Deep-brain magnetic stimulation as add-on treatment to lithium carbonate in the treatment of bipolar depression: study protocol for a randomized, double-blind, sham-controlled trial

Background and objectives: Bipolar disorder is a highly prevalent mental disorder. In clinical practice, mood stabilizers such as lithium carbonate are the conventional treatment for bipolar disorder. However, these drugs have slow onset of action and are not sufficiently effective in the acute phase. Deep-brain magnetic stimulation was hypothesized to have significant therapeutic effects in patients with major depressive disorder by entrainment of neural oscillations. In previous clinical trials, deep-brain magnetic stimulation showed good outcomes in the treatment of unipolar depression. However, randomized controlled trials that verify these results are lacking. Therefore, the current proposal intends to address this issue. Design: A single-center, randomized, double-blind, sham-controlled trial. Methods: Sixty patients aged 18–60 years who have been diagnosed with bipolar disorder at Beijing Anding Hospital, Capital Medical University of China, will be included and randomly divided into experimental and control groups (n = 30 per group). Patients in the experimental group will be treated with deep-brain magnetic stimulation plus lithium carbonate for 2 weeks followed by subsequent treatment with only lithium carbonate for 4 weeks. Patients in the control group will be treated with the same protocol, except they will receive sham stimulation. Outcome measures: The primary outcome measure is the change in score on the 17-Item Hamilton Rating Scale for Depression at weeks 2 and 6. The secondary outcome measures include response rate, complete remission rate (clinical cure rate), and changes in scores on the Hamilton Anxiety Rating Scale, 16-Item Quick Inventory of Depressive Symptomatology Self-Report, Generalized Anxiety Disorder-7, 9-Item Patient Health Questionnaire, Young Mania Rating Scale, Clinical Global Impression-Bipolar Disorder, and Montreal Cognitive Assessment at visit points relative to baseline scores. The safety evaluation indicators are the incidence of adverse events and the rate of manic switch. Discussion: The trial will verify the effectiveness of deep-brain magnetic stimulation with lithium carbonate in the treatment of bipolar disorder, providing evidence as to whether this combined therapy has the potential to be new alternative treatment for bipolar disorder. Ethics and dissemination: The trial was approved by the Ethics Committee of Beijing Anding Hospital, Capital Medical University in China (approval No. 201777FS-2) on October 27, 2017. Design of the trial was completed on June 28, 2017, and the trial registration was completed at the Chinese Clinical Trial Registry on November 10, 2017. Recruitment was initiated in January 2018 and it is expected to be completed in December 2018. Follow-up visit will end in June, 2019. Data analysis will be completed in December 2019. The results of the study will be disseminated through presentations at scientific meetings and/or in peer-reviewed publications. Anonymized trial data will be available indefinitely at www.figshare.com. Trial registration: The trial has been registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR-INR-17013338) and the version number is 2.1.