Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Abstract

Background: Depression and anxiety are prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine has many properties that make it an interesting candidate for rapidly treating depression and anxiety in patients receiving hospice care. To test this hypothesis, a 28-day, open-label, proof-of-concept trial of daily oral ketamine administration was conducted in order to evaluate the tolerability, potential efficacy, and time to potential efficacy in treating depression and anxiety in patients receiving hospice care. Methods:In this open-label study, 14 subjects with symptoms of depression or depression mixed with anxiety warranting psychopharmacological intervention received daily oral doses of ketamine hydrochloride (0.5 mg/ kg) over a 28-day period. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS), which was used to rate overall depression and anxiety symptoms at baseline, and on days 3, 7, 14, 21, and 28. Results: Over the 28-day trial there was significant improvement in both depressive symptoms (F 5,35 = 8.03, p = 0.002, g 2 = 0.534) and symptoms of anxiety (F 5,35 = 14.275, p < 0.001, g 2 = 0.67) for the eight subjects that completed the trial. One hundred percent of subjects completing the trial responded to ketamine for both anxiety and depression. A significant response in depressive symptoms occurred by day 14 for depression (mean D = 3.5, d = 1.14, 95% CI = 1.09-5.9, p = 0.01) and day 3 for anxiety (mean D = 2.4, d = 0.67, 95% CI = 1.0-3.7, p = 0.004). These improvements remained significant through day 28 for both depression (mean D = 4.0, d = 1.34, 95% CI = 2.3-5.9, p = 0.001) and anxiety (mean D = 6.09, d = 1.34, 95% CI = 3.6-8.6, p < 0.001). Side effects were rare, the most common being diarrhea, trouble sleeping, and trouble sitting still. Conclusions: Patients who received daily oral ketamine experienced a robust antidepressant and anxiolytic response with few adverse events. The response rate for depression is similar to those found with IV ketamine; however, the time to response is more protracted. The findings of the potential efficacy of oral ketamine for depression and the response of anxiety symptoms are novel. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the efficacy and safety of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care or other subject populations.

A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes

“…Indeed, the palliative field has shown great interest in the potential for the use of ketamine in the management of depressive symptoms at the end of life (Irwin et al 2013).…”

Intranasal Drug Delivery in Neuropsychiatry: Focus on Intranasal Ketamine for Refractory Depression

“…39 Interestingly, both oral and sublingual ketamine have been trialled in depression. In a 4-week, proof-of-concept study, Irwin et al 40 administered oral ketamine (0.5 mg/ kg/d) to 14 mildly anxious and depressed patients in hospice care. Four patients dropped out because of nonresponse, and 2, for reasons unrelated to ketamine.…”

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

“…While more work is needed to further explore repeated dosing, other studies have examined alternative methods of delivery: oral [Irwin and Iglewicz, 2010;Paslakis et al 2010;Irwin et al 2013;De Gioannis and De Leo, 2014], intramuscular [Cusin et al 2012], sublingual [Lara et al 2013], and most recently, intranasal [Lapidus et al 2014], which will be reviewed in detail as follows.…”