Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder
Study Details
Study Description
Brief Summary
This study evaluates the efficacy of an accelerated schedule of theta-burst stimulation for treating manic episodes in bipolar disorder. In this open-label study, all participants will receive accelerated theta-burst stimulation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful in real-world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session over 4-6 weeks). Recently, researchers have modified the treatment parameters to reduce treatment times with some preliminary success. In a recent study, an accelerated paradigm showed a significant antidepressant effect (90% remission rate) in individuals with treatment-resistant depression (TRD), in only 5 days. Additionally, 5 participants from this study carried a bipolar diagnosis and responded similarly, with no adverse events experienced or manic/hypomanic conversion observed during the treatment series. In parallel to this, evidence in the literature shows that right prefrontal rapid TMS is safe and efficacious in the treatment of bipolar mania showing laterality opposed to the proposed effect of rapid TMS in depression.
The current trial intends to utilise this modified design, i.e., an accelerated theta burst stimulation treatment over the right prefrontal cortex, for manic episodes in bipolar disorder. The trial also aims to look at the change in clinical measures and neuroimaging biomarkers.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Right DLPFC aiTBS stimulation
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Device: Accelerated intermittent theta-burst stimulation over right DLPFC
All participants will receive accelerated intermittent theta-burst stimulation to the right DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance.
Stimulation will be delivered to right-DLPFC using the Brainsway stimulator.
|
Outcome Measures
Primary Outcome Measures
- Change from baseline Young Mania Rating Scale (YMRS) [Baseline and immediate post-treatment]
The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. Typical YMRS baseline scores can vary a lot. They depend on the patients' clinical features such as mania (YMRS = 12), depression (YMRS = 3), or euthymia (YMRS = 2).
Secondary Outcome Measures
- Change from baseline Montgomery Asberg Depression Rating Scale (MADRS) [Baseline and immediate post-treatment]
A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The MADRS uses a 0 to 6 severity scale, scored following the interview. Scoring/Interpretation: Higher scores indicate increasing depressive symptoms. ... Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.
- Change from baseline functional connectivity as measured by MR imaging [Baseline and immediate post-treatment]
Pre- and post resting state functional connectivity and structural T1-weighted MRI scans to determine the anti-correlated LDLPFC and SCC treatment location. The identified cluster with the greatest anti-correlation between the LDLPFC and SCC will have been utilized for the targeted aiTBS treatment. This algorithm will have also been applied to the post-imaging sessions to give measurements of voxel-wise blood flow in this anti-correlation targeted brain ROI.
- Change from baseline Hamilton Rating Scale for Depression (HAM-6) [Baseline and immediate post-treatment]
A 6-item clinical assessment measuring depressive symptoms. Scores range from 0-24 with scores >5 indicating clinical levels of depressive symptoms.
- Change from baseline Beck Depression Inventory (BDI-II) [Baseline and immediate post-treatment]
The Beck Depression Inventory (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. Scores: 0-13= minimal depression, 14-19=mild depression, 20-28=moderate depression, 29-63=severe depression
- Change in Scale of Suicidal Ideation (SSI) score [Baseline and immediate post-treatment]
19-item clinician administered assessment to measure the intensity, pervasiveness, and characteristics of suicidal ideation in adults. Scores range from 0-38, with a score higher than 6, indicating active suicidal ideation.
- Change in baseline Altman Self-Rating Mania Scale (ASRM) [Baseline and immediate post-treatment]
The ASRM is a 5-item self rating mania scale, designed to assess the presence and/or severity of manic symptoms. Interpretation: A score of 6 or higher indicates a high probability of a manic or hypomanic condition A score of 6 or higher may indicate a need for treatment and/or further diagnostic workup A score of 5 or lower is less likely to be associated with significant symptoms of mania
- Change from baseline Internal State Scale (ISS) [Baseline and immediate post-treatment]
Independent assessment of manic and depressive symptoms by self- rating scale characteristics and implications for the study of mania. The ISS contains a series of visual analogue scale (VAS) items consisting of statement followed by a by eleven "bins" (equivalent to 0-10, 11-20, …91-100). In Likert-based scoring, the first bin is scored as zero, the second as 10, and so on to theeleventh bin which is scored as 100. Scoring: >155: (Hypo)Mania >155: Mixed State <155: Euthymia <155: Depression
- Change in Columbia Suicide Severity Rating Scale (C-CSSRS), self-report version [Baseline and immediate post-treatment]
A self-report measure of the Columbia Suicide Severity Rating Scale (C-CSSRS). This questionnaire was developed to rate suicidal ideation and behavior. It rates a person's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors. The scale identifies specific behaviors which may be indicative of a person's intent to complete suicide. An person exhibiting even a single behavior identified by the scale was 8 to 10 times more likely to complete suicide.
Other Outcome Measures
- Change in resting-state recordings and TMS-evoked potentials in EEG data. [Baseline and immediate post-treatment]
EEG recordings will be made before and after the treatment course to differences in EEG data associated with hypomania/mania and treatment response (e.g. amplitude & latency of tms-evoked potentials (TEPs), spatio-temporal distribution of TEPs and resting-state connectivity)
- Change in heart rate variability [Baseline and immediate post-treatment]
Polar H10 heart rate monitor will be used to measure heart rate variability
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participants aged 18yo-80yo with a primary diagnosis of bipolar I or II disorder in a current hypomanic/manic episode or bipolar affective disorder II in a current hypomanic/manic episode.
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Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
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Currently experiencing a hypomanic/manic episode according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
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Meet the threshold on the total HAMD17 score of >/=20 prior to aiTBS.
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Meet the threshold on the BDI-II score of >/=17 prior to aiTBS.
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Not currently experiencing psychosis (MINI)
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Must have a stable psychiatrist during study enrollment
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Must be on a mood stabilizer regimen
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Meet the threshold on the MADRS, with a total score of >/=20 prior to aiTBS.
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History of ECT intolerance or exposure is permitted.
Exclusion Criteria:
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Any structural lesion e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke effecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.
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Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear implants
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History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)
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Shrapnel or any ferromagnetic item in the head
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Pregnancy
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Autism Spectrum disorder
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Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation
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Active substance abuse (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines
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Cognitive impairment (including dementia)
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Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)
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Current psychosis
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Showing symptoms of withdrawal from alcohol or benzodiazepines
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IQ<70
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Parkinsonism or other movement d/o determined by PI to interfere with treatment
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Any other indication the PI feels would comprise data.
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A diagnosis of obsessive-compulsive disorder (OCD)
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Any history of psycho surgery for depression
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Any history of myocardial infarction, CABG, CHF, or other cardiac history
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The presence or diagnosis of prominent anxiety disorder, personality disorder or dysthymia
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History of intractable migraine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford Hospital | Palo Alto | California | United States | 94304 |
Sponsors and Collaborators
- Stanford University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 52635