Treatments for Psychogenic Nonepileptic Seizures (NES) (NES)
|Convulsion, Non-Epileptic Conversion Disorder Depression Stress Disorders, Post-Traumatic||Drug: sertraline Drug: placebo||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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|
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
|Study Start Date:||December 2003|
|Study Completion Date:||June 2009|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
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
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
flexible dose placebo
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00159965
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00159965
|United States, Rhode Island|
|Rhode Island Hospital|
|Providence, Rhode Island, United States, 02903|
|Principal Investigator:||W. Curt LaFrance, Jr., MD, MPH||Rhode Island Hospital/Brown Medical School|