Cognitive Flexibility in Depression and TMS Response

NCT ID: NCT06775054

Last Updated: 2025-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-15
• Study Completion Date: 2024-03-15

Brief Summary

The primary aim of this study is to determine the level of cognitive flexibility in patients with TRD before treatment and to explore whether there is a relationship with their response to TMS treatment. More specifically, the study aims to identify the role of cognitive flexibility as a neurocognitive marker that could predict whether patients planned to undergo TMS treatment will respond to the treatment. The main focus of this study is to ascertain whether the data obtained have practical implications, particularly regarding the identification of TRD patients who do not respond to TMS treatment in advance.

Detailed Description

The primary aim of this prospective study is to determine the level of cognitive flexibility in patients with treatment-resistant depression (TRD) before treatment and to explore whether there is a relationship between cognitive flexibility and their response to TMS treatment. TRD represents a subset of major depressive disorder in which patients do not adequately respond to conventional antidepressant treatments. Emerging evidence suggests that TMS, a noninvasive brain stimulation technique, can effectively alleviate symptoms in TRD patients. However, the Stanford Accelerated Intelligent Neuromodulation Therapy study suggests that 20% of the TRD group may not respond to treatment and could represent an endophenotypic subgroup. In this context, patients with better cognitive flexibility may show a better response to TMS, and the addition of behavioral methods to enhance flexibility could be considered as an adjunct to TMS treatment.

The study will enroll 49 patients diagnosed with treatment-resistant depression (TRD) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Participants will undergo a TMS treatment regimen using the MagVenture™ X100™ device. The treatment protocol will consist of 20 sessions over four weeks, delivering 18,000 pulses in total (using theta burst stimulation). The stimulation will target the left dorsolateral prefrontal cortex, with parameters designed to achieve optimal therapeutic effects while minimizing side effects. Motor threshold measurements will be conducted prior to treatment initiation and adjusted weekly to maintain consistent treatment intensity.

A control group consisting of 65 healthy participants will undergo a single evaluation for neuropsychological and psychometric assessments, with no treatment or follow-up.

Before starting TMS treatment, all patients will undergo a neuropsychological test battery, including the Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT, Verbal Fluency (VF) Tests to determine their cognitive flexibility levels. The Cognitive Flexibility and Control Scale (CFCS), a self-report measure, will be administered to patients who meet the eligibility criteria. Psychiatric assessments will include the Patient Health Questionnaire (PHQ-9) to evaluate changes in depressive symptoms, while the Clinical Global Impression - Severity (CGI-S) and Clinical Global Impression - Improvement (CGI-I) scales will be administered before and after the 20 sessions of TMS treatment.

The primary objective is to assess improvements in symptom severity and the relationship with cognitive flexibility, as measured by the neurocognitive test battery. This will provide valuable insights for clinicians to better understand which patients are most likely to benefit from TMS treatment. The secondary objectives include identifying clinical and neurocognitive features in patients who do not respond to TMS treatment, assessing side effects, and examining whether concurrent medication, such as anti-obsessive medications, influences the efficacy of TMS therapy.This study will offer valuable data for clinicians and researchers, ultimately guiding safer and more effective use of TMS in psychiatric practice.

Conditions

Depression - Major Depressive Disorder; Cognitive Flexibility; Treatment Response; Side Effects

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Cognitive Flexibility and TMS

Treatment resistant depression group Participants will be treated with transcranial magnetic stimulation (TMS) using the MagVenture™ X100™ device. The treatment includes 20 sessions over 4 weeks, delivering 18000 pulses in total. The stimulation targets the left dorsolateral prefrontal cortex, with parameters set to achieve optimal therapeutic effects without inducing adverse side effects. Motor threshold measurements are conducted prior to the initiation of treatment and adjusted weekly to maintain consistent treatment intensity.

A comprehensive neuropsychological test battery, including the Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Verbal Fluency (VF) tests, was administered to all patients prior to the initiation of treatment. Clinical assessment scales, including the Patient Health Questionnaire-9 (PHQ-9), Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement (CGI-I) scales, were administered both before and after TMS

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type: DEVICE

Transcranial Magnetic Stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain. It is primarily used to treat depression, particularly in patients who have not responded to traditional treatments such as selective serotonin reuptake inhibitors (SSRIs) or psychotherapy. The most common target area is the dorsolateral prefrontal cortex, which is often underactive in individuals with depression. TMS devices, such as the FDA-approved Magventure system, deliver magnetic pulses to stimulate or inhibit brain activity in the targeted region. This process is believed to help reset or normalize patterns of neural activity associated with depression and other psychiatric disorders. TMS offers a promising alternative for individuals struggling with depression, providing a non-invasive approach with relatively few side effects and notable potential benefits.

Interventions

Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain. It is primarily used to treat depression, particularly in patients who have not responded to traditional treatments such as selective serotonin reuptake inhibitors (SSRIs) or psychotherapy. The most common target area is the dorsolateral prefrontal cortex, which is often underactive in individuals with depression. TMS devices, such as the FDA-approved Magventure system, deliver magnetic pulses to stimulate or inhibit brain activity in the targeted region. This process is believed to help reset or normalize patterns of neural activity associated with depression and other psychiatric disorders. TMS offers a promising alternative for individuals struggling with depression, providing a non-invasive approach with relatively few side effects and notable potential benefits.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

Diagnosed with Major Depressive Disorder according to DSM-5 TR.

• Diagnosed with Obsessive-Compulsive Disorder according to DSM-5 TR.
• Lack of response to treatment after being administered at least two different antidepressants and anti-obsessive agents at effective doses and durations.
• The clinical condition cannot be better explained by a metabolic or organic disorder.
• Routine electroencephalography (EEG) findings before TMS do not indicate electrical activity consistent with an epileptic focus.
• Routine blood tests before TMS show no conditions that could affect treatment levels, particularly thyroid issues, vitamin deficiencies, or inflammation parameters that might cause depression or cognitive impairment (consultation with relevant departments if necessary).
• No history of hearing loss identified during routine evaluations (if a history of hearing loss exists, consultation will be requested; if none, the process will proceed accordingly).

Exclusion Criteria

• According to the pre-TMS risk assessment form, there is a contraindication for treatment,
• Epileptic focus is detected in the pre-TMS electroencephalography findings,
• Previous head trauma, loss of consciousness and intra-cerebral surgery,
• A metal particle caused by an aneurysm clip, connection tongs or explosive substances that will affect the electromagnetic field in the brain,
• A significant disorder in the thyroid hormone profile in routine blood checks before TMS,
• A significant increase in inflammation markers in routine checks before TMS,
• A vitamin deficiency that may cause cognitive impairment or forgetfulness in routine blood checks before TMS,
• A presence of electrolyte imbalance in routine blood checks before TMS,
• The patient has previously had a psychotic attack or bipolar mood attack,
• The patient has previously had a substance-induced psychosis or bipolar mood disorder,
• The patient has previously used substances known as alcohol, drugs or stimulants according to DSM-V TR and semi-structured clinical interview (SCID-5 TR) have abuse or addiction (except if they have not used in the last 12 months or have not abused alcohol),
• Those who want to terminate TMS treatment voluntarily, Note:If an unexpected clinical situation occurs during TMS treatment, the patient will be excluded from the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gulhane Training and Research Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Beyazit Garip

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

BEYAZIT GARİP, Medical Doctor

Role: PRINCIPAL_INVESTIGATOR

Gulhane Trainin and Research Hospital

Locations

Gulhane Training and Research Hospital

Ankara, Ankara, Turkey (Türkiye)

Countries

Turkey (Türkiye)

Other Identifiers

2023-19 / TMS

Identifier Type: -

Identifier Source: org_study_id