Interventieonderzoek (trials en cohort)
Study reference Study characteristics Patient characteristics Intervention (I) Comparison / control (C) Follow-up Outcome measures and effect size Comments

Goldstein, 2010

Type of study:

RCT

 

Setting:

Outpatient psychiatric setting

 

Country:

UK

 

Source of funding:

Supported by Guy’s and St. Thomas’ Charitable Foundation

Inclusion criteria:

Age 18-70 yr, clinical diagnosed Psychogenic nonepileptic seizures (PNES)

 

Exclusion criteria:

Comorbid history of epilepsy, <2PNES/month, current drug or alcohol misuse, benzodiazepine use exceeding equivalent of 10 mg diazepam/day and IQ<70.

 

N=66

 

Intervention group:

N=33

 

Mean age ± SD:

37.4±12.6

 

Sex: 27% M / 73% F

 

Control group:

N=33

 

Mean age ± SD:

35.9±15.1

 

Sex: 21% M / 79% F

 

Groups comparable at baseline?

yes

Cognitive-behavioral therapy (CBT)

 

Participants were offered up to 12 weekly/fortnightly hour-long outpatient sessions of CBT. Sessions involved enabling patients to interrupt responses experienced at the start of seizure, encouraging to engage in activities they were avoiding and addressing negative thoughts and illness beliefs.

Standard medical care (SMC)

 

Clinic review by a neuropsychiatrist by clinical need. Sessions were supportive in nature and provided explanations obout the psychological basis of seizures and supervised withdrawal of AEDs.

Endpoint of follow-up:

Primary: seizure frequency at the end of treatment and at 6-month follow-up

Secondary: 3 months of seizure freedom at 6-month follow-up, measures of psychosocial functioning, health service use and employment

 

Duration of follow-up:

6 months

 

For how many participants were no complete outcome data available?

 

Intervention group:

N (%):3/33 (9%)

 

Control group:

N (%):4/33 (12%)

 

Reasons for incomplete outcome data described?

No/loss contact with service, deceased (suicide)

 

Significant differences between groups?

no

Seizure frequency:

Large between group effect size of 0.75 at end of treatment and (medium) 0.42 at follow up

 

Seizure freedom:

CBT to SMC Odds Ratio 3.123 (95%CI 0.852-11.468; p=0.086)

Absolute risk reduction for not being seizure-free at follow-up: 19.5%

- no control group with no treatment

- SMC condition did not control for therapist contact, which was greater in the CBT group

- whether patients were receiving CBT could not be concealed from neuopsychiatrists providing SMC

- small sample size (n=66)

- potential selection bias to chronic, more difficult-to-treat patients

- longer follow-up would provide better comparison

LaFrance, 2010

Type of study:

Pilot double-blind RCT

 

Setting:

Rhode Island Hospital neuropsychiatry clinic (outpatient)

 

Country:

USA

 

Source of funding:

Dr. LaFrance receives research support from the NIH (NINDS 5K23NS045902), Rhode Island Hospital, the American Epilepsy Society, the Epilepsy Foundation and the Siravo Foundation.

Inclusion criteria:

Age 18-65 yr, diagnosed PNES with vEEG, experience of at least 1 event in the month before enrolling

 

Exclusion criteria:

subjective sensory seizures without apparent loss of consciousness or behavioural arrest, not clearly distinguishable mixed epileptic seizures and PNES, use of monoamine oxidase inhibitors or pimozide 30 days before study, optimized  sertraline, current psychosis, suicidality, DMS-IV substance dependence diagnosis, inability to complete written surveys, pending litigation, disability application.

 

N: 38

 

Intervention group:

N: 19

 

Mean age ± SD:

38 ±13.9

 

Sex: 15.8% M (N=3) / 84.2% F (n=16)

 

Control group:

N: 19

 

Mean age ± SD:

34.4 ±12.6

 

Sex: 31.6% M (n=6) / 68.4% F (n=13)

 

Groups comparable at baseline?

Patients in placebo group showed slightly higher unemployment, anxiety and Axes2 diagnoses, AED use and a family history of seizures. Patients in the seizure group reported slightly higher frequency of mood diagnoses, trauma history, prior treatment with antidepressants or psychotherapy and seizures. However no significant differences were found.

Sertraline (flexible dose)

 

Initiated at 25 mg  increased in biweekly intervals to 50 mg and then 50 mg increments to a max of 200 mg, unless limited by side-effects

Placebo

Endpoint of follow-up:

Primary outcomes: PNES frequency and comorbid symptom outcomes

Secondary outcomes: psychiatric symptom scales and psychosocial variables

 

Duration of follow-up: 2 wk baseline and 12 wk treatment

 

For how many participants were no complete outcome data available?

 

Intervention group:

N (%): 7/19 (36.8%)

 

Control group:

N (%): 5/19 (26.3%)

 

Reasons for incomplete outcome data described?

I: dropped (n=2), lost to follow-up (n=1) exited for other treatment (n=1), wanted known medication (n=2), had upcoming surgery (n=1)

C: dropped (n=2), side effects (n=1), fear of weight gain (n=1), wanted to discontinue medication (n=1)

 

Significant differences between groups?

no

Reduction in seizure rates from baseline to final visit:

I: 22.24 - 12.18 (45%) p=0.03
C 13.38 – 14.38 (-8%) p=0.78

 

50% reduction in seizure frequency

I: 8/17

C: 3/16

P= 0.18

 

No significant between-group differences in psychiatric symptoms or psychosocial variables

- pilot was not powered for establishing treatment efficacy

LaFrance, 2009

Type of study:

Prospective cohortstudy

 

Setting:

Rhode Island Hospital neuropsychiatry clinic (outpatient)

 

Country:

USA

 

Source of funding:

Dr. LaFrance received grants from NINDS and from the Epilepsy Foundation for treatments of PNES

Inclusion criteria:

Age ≥16 yr, vEEG diagnosis of PNES

 

Exclusion criteria:

Equivocal diagnosis on vEEG. presence of current psychosis, current suicidality, current substance dependence, mental retardation, pending litigation, disability application

 

N=21

 

Mean age ± SD:

36±10.4

 

Sex: 19% M / 81% F

 

Other important characteristics:

76% was currently unemployed, above 50% experienced mood and/or anxiety disorders and above 90% had a history of treama/abuse

Cognitive behavioural therapy

 weekly 1-hour sessions

No control

Endpoint of follow-up:

Primary outcome: Reduction of PNES frequency

Secondary outcome: psychiatric symptom scales and psychosocial variables

 

Duration of follow-up:

2 wk baseline period, 12 wk treatment period, 12 months of follow-up

 

For how many participants were no complete outcome data available?

N (%): 4/21 (19%)

 

Reasons for incomplete outcome data described?

Discontinued (n=2), shoulder pain, not able to complete written workbook assignments (n=1) and lost to follow-up (n=1)

Mean seizure frequency difference from pre-enrollment to completion: 10.9 (SD 13.9) to 7.1 (SD 14.6 )per week

 

50% reduction in seizure frequency: 16/21 (76%)

 

No seizures per week at final CBT session: 11/17 (65%)

 

Mean scores on scales of depression, anxiety, somatic symptoms, quality of life and psychosocial functioning showed improvement from baseline to final session

- small study population

Lafrance, 2014

Type of study:

RCT

 

Setting:

3 academic medical centers

 

Country:

USA

 

Source of funding:

Supported by the American Epilepsy Society amd nu yje Research Infrastructure Award from the Epilepsy Foundation. The funders had no role in the design and conduct of the study, the data, the manuscript or the publication

 

Inclusion criteria:

Age ≥18 – 65 yr, vEEG diagnosis of PNES, at least 1 event in previous month.

 

Exclusion criteria:

Concurrent mixed epilepsy and PNES or equivocal vEEG findings in discerning between epilepsy and PNES; use of monoamine oxidase inhibitor or pimozide in previous month; current use of sumatriptan succinate or other serotonin 1 receptor agonist; allergy or sensitivity to sertraline; current enrollment in CBT for PNES; current or past year self mutilation; frank psychosis; current suicidality with intent to harm self; serious illness; active substance or alcohol use or dependence that could interfere with participation; pending litigation; and current application for long-term disability.

N=38

I1:

N= 9

Mean age ± SD:

37.9±11.5

Sex: 22.2% M / 77.8% F

I2

N=9

Mean age ± SD:

39.7±11.7

Sex: 11.1% M / 88.9% F

I3

N=10

Mean age ± SD:

39.1±13.2

Sex: 0% M / 100% F

C

N=10

Mean age ± SD:

41.6±8.3

Sex: 0% M / 100% F

 

Groups comparable at baseline?

Yes

 

Different PNES treatments:

1. CBT-informed psychotherapy (CBT-ip)

2. flexible-dose sertraline

3. combined CBT-ip and sertraline

Standard medical care (treatment as usual)

Endpoint of follow-up: NR

Primary outcome: Reduction of PNES frequency

 

Duration of follow-up:

NR

 

For how many participants were no complete outcome data available?

N (%): 7/38 (18%)

 

Reasons for incomplete outcome data described?

Yes, pariticipants discontinued (n=4) or were lost to follow-up (n=3)

 

Mean seizure frequency difference from pre-enrollment to completion:

I1: -51.4 (p=0.01)

I2: -26.5 (p=0.08)

I3: -59.3 (p=0.008)

C: -0 (p=0.19)

The study was not powered to detect between-group differences, but was designed for within-group analyses

Study was not powered to analyse between-group differences