:

* Video electroencephalogram (vEEG) confirmed diagnosis of NES
* Have at least one nonepileptic seizure per month
* Comorbid diagnosis of either depression, anxiety, or post traumatic stress disorder (PTSD)
* Able to complete self report symptom scales
* Not receiving optimized antidepressant medication

Exclusion Criteria:

* Equivocal electroencephalogram (EEG) findings
* Current suicidality, litigation, or self-mutilation
* Using monoamine oxidase inhibitors (MAOIs), pimozide, or sumatriptan
* Allergy/sensitivity to sertraline
* Current alcohol/drug dependence
* Serious medical illness requiring current hospitalization

Primary outcomes:
measure: Number of Nonepileptic Seizures (NES)
timeFrame: bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
Secondary outcomes:
measure: Beck Depression Inventory-II (BDI-II)
timeFrame: bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
measure: Modified Hamilton Depression Scale (MHRS)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Global Assessment of Functioning (GAF)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Davidson Trauma Scale (DTS)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Barratt Impulsivity Scale (BIS)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Dissociative Experiences Scale (DES)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Symptom Checklist 90 (SCL-90)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Oxford Handicap Scale (OHS)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Clinical Global Impressions - Severity (CGI-S)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Clinical Global Impressions - Improvement (CGI-I)
timeFrame: Weeks 2, 6, 10
measure: Family Assessment Device (FAD)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Longitudinal Interval Follow-Up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
measure: Quality of Life in Epilepsy-31 (QOLIE-31)
timeFrame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Other outcomes:
Locations:
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
affiliation: Rhode Island Hospital/Brown Medical School
name: W. Curt LaFrance, Jr., MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: LaFrance WC Jr, Devinsky O. The treatment of nonepileptic seizures: historical perspectives and future directions. Epilepsia. 2004;45 Suppl 2:15-21. doi: 10.1111/j.0013-9580.2004.452002.x.
citation: LaFrance WC. How many patients with psychogenic nonepileptic seizures also have epilepsy? Neurology. 2002 Mar 26;58(6):990; author reply 990-1. doi: 10.1212/wnl.58.6.990. No abstract available.
citation: LaFrance WC Jr, Alper K, Babcock D, Barry JJ, Benbadis S, Caplan R, Gates J, Jacobs M, Kanner A, Martin R, Rundhaugen L, Stewart R, Vert C; NES Treatment Workshop participants. Nonepileptic seizures treatment workshop summary. Epilepsy Behav. 2006 May;8(3):451-61. doi: 10.1016/j.yebeh.2006.02.004. Epub 2006 Mar 15.
citation: LaFrance WC Jr, Barry JJ. Update on treatments of psychological nonepileptic seizures. Epilepsy Behav. 2005 Nov;7(3):364-74. doi: 10.1016/j.yebeh.2005.07.010. Epub 2005 Sep 16.
citation: LaFrance WC Jr, Rusch MD, Machan JT. What is "treatment as usual" for nonepileptic seizures? Epilepsy Behav. 2008 Apr;12(3):388-94. doi: 10.1016/j.yebeh.2007.12.017. Epub 2008 Feb 20.
citation: LaFrance WC Jr. Psychogenic nonepileptic seizures. Curr Opin Neurol. 2008 Apr;21(2):195-201. doi: 10.1097/WCO.0b013e3282f7008f.
citation: LaFrance WC Jr, Devinsky O. Treatment of nonepileptic seizures. Epilepsy Behav. 2002 Oct;3(5 Suppl):19-23. doi: 10.1016/s1525-5069(02)00505-4.
citation: LaFrance WC Jr, Benbadis SR. Avoiding the costs of unrecognized psychological nonepileptic seizures. Neurology. 2006 Jun 13;66(11):1620-1. doi: 10.1212/01.wnl.0000224953.94807.be. No abstract available.
citation: LaFrance WC Jr, Blum AS, Miller IW, Ryan CE, Keitner GI. Methodological issues in conducting treatment trials for psychological nonepileptic seizures. J Neuropsychiatry Clin Neurosci. 2007 Fall;19(4):391-8. doi: 10.1176/jnp.2007.19.4.391.
citation: LaFrance WC Jr, Syc S. Depression and symptoms affect quality of life in psychogenic nonepileptic seizures. Neurology. 2009 Aug 4;73(5):366-71. doi: 10.1212/WNL.0b013e3181b04c83.
citation: LaFrance WC Jr, Keitner GI, Papandonatos GD, Blum AS, Machan JT, Ryan CE, Miller IW. Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures. Neurology. 2010 Sep 28;75(13):1166-73. doi: 10.1212/WNL.0b013e3181f4d5a9. Epub 2010 Aug 25.