Using theta-burst stimulation to treat bipolar depression

Theta-Burst Stimulation for Bipolar Depression

This study is testing if a new brain stimulation technique can help people with bipolar disorder who haven't found relief from their depression.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 124 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Centre for Addiction and Mental Health (other)
• Locations: 2 sites (Toronto, Ontario and 1 other locations)
• Trial ID: NCT06370988 on ClinicalTrials.gov

What this trial studies

This trial aims to evaluate the effectiveness of intermittent theta-burst stimulation (iTBS) in alleviating symptoms of depression in individuals with treatment-resistant bipolar disorder. Participants will be randomly assigned to receive either active iTBS stimulation or a sham treatment over a 30-day period, followed by a 6-week follow-up. Depression and mania symptoms will be monitored using standardized scales throughout the treatment and follow-up phases to assess efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-65 with a DSM 5 diagnosis of bipolar disorder who have not responded to previous treatments for depression.

Not a fit: Patients currently experiencing a mixed or manic episode or those who have recently changed their psychotropic medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from treatment-resistant bipolar depression.

How similar studies have performed: Other studies utilizing transcranial magnetic stimulation have shown promise in treating various forms of depression, suggesting potential for success with this approach.

Eligibility criteria

Inclusion Criteria

The participant must meet all of the inclusion criteria to eligible for this clinical trial:

1. Must be deemed to have capacity to provide informed consent;
2. Must be an outpatient
3. Have a DSM 5 diagnosis of bipolar disorder (type I or II), current episode depressed confirmed by Mini-International Neuropsychiatric Interview version 7.0.2 (MINI);
4. Age 18-65;
5. failure to achieve a clinical response to ≥1 adequate treatment trial for bipolar depression based on the Antidepressant Treatment History Form - Short Form (ATHF-SF) OR unable to tolerate at least 2 separate inadequate treatment trials for bipolar depression;43
6. moderately severe depression with a score ≥ 15 on the PHQ-9;44
7. not currently experiencing a mixed or manic episode (YMRS ≤10);
8. no increase or initiation of psychotropic medication with intention of treating depressive symptoms in the 4 weeks prior to screening. This excludes targeted treatment of insomnia with trazodone, melatonin, low-dose doxepin \[3-6mg\], low-dose benzodiazepines \[≤2mg lorazepam daily equivalent\], non-benzodiazepine benzodiazepine receptor agonists, or orexin antagonists;
9. able to adhere to the treatment schedule;
10. pass the TMS adult safety screening questionnaire.45

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this clinical trial:

1. have a history of MINI diagnosis of a substance use disorder (other than nicotine and/or caffeine) within the last 3 months;
2. have a concomitant major unstable medical illness;
3. have active suicidal intent (assessed during HRSD-17 Item 3 and SSRS as imminent intent to act on specific plan, confirmed by psychiatric staff);
4. are pregnant or intend to get pregnant during the study;
5. have a lifetime MINI diagnosis of schizophrenia or schizoaffective disorder;
6. have psychotic symptoms within the current episode;
7. have a MINI anxiety disorder, trauma-related disorder, obsessive compulsive disorder, or personality disorder assessed by a study investigator to be primary and/or causing greater impairment than BD-DE;
8. failure of an adequate acute course of ECT as defined by ATHF-SF during the current episode;
9. have received any rTMS before due to potential to compromise blinding of treatment allocation;
10. have any clinically significant neurological disorder (e.g., recent major cerebrovascular accident), or any history of seizure except those therapeutically induced by ECT or with clear precipitant (e.g., febrile seizure of childhood, alcohol withdrawal, etc.);
11. have any intracranial implant (e.g., aneurysm clips, shunts, stimulators,) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
12. are participating in psychotherapy for less than 3 months. Patients will be permitted if they have been in stable treatment for at least 3 months prior to study entry, with no anticipated change in the frequency of therapeutic sessions, or focus of therapeutic sessions over the duration of the study;
13. are currently taking lorazepam \>2 mg daily (or equivalent) due to the potential to limit rTMS efficacy;
14. are currently taking any dose of an anticonvulsant due to the potential to limit rTMS efficacy. If anticonvulsants have been discontinued prior to screening, at least 5 half-lives have elapsed until screening to allow sufficient drug clearance;
15. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Where this trial is running

Toronto, Ontario and 1 other locations

• University Health Network — Toronto, Ontario, Canada (RECRUITING)
• Centre for Addiction and Mental Health — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Study coordinator: Elizabeth Clancy

Conditions: Bipolar Depression, Bipolar Disorder, Treatment- Resistant Bipolar Disorder, Type 2 Bipolar Disorder, Transcranial Magnetic Stimulation, Repetitive Transcranial Magnetic Stimulation, rTMS, iTBS