Transcranial magnetic stimulation combined with duloxetine improves attentional negativity bias in patients with depression: pilot study for a future trial

Abstract

Background and objective: Patients with depression often have cognitive deficits in perception, attention, executive control, and decision-making. Attentional negativity bias is a prominent symptom of depression. Indeed, during processing of negative emotional stimuli, the bilateral amygdala is over-activated, while prefrontal cortical activity decreases from baseline in patients with depression. Previous studies have reported that transcranial magnetic stimulation (TMS) can increase synaptic excitability. In this study, we investigate the effects of TMS combined with duloxetine versus duloxetine alone on attentional negativity bias in patients with depression. Subjects and Methods: A multi-center, randomized, double-blind, sham-stimulation, parallel-control trial will be conducted in Beijing Anding Hospital of Capital Medical University, Beijing, China. In the trial, 406 patients with depression will be included and will be randomly divided into a study group and a control group (n = 203 patients per group). Patients in both groups will receive oral administration of 60 mg/d duloxetine for 6 successive weeks, while patients in the study and control groups will undergo simultaneous TMS or sham-stimulation, respectively. The latter interventions will be performed once daily, five times a week with a 2 day interval between the first five and the last five procedures (10 times in total). This study was approved by Hospital Ethics Committee, Beijing Anding Hospital of Capital Medical University, China (approval No. 2017-79-2017111-2) on December 20, 2017. Protocol version: 3.0. Outcome measures: The primary outcome measure is effectiveness rate of the Hamilton Rating Scale for Depression–17-Item (HAMD17) after 6 weeks of treatment. The secondary outcome measures are: complete remission rate after 6 weeks of treatment; effectiveness rate after 1, 2, and 4 weeks of treatment; changes in HAMD17, Athens Insomnia Scale, Digit Symbol Substitution Test, 16-Item Quick Inventory of Depressive Symptomatology Self-Report Scale, 7-Item Generalized Anxiety Disorder Scale, Sheehan Disability Scale, Perceived Deficits Questionnaire-Depression, Arizona Sexual Experience Scale, and Mini-International Neuropsychiatric Interview suicide scores after 1, 2, 4, and 6 weeks of treatment relative to baseline; electroencephalogram results after 2 and 6 weeks of treatment; and safety indicators and adverse events after 6 weeks of treatment. Discussion: We plan to perform a study to provide preliminary evidence for the use of TMS combined with duloxetine to improve the attentional negativity bias in patients with depression. Trial registration: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-INR-17014075) on December 21, 2017.