Treatments for Psychogenic Nonepileptic Seizures (NES) (NES)

November 7, 2014 updated by: W. Curt LaFrance Jr., M.D., Rhode Island Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: sertraline
flexible dose sertraline, 25 to 200mg titration as tolerated, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Drug: sertraline
flexible dose sertraline
Other Names:
  • Zoloft
Placebo Comparator: placebo
flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Drug: placebo
flexible dose placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Nonepileptic Seizures (NES)
Time Frame: bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
psychogenic nonepileptic seizure (NES) frequency, collected prospectively, using a daily seizure calendar; aggregated into biweekly intervals.
bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Beck Depression Inventory-II (BDI-II)
Time Frame: bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
The BDI-II assesses depression severity from "0" (no Depression-related symptom) to "3" (severe) on each question. The highest possible score is "51", relating to the worst outcome.
bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
Modified Hamilton Depression Scale (MHRS)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The MHRS assesses the severity of Depression-related symptoms from "0" (not present) to "2", "3" or "4" (severe) on each question. The highest possible score is "72", relating to the worst outcome.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Global Assessment of Functioning (GAF)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
This GAF rating scale ranges from 0 (worst) to 100 (best) and is used for evaluating the overall functioning of a subject during a specified time period on a continuum from psychological or psychiatric sickness to health.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Davidson Trauma Scale (DTS)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The DTS is a 17-item self-report scale measuring each Diagnostic and Stastical Manual of Mental Disorders-4th Edition (DSM-IV) symptom of post-traumatic stress disorder (PTSD) on 5-point frequency (0-not at all to 4-everyday) and severity (0-not at all distressing to 4-extremely distressing) scales. The highest possible score is 136 and relates to the worst outcome.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Barratt Impulsivity Scale (BIS)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The BIS is a 30 item self-report measure that characterizes four aspects of impulsiveness, and ranges from "rarely/ never" to "almost always" with a score of "1" to "4" possible on each question, giving a maximum possible score of 120 and minimum possible score of 30. Selected questions are reversed scored. Higher scores relate to a worse outcome.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Dissociative Experiences Scale (DES)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The DES is a 28 item self-report questionnaire designed to quantify dissociative experiences which identifies disturbances in memory, identity, cognition, derealization, depersonalization, absorption and imagination. A visual analogue scale is used ranging from 0% ("This never happens to you") to 100% ("This always happens to you"). The score is divided by 28 items to yield a range of 0 to 100%, with a higher score relating to a higher degree of dissociation.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Symptom Checklist 90 (SCL-90)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The SCL-90 is a 90 item self-report clinical rating scale oriented toward symptomatic behavior of outpatients, assessing from "0" (not at all bothered) to "4" (extremely bothered). The highest possible overall score is 360 and relates to a worse outcome.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Oxford Handicap Scale (OHS)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The OHS is a brief clinician scored assessment of symptoms and lifestyle interference and the 6 grades of disability are based on the modified Rankin Scale, ranging from "0" (no symptoms) to "5" (severe handicap). A higher score relates to a worse outcome.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Clinical Global Impressions - Severity (CGI-S)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The CGI-S is the first item of a two-item global rating scale, where each item is on a 7 point scale ranging from normal ("1") to among the most extremely ill patients ("7"). A higher score relates to a higher severity of illness.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Clinical Global Impressions - Improvement (CGI-I)
Time Frame: Weeks 2, 6, 10
The CGI-I is the second item of a two item global rating scale, where each item is on a 7 point scale ranging from very much improved ("1") to very much worse ("7"). A lower score represents a higher improvement.
Weeks 2, 6, 10
Family Assessment Device (FAD)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The FAD is a 60 item self-report questionnaire designed to assess the six dimensions of the McMaster Model of Family Functioning, as well as overall level of family functioning through the General Functioning Scale. Each question is scored on a "1" to "4" scale, with a higher mean score relating to a worse general functioning.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Longitudinal Interval Follow-Up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
The LIFE-RIFT interview is a brief semi-structured interview, which measures functional impairment, targeting four domains: work, interpersonal relations, recreation and global satisfaction. Work, recreation and global satisfaction are rated on a "1" (very good/ no impairment) to "5" (very poor/ severe impairment) scale, and interpersonal relations is rated on a "1" (very good) to "7" (variable) scale. The highest score possible is 20 and relates to a more severe impairment. The lowest possible score is 3.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Quality of Life in Epilepsy-31 (QOLIE-31)
Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
This is a 31-item self-report scale used in the seizure population to evaluate Quality of Life. The lowest possible score is 0 and the highest possible score is 100, reflecting a better quality of life.
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rhode Island Hospital

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: W. Curt LaFrance, Jr., MD, MPH, Rhode Island Hospital/Brown Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

June 1, 2008

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 10, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

November 20, 2014

Last Update Submitted That Met QC Criteria

November 7, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5K23NS045902-05 (U.S. NIH Grant/Contract)
  • 5K23NS045902 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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