Theta buRst stImulation for aDolescent dEpressioN feasibiliTy study: The TRIDENT study

Background: Depression is a leading cause of disability in adolescence. NICE guidance on the treatment of adolescent depression recommends psychological therapy or antidepressant medication. The number of antidepressants known to be effective in adolescents is limited and there is an increased risk of suicidality in this group. Psychological therapy is not effective for everyone. There is a lack of clarity over what to offer adolescents who have not responded to an antidepressant and psychological therapy. Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation which is effective in adults with treatment resistant depression. A form of rTMS called intermittent Theta Burst Stimulation (iTBS) can be delivered in a shorter timeframe and is as tolerable as traditional rTMS. Currently there are areas of uncertainty which means we do not know whether a full scale RCT of TMS for adolescents with depression would be possible within the NHS. TRIDENT addresses these knowledge gaps. Research question: Is it feasible to conduct a study to examine the effectiveness of iTBS for adolescents with depression that has not responded to at least one antidepressant and one psychological therapy? Primary objective: To complete a double-blind feasibility trial including a sham arm to assess recruitment, adherence and outcome data completion at 8 weeks post-randomisation. Secondary objectives are to evaluate: A] acceptability of iTBS to patients, and family/ carers across different ethnic and socioeconomic groups. B] views and knowledge of CAMHS clinicians about TMS. C] capacity in NHS TMS services to deliver a full trial. D] change in depression, anxiety, psychological functioning, self-harm/suicidal acts, quality of life, social functioning, sleep, relationships, cognition, and adverse events at 4 and 8 weeks. E] and to optimise iTBS, sham and trial procedures maximising their feasibility, acceptability, and efficiency Methods: We will complete a feasibility trial and nested studies. The primary outcomes will be to evaluate: i] recruitment over 12 months; ii] intervention adherence; iii] and data completion of a depression outcome measure at 8 weeks post-randomisation. We will also assess a broad range of clinical outcomes relevant to adolescents with depression. To assess views of CAMHS clinicians about TMS we will use a mixed methods approach involving an electronic survey and focus groups. To evaluate acceptability to participants and family / carers we will use mixed methods including a PPI developed acceptability measure that trial participants will complete, and individual qualitative interviews. Thematic analysis will be completed on qualitative interviews. So that we can understand capacity in NHS TMS services to deliver a full scale RCT we will survey all mental health Trusts about how they operate. During the study we will learn how to optimise iTBS, sham and trial procedures, maximising their feasibility and acceptability. Study length: 26 months. Anticipated impact and dissemination: We will answer the question: Is it feasible to conduct a study to examine the effectiveness of rTMS for adolescents with depression that has not responded to at least one antidepressant and psychological therapy? Dissemination will be via open access publications, conferences, public engagement events, and blogs. Results will inform stakeholders about TMS, and research funders on the feasibility of a full-scale trial.