TMS vs Conventional Therapy for the Treatment of Functional Neurological Non Epileptic Seizure Disorder

Study Overview
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Brief Summary
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The aim of the study is to compare the effect of Transcranial Magnetic Stimulation (TMS) versus treatment with selective serotonin reuptake inhibitors (SSRIs), in patients with diagnosis of Functional Neurological Non Epileptic Seizure Disorder (PNES).

Detailed Description
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This study consists of a single-blind Randomized Controlled Clinical Trial comprised of 20 patients with diagnosis of Psychogenic Non Epileptic Seizures (PNES), distributed in 2 arms of 10 patients each. Patients (n=20) will be randomly assigned (using the block randomization method) to one of the groups. Both groups of patients will be receiving their usual medical treatment (SSRIs), one group will receive in addition a therapeutic scheme with active TMS, while the second group will receive the same scheme, but with a sham TMS coil to decrease the bias of placebo effect.

Official Title
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Controlled Clinical Trial of Transcranial Magnetic Stimulation Versus Conventional Therapy for the Treatment of Functional Neurological Non-Epileptic Seizure Disorder: A Pilot Study

Conditions
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Psychogenic Non-Epileptic Seizure

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation
* Device: Sham Transcranial Magnetic Stimulation coil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of PNES, based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and the ILAE, confirmed by video recording and/or V-EEG monitoring, and who have a monthly seizure frequency greater than 3. Patients who have a record at the institute with the diagnosis of PNES. Patients with an encephalic MRI. Patients who give their written consent to participate in the protocol. Patients who have not had any changes in the pharmacological treatment in the last 6 weeks. Exclusion Criteria: Patients who cannot answer the scales and other clinimetric instruments. Patients with a history of previous or current epilepsy. Patients with other major neurological comorbidities (tumor, cerebrovascular event (CVE), cranioencephalic trauma (TBI)). Patients currently taking medications that lower the seizure threshold (Bupropion). Patients with psychiatric comorbidities such as psychosis/bipolar disorder/substance abuse. Patients with certain implanted metallic devices (pacemakers). Pregnant women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-blind randomized controlled clinical trial. Non-probabilistic sampling of consecutive cases randomized to each arm of the study. The study will consist of a control group and a study group. The study group will receive a therapeutic scheme with Transcranial Magnetic Stimulation (TMS) + usual pharmacological treatment and the control group will receive an identical scheme with TMS simulated with a sham coil + usual pharmacological treatment.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial Magnetic Stimulation + usual treatment with SSRIs<br>Transcranial Magnetic Stimulation + SSRIs The TMS group will be comprised of 10 patients, each subject will receive 12 sessions of low frequency (1 Hz) rTMS over right dorsolateral prefrontal cortex with a total of 1500 each session. All patients will continue with the usual treatment established by their treating physician. Those who do not have a previous pharmacological treatment will start a protocol with sertraline, which should be started at a 50 mg/day dosage. | Device: Transcranial Magnetic Stimulation<br>* The TMS group will be comprised of 10 patients, each subject will receive 12 sessions of low frequency (1 Hz) rTMS over the right dorsolateral prefrontal cortex with a total of 1500 pulses in each session. Each session will last approximately 30 minutes. There will be one session per day, five sessions per week. The total duration of the treatment will be four weeks. All patients will continue with the usual treatment established by their treating physician. Those who do not have a previous pharmacological treatment will start a protocol with sertraline, which should be started at a 50 mg/day dosage.<br>* Other names: rTMS;|
| Sham Comparator: Sham TMS coil + usual treatment with SSRIs<br>The sham TMS coil group will be comprised of 10 patients, sham TMS stimulation will be performed with the B-65 coil, which has similar sound and scalp contact to those experienced during active stimulation. The duration of treatment will be the same as in the experimental arm. All patients will continue with the usual treatment established by their treating physician. Those who do not have a previous pharmacological treatment will start a protocol with sertraline, which should be started at a 50 mg/day dosage. | Device: Sham Transcranial Magnetic Stimulation coil<br>* Simulated TMS stimulation will be performed with a Sham TMS coil, which has a sound and scalp contact similar to those experienced during active stimulation. The duration of the treatment will be the same as in the experimental arm. All patients will continue with the usual treatment established by their treating physician. Those who do not have a previous pharmacological treatment will start a protocol with sertraline, which should be started at a 50 mg/day dosage.<br>* Other names: Sham TMS coil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PNES count (1/4) | Participants in both groups will registered in a specific chart, daily psychogenic non-epileptic seizure activity. | Baseline PNES count (Starting 1 month before TMS treatment) | 
| PNES count (2/4) | Participants in both groups will registered in a specific chart, daily psychogenic non-epileptic seizure activity. | Change from Baseline PNES count (immediately after the session 12th -last session-) | 
| PNES count (3/4) | Participants in both groups will registered in a specific chart, daily psychogenic non-epileptic seizure activity. | Change from Baseline PNES count at month 1 post treatment | 
| PNES count (4/4) | Participants in both groups will registered in a specific chart, daily psychogenic non-epileptic seizure activity. | Change from Baseline PNES count at month 2 post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychometric self-assessment scales (BDI-II) 1/4 | 1.0) Mood: Beck Depression Inventory-II (BDI-II) Minimum score: 0 Maximum score: 63 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression 31-40: Severe depression over 40: Extreme depression *Higher scores mean a worse outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (BDI-II) 2/4 | 1.1) Mood: Beck Depression Inventory-II (BDI-II) Minimum score: 0 Maximum score: 63 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression 31-40: Severe depression over 40: Extreme depression *Higher scores mean a worse outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (BDI-II) 3/4 | 1.2) Mood: Beck Depression Inventory-II (BDI-II) Minimum score: 0 Maximum score: 63 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression 31-40: Severe depression over 40: Extreme depression *Higher scores mean a worse outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (BDI-II) 4/4 | 1.3) Mood: Beck Depression Inventory-II (BDI-II) Minimum score: 0 Maximum score: 63 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression 31-40: Severe depression over 40: Extreme depression *Higher scores mean a worse outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (DES) 1/4 | 2.0) Dissociation : Dissociative Experience Scale (DES). Minimum score: 0 Maximum score: 100 High levels of dissociation are indicated by scores of 30 or more, scores under 30 indicate low levels. *Higher scores mean a worse outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (DES) 2/4 | 2.1) Dissociation : Dissociative Experience Scale (DES). Minimum score: 0 Maximum score: 100 High levels of dissociation are indicated by scores of 30 or more, scores under 30 indicate low levels. *Higher scores mean a worse outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (DES) 3/4 | 2.2) Dissociation : Dissociative Experience Scale (DES). Minimum score: 0 Maximum score: 100 High levels of dissociation are indicated by scores of 30 or more, scores under 30 indicate low levels. *Higher scores mean a worse outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (DES) 4/4 | 2.3) Dissociation : Dissociative Experience Scale (DES). Minimum score: 0 Maximum score: 100 High levels of dissociation are indicated by scores of 30 or more, scores under 30 indicate low levels. *Higher scores mean a worse outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (PTSD) 1/4 | 3.0) PTSD/Trauma/Resilience: PTSD Symptom Severity Scale. Minimum score: 0 Maximum score: 80 *Higher scores mean a worse outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (PTSD) 2/4 | 3.1) PTSD/Trauma/Resilience: PTSD Symptom Severity Scale. Minimum score: 0 Maximum score: 80 *Higher scores mean a worse outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (PTSD) 3/4 | 3.2) PTSD/Trauma/Resilience: PTSD Symptom Severity Scale. Minimum score: 0 Maximum score: 80 *Higher scores mean a worse outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (PTSD) 4/4 | 3.3) PTSD/Trauma/Resilience: PTSD Symptom Severity Scale. Minimum score: 0 Maximum score: 80 *Higher scores mean a worse outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (MoCA) 1/4 | 4.0) Education and Cognition: Montreal Cognitive Assessment (MoCA). Minimum score: 0 Maximum score: 30 Normal score: 26-30 Probable Neurocognitive Dissorder: 0-25 *Higher scores mean a better outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (MoCA) 2/4 | 4.1) Education and Cognition: Montreal Cognitive Assessment (MoCA). Minimum score: 0 Maximum score: 30 Normal score: 26-30 Probable Neurocognitive Dissorder: 0-25 *Higher scores mean a better outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (MoCA) 3/4 | 4.2) Education and Cognition: Montreal Cognitive Assessment (MoCA). Minimum score: 0 Maximum score: 30 Normal score: 26-30 Probable Neurocognitive Dissorder: 0-25 *Higher scores mean a better outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (MoCA) 4/4 | 4.3) Education and Cognition: Montreal Cognitive Assessment (MoCA). Minimum score: 0 Maximum score: 30 Normal score: 26-30 Probable Neurocognitive Dissorder: 0-25 *Higher scores mean a better outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (WHOQOL-BREF) 1/4 | 5.0) Quality of life: WHOQOL-BREF (World Health Organization Quality of Life-BREF). Minimum score: 0 Maximum score: 100 *Higher scores mean a better outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (WHOQOL-BREF) 2/4 | 5.1) Quality of life: WHOQOL-BREF (World Health Organization Quality of Life-BREF). Minimum score: 0 Maximum score: 100 *Higher scores mean a better outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (WHOQOL-BREF) 3/4 | 5.2) Quality of life: WHOQOL-BREF (World Health Organization Quality of Life-BREF). Minimum score: 0 Maximum score: 100 *Higher scores mean a better outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (WHOQOL-BREF) 4/4 | 5.3) Quality of life: WHOQOL-BREF (World Health Organization Quality of Life-BREF). Minimum score: 0 Maximum score: 100 *Higher scores mean a better outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (King's) 1/4 | 6.0) King's Internalized Stigma Scale. Minimum score: 0 Maximum score: 112 *Higher scores mean a worse outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (King's) 2/4 | 6.1) King's Internalized Stigma Scale. Minimum score: 0 Maximum score: 112 *Higher scores mean a worse outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (King's) 3/4 | 6.2) King's Internalized Stigma Scale. Minimum score: 0 Maximum score: 112 *Higher scores mean a worse outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (King's) 4/4 | 6.3) King's Internalized Stigma Scale. Minimum score: 0 Maximum score: 112 *Higher scores mean a worse outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (OCI-R) 1/4 | 7.0) Obsessions/compulsions: The Obsessive-Compulsive Inventory Short Version (OCI-R) Minimum score: 0 Maximum score: 72 *Higher scores mean a worse outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (OCI-R) 2/4 | 7.1) Obsessions/compulsions: The Obsessive-Compulsive Inventory Short Version (OCI-R) Minimum score: 0 Maximum score: 72 *Higher scores mean a worse outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (OCI-R) 3/4 | 7.2) Obsessions/compulsions: The Obsessive-Compulsive Inventory Short Version (OCI-R) Minimum score: 0 Maximum score: 72 *Higher scores mean a worse outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (OCI-R) 4/4 | 7.3) Obsessions/compulsions: The Obsessive-Compulsive Inventory Short Version (OCI-R) Minimum score: 0 Maximum score: 72 *Higher scores mean a worse outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (BAI) 1/4 | 8.0) Beck Anxiety Inventory (BAI). Minimum score: 0 Maximum score: 63 Minimal: 0 - 7 Mild: 8 - 15 Moderate: 16 - 25 Severe: 26 - 63 *Higher scores mean a worse outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (BAI) 2/4 | 8.1) Beck Anxiety Inventory (BAI). Minimum score: 0 Maximum score: 63 Minimal: 0 - 7 Mild: 8 - 15 Moderate: 16 - 25 Severe: 26 - 63 *Higher scores mean a worse outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (BAI) 3/4 | 8.2) Beck Anxiety Inventory (BAI). Minimum score: 0 Maximum score: 63 Minimal: 0 - 7 Mild: 8 - 15 Moderate: 16 - 25 Severe: 26 - 63 *Higher scores mean a worse outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (BAI) 4/4 | 8.3) Beck Anxiety Inventory (BAI). Minimum score: 0 Maximum score: 63 Minimal: 0 - 7 Mild: 8 - 15 Moderate: 16 - 25 Severe: 26 - 63 *Higher scores mean a worse outcome. | Change from Baseline score at month 2 post treatment | 
| Psychometric self-assessment scales (HADS) 1/4 | 9.0) Anxiety: Hospital Anxiety and Depression Scale (HADS). Depression (D): Minimum score: 0 Maximum score: 21 Anxiety (A): Minimum score: 0 Maximum score: 21 *Higher scores mean a worse outcome. | Baseline score (1 month before TMS treatment) | 
| Psychometric self-assessment scales (HADS) 2/4 | 9.1) Anxiety: Hospital Anxiety and Depression Scale (HADS). Depression (D): Minimum score: 0 Maximum score: 21 Anxiety (A): Minimum score: 0 Maximum score: 21 *Higher scores mean a worse outcome. | Change from Baseline score (immediately after the 12th session -last session-) | 
| Psychometric self-assessment scales (HADS) 3/4 | 9.2) Anxiety: Hospital Anxiety and Depression Scale (HADS). Depression (D): Minimum score: 0 Maximum score: 21 Anxiety (A): Minimum score: 0 Maximum score: 21 *Higher scores mean a worse outcome. | Change from Baseline score at month 1 post treatment | 
| Psychometric self-assessment scales (HADS) 4/4 | 9.3) Anxiety: Hospital Anxiety and Depression Scale (HADS). Depression (D): Minimum score: 0 Maximum score: 21 Anxiety (A): Minimum score: 0 Maximum score: 21 *Higher scores mean a worse outcome. | Change from Baseline score at month 2 post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation, Selective Serotonin Reuptake Inhibitor, Functional Neurological Disorder