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

Psychogenic Non-Epileptic Seizure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05241366
• Other study ID #: 16/21
• Status: Completed
• Phase: N/A
• Start date: February 14, 2022
• Est. completion date: July 31, 2023

Study information

• Verified date: September 2023
• Source: El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 31, 2023
• Est. primary completion date: May 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Patients who have a record at the institute with the diagnosis of PNES.

3. Patients with an encephalic MRI.

4. Patients who give their written consent to participate in the protocol.

5. Patients who have not had any changes in the pharmacological treatment in the last 6 weeks.

Exclusion Criteria:

1. Patients who cannot answer the scales and other clinimetric instruments.

2. Patients with a history of previous or current epilepsy.

3. Patients with other major neurological comorbidities (tumor, cerebrovascular event (CVE), cranioencephalic trauma (TBI)).

4. Patients currently taking medications that lower the seizure threshold (Bupropion).

5. Patients with psychiatric comorbidities such as psychosis/bipolar disorder/substance abuse.

6. Patients with certain implanted metallic devices (pacemakers).

7. Pregnant women.

Related Conditions & MeSH terms

• Epilepsy
• Psychogenic Non-Epileptic Seizure
• Seizures

Intervention

Device:
• Transcranial Magnetic Stimulation
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.
• Sham Transcranial Magnetic Stimulation coil
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.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Neurologia Y Neurocirugia Mvs	Mexico	Ciudad De Mexico

Sponsors (1)

Lead Sponsor	Collaborator
El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Country where clinical trial is conducted

Mexico, 

References & Publications (15)

Agarwal R, Garg S, Tikka SK, Khatri S, Goel D. Successful use of theta burst stimulation (TBS) for treating psychogenic non epileptic seizures (PNES) in a pregnant woman. Asian J Psychiatr. 2019 Jun;43:121-122. doi: 10.1016/j.ajp.2019.05.013. Epub 2019 May 8. No abstract available. — View Citation

Benbadis SR, Allen Hauser W. An estimate of the prevalence of psychogenic non-epileptic seizures. Seizure. 2000 Jun;9(4):280-1. doi: 10.1053/seiz.2000.0409. — View Citation

Dafotakis M, Ameli M, Vitinius F, Weber R, Albus C, Fink GR, Nowak DA. [Transcranial magnetic stimulation for psychogenic tremor - a pilot study]. Fortschr Neurol Psychiatr. 2011 Apr;79(4):226-33. doi: 10.1055/s-0029-1246094. Epub 2011 Apr 8. German. — View Citation

Duncan R, Razvi S, Mulhern S. Newly presenting psychogenic nonepileptic seizures: incidence, population characteristics, and early outcome from a prospective audit of a first seizure clinic. Epilepsy Behav. 2011 Feb;20(2):308-11. doi: 10.1016/j.yebeh.2010.10.022. Epub 2010 Dec 30. — View Citation

Kanemoto K, LaFrance WC Jr, Duncan R, Gigineishvili D, Park SP, Tadokoro Y, Ikeda H, Paul R, Zhou D, Taniguchi G, Kerr M, Oshima T, Jin K, Reuber M. PNES around the world: Where we are now and how we can close the diagnosis and treatment gaps-an ILAE PNES Task Force report. Epilepsia Open. 2017 Jun 23;2(3):307-316. doi: 10.1002/epi4.12060. eCollection 2017 Sep. Erratum In: Epilepsia Open. 2019 Jan 07;4(1):219. — View Citation

LaFrance WC Jr, Keitner GI, Papandonatos GD, Blum AS, Machan JT, Ryan CE, Miller IW. Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures. Neurology. 2010 Sep 28;75(13):1166-73. doi: 10.1212/WNL.0b013e3181f4d5a9. Epub 2010 Aug 25. — View Citation

LaFrance, W., & Blumer, D. (2018). Pharmacological Treatments for Psychogenic Nonepileptic Seizures. University of Warwick. Retrieved from: https://www.cambridge.org/core.

Nightscales R, McCartney L, Auvrez C, Tao G, Barnard S, Malpas CB, Perucca P, McIntosh A, Chen Z, Sivathamboo S, Ignatiadis S, Jones S, Adams S, Cook MJ, Kwan P, Velakoulis D, D'Souza W, Berkovic SF, O'Brien TJ. Mortality in patients with psychogenic nonepileptic seizures. Neurology. 2020 Aug 11;95(6):e643-e652. doi: 10.1212/WNL.0000000000009855. Epub 2020 Jul 20. — View Citation

Parain D, Chastan N. Large-field repetitive transcranial magnetic stimulation with circular coil in the treatment of functional neurological symptoms. Neurophysiol Clin. 2014 Oct;44(4):425-31. doi: 10.1016/j.neucli.2014.04.004. Epub 2014 May 15. — View Citation

Peterson KT, Kosior R, Meek BP, Ng M, Perez DL, Modirrousta M. Right Temporoparietal Junction Transcranial Magnetic Stimulation in the Treatment of Psychogenic Nonepileptic Seizures: A Case Series. Psychosomatics. 2018 Nov;59(6):601-606. doi: 10.1016/j.psym.2018.03.001. Epub 2018 Mar 7. — View Citation

Peterson, K., et al. (2017). Transcranial Magnetic Stimulation in the treatment of non-epileptic seizures: A Case Series. Max Rady College of Medicine. University of Manitoba.

Pollak TA, Nicholson TR, Edwards MJ, David AS. A systematic review of transcranial magnetic stimulation in the treatment of functional (conversion) neurological symptoms. J Neurol Neurosurg Psychiatry. 2014 Feb;85(2):191-7. doi: 10.1136/jnnp-2012-304181. Epub 2013 Jan 8. — View Citation

van der Kruijs SJ, Bodde NM, Vaessen MJ, Lazeron RH, Vonck K, Boon P, Hofman PA, Backes WH, Aldenkamp AP, Jansen JF. Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures. J Neurol Neurosurg Psychiatry. 2012 Mar;83(3):239-47. doi: 10.1136/jnnp-2011-300776. Epub 2011 Nov 5. — View Citation

van der Kruijs SJ, Jagannathan SR, Bodde NM, Besseling RM, Lazeron RH, Vonck KE, Boon PA, Cluitmans PJ, Hofman PA, Backes WH, Aldenkamp AP, Jansen JF. Resting-state networks and dissociation in psychogenic non-epileptic seizures. J Psychiatr Res. 2014 Jul;54:126-33. doi: 10.1016/j.jpsychires.2014.03.010. Epub 2014 Mar 21. — View Citation

Varia I, Logue E, O'connor C, Newby K, Wagner HR, Davenport C, Rathey K, Krishnan KR. Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin. Am Heart J. 2000 Sep;140(3):367-72. doi: 10.1067/mhj.2000.108514. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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-)
Primary	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
Primary	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	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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-)
Secondary	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
Secondary	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