Treatments for Psychogenic Nonepileptic Seizures (NES)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Rhode Island Hospital
ClinicalTrials.gov Identifier:
NCT00159965
First received: September 8, 2005
Last updated: January 4, 2011
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Convulsion, Non-Epileptic
Conversion Disorder
Depression
Stress Disorders, Post-Traumatic
Drug: sertraline
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Rhode Island Hospital:

Primary Outcome Measures:
  • Number of Nonepileptic Seizures (NES) [ Time Frame: bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12 ] [ Designated as safety issue: No ]
    psychogenic nonepileptic seizure (NES) frequency, collected prospectively, using a daily seizure calendar; aggregated into biweekly intervals.


Secondary Outcome Measures:
  • Beck Depression Inventory-II (BDI-II) [ Time Frame: bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12 ] [ Designated as safety issue: No ]
    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.

  • Modified Hamilton Depression Scale (MHRS) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Global Assessment of Functioning (GAF) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Davidson Trauma Scale (DTS) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Barratt Impulsivity Scale (BIS) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Dissociative Experiences Scale (DES) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Symptom Checklist 90 (SCL-90) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Oxford Handicap Scale (OHS) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impressions - Severity (CGI-S) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impressions - Improvement (CGI-I) [ Time Frame: Weeks 2, 6, 10 ] [ Designated as safety issue: No ]
    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.

  • Family Assessment Device (FAD) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Quality of Life in Epilepsy-31 (QOLIE-31) [ Time Frame: Baseline and weeks 2, 6, 10 (total time frame of 12 weeks) ] [ Designated as safety issue: No ]
    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.


Enrollment: 38
Study Start Date: December 2003
Study Completion Date: June 2009
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00159965

Locations
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
Rhode Island Hospital
Investigators
Principal Investigator: W. Curt LaFrance, Jr., MD, MPH Rhode Island Hospital/Brown Medical School
  More Information

Additional Information:
Publications:

Responsible Party: W. Curt LaFrance, Jr., MD, MPH / Director of Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital
ClinicalTrials.gov Identifier: NCT00159965     History of Changes
Other Study ID Numbers: 5K23 NS 045902-05, 5K23NS045902
Study First Received: September 8, 2005
Results First Received: August 11, 2010
Last Updated: January 4, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Rhode Island Hospital:
nonepileptic seizure
pseudoseizure
conversion disorder
psychogenic
Depression
Anxiety
Abuse
post-traumatic stress disorder
sertraline
serotonin
randomized controlled trial

Additional relevant MeSH terms:
Conversion Disorder
Hysteria
Dissociative Disorders
Depression
Depressive Disorder
Seizures
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Somatoform Disorders
Mental Disorders
Histrionic Personality Disorder
Personality Disorders
Behavioral Symptoms
Mood Disorders
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Anxiety Disorders
Sertraline
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 31, 2014