Cognitive Flexibility in Depression and TMS Response

NCT06775054 | Completed

• 1 other identifier: 2023-19 / TMS
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Depression; TMS; TRD; WCST; TMT; VF

Outcome Measures

Primary Outcomes (6)

• Assessing Cognitive Flexibility in TMS Treatment:WCST

  Cognitive flexibility will be evaluated in cases of treatment-resistant depression using a neuropsychological test battery. This battery will be applied only before the TMS treatment. Wisconsin Card Sorting Test (WCST): The WCST evaluates cognitive flexibility, problem-solving skills, and executive functioning. It measures an individual's ability to adapt to changing rules or conditions and to shift cognitive strategies when faced with new tasks. This test assesses the ability to overcome perseveration (sticking to an incorrect rule) and adapt to the correct rule based on feedback. The WCST uses a deck of 128 cards, each with one of four shapes (circle, triangle, star, or cross), in one of four colors (red, green, yellow, or blue), and with one of four numbers (1, 2, 3, or 4). It is valuable for understanding how patients adapt to new information, shifting circumstances, and challenges, making it a key part of cognitive evaluations in clinical settings.

  From enrollment to the end of treatment at 4 weeks

• Exploring Changes in Task-Switching Ability: The Effect of TMS on TMT Performance

  The Trail Making Test (TMT) is a widely used neuropsychological assessment tool designed to evaluate cognitive functions, including executive functioning, cognitive flexibility, visual attention, and processing speed. The test is divided into two parts: TMT-A and TMT-B, each measuring different cognitive aspects. Cognitive Aspects Measured by TMT: Cognitive Flexibility: The ability to switch between tasks (TMT-B) and adjust strategies is a key indicator of executive functioning. Poor performance on TMT-B may suggest deficits in cognitive flexibility. Attention and Processing Speed: TMT-A measures basic processing speed and attention. Delays or errors in completing the test can indicate difficulties with these cognitive domains. Executive Functioning: Both parts of the TMT assess aspects of executive functioning, particularly planning, mental flexibility, and working memory.

  From enrollment to the end of treatment at 4 weeks

• Evaluating Changes in Verbal Fluency Pre- and Post-TMS Treatment

  Verbal fluency (VF) tasks are widely used in neuropsychological assessments to measure cognitive functions such as language production, executive control, and semantic memory. These tasks provide valuable insights into the cognitive abilities of individuals, especially those with psychiatric and neurological conditions. The primary aim of this evaluation is to assess changes in verbal fluency performance in individuals undergoing TMS treatment for depression, specifically treatment-resistant depression. Verbal fluency is commonly assessed through two main types of tasks: Phonemic Fluency: The ability to generate words beginning with a specific letter (e.g., "K" "A," or "S") within a set time limit. Semantic Fluency: The ability to generate words belonging to a specific category (e.g., animals, fruits, etc.) within the same time limit.

  From enrollment to the end of treatment at 4 weeks

• Cognitive Flexibility as a Predictor of Transcranial Magnetic Stimulation Outcomes

  The relationship between cognitive flexibility, assessed through neuropsychological tests (WCST, TMT, VF), will be evaluated prior to the TMS procedure. For cases of treatment-resistant depression, a ≥ 50% reduction in the PHQ-9 score is generally considered a clinically significant response to treatment. The PHQ-9 score ranges from a minimum of 0, indicating no depressive symptoms, to a maximum of 27, indicating severe depressive symptoms. The interpretation of PHQ-9 scores is as follows: 0-4 indicates minimal or no depression, 5-9 indicates mild depression, 10-14 indicates moderate depression, 15-19 indicates moderately severe depression, and 20-27 indicates severe depression.

  From enrollment to the end of treatment at 4 weeks

• Assessing Depression Severity Before and After Transcranial Magnetic Stimulation Treatment

  A ≥ 50% reduction in the PHQ-9 score is often considered a clinically significant response to treatment. The PHQ-9 scoring ranges from a minimum score of 0, indicating no depressive symptoms, to a maximum score of 27, indicating severe depressive symptoms. The interpretation of PHQ-9 scores is as follows: 0-4 indicates minimal or no depression, 5-9 indicates mild depression, 10-14 indicates moderate depression, 15-19 indicates moderately severe depression, and 20-27 indicates severe depression.

  From enrollment to the end of the treatment at 4 weeks.

• Evaluating Response to TMS Treatment Using the Clinical Global Impression Scale (CGI)

  Patients undergoing TMS treatment will be evaluated using the Clinical Global Impression (CGI) scale, which will be applied both before and after the TMS treatment to assess changes in clinical status. The CGI is a standardized tool consisting of two main components: CGI-Severity (CGI-S), which evaluates the severity of the patient's condition on a 7-point scale (1 = normal, 7 = extremely ill), and CGI-Improvement (CGI-I), which assesses the degree of improvement or worsening compared to baseline on a similar 7-point scale (1 = very much improved, 7 = very much worse). This scale provides clinicians with a practical and reliable method for monitoring the effectiveness of treatment and patient progress over time.

  From enrollment to the end of treatment at 4 weeks

Secondary Outcomes (3)

• Tracking Depression Severity Changes

  From enrollment to the end of treatment at 4 weeks

• Side Effect Assessment

  From enrollment to the end of treatment at 4 weeks

• Drug Interaction Effects

  From enrollment to the end of treatment at 4 weeks

Study Arms (1)

Cognitive Flexibility and TMS

EXPERIMENTAL

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

Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation 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.

Cognitive Flexibility and TMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gulhane Training and Research Hospital: lead

Study Sites (1)

Gulhane Training and Research Hospital

Ankara, Ankara, 06000, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• BEYAZIT GARİP, Medical Doctor

  Gulhane Trainin and Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The Treatment-Resistant Depression (TRD) patient group will be evaluated before and after Transcranial Magnetic Stimulation (TMS) treatment. There will also be a control group consisting of healthy participants, who will undergo a single neuropsychological and clinical assessment. Cognitive flexibility will only be evaluated before the TMS procedure using neuropsychological assessment tools.

Study Record Dates

• First Submitted: December 29, 2024
• First Posted: January 14, 2025
• Study Start: March 15, 2023
• Primary Completion: March 15, 2024
• Study Completion: March 15, 2024
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: The data will be made available immediately after the publication, and will remain available for at least 5 years.
• Access Criteria: Anyone who wishes to access the data

Locations

TU (1)