Randomised double-blind controlled trial of connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment resistant moderate to severe depression: evaluation of efficacy, cost effectiveness and mechanism of action.
Professor Richard Morriss
Nottinghamshire Healthcare NHS Foundation Trust
NIHR (EME Programme)
Trial Registration Number
Depression is the 2nd leading cause of disability worldwide and suicide from depression is the biggest killer in people aged 15-49 years. Antidepressants and talking therapies help two thirds of people with depression, but the remaining third have treatment resistant depression (TRD). Until recently, a few patients with TRD were offered Electroconvulsive Therapy (ECT), but they may not accept this treatment due to its possible side effects. An alternative treatment called transcranial magnetic stimulation (TMS) has recently been used employing magnets and not requiring an anaesthetic. In December 2015, NICE reviewed the evidence for TMS and advised that it may be used to treat depression. NICE reports that TMS is safe and effective in reducing symptoms for a short while, but has asked for further research to be carried out. In this trial we compare rTMS the standard treatment and a novel type of TMS called theta-burst stimulation (TBS). A pilot study showed that TBS guided by a brain scan (cgiTBS) can maintain the improvement longer than the rTMS treatment but this needs further research before it is used in clinical practice. Patients with depression experience changes in some parts of the brain particularly in the frontal area. If an intervention is delivered precisely to these specific parts of the brain, it may avoid unwanted effects and improve the outcome, based on a brain scan, for each patient a specific point in the brain is identified to deliver the magnetic pulses.
Number of Participants
The study is a multicentre parallel group, double blind, randomised controlled trial of the efficacy of cgiTBS versus no connectivity guided standard rTMS in patients with a diagnosis of moderate to severe depression who are diagnosed as treatment resistant depression (TRD)
Participants will receive an eligibility assessment by telephone and if eligible they will be asked to attend a baseline assessment, where consent will be obtained and a further eligibility assessment will be conducted. MRI scan will be performed for all participants to establish site of stimulation for TMS Treatment. Allocation of treatment will be completed on the first day of TMS treatment where participant will attend 20 treatment session over 4- 6 weeks.
8 and 16 weeks post randomisation follow up assessments will be performed with an additional MRI scan at 16 weeks to assess treatment response.
Final follow up assessment and completion of the study is at 26 weeks post randomisation, participant will also be advised of the treatment they have received.