New parameters for brain stimulation in the treatment of depression

INTERVENTION: 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% 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 Dr Joseph Lee at the SCGH; Mental Health Unit; Neurophysiology Service. Dr Greg Price will deliver the treatment protocol and Dr Joseph Lee will do psychological assessments. The study will consist of 4 weeks of treatment comprising 20 sessions (weekdays for 4 weeks) of rTMS to the left dorsolateral prefrontal cortex. Patients will be randomly assigned to the standard protocol (100%MT;1000mT) or add‐on protocol (standard protocol+50mT) stimulation group. Standard protocol: patients will receive 40 trains of rTMS at 10Hz at 100%MT equivilent to 1000mT, with an inter‐train interval of 30 seconds comprising of a total of 20 sessions (weekdays for 4 weeks) Add on protocol: patients will receive alternating trains during the session of standard protocol rTMS (10 trains of rTMS at 10Hz at 100%MT) followed by 50 mT rTMS (10 trains of rTMS at 10Hz at 1%MT) with an inter‐train interval of 15 seconds repeated till a total of 80 trains of 10Hz stimulation is provided comprising of a total of 20 sessions (weekdays for 4 weeks) CONDITION: Depression; ; Depression Mental Health ‐ Depression PRIMARY OUTCOME: ; Outcome Name: Depression; Metric/method of measurement: The primary endpoint will be the percentage change in HAM‐D‐21 response (score), defined by a significant change from the initial score on the Hamilton Depression Scale (HAM‐D‐21); [Timepoint: Directly following end of 4 week treatment period; ] number of remissions defined by a HAM‐D‐21 score of <8 directly following 4 week treatment period and 6 months after; [Time points: Baseline, Immediately after end of 4 week rTMS treatment period and 6 months after treatment commencement.] SECONDARY OUTCOME: the change and presence of predictive markers of the therapeutic response: serum biomarkers (3‐methylhistidine) [Time points: Baseline, Immediately after end of 4 week rTMS treatment period and 6 months after treatment commencement.] the change and presence of predictive markers of the therapeutic response: serum biomarkers (a amino‐nbutyric acid)[Time points: Baseline, Immediately after end of 4 week rTMS treatment period and 6 months after treatment commencement.] 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.