None listed
Conditions
Brief summary
Non-invasive brain stimulation offers new hope to individuals suffering from depression who do not respond to standard therapy. Recent work demonstrates brain stimulation clinical outcomes might be substantially improved by adjusting the exact position, at which brain stimulation is applied, to directly modulate a brain circuit involved in depression. We aim to test this in a large clinical trial comparing this new targeted brain stimulation approach with a conventional brain stimulation therapy.
Interventions
Transcranial Magnetic Stimulation (TMS) is a promising non-invasive therapy (ie. it does not involve surgery or the introduction of instruments into the body) for treatment of difficult to treat depression, but while life-changing for some individuals, others receive little benefit. Emerging research suggests that TMS clinical benefits might be related to the precise part of the brain at which TMS is delivered.
This study aims to compare the clinical benefits of two different methods of TMS tre
Transcranial Magnetic Stimulation (TMS) is a promising non-invasive therapy (ie. it does not involve surgery or the introduction of instruments into the body) for treatment of difficult to treat depression, but while life-changing for some individuals, others receive little benefit. Emerging research suggests that TMS clinical benefits might be related to the precise part of the brain at which TMS is delivered. This study aims to compare the clinical benefits of two different methods of TMS treatment delivery. We will compare current TMS treatment where the stimulation target is based on the size of a person’s scalp to a newer approach where the stimulation target is more tailored and specific (optimised) and based on a person’s brain Magnetic Resonance Imaging (MRI) scan image. Both treatment methods target areas in the front of the brain and use a standard daily 4-week course of TMS normally used in clinical care. We are internationally recognised for our expertise in this area. TMS is an established and approved therapy for treatment of difficult to treat depression under the Medicare Benefits Scheme. The TMS device used in this study has been approved by the Therapeutic Goods Administration for the treatment of depression. TMS therapy will be delivered once daily, 5x per week (M-F) for 4 weeks by a trained clinician, following completion of an MRI scan up to a week before the first treatment session. TMS will be administered with a magnetic stimulator using a figure-of-8 coil. Resting motor threshold will be defined as 5/10 muscle twitches at the first dorsal interosseus muscle elicited by single pulse TMS delivered to the motor cortex representation of this muscle. One session of intermittent theta burst stimulation will be delivered in each treatment session. Intermittent theta burst stimulation will be delivered at 120% of resting motor threshold (600 pulses; triplet 50 Hz bursts, repeated at 5 Hz; 2 s on and 8 s off; 600 pulses per session; total duration of 3 min 9s). The dorsolateral prefrontal cortex (DFPLC) stimulation site will be individually tailored according to brain connectivity with the subgenual cingulate cortex (SGC); this computational pipeline is detailed in Cash et al., 2021. To ensure blinding, the Beam F3 coordinate will be measured manually for all individuals prior to commencing the course of treatment and all TMS sessions will be performed using neuronavigation. The aim of the present work is to compare two of these methods, whereby the neuronavigated DLPFC target is informed by person-specific brain connectivity but remains within the bounds of the conventional stimulation area.
Sponsors
The University of Melbourne
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
• MADRS score greater than or equal to 20 (moderate-to-severe depression severity) within 7 days of baseline visit • Diagnosis of major depressive episode (MDE), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder or bipolar affective disorder. • Failure to respond to adequate trials of 2 antidepressant medications which involved treatment for minimum 4 weeks at effective dose. • No change to antidepressant medication and other psychoactive medications in the four weeks prior to screening, nor during the study or until completion of all follow-up assessments. • No initiation of new antidepressant therapy in the four weeks prior to screening. • Ability to provide written informed consent (including adequate intellectual capacity and fluency in the English language). • Referral from a psychiatrist who continues to be responsible for the patient’s care.
Exclusion criteria
• Likely to be unable to comply with the requirements of informed consent or comply with the study protocol, as determined by a study doctor or delegate. • Diagnosis of psychotic disorder. • Diagnosis of rapid cycling bipolar disorder; defined as greater than or equal to 4 episodes, including major depressive, manic, hypomanic, or mixed, within the past 12 months. • Presentation is mainly due to another mental disorder other than depression. • Presence of acute medical illness that could interfere with study participation, including significant neurological disorder that will affect the participant’s response to TMS. • A moderate-to-severe substance use disorder (for other drugs) within the past 6 months, according to DSM-5 criteria. • Women of child-bearing potential who are pregnant, breastfeeding, trying to become pregnant or become pregnant during the course of the trial. • Ongoing treatment with electroconvulsive therapy or ketamine. • Contraindications to Magnetic Resonance Imaging (MRI) (e.g. metallic foreign bodies, pacemaker, metal pins or metal piercings) or TMS (e.g. history of seizures or epilepsy, Cochlear implants, brain pathology detected from MRI) as evaluated by the study doctor and CPI. Significant suicide risk, as informed by the Columbia-Suicide Severity Rating Scale (C-SSRS), at the discretion of the study doctor and CPI. • Exposure to any investigational drug within the 4 weeks prior to screening or currently taking part in another intervention trial.
Outcome results
None listed