Trial Outcomes & Findings for Treatments for Psychogenic Nonepileptic Seizures (NES) (NCT NCT00159965)

NCT ID: NCT00159965

Last Updated: 2014-11-20

Results Overview

psychogenic nonepileptic seizure (NES) frequency, collected prospectively, using a daily seizure calendar; aggregated into biweekly intervals.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 38 participants
• Primary outcome timeframe: bi-weekly at baseline and weeks 2, 4, 6, 8, 10, 12
• Results posted on: 2014-11-20

Participant Flow

Patients were referred to the Rhode Island Hospital (RIH) neuropsychiatry/behavioral neurology clinic between July 2002 and June 2008, after being diagnosed with psychogenic nonepileptic seizures (PNES). PNES diagnosis was established by capturing at least one of the patient's typical PNES on video electroencephalogram (vEEG).

Participant milestones

Measure	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	Placebo flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Overall Study STARTED	19	19
Overall Study COMPLETED	12	14
Overall Study NOT COMPLETED	7	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatments for Psychogenic Nonepileptic Seizures (NES)

Baseline characteristics by cohort

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	38 years STANDARD_DEVIATION 13.9 • n=5 Participants	34.4 years STANDARD_DEVIATION 12.6 • n=7 Participants	36.2 years STANDARD_DEVIATION 13.2 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	13 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	19 participants n=7 Participants	38 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Number of Nonepileptic Seizures (NES) Baseline (retrospective 2 weeks prior)	5.0 seizures Standard Deviation 43.5	6.0 seizures Standard Deviation 12.1
Number of Nonepileptic Seizures (NES) Week 2 (prospectively collected from day 1-14)	3.0 seizures Standard Deviation 37.7	6.0 seizures Standard Deviation 8.5
Number of Nonepileptic Seizures (NES) Week 4	2.0 seizures Standard Deviation 31.5	5.0 seizures Standard Deviation 10.6
Number of Nonepileptic Seizures (NES) Week 6	1.0 seizures Standard Deviation 31.5	3.0 seizures Standard Deviation 16.4
Number of Nonepileptic Seizures (NES) Week 8	1.0 seizures Standard Deviation 24.4	3.0 seizures Standard Deviation 17.4
Number of Nonepileptic Seizures (NES) Week 10	2.5 seizures Standard Deviation 30.7	7.0 seizures Standard Deviation 12.4
Number of Nonepileptic Seizures (NES) Week 12	0.0 seizures Standard Deviation 20.3	6.0 seizures Standard Deviation 14.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Beck Depression Inventory-II (BDI-II) Baseline	16.7 Units on a scale Standard Deviation 13.0	22.1 Units on a scale Standard Deviation 13.9
Beck Depression Inventory-II (BDI-II) Exit	11.7 Units on a scale Standard Deviation 11.5	17.0 Units on a scale Standard Deviation 13.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Modified Hamilton Depression Scale (MHRS) Baseline	17.8 units on a scale Standard Deviation 21.0	16.8 units on a scale Standard Deviation 8.8
Modified Hamilton Depression Scale (MHRS) Exit	11.6 units on a scale Standard Deviation 9.0	13.3 units on a scale Standard Deviation 8.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Global Assessment of Functioning (GAF) Exit	56.8 Units on a scale Standard Deviation 11.0	52.0 Units on a scale Standard Deviation 7.9
Global Assessment of Functioning (GAF) Baseline	53.3 Units on a scale Standard Deviation 10.3	49.1 Units on a scale Standard Deviation 7.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Davidson Trauma Scale (DTS) Baseline	52.5 units on a scale Standard Deviation 31.6	48.1 units on a scale Standard Deviation 40.0
Davidson Trauma Scale (DTS) Exit	40.3 units on a scale Standard Deviation 36.9	43.4 units on a scale Standard Deviation 40.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Barratt Impulsivity Scale (BIS) Baseline	57.8 Units on a scale Standard Deviation 16.5	72.6 Units on a scale Standard Deviation 17.8
Barratt Impulsivity Scale (BIS) Exit	64.9 Units on a scale Standard Deviation 13.2	66.2 Units on a scale Standard Deviation 15.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Dissociative Experiences Scale (DES) Baseline	21.0 units on a scale Standard Deviation 19.7	17.4 units on a scale Standard Deviation 11.0
Dissociative Experiences Scale (DES) Exit	8.5 units on a scale Standard Deviation 13.2	12.1 units on a scale Standard Deviation 12.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Symptom Checklist 90 (SCL-90) Baseline	84.9 Units on a scale Standard Deviation 73.3	109.4 Units on a scale Standard Deviation 70.9
Symptom Checklist 90 (SCL-90) Exit	78.9 Units on a scale Standard Deviation 67.2	91.4 Units on a scale Standard Deviation 77.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Oxford Handicap Scale (OHS) Baseline	3.1 Units on a scale Standard Deviation 0.8	3.4 Units on a scale Standard Deviation 0.7
Oxford Handicap Scale (OHS) Exit	2.3 Units on a scale Standard Deviation 1.3	2.6 Units on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Clinical Global Impressions - Severity (CGI-S) Baseline	4.9 Units on a scale Standard Deviation 0.8	5.1 Units on a scale Standard Deviation 0.6
Clinical Global Impressions - Severity (CGI-S) Exit	3.3 Units on a scale Standard Deviation 1.6	3.9 Units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Clinical Global Impressions - Improvement (CGI-I)	2.9 Units on a scale Standard Deviation 1.4	3.5 Units on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Family Assessment Device (FAD) Baseline	2.0 General Functioning Subscale Score Standard Deviation 0.7	2.0 General Functioning Subscale Score Standard Deviation 0.5
Family Assessment Device (FAD) Exit	2.0 General Functioning Subscale Score Standard Deviation 0.6	2.2 General Functioning Subscale Score Standard Deviation 0.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Longitudinal Interval Follow-Up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT) Baseline	11.8 Units on a scale Standard Deviation 3.6	13.9 Units on a scale Standard Deviation 3.8
Longitudinal Interval Follow-Up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT) Exit	11.8 Units on a scale Standard Deviation 4.8	13.8 Units on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Sertraline n=19 Participants 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	Placebo n=19 Participants flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Quality of Life in Epilepsy-31 (QOLIE-31) Baseline	48.4 Units on a scale Standard Deviation 20.7	38.2 Units on a scale Standard Deviation 19.0
Quality of Life in Epilepsy-31 (QOLIE-31) Exit	56.7 Units on a scale Standard Deviation 25.1	46.9 Units on a scale Standard Deviation 24.0

Adverse Events

Sertraline

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Sertraline n=19 participants at risk 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	Placebo n=19 participants at risk flexible dose placebo, administered over 12 weeks with a two week untreated lead in period monitoring their baseline NES
Nervous system disorders tiredness/ sleepiness	5.3% 1/19 • Number of events 1 • 12 weeks	21.1% 4/19 • Number of events 4 • 12 weeks

Additional Information

W. Curt LaFrance, Jr., MD, MPH

Rhode Island Hospital

Phone: 401-444-3534

Email: William_LaFrance_Jr@Brown.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place