Off-label use of transmucosal ketamine as a rapid-acting antidepressant: a retrospective chart review

Abstract

ObjectiveThis study evaluated the effectiveness and safety of subanesthetic doses of ketamine using an off-label, transmucosal administration route in patients with treatment-resistant depression.MethodsA retrospective chart review was conducted to identify patients who met the inclusion criteria for treatment-resistant major depressive disorder. Seventeen such patients who received subanesthetic doses of ketamine were included. Patient demographics, efficacy (drug refill, clinician notes), side effects, and concurrent medications were assessed.ResultsBenefit from low-dose transmucosal ketamine was noted in 76% of subjects (average age 48 years, 88% female), with a dose duration lasting 7–14 days. No notable side effects were noted. The most common classes of concurrent medications to which ketamine was added were serotonin–norepinephrine reuptake inhibitors (59%), stimulants (47%), folate replacement (47%), and benzodiazepines (47%).ConclusionOur results provide preliminary evidence of the effectiveness and safety of low-dose transmucosal ketamine in treatment-resistant patients. A controlled, prospective pilot study is warranted to validate these findings.

Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines

“…ketamine as a second-line augmenter and highlighted the potential for this to be superseded by its intranasal form in the near future ( Daly et al, 2018 ). They also cited studies of intramuscular and subcutaneous administration, sublingual administration, and transmucosal routes ( Lara et al, 2013 ; Nguyen et al, 2015 ; Loo et al, 2016 ). They discussed the very rapid response rates and high short-term remission rates and mentioned evidence of maintained response if repeated doses are administered (not referenced).…”

Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability

“…24,53 We included 11 controlled and uncontrolled trials, case series, and case reports on maintenance oral ketamine treatment, including 199 unipolar (approximately 93%) and bipolar (approximately 7%) patients with treatmentresistant depression. 11,12,25,28,31,32,34,35,37,43,52 Duration and frequency of treatment varied widely, from 6 weeks to 3 years and from 3 times a day to once a month. In some studies frequency was individually tailored, in some dosing was individually tailored, and in some both were.…”

“…Two controlled trials, one uncontrolled trial, and six case series and reports presented results of maintenance treatment within the first 6 months after initial response. 12,25,28,32,34,35,37,43,52 Although the RCTs were not designed to study maintenance treatment, in both studies ketamine treatment was offered for more than 4 weeks, therewith meeting our intervention criteria. In the first RCT, including 40 patients, antidepressant effects were superior for ketamine versus diclofenac after 3 weeks of treatment when measured by the Hospital Anxiety and Depression Score (HADS).…”

“…Finally, of the 28 patients included in the six case series and reports, 100% showed sustained response. 25,28,34,37,43,52 No differences in effectiveness were found when comparing the results of studies with different treatment frequencies or sample sizes. The number of patients with bipolar depression was too small to be able to distinguish differences in effectiveness regarding diagnostic categories.…”

“…Mid-term (6 months to 1 year) and long-term (≥1 year) efficacy data were reported in three case series 11,31,43 and two case reports. 28,52 Of the 14 initial responders included in the three case studies and case reports reporting on mid-term sustained response rates, 13 (93%) showed sustained response after 6 months to 1 year of maintenance treatment.…”