Mapping the Use of Ketamine in Treatment-Resistant Depression and Other Psychiatric Disorders: A Scoping Review of Practice Patterns, Efficacy, and Patient Demographic Trends.

Background: Ketamine has emerged as a novel treatment for psychiatric disorders, particularly treatment-resistant depression (TRD). Although intravenous (IV) ketamine is not approved by the Food and Drug Administration (FDA) for TRD, esketamine, an FDA-approved therapeutic, has contributed to the widespread clinical use of off-label IV ketamine across the United States. This scoping review highlights significant shifts in ketamine therapy, particularly after FDA approval of esketamine, the impact of COVID-19 on treatment accessibility, and increased regulatory scrutiny from the Drug Enforcement Administration (DEA) and FDA.

Areas of uncertainty: What are the current practice patterns, patient demographics, and barriers to accessing ketamine for psychiatric disorders, particularly TRD?

Data sources: This scoping review focused on provider utilization patterns (including frequency of ketamine administration, provider roles, and treatment settings), preferred administration methods (IV infusions, intramuscular injections, and other routes), and patient characteristics (age, sex, socioeconomic status, and primary psychiatric diagnoses treated). The Web of Science, PubMed, CBM, MEDLINE, Cochrane Library, University Theses, and Embase databases were searched.

Results: Two survey-based studies were included. IV administration was the most common method of administration reported in both studies, with alternative methods such as intramuscular and sublingual routes emerging in limited use. Patients receiving ketamine therapy were predominantly middle aged (36-64 years old), with financial barriers identified as a notable obstacle because of limited insurance coverage. Access to ketamine was limited in rural areas, illustrating the need for expanded provider networks. Private clinics exhibited greater flexibility in treatment approaches than hospital settings, which adhered to standardized protocols. The absence of long-term outcome data and variability in treatment protocols emphasize the need for standardized practices and further research.

Conclusions: This scoping review highlights the widespread use of ketamine for TRD, but reveals significant variability in practice patterns and accessibility barriers. Findings emphasize the need for standardized protocols, expanded insurance coverage, and further research to optimize the role of ketamine in psychiatric care.