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Treatments for Psychogenic Nonepileptic Seizures (NES) (NES)

Primary Purpose

Convulsion, Non-Epileptic, Conversion Disorder, Depression

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
sertraline
placebo
Sponsored by
Rhode Island Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Convulsion, Non-Epileptic focused on measuring nonepileptic seizure, pseudoseizure, conversion disorder, psychogenic, Depression, Anxiety, Abuse, post-traumatic stress disorder, sertraline, serotonin, randomized controlled trial

Eligibility Criteria

18 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rhode Island Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

sertraline

placebo

Arm Description

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

flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES

Outcomes

Primary Outcome Measures

Number of Nonepileptic Seizures (NES)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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.

Full Information

First Posted
September 8, 2005
Last Updated
November 7, 2014
Sponsor
Rhode Island Hospital
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT00159965
Brief Title
Treatments for Psychogenic Nonepileptic Seizures (NES)
Acronym
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

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rhode Island Hospital
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sertraline
Arm Type
Active Comparator
Arm Description
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
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Intervention Type
Drug
Intervention Name(s)
sertraline
Other Intervention Name(s)
Zoloft
Intervention Description
flexible dose sertraline
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
flexible dose placebo
Primary Outcome Measure Information:
Title
Number of Nonepileptic Seizures (NES)
Description
psychogenic nonepileptic seizure (NES) frequency, collected prospectively, using a daily seizure calendar; aggregated into biweekly intervals.
Time Frame
bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
Secondary Outcome Measure Information:
Title
Beck Depression Inventory-II (BDI-II)
Description
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.
Time Frame
bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
Title
Modified Hamilton Depression Scale (MHRS)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Global Assessment of Functioning (GAF)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Davidson Trauma Scale (DTS)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Barratt Impulsivity Scale (BIS)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Dissociative Experiences Scale (DES)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Symptom Checklist 90 (SCL-90)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Oxford Handicap Scale (OHS)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Clinical Global Impressions - Severity (CGI-S)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Clinical Global Impressions - Improvement (CGI-I)
Description
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.
Time Frame
Weeks 2, 6, 10
Title
Family Assessment Device (FAD)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Longitudinal Interval Follow-Up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)
Title
Quality of Life in Epilepsy-31 (QOLIE-31)
Description
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.
Time Frame
Baseline and weeks 2, 6, 10 (total time frame of 12 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
W. Curt LaFrance, Jr., MD, MPH
Organizational Affiliation
Rhode Island Hospital/Brown Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15186340
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.
Results Reference
background
PubMed Identifier
11914432
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.
Results Reference
background
PubMed Identifier
16540377
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.
Results Reference
background
PubMed Identifier
16150653
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.
Results Reference
background
PubMed Identifier
18282812
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.
Results Reference
background
PubMed Identifier
18317280
Citation
LaFrance WC Jr. Psychogenic nonepileptic seizures. Curr Opin Neurol. 2008 Apr;21(2):195-201. doi: 10.1097/WCO.0b013e3282f7008f.
Results Reference
background
PubMed Identifier
12609316
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.
Results Reference
background
PubMed Identifier
16769930
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.
Results Reference
background
PubMed Identifier
18070841
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.
Results Reference
result
PubMed Identifier
19652140
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.
Results Reference
result
PubMed Identifier
20739647
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.
Results Reference
result
Links:
URL
http://www.brown.edu/Departments/Clinical_Neurosciences/neuropsychiatry
Description
Brown Medical School Clinical Neurosciences

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Treatments for Psychogenic Nonepileptic Seizures (NES)

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