Gurleen K. Multani


Introduction: Individuals with treatment resistant depression (TRD) are those with severe major depressive disorder who fail to respond to conventional pharmacological treatment. As a result, novel technologies in the field of neuromodulation have been investigated to alleviate depressive symptoms in this population. One such neuromodulation therapy is deep brain stimulation (DBS), in which electrodes are neurosurgically implanted into target regions of the brain associated with depression, such as the subgenual anterior cingulate cortex (sgACC). While previous studies have explored the use of DBS as a therapy for TRD, few studies with adequate statistical power have explored the sustained antidepressant effects of DBS when targeting the sgACC of the brain.

Methods: This study aims to explore the long-term effects in DBS patients for TRD by measuring changes in cerebral blood flow and cerebral metabolic rate in the sgACC, and its correlation to changes in self-reported depressive symptoms. Forty-five participants will be enlisted into this study. Psychometric evaluation and positron-emission topography imaging will be conducted prior to neurosurgery. Electrodes will be implanted into the sgACC, with extension wires attaching the electrodes to the internal pulse generator. In the six-week blinded phase, progressive increases in stimulation will be administered within the blinded group and sham stimulation in controls. The three-month open label phase will administer the same degree of high-frequency biphasic stimulation to the control and blinded groups and assess depression scores, neuroimaging, and adverse events. After cessation of active stimulation, a one-year, three-year, seven-year, and ten-year follow-up will monitor changes in antidepressant effects of DBS using simple linear contrasts and paired-sample t-tests.

Expected Results: This study expects to find a sustained antidepressant response marked by decreases in sgACC metabolism and cerebral blood flow, and a reduction in self-report depression scores.

Discussion: The use of DBS shows promise as a successful treatment intervention with sustained long-term effects for individuals with TRD. Additional secondary outcomes to be expected are improved quality of life and health behaviours.

Conclusion: Though minor fluctuations are expected due to the presence of comorbidities, this study expects to showcase the long-term efficacy of deep brain stimulation for treatment resistant depression.

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Research Protocol