Depression > Intermittent Theta Burst Stimulation

Theta Burst Stimulation for Alcoholism

(CDiA-P4 Trial)

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antidepressants, SUD agonists

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Unstable illness, Pregnancy, Dementia, others

No Placebo Group

Approved in 2 jurisdictions

Trial Summary

What is the purpose of this trial?

The prefrontal cortex, although well established as an efficacious target for the treatment of major depressive disorder (MDD), has recently come into favour as a therapeutic target for alcohol use disorders (AUD). Depressive symptoms are also highly prevalent in individuals with AUD. A number of cognitive and psychological processes stemming from the prefrontal cortex, a common treatment target for repetitive transcranial magnetic stimulation (rTMS), are disrupted in both MDD and AUD. The proposed study will enhance the development of theta burst stimulation (TBS) as a new intervention for AUD in the context of depressive symptoms and uses integrated TMS-EEG to identify neurophysiological targets of executive dysfunction in this disorder.

Will I have to stop taking my current medications?

You will need to keep your current antidepressant medications and medications for alcohol use disorder the same during the study. If you are on SUD agonist therapies, you should continue taking them as managed by your clinical team.

What data supports the effectiveness of this treatment for alcoholism?

Intermittent theta burst stimulation (iTBS) is a promising treatment for alcohol use disorder, as it has shown similar effectiveness to other established treatments for depression and has been suggested to reduce brain reactivity to alcohol cues, potentially decreasing drinking behavior.

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Is theta burst stimulation safe for humans?

Research shows that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated in humans, with no adverse events reported in studies involving patients with bipolar depression and treatment-resistant depression.

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How is the treatment Intermittent Theta Burst Stimulation (iTBS) different from other treatments for alcohol use disorder?

Intermittent Theta Burst Stimulation (iTBS) is a unique treatment for alcohol use disorder because it uses a non-invasive technique called repetitive transcranial magnetic stimulation (rTMS) to target specific brain areas, potentially reducing cravings and brain reactivity to alcohol cues. Unlike traditional rTMS, iTBS sessions are much shorter, lasting only about 3 minutes, which may improve patient comfort and adherence.

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Eligibility Criteria

This trial is for adults aged 18-59 with alcohol use disorder (AUD) and major depressive disorder (MDD), without psychotic symptoms. Participants must be able to consent, adhere to the study schedule, maintain current medications constant, and not have used problematic substances other than nicotine or caffeine in the last month. Exclusions include dementia, significant medical or neurological disorders, non-English speakers, pregnancy intention during the study period, ECT failure history, metal implants near head or specific medication that affects rTMS efficacy.

Inclusion Criteria

Patients screened positive for a Major Depressive Episode (MDE) based on the MINI without psychotic symptoms

I am willing and able to agree to treatment.

Patients have a Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) diagnosis of AUD based on the MINI

Exclusion Criteria

Patients have possible or probable dementia based on cognitive assessments

Patients have a concomitant major unstable medical illness

I have a condition or take medication that could lead to severe depression or affect my thinking.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 treatments of active or sham repetitive transcranial magnetic stimulation (rTMS) over 4 weeks

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The trial tests intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation targeting the prefrontal cortex to treat AUD with coexisting depressive symptoms. It compares iTBS against sham stimulation—a placebo-like treatment—to evaluate its effectiveness on cognitive functions disrupted by both conditions.

Group I: Active Bilateral Active Control 1 Intervention

Bilteral TBS, applied as cTBS over the right DLPFC followed by iTBS over the left DLPFC

Group II: Sham Placebo Group 1 Intervention

Sham TBS

Intermittent Theta Burst Stimulation is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as iTBS for:

• Treatment-resistant depression

🇪🇺 Approved in European Union as iTBS for:

• Treatment-resistant depression

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Centre for Addiction and Mental Health Toronto, Canada

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016] To identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS).

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Intermittent Theta Burst Stimulation (iTBS) in Patients With Alcohol Use Disorder: Study Protocol for a Randomized Controlled Trial. [2022] Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation technique which has a treatment potential for alcohol use disorder. Intermittent theta burst stimulation (iTBS) is a new rTMS technique which is shorter in duration and thus with better tolerability and shows similar efficacy as rTMS for the treatment of depression. The effect of iTBS on reducing craving in alcohol use disorder patients requires further investigation.

3. United States pubmed.ncbi.nlm.nih.gov

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study. [2023] Alcohol use disorder (AUD) is associated with elevated brain response to cues. Recent studies have suggested that theta burst stimulation (TBS) to the medial prefrontal cortex (MPFC) can decrease reactivity to cues in a transdiagnostic manner. The goal of this clinical trial was to evaluate the effect of continuous TBS as a tool to decrease drinking behavior and brain reactivity to alcohol cues among individuals with AUD.

4. United States pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). [2022] Recently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS.

5. Netherlands pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation in Veterans with Mild Alcohol Use Disorder. [2022] Alcohol use disorder (AUD) is highly comorbid with depression and posttraumatic stress disorder (PTSD) and can complicate their treatment. Transcranial magnetic stimulation is a promising treatment for these disorders, yet prior research often excluded AUD patients out of concern for safety or poorer outcomes. To this end, we revisited a prior study of intermittent theta burst stimulation (iTBS) for PTSD, to evaluate whether mild AUD impacted safety and clinical outcomes.

6. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020] The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.

7. England pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. [2022] Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.