Accelerated Theta Burst Transcranial Magnetic Stimulation (TBS) for Depression

This is a single blind randomised controlled trial investigating whether response to repetitive Transcranial Magnetic Stimulation (rTMS) can be substantially enhanced through the use of an accelerated Theta Burst Stimulation (TBS) treatment protocol. The relative efficacy of standard rTMS and two different strengths of TBS will be compared to explore this, and the most effective TBS treatment parameters. Participants will be randomly allocated to one of three treatment conditions: • standard rTMS • low intensity TBS, or • high intensity TBS. All groups will receive 20 active treatments. All participants will take part in interviews at baseline, week 1, 2, 4 and 8-10 weeks. Participants responding to the treatment will be followed up for six months. The participant and the treater will be aware of the treatment condition. The person conducting weekly reviews will be blinded to the participant’s treatment group. Treatment Standard rTMS Participants in standard rTMS will receive one treatment a day for 20 treatment days over 4 weeks. Each treatment session will involve the provision of 75 trains of 10 Hz rTMS to the left dorsolateral prefrontal cortex, in 4 second pulse trains, with 26 second inter-train intervals. Each treatment session will take approximately 37.5 minutes. TBS treatment Participants in the TBS groups will receive 11 sessions over 4 days in week 1 (2 sessions on day 1, and 3 sessions each on days 2, 3 and 4), and 9 sessions over 3 days in week 2 (3 sessions per day). Each treatment session will involve 3-pulse 50 Hz bursts applied bilaterally, to the right then left to the dorsolateral prefrontal cortices, at 5 Hz (ie 50 Hz burst of 3 pulses delivered every 200 msec). Right sided cTBS will involve a continuous 600 pulse sequence over 40 seconds. Left sided iTBS will involve a 2-seconds of TBS repeated every 10 seconds (i.e. 2 seconds of TBS followed by an 8 second rest), delivered over 180 seconds. Each TBS treatment session will take approximately 4 minutes. Where multiple sessions are provided in one day, there will be a minimum of 15 minutes break between the treatment sessions. Both rTMS and TBS treatments involve the application of magnetic stimulation to the dorsolateral prefrontal cortex (DLPFC). During treatment patients will be reclined in a comfortable chair and will be alert and awake. The sensation associated with treatment is usually well tolerated, with most people describing it as a tapping sensation. The treatment intensity for each person for both rTMS and TBS is determined as a percentage of their resting motor threshold (RMT), which is measured by administering single pulse TMS to the motor cortex (area of the brain responsible for muscle control). Standard rTMS treatment will be applied at 120% of the RMT, low intensity TBS at 80% of the RMT, and high intensity TBS at 120% of the RMT. All treatments will be conducted by a qualified TMS nurse. Participants will be monitored at all times, and each treatment time, date and dosage will be logged on a participant's treatment sheet. Intervention adherence and fidelity will be monitored by the TMS accredited nursing staff providing the treatments, and study personnel, including Principal and Associated Investigators, who are trained in the provision and clinical supervision of rTMS/TBS therapy.