Date of Award


Document Type

Scholarly Project

Degree Name

Master of Physician Assistant Studies (MPAS)


Physician Assistant Studies

First Advisor

Jay Metzger


Treatment-resistant depression; Major depression disorder; Ketamine; Adverse effects; Safety; Pathophysiology; Typical antidepressants


Despite pharmacological advancements, depression continues to be considered the third leading cause of disability in the world. Although depressive symptoms may decrease within a few weeks after beginning typical antidepressants, there are still about one-third of individuals that fail to respond and do not achieve recovery. The symptoms not resolved by antidepressant therapy ultimately leads to decreased quality of life, decreased productiveness of the individual, increased hospitalizations, higher health care costs, and increased rates of suicide. As a result, the clinical use of ketamine in refractory depression is increasing because of the antidepressant properties found in a multitude of studies. The goal of this literature review is to determine the most efficacious treatment option for treatment-resistant depression (TRD), whether it be typical antidepressants or the intravenous infusion of ketamine. A comprehensive literature review was completed, with the use of various electronic databases, which included PubMed, Access Medicine, and Clinical Key. The studies included clinical trials, meta-analyses, randomized controlled trials, and systemic reviews. The research suggested evidence of improvement in symptoms of depression and suicidal ideation with the use of IV ketamine. However, the adverse effects associated with the use of ketamine need to be considered before beginning the use of ketamine for treatment. Additional clinical research does need to be done to further investigate the adverse effects associated with the chronic use of ketamine in TRD or refractory depression.