aiTBS for Pharmacological Treatment-Resistant Bipolar Depression

JRCT ID: jRCTs042240019

Registered date:22/04/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pharmacological treatment-resistant bipolar depression (DSM-5-TR based on SCID-5-RV)
• Date of first enrollment: 22/04/2024
• Target sample size: 22
• Study type: Interventional
• Intervention(s): aiTBS

Outcome(s)

Primary Outcome

Response* rate at any week of follow-up until week 4
* The definition
Participant who will achieve a 50% or greater improvement in MADRS total score from baseline to week 4.

Secondary Outcome

1. Remission* rate at any week of follow-up until week 4
* The definition
Participant will achieve a MADRS total score of 10 or less from baseline to week 4.
2. Change in depression symptoms (mean change from baseline to day 5-7, week 2, 4, and 6 in MADRS total score)
3. Change in bipolar depression severity (mean change from baseline to day 5-7, week 2, 4, and 6 in CGI-S score)
4. Change in treatment efficacy for bipolar depression (mean change from baseline to day 5-7, week 2, 4, and 6 in CGI-I score)
5. Change in bipolar mania severity (mean change from baseline to day 5-7, week 2, 4, and 6 in CGI-S score)
6. All-cause discontinuation
7. Discontinuation due to adverse events
8. Incidence of total adverse events
9. Incidence of serious adverse events
10. Mortality rate
11. Incidences of individual adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 65age old
• Gender: Both

Include criteria

1. The clinical trial will be described in detail to the individuals, and would be written informed consent will be obtained from all participants and their guardians
2. Individuals age: 18 >= years old and < 65 years old
3. Individuals who will meet the DSM-5-TR criteria for bipolar depression (type I) (based on SCID-5-RV)
4. Individuals who will be diagnosed with pharmacological treatment-resistant* bipolar depression

* The definition
A individual who will not respond to at least two mood stabilizers or second-generation antipsychotics (valproate, lamotrigine, quetiapine extended-release, lurasidone, or olanzapine that are reported to have an efficacy for bipolar depression by a network meta-analysis (Yildiz 2023)) with a sufficient dose (within the doses approved in Japan) for 2 weeks or more (CGI-S >= 4, we will confirm the result from their medical records). If the individuals are receiving the combination therapy with two or more these drugs, we will select a candidate drug that had the highest dose of among the drugs (the Defined Daily Dose (https://www.who.int/tools/atc-ddd-toolkit/about-ddd). If there are two or more drugs that used the same equivalent dose during the same period, we will select one of these drugs for the evaluation of the definition.

5. Individuals who will have a HAM-D17 total score of 20 or higher at baseline

Exclude criteria

1. Individuals with metal implants or devices close to the stimulation site (e.g., cochlear implants, surgical clips with magnetic properties, or neurostimulators such as deep brain stimulation or vagus nerve stimulation), individuals with a cardiac pacemaker
2. Individuals with metal implants or devices not close to the stimulation site (e.g., implanted medication pumps), titanium products in their heads, magnetic dentures/implants
3. Individuals with a history of seizures, a history of intracranial lesions at risk for seizures, individuals taking drugs that reduce seizure threshold (methylphenidate or ketamine), individuals with alcohol/caffeine/stimulants abuse or withdrawal symptoms, pregnant individuals, individuals with severe physical disease
4. Individuals with a history of receiving rTMS in the current depressive episode
5. Individuals diagnosed with dementia, organic or symptomatic mood disorder
6. Individuals with unimproved depressive symptoms due to poor adherence to pharmacological treatment
7. Individuals diagnosed with substance or medication-induced mood disorder
8. Individuals who will answer "yes" at baseline to the following questions: "Do you have any suicidal ideations although you do not have any plans for committing suicide? or "Do you have any suicidal ideations and any plans for committing suicide?"
9. Individuals judged to be inappropriate by researchers

Related Information

• Primary Sponsor: Kishi Taro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development