Cognitive Behavioral Therapy for Nonepileptic Seizures

Overseen By Aaron Fobian, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Epilepsy, Other therapy, Severe mental illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

Duration: 12 weeks

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new therapy called Retraining and Control Therapy (ReACT), designed to help young people aged 11-18 manage psychogenic non-epileptic seizures (PNES). These seizures resemble epilepsy but lack a clear medical cause. The study aims to determine if ReACT can help participants feel more in control and reduce their expectations of severe symptoms during stressful situations. Participants will attend twelve therapy sessions and engage in tasks like holding their hand in cool water to measure their response to pain. Ideal candidates for this study are children diagnosed with PNES who experience at least four episodes a month and do not have epilepsy. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research that could improve management strategies for PNES in young people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Retraining and Control Therapy (ReACT) is generally easy for people to handle. Studies on ReACT for conditions like psychogenic non-epileptic seizures (PNES) have demonstrated good results without major safety issues. Specifically, research involving both adults and children indicated that ReACT can improve symptoms by changing thoughts and behaviors related to seizures. No significant negative effects have been reported.

The pain relief and sensitivity lotions used in the cold pressor test (CPT) are standard products commonly used in similar tests and are not expected to cause harm. Overall, previous studies suggest that the treatments in this trial are safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the ReACT cognitive behavioral therapy for nonepileptic seizures (PNES) because it offers a unique approach to managing this condition. Unlike traditional treatments, which often focus on medication and generalized therapy, ReACT specifically targets the psychological aspects contributing to PNES through structured therapy sessions. Additionally, the trial explores the potential benefits of booster sessions, which could enhance long-term outcomes by reinforcing therapeutic gains. Such features make ReACT a promising alternative for those looking for a more tailored and potentially effective way to manage PNES.

What evidence suggests that this trial's treatments could be effective for pediatric psychogenic non-epileptic seizures?

Research has shown that Retraining and Control Therapy (ReACT), which participants in this trial may receive, effectively helps young people with psychogenic non-epileptic seizures (PNES) by enhancing their control over symptoms. Studies have found that ReACT addresses exaggerated fears about symptoms, known as catastrophic symptom expectations, and helps reduce seizure frequency. Early results suggest that this therapy leads to lasting improvement, with patients experiencing fewer seizures even a year after treatment. ReACT changes thoughts and behaviors, directly tackling the cause of seizures rather than just focusing on mood or stress. This method has proven effective for both children and adults with PNES. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for young people aged 9-18 with a diagnosis of psychogenic non-epileptic seizures (PNES) confirmed by video-EEG. They must experience at least four PNES per month and have a family member willing to participate. It's not suitable for those with severe mental illness, other nonepileptic events, participation in another therapy, severe intellectual disability, or comorbid epilepsy.

Inclusion Criteria

A family member agrees to join the study with me.

My seizures have been diagnosed as non-epileptic by a doctor using a special video test.

A family member I choose is willing to participate in the study with me.

Exclusion Criteria

I have epilepsy in addition to my primary condition.

I experience fewer than 4 psychogenic non-epileptic seizures monthly.

I experience sudden episodes not caused by epilepsy, such as those related to sleep disorders or migraines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants and their parents complete questionnaires and assessments including demographics, mood, suicidality, and PNES symptoms. Initial Cold Pressor Test (CPT) is conducted.

1 day

1 visit (in-person)

Treatment

Participants undergo 12 weekly sessions of Retraining and Control Therapy (ReACT) to address sense of control and catastrophic symptom expectations.

12 weeks

12 visits (1 in-person, 11 virtual)

Post-Treatment Assessment

Participants return for post-treatment assessments 1 week after the 8th and 12th therapy sessions to perform tasks and fill out questionnaires.

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for PNES frequency and complete long-term follow-up visits via Zoom at 6 months and 12 months after the 12th treatment session.

12 months

2 visits (virtual)

Booster Sessions (Optional)

Half of the participants receive 2 booster therapy sessions at 3 months and 9 months after the 12th treatment session.

6 months

2 visits (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• ReACT

Trial Overview The study tests Retraining and Control Therapy (ReACT), which aims to improve the sense of control and reduce catastrophic symptom expectations in children with PNES through twelve sessions. The effectiveness will be measured using tasks like holding a hand in cool water and questionnaires before treatment, after certain sessions, and up to one year later.

How Is the Trial Designed?

Group I: ReACT for PNES- No Booster therapy sessions Experimental Treatment 1 Intervention

After completing the 12 ReACT treatment sessions, half of the participants will be randomized to not receive the 2 booster therapy sessions.

Group II: CPT- Pain sensitivity lotion Experimental Treatment 1 Intervention

During the initial visit participant will do the cold pressor test twice to assess catastrophic symptom expectation. After completing the 1st CPT, participants will be randomized to receive a pain relief lotion or pain sensitivity lotion. Participants will then repeat the CPT with the lotion applied to their hand.

Group III: CPT- Pain relief lotion Experimental Treatment 1 Intervention

During the initial visit participant will do the cold pressor test twice to assess catastrophic symptom expectations. After completing the 1st CPT, participants will be randomized to receive a pain relief lotion or pain sensitivity lotion. Participants will then repeat the CPT with the lotion applied to their hand.

Group IV: Healthy Control Active Control 1 Intervention

Healthy controls are matched to participants with PNES based on age (+ or - 1 year), gender, race and family income. Healthy controls and their parent come for 1 baseline laboratory visit and a follow up visit 13 weeks after the baseline visit. These visits will be identical to baseline and follow-up visits of children with PNES.

Group V: ReACT for PNES- Booster therapy sessions Active Control 1 Intervention

After completing the 12 therapy sessions, half of the participants will be randomized to receive 2 booster therapy sessions, 3 months and 9 months after the 12th ReACT treatment session.

ReACT is already approved in United States for the following indications:

Approved in United States as ReACT for:

• Pediatric functional seizures

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In-session seizures are more common in patients with psychogenic nonepileptic seizures (PNES), occurring in 1 in 36 therapy sessions, compared to 1 in 136 sessions for patients with epilepsy, indicating a significantly higher risk for PNES patients (odds ratio 4.4).

Despite the occurrence of in-session seizures, they rarely disrupted therapy significantly and were typically managed effectively by therapists, suggesting that psychological treatments can be safely conducted with appropriate seizure management plans in place.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The frequency and management of seizures during psychological treatment among patients with psychogenic nonepileptic seizures and epilepsy. Kemp, S., Graham, CD., Chan, R., et al.[2018]

In a clinical trial with 21 outpatients diagnosed with psychogenic nonepileptic seizures (PNES), cognitive behavioral therapy (CBT) significantly reduced seizure frequency, with 11 out of 17 participants reporting no seizures by the end of treatment.

CBT also led to improvements in psychiatric symptoms, psychosocial functioning, and quality of life, indicating its effectiveness not just for seizure reduction but also for overall mental health and well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy for psychogenic nonepileptic seizures. LaFrance, WC., Miller, IW., Ryan, CE., et al.[2018]

Psychogenic nonepileptic seizures (PNES) are classified as a conversion disorder and require interdisciplinary management that focuses on modifiable risk factors, with patient engagement being a critical but challenging first step.

Cognitive-behavioral therapy has shown promise in treating PNES, and a preliminary study of mindfulness-based psychotherapy in 6 patients suggests it is feasible and should be explored further in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of psychogenic nonepileptic seizures: updated review and findings from a mindfulness-based intervention case series. Baslet, G., Dworetzky, B., Perez, DL., et al.[2018]

A specialized clinic for treating nonepileptic seizures (NES) was established, combining neurology and psychiatry services, and successfully treated 106 patients with a high retention rate of 65.4% after referral and 84.0% adherence to group therapy.

The clinic model not only provided effective psychological care but also led to a decrease in healthcare utilization, indicating its potential to improve access to care for both NES and epilepsy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of a multidisciplinary group therapy clinic for the treatment of nonepileptic seizures. Libbon, R., Gadbaw, J., Watson, M., et al.[2020]

Cognitive behavior therapy (CBT) significantly reduced levels of depression and anxiety in 14 patients with epilepsy and comorbid dissociative seizures, indicating its effectiveness in addressing these psychological issues.

While the frequency of dissociative seizures decreased after CBT treatment, this change was not statistically significant, suggesting that further research is needed to fully understand the impact of CBT on seizure frequency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavior therapy for comorbid dissociative seizures in patients with epilepsy. Berry, AJ., Yuksel, M., Proctor, BJ., et al.[2021]

Cognitive behavioral therapy (CBT) has shown efficacy in treating psychogenic nonepileptic seizures (PNES), with evidence from a pilot randomized controlled trial indicating it is more effective than standard medical care.

While the antidepressant sertraline did not significantly reduce seizure frequency compared to placebo, it did lead to a notable decrease in symptoms from pre- to post-treatment, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychogenic nonepileptic seizures: a treatment review. What have we learned since the beginning of the millennium? Baslet, G.[2021]

In a study of 147 patients with psychogenic nonepileptic seizures (PNESs) followed for an average of 4.2 years, 28.6% achieved seizure remission, but nearly half of those remained unproductive, indicating that seizure control alone does not guarantee overall well-being.

Patients who stopped having seizures still reported significant ongoing psychological issues, suggesting that treatment for PNESs should address both seizure management and mental health to improve overall outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring outcome in psychogenic nonepileptic seizures: how relevant is seizure remission? Reuber, M., Mitchell, AJ., Howlett, S., et al.[2019]

A systematic review of 12 studies involving 343 participants found that while some psychological therapies, particularly cognitive behavioral therapy (CBT), showed promise in reducing seizure frequency, the overall evidence for effective treatment of non-epileptic seizures is limited and of low reliability.

Most studies reported improvements with various interventions, but due to high risk of bias and heterogeneity in study designs, more rigorous randomized controlled trials are necessary to establish effective treatments for non-epileptic seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychological and behavioural treatments for adults with non-epileptic attack disorder. Martlew, J., Pulman, J., Marson, AG.[2022]

In a study of 105 patients with psychogenic nonepileptic seizures (PNES), those who adhered to psychotherapy (attending at least 8 sessions) experienced an 84% reduction in seizure frequency compared to 61% in those who did not adhere, indicating that consistent therapy can significantly improve outcomes.

Adherence to psychotherapy was also linked to improved quality of life and reduced emergency department visits, suggesting that engaging in treatment can lead to better overall health management for individuals with PNES.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Works, So Who's Afraid of PNES? Salpekar, J.[2020]

The primary treatment goal for nonepileptic seizures (NES) is to improve quality of life by reducing seizure frequency through a combination of education, mental health support, and gradual weaning off anticonvulsants.

With appropriate diagnosis and treatment, approximately 45% of NES patients can become seizure-free, and an additional one-third may experience a reduction in seizure frequency, highlighting the effectiveness of integrated psychiatric care alongside psychotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonepileptic Seizures. Bowman, ES.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7448150/

Retraining and control therapy for pediatric psychogenic ... ReACT aimed to retrain classically conditioned, involuntary PNES by targeting catastrophic symptom expectations and a low sense of control over symptoms.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589986421000770

One-year follow-up of treatment outcomes and patient ... This study confirms long-term maintenance of FS-reduction after ReACT and supports the efficacy of targeting FS directly as opposed to mood or stress for ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02801136?cond=Non-Epileptic%20Seizures&viewType=Table&rank=6

NCT02801136 | Treatment Outcomes of ReACT for PNES This research study is examining the effects of Retraining and Control Therapy (ReACT; an intervention focused on changing behaviors and thoughts) for ...

4. seizure-journal.com seizure-journal.com/article/S1059-1311(21)00314-9/fulltext

Retraining and Control Therapy (ReACT) is a bottom-up ... The effectiveness of psychological interventions for children and adolescents with non-epileptic seizures.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06570954

Retraining and Control Therapy (ReACT)- Adults The purpose of this study is to assess sense of control and catastrophic symptom expectations as targets for Retraining and Control Therapy (ReACT- an ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06007053?term=AREA%5BConditionSearch%5D(Epileptic%20seizure)&rank=8

Retraining and Control Therapy (ReACT) R33 Phase Measured by Psychogenic Non-epileptic Seizures (PNES) diary, including frequency, premonitory symptoms, description of PNES symptoms and duration. Assessed 30 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525505023000616

Sense of control, selective attention, cognitive inhibition ... Retraining and Control Therapy (ReACT), which targets these factors, has been shown in a randomized controlled trial to be effective in improving pediatric FS ...