A Survey of the Clinical, Off-Label Use of Ketamine as a Treatment for Psychiatric Disorders

To the Editor: Since 2000, several small randomized controlled trials have demonstrated that ketamine has potent and rapid-acting antidepressant effects in patients with treatment-resistant depression (1). Despite a lack of long-term data or Food and Drug Administration indication, many community providers and academic centers have begun offering ketamine treatment to patients with major depressive disorder and with other psychiatric disorders, determining the existing evidence justifies use for some individuals. The practice patterns of such providers have not been studied.

Method

From September 2016 through January 2017, a web-based survey was sent to physicians nationwide inquiring whether their clinical practices use ketamine for psychiatric disorders. Physicians were identified through a systematic web search for sites advertising ketamine treatments for depression and through our relationships with academic and community colleagues. The study was considered exempt from a full evaluation from an institutional review board.

Results

We identified 85 providers through our search. Survey requests were sent to 76 providers (e-mail addresses could not be acquired for nine), and responses were received from 57 (75.0%). Most (73.7%) survey respondents worked in private practice, with a minority in academic settings (14.0%) or in health maintenance organizations (8.8%), with a regional distribution as follows: West Coast (31.6%), Northeast (19.3%), Southeast (15.8%), Mountain West (10.5%), Mid-Atlantic (10.5%), and Midwest (8.8%). Most (66.7%) providers were trained in psychiatry, with others trained in anesthesiology (22.8%), emergency medicine (3.5%), or family medicine (3.5%). Most providers (73.7%) administered ketamine in an office-based setting, with a minority (21.1%) administering ketamine in a hospital-based setting or in a surgical or procedural suite. The majority of practitioners reported starting to provide ketamine for psychiatric disorders relatively recently, with a notable increase in the cumulative number of such providers since 2012 (Figure 1).

The most commonly reported diagnosis treated was major depressive disorder (72.2%), followed by bipolar disorder (15.1%) and posttraumatic stress disorder (5.7%). Most providers (87.7%) reported administering ketamine via an intravenous route, with a minority reporting using an oral (22.8%) or an intranasal (19.3%) formulation. Among providers reporting intravenous administration, 44.0% reported using a dosage of 0.5 mg/kg infused over 40–45 minutes, the typical dosage in most research protocols (2); a minority reported using a range of dosages between 0.5 and 1.0 mg/kg (12.0%) or between 0.5 and 3.0 mg/kg (14.0%).

Approximately half of providers reported monitoring heart rate (48.1%) and pulse oximetry (54.0%) at least every 5 minutes during the infusion, with 25.9% monitoring blood pressure at least every 5 minutes. Most providers reported monitoring heart rate (77.8%), pulse oximetry (80.0%), and blood pressure (75.9%) at least every 15 minutes during the infusion. Few providers reported no monitoring of heart rate (1.9%), pulse oximetry (10.0%), and blood pressure (1.9%).

Most providers (89.5%) reported offering ketamine on a continuation or maintenance basis (defined as a time period greater than 1 month). Providers reported the average frequency of maintenance treatments as monthly (29.8%), once per 3 weeks (21.1%), once per 2 weeks (12.3%), or less than monthly (15.8%). Providers reported that 64% of patients paid for the ketamine treatment out of pocket, with 23% of patients having a portion of the cost reimbursed by insurance and 13% of patients having other payment structures.

Discussion

This is the first attempt to characterize practice patterns among physicians providing ketamine as a treatment for psychiatric disorders. Although there are limitations to this approach, including the inability to ensure that this is a representative sample of all ketamine providers across the country, we identified a rapidly growing number of physicians in a variety of specialties and geographic locations offering ketamine treatment for psychiatric disorders. Various dosing protocols were reported, although the majority of research studies have used only one protocol (2). These results underscore the urgent need for more research on the use of ketamine in psychiatric disorders in clinical settings in order to establish evidence-based treatment regimens and the safety of long-term use. The growing use of ketamine in this population, coupled with the concern for potential adverse clinical consequences of repeated dosing (e.g., abuse liability [3], cognitive impairment [4]), argues for the importance of a registry (5) to longitudinally follow psychiatric patients who receive ketamine.