Transcranial Magnetic Stimulation in Patients with Dual Disorders

NCT06765824 | Not Yet Recruiting Phase 3 FDA Device

• 1 other identifier: CEIm-64-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

According to the WHO, 280 million people are diagnosed with depression, the prevalence of which is almost twice as high in women as in men, with the incidence among young people increasing in recent years. Another public health problem in Spain is tobacco consumption, with one in four adults being tobacco users. The presence of an addiction and another mental illness in the same patient is called dual disorder, and it is very common for depression to be associated with smoking. This is due to a shared biopsychosocial vulnerability between the two disorders. Although there are currently pharmacological treatments that address both disorders, their efficacy is limited; in this sense, transcranial magnetic stimulation (TMS) offers a way to treat these dual disorders. TMS is a technique in which a magnetic field is applied to the cortex through a coil, generating an electric current that can induce changes in the different neurotransmitter systems, stimulating or inhibiting them. A randomised, double-blind, placebo-controlled clinical trial is proposed to evaluate the efficacy of TMS in the treatment of a sample of 36 patients with resistant major depression and nicotine dependence. Both depression and smoking will be assessed at baseline, at various times during treatment and at the end of the study using psychometric tests, neurophysiological and biochemical assessments. It is expected that the experimental group will show improvements in depression, nicotine dependence and certain cognitive functions. TMS treatment of dual disorders (resistant depression + smoking) could represent a health and social advance, especially for women.

Conditions

Major Depression; Tobacco Addiction

Keywords

Transcranial Magnetic Stimulation; Major depressive disorder; Tobacco Addiction; Dual disorder

Outcome Measures

Primary Outcomes (7)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of transcranial magnetic stimulation in the treatment of resistant major depression and smoking, in patients with dual diagnosis..

  The tolerability of the treatment will be measured by means of a qualitative questionnaire (YES/NO), to be filled out by the patient. The possible side effects that will be taken into account are: epileptic crisis, manic shift, syncope, transient headache, localized pain in the area of application, neck pain, paresthesia, toothache, transient changes in hearing and scalp burns.

  Baseline and day 5, 10, 15 and 18. Baseline and day 108 (booster doses completed).

• Evaluation of the efficacy of transcranial magnetic stimulation in the treatment of resistant major depression in patients with dual disorder through the Hamilton Rating Scale.

  The effectiveness of the treatment applied will be through the evaluation of the changes produced in the affective symptoms. These changes will be evaluated with the following clinical scales: \- Hamilton Rating Scale for Depression (HDRS). Classification of symptoms: 0 - absent; 1 - mild; 2 - moderate; 3 - severe; 4 - incapacitating. In general the higher the total score the more severe the depression. HAM-D score level of depression: 10 - 13 mild; 14-17 mild to moderate; \>17 moderate to severe.

  Baseline. Baseline and day 9 and 18. Baseline and day 108 (booster doses completed).

• Evaluation of the efficacy of transcranial magnetic stimulation in the treatment of resistant major depression in patients with dual disorder through Clinical Global Impression Scale.

  The effectiveness of the treatment applied will be through the evaluation of the changes produced in the affective symptoms. These changes will be evaluated with the following clinical scales: -Clinical Global Impression (CGI) The scale consists of two sections: severity of the disease and improvement. Scores range from 1 to 7. Higher scores correspond to more severe symptoms and no improvement. A score of 0 corresponds to no evaluation.

  Baseline. Baseline and day 9 and 18. Baseline and day 108 (booster doses completed)

• Evaluation of the efficacy of transcranial magnetic stimulation in the treatment of resistant major depression and smoking in patients with dual disorder.

  The effectiveness of the treatment applied will be through the evaluation of the changes produced in the affective symptoms. These changes will be evaluated with the following clinical scales: \- Montgomery-Asberg Depression Rating Scale (MADRS) It is a 10-item scale. For each item, the scale includes 7 levels of intensity/severity, scored from 0 to 6, of which 4 (0-2-4-6) are predefined and the remaining 3 (1-3-5) are reserved for intermediate situations in which it is not possible to clearly assign the degree of symptomatic intensity to any of the previous levels. A score below 10 points is considered to indicate the absence of depressive disorder.

  Baseline. Baseline and day 9 and 18. Baseline and 3 months (booster doses completed)

• Evaluation of the efficacy of transcranial magnetic stimulation in the treatment of smoking in patients with dual disorder.

  The effectiveness of the treatment applied will be through the evaluation of the changes produced in the tobacco addiction. These changes will be evaluated with the following clinical scales: \- Fagerström test for Nicotine Dependence The scale consists of 8 items, in which scores range from 0 to 10 points. Low dependency: 0-3 Moderate dependency: 4-7 High dependency: 8-10

  Baseline. Baseline and day 9 and 18. Baseline and day 108 (booster doses completed)

• Evaluation of the efficacy of transcranial magnetic stimulation in the treatment of resistant major depression and smoking in patients with dual disorder.

  The effectiveness of the treatment applied will be through the evaluation of the changes produced in the tobacco addiction. These changes will be evaluated with the following clinical scales: \- Pack-year ratio calculation

  Baseline. Baseline and day 108 (booster doses completed)

• Evaluation of the efficacy of transcranial magnetic stimulation in the treatment of resistant major depression and smoking in patients with dual disorder.

  The effectiveness of the treatment applied will be through the evaluation of the changes produced in the tobacco addiction. These changes will be evaluated with the following clinical scales: \- Smoking Diary

  Baseline. Day 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and 18. Baseline and day 108 (booster doses complete)

Secondary Outcomes (4)

• Detection by clinical scales of changes produced in different cognitive functions after treatment with transcranial magnetic stimulation in patients with dual diagnosis (resistant major depression and smoking).

  Baseline. Baseline and day 9 and 18. Baseline and day 108 (booster doses completed)

• Detection by clinical scales of changes produced in different cognitive functions after treatment with transcranial magnetic stimulation in patients with dual diagnosis (resistant major depression and smoking).

  Baseline. Baseline and day 9 and 18. Baseline and day 108 (booster doses completed)

• Detection by neurophysiological tests of changes produced in different cognitive functions after treatment with transcranial magnetic stimulation in patients with dual diagnosis (resistant major depression and smoking).

  Baseline. Baseline and day 9 and 18. Baseline and 3 months (booster doses completed)

• Detection by neurophysiological tests of changes produced in different cognitive functions after treatment with transcranial magnetic stimulation in patients with dual diagnosis (resistant major depression and smoking).

  Baseline. Baseline and day 9 and 18. Baseline and day 108 (booster doses completed)

Study Arms (2)

Transcranial Magnetic Stimulation-Active Coil

EXPERIMENTAL

Patients in the experimental group will receive transcranial magnetic stimulation treatment using an active coil, cool-B70. The protocol to be administered is composed of 36 sessions that will be divided into two sessions per day, with a 50-minute break between sessions. For three months after the main treatment (protocol described above), a booster dose will be administered once a week.

Device: Repetitive Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation-Sham coil

SHAM COMPARATOR

The control group will receive the same protocol as the experimental group, with the main difference being that this group receives treatment through a placebo coil, MCF-P-B70. The placebo coil maintains the appearance and sound of the one that administers the active treatment, but differs from this in that it does not generate an effective magnetic field capable of generating depolarization in the stimulated brain area.

Device: Transcranial Magnetic Stimulation Sham

Interventions

Repetitive Transcranial Magnetic Stimulation DEVICE

The protocol will be applied with the MagVenture R30 stimulation device and the cool-B70 coil for active treatment. The protocol will consist of two sessions per day, with a 50-minute break between sessions, every day of the week (Monday to Friday) for three and a half weeks (a total of 36 sessions). Each session will consist of the application of a 1Hz protocol (2000 pulses at 120% of the motor threshold) in the right dorsolateral prefrontal cortex (F4) followed by an intermittent theta-burst protocol (1800 pulses at 90% of the motor threshold) in the left dorsolateral prefrontal cortex (F3). The cortical target localization will be performed using the beam-F3/F4 technique that combines different electroencephalographic positioning parameters and measurements to accurately locate said cortical targets. The motor threshold of each patient will be calculated at the beginning of each week of treatment using an electromyography system.

Transcranial Magnetic Stimulation-Active Coil

Transcranial Magnetic Stimulation Sham DEVICE

The same protocol described in the intervention group will be carried out in the control group. The device used is the same, the difference is the coil that maintains the same appearance and generates the same sound as the active treatment coil, but unlike the latter, it does not produce an effective magnetization to depolarize the cerebral cortex on which we act.

Transcranial Magnetic Stimulation-Sham coil

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients over 18 years of age being monitored in the mental health area of the province of Castellón, with a dual disorder: major depression and substance abuse disorder
• Patients who are refractory to two or more lines of pharmacological treatments, ensuring correct completion beforehand
• Acceptance of informed consent

You may not qualify if:

• Psychotic symptoms or catatonia
• Other addictions, or psychiatric or personality disorders
• Language barrier
• Mental retardation that will interfere with the ability to understand and subsequent acceptance or rejection of informed consent
• Patients diagnosed with epilepsy
• Patients diagnosed with a space-occupying lesion in the brain
• Tinnitus
• Confirmed pregnancy; if suspected, a test will be requested
• Metal piece in the body or implanted medical device, except for dental material

Sponsors & Collaborators

• Cardenal Herrera University: lead
• Hospital Provincial de Castellon: collaborator

Study Sites (1)

Consorcio Hospitalario Provincial de Castellón

Castellon, Castellón, 12002, Spain

Location

Related Publications (13)

• Young JR, Galla JT, Appelbaum LG. Transcranial Magnetic Stimulation Treatment for Smoking Cessation: An Introduction for Primary Care Clinicians. Am J Med. 2021 Nov;134(11):1339-1343. doi: 10.1016/j.amjmed.2021.06.037. Epub 2021 Aug 15.

  PMID: 34407423 BACKGROUND

• Prochaska JJ, Benowitz NL. Current advances in research in treatment and recovery: Nicotine addiction. Sci Adv. 2019 Oct 16;5(10):eaay9763. doi: 10.1126/sciadv.aay9763. eCollection 2019 Oct.

  PMID: 31663029 BACKGROUND

• Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.

  PMID: 22193671 BACKGROUND

• Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. 2016 May-Jun;9(3):336-346. doi: 10.1016/j.brs.2016.03.010. Epub 2016 Mar 16.

  PMID: 27090022 BACKGROUND

• Mahoney JJ 3rd, Hanlon CA, Marshalek PJ, Rezai AR, Krinke L. Transcranial magnetic stimulation, deep brain stimulation, and other forms of neuromodulation for substance use disorders: Review of modalities and implications for treatment. J Neurol Sci. 2020 Nov 15;418:117149. doi: 10.1016/j.jns.2020.117149. Epub 2020 Sep 20.

  PMID: 33002757 BACKGROUND

• Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1.

  PMID: 31901449 BACKGROUND

• Kuehner C. Why is depression more common among women than among men? Lancet Psychiatry. 2017 Feb;4(2):146-158. doi: 10.1016/S2215-0366(16)30263-2. Epub 2016 Nov 15.

  PMID: 27856392 BACKGROUND

• Koutsomitros T, Evagorou O, Schuhmann T, Zamar A, Sack AT. Advances in transcranial magnetic stimulation (TMS) and its applications in resistant depression. Psychiatriki. 2021 Dec;32(Supplement I):90-98. doi: 10.22365/jpsych.2021.054.

  PMID: 34990384 BACKGROUND

• Ferrarelli F, Phillips ML. Examining and Modulating Neural Circuits in Psychiatric Disorders With Transcranial Magnetic Stimulation and Electroencephalography: Present Practices and Future Developments. Am J Psychiatry. 2021 May 1;178(5):400-413. doi: 10.1176/appi.ajp.2020.20071050. Epub 2021 Mar 3.

  PMID: 33653120 BACKGROUND

• Echeverria I, Cotaina M, Jovani A, Mora R, Haro G, Benito A. Proposal for the Inclusion of Tobacco Use in Suicide Risk Scales: Results of a Meta-Analysis. Int J Environ Res Public Health. 2021 Jun 5;18(11):6103. doi: 10.3390/ijerph18116103.

  PMID: 34198855 BACKGROUND

• Cui Y, Fang H, Bao C, Geng W, Yu F, Li X. Efficacy of Transcranial Magnetic Stimulation for Reducing Suicidal Ideation in Depression: A Meta-Analysis. Front Psychiatry. 2022 Jan 18;12:764183. doi: 10.3389/fpsyt.2021.764183. eCollection 2021.

  PMID: 35115959 BACKGROUND

• Burke MJ, Fried PJ, Pascual-Leone A. Transcranial magnetic stimulation: Neurophysiological and clinical applications. Handb Clin Neurol. 2019;163:73-92. doi: 10.1016/B978-0-12-804281-6.00005-7.

  PMID: 31590749 BACKGROUND

• Brini S, Brudasca NI, Hodkinson A, Kaluzinska K, Wach A, Storman D, Prokop-Dorner A, Jemiolo P, Bala MM. Efficacy and safety of transcranial magnetic stimulation for treating major depressive disorder: An umbrella review and re-analysis of published meta-analyses of randomised controlled trials. Clin Psychol Rev. 2023 Mar;100:102236. doi: 10.1016/j.cpr.2022.102236. Epub 2022 Dec 8.

  PMID: 36587461 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Alejandro Fuertes, Associate Professor

  Cardenal Herrera University

  STUDY DIRECTOR

Central Study Contacts

Gonzalo Rafael Haro Cortés, Professor

CONTACT

+34 636993509; gonzalo.haro@uchceu.es

Marta Badenes, Associate professor

CONTACT

+34 649466277; marta.badeneslengua@uchceu.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical specialist in Psychiatry. Head of the dual disorders program at the "Hospital Provincial de Castellón". Professor in the Department of Medicine and Surgery at the "Universidad Cardenal Herrera-CEU", CEU Universities.

Model Details: Patients who meet the inclusion criteria will be randomized into a control group, which will receive the active treatment. The control group will receive placebo.

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: January 9, 2025
• Study Start: February 1, 2025
• Primary Completion: February 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)