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Major Depressive Disorder (MDD) is prevalent in patients with advanced cancer, and can have a negative impact on patients' quality of life. Available antidepressants, often have delayed benefits of several weeks, and therefore are of limited utility in the palliative care setting. Psychostimulants provide more rapid onset of action, but frequently require dose escalation because of problems with tolerance. There is a growing body of evidence that N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, signficantly and rapidly improve depressive symptoms in treatment resistant depression. However, studies conducted to date have not included advanced cancer patients. We report on a case where intravenous ketamine 'bursts' (0.5 mg/kg infused over 60 minutes) were used to treat an intractable MDD in a patient with metastatic prostate cancer. Initial positive response was not sustained, and response to a repeat treatment was even more transient. Adverse effects were mild and self-limiting. We conclude that a well-designed, randomized study of IV ketamine "bursts" in cancer patients suffering from depression is needed to further establish the role and appropriate dosing of ketamine in this patient population. Given that ketamine can be used as an adjuvant for difficult pain syndromes in cancer patients, it would be of interest to assess its impact on the mood in patients receiving this treatment for pain.

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Background Major depressive disorder (MDD) is the second highest cause of disability worldwide. Standard treatments for MDD include medicine and talk therapy; however, approximately 1 in 5 Canadians fail to respond to these approaches and must consider alternatives. Transcranial direct current stimulation (tDCS) is a safe, noninvasive method that uses electrical stimulation to change the activation pattern of different brain regions. By targeting those regions known to be affected in MDD, tDCS may be useful in ameliorating treatment-resistant depression. Objective The objective of the Neurostimulation of the Brain in Depression trial is to compare the effectiveness of active versus sham tDCS in treating patients with ultraresistant MDD. The primary outcome will be the improvement in depressive symptoms, as measured by the change on the Mongtomery-Asberg Depression Rating Scale. Secondary outcomes will include changes in the Quick Inventory of Depressive Symptomatology Scale (subjective assessment), the World Health Organization Disability Assessment Schedule 2.0 (functional assessment), and the Screen for Cognitive Impairment in Psychiatry (cognitive assessment). Adverse events will be captured using the Young Mania Rating Scale; tDCS Adverse Events Questionnaire; Frequency, Intensity, and Burden of Side Effects Rating Scale; and Patient-Rated Inventory of Side Effects Scale. A parallel component of the study will involve assaying for baseline language function and the effect of treatment on language using an exploratory acoustic and semantic corpus analysis on recorded interviews. Participant accuracy and response latency on an auditory lexical decision task will also be evaluated. Methods We will recruit inpatients and outpatients in the city of Edmonton, Alberta, and will deliver the study interventions at the Grey Nuns and University of Alberta Hospitals. Written informed consent will be obtained from all participants before enrollment. Eligible participants will be randomly assigned, in a double-blinded fashion, to receive active or sham tDCS, and they will continue receiving their usual pharmacotherapy and psychotherapy throughout the trial. In both groups, participants will receive 30 weekday stimulation sessions, each session being 30 minutes in length, with the anode over the left dorsolateral prefrontal cortex and the cathode over the right. Participants in the active group will be stimulated at 2 mA throughout, whereas the sham group will receive only a brief period of stimulation to mimic skin sensations felt in the active group. Measurements will be conducted at regular points throughout the trial and 30 days after trial completion. Results The trial has been approved by the University of Alberta Research Ethics Board and is scheduled to commence in June 2021. The target sample size is 60 participants. Conclusions This is a protocol for a multicenter, double-blinded, randomized controlled superiority trial comparing active versus sham tDCS in patients with treatment-resistant MDD. Trial Registration ClinicalTrials.gov NCT04159012; http://clinicaltrials.gov/ct2/show/NCT04159012. International Registered Report Identifier (IRRID) PRR1-10.2196/22805