None listed
Conditions
Brief summary
Depression is one of the most prevalent and costly medical conditions worldwide (WHO, 2012). Although antidepressant medication is effective for many patients, up to 40% remain drug-resistant. Non invasive brain stimulation in the form of repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression with response rates of up to 60%. However, outcomes are variable both within and between individuals, suggesting that treatment protocols remain suboptimal. This variability is not surprising because non-invasive brain stimulation techniques were first developed in humans with no systematic “bench-to-bedside” evaluation of protocols, resulting in poorly defined clinical guidelines. Our lab has compared a range of brain stimulation protocols in a preclinical model of treatment resistant depression, and has shown that rTMS delivered at a 50mT intensity (at cortex) matches the behavioural effects obtained with rTMS delivered at 100% motor threshold equivalent to 1000mT intensity (currently used in human patients). However our 50mT protocol has additional benefits: it causes structural changes in the brain, leading to long lasting improvements in mood and cognition. This project will test efficacy of our low intensity protocol (50mT)as an add-on to the gold standard protocol (100%;1000mT) in a patient cohort (40 participants), using psychiatric assessment to evaluate changes in mood and cognition, and detection of two novel blood biomarkers for predictive ability. Significance: first pre clinically validated rTMS protocol for human treatment; establish a pipeline for translation of other rTMS protocols arising from basic research at the Perron Institute.
Interventions
rTMS will be delivered in a head to head trial at an intensity of 50mT (estimated at 50mT at the level of the cortical surface) as an add on to the standard FDA-approved protocol of 100-120% of Motor Threshold equivalent to ~1000mT; (Gaynes et al., 2014; O’Reardon et al., 2007; Price et al., 2010) in a patient cohort, to compare outcomes to the standard protocol alone.
Treatment resistant patients (n=40; male and female) will be recruited through collaboration with Dr Greg Price and Clinical Ps
rTMS will be delivered in a head to head trial at an intensity of 50mT (estimated at 50mT at the level of the cortical surface) as an add on to the standard FDA-approved protocol of 100-120% of Motor Threshold equivalent to ~1000mT; (Gaynes et al., 2014; O’Reardon et al., 2007; Price et al., 2010) in a patient cohort, to compare outcomes to the standard protocol alone. Treatment resistant patients (n=40; male and female) will be recruited through collaboration with Dr Greg Price and Clinical Psychiatrist, Dr Mark McAndrew at the SCGH; Mental Health Unit; Neurophysiology Service. Dr Greg Price will deliver the treatment protocol and Dr Mark McAndrew will do psychological assessments. The study will consist of 4-6 weeks of treatment comprising 20-30 sessions (weekdays only) of rTMS to the left dorsolateral prefrontal cortex. Patients will be randomly assigned to the standard protocol (100-120%MT;1000mT) or add-on protocol (standard protocol+50mT) stimulation group. Standard protocol: patients will receive 75 trains of rTMS at 10Hz equivalent to ~ 1000mT:100-120% MT, with an inter-train interval of 30 seconds comprising of a total of 20-30 sessions (weekdays for 4-6 weeks) Add on protocol: patients will receive alternating trains during the session of standard protocol rTMS: (1 train of rTMS at 10Hz at 100-120%MT) followed by 50 mT rTMS (1 train of rTMS at 10Hz at ~10% Maximum Stimulator Output*) with an inter-train interval of 15 seconds repeated till a total of 150 trains of 10Hz stimulation is provided comprising of a total of 20-30 sessions (weekdays for 4-6 weeks) *10% Maximum Stimulator output is equivalent to ~50 mT at cortex.
Sponsors
University Of Western Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ICD-10-AM diagnosis of major depression. Subsequent depression scale scores will act as a validation check (any discrepancies to be reviewed by PI), but initial inclusion will be purely by clinical diagnosis. Aged above 18 years Participants need not meet formal criteria for treatment resistance, but must have shown an unsatisfactory response to a previous treatment regime. The judgement to recommend a participant for this trial is, therefore, explicitly a clinical decision by the recruiting physician. However, we do require that the antidepressant medication regime be stable in type and dosage for 4 weeks prior to the rTMS trial.
Exclusion criteria
Presence of cardiac pacemakers, medication pumps, cochlear implants or metal objects in the head or eyes that could be dangerous if heated or moved by the magnetic pulses. Significant medical illness, substantial risk of suicide, current psychosis, current substance dependence, a history of seizures, epilepsy, stroke or major head trauma, or a history of alcohol dependence.
Outcome results
None listed