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Background: Major depressive disorder is the leading cause of mental health-related burden globally and up to one-third of major depressive disorder patients never achieve remission. Transcranial Direct Current Stimulation is a non-invasive intervention used to treat individuals diagnosed with major depressive disorder and bipolar disorder. Since the last transcranial direct current stimulation review specifically focusing on cognitive symptoms in major depressive disorder, twice as many papers have been published. Methods: A systematic review was conducted with 5 electronic databases from database inception until March 21, 2022. Randomized controlled trials with at least 1 arm evaluating transcranial direct current stimulation in adults (diagnosed with major depressive disorder or bipolar disorder using the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria) aged 18 or older were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. Results: : A total of 972 participants were included across 14 studies (60.5% female; mean age of 47.0 years [SD = 16.8]). Nine studies focused on participants with major depressive disorder and all studies used the Diagnostic and Statistical Manual of Mental Disorders to diagnose the participants. Seven out of the 14 studies showed significant improvements in at least 1 cognitive outcome measure in the active transcranial direct current stimulation group compared to the sham group. Several cognitive measures were used across studies, and 12 of the 14 studies reported mild-to-moderate side effects from treatment. Conclusion: : Current transcranial direct current stimulation literature has shown limited evidence for the treatment of cognitive impairments in major depressive disorder and bipolar disorder. Future research that applies machine learning algorithms may enable us to distinguish responders from non-responders, increasing clinical benefits of transcranial direct current stimulation.
ABSTRACT
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.
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Introduction: Treatment Resistant Depression (TRD) is a common and burdensome condition with poor outcomes and few treatment options. Esketamine is the S-enantiomer of ketamine and has recently been FDA approved in the United States for treating depression that has failed to respond to trials of two or more antidepressants. Areas covered: This review will briefly discuss current treatment options for TRD, then review esketamine. Relevant literature was identified through online database searches, and clinical trial data were provided by Janssen Pharmaceuticals. Pharmacology, including kinetics and dynamics, is discussed, then clinical data regarding efficacy and safety for esketamine from Phase 2-3 trials are reviewed. Expert opinion: In the expert opinion, the authors discuss multiple factors including patient, physician, and social factors that will influence the use of esketamine. While the efficacy of esketamine compared to off-label use of racemic ketamine remains unclear, both esketamine's approval for use in TRD and longer-term safety data may position it preferentially above racemic ketamine, although factors such as cost and monitoring requirements may limit its use. While questions remain regarding duration and frequency of treatment, as well as addictive potential, esketamine is a novel treatment option offering new hope for TRD.
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Antidepressive Agents/therapeutic use , Depressive Disorder, Treatment-Resistant/drug therapy , Ketamine/therapeutic use , HumansABSTRACT
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.
