Safety, effectiveness and tolerability of sublingual ketamine in depression and anxiety: A retrospective study of off-label, at-home use

Introduction

Major depressive disorder (MDD) is highly prevalent and frequently resistant to first-line treatments: roughly half of patients respond to standard antidepressants and about 30% meet criteria for treatment‑resistant depression (TRD). Comorbid anxiety—particularly generalized anxiety disorder (GAD)—is common in people with TRD, worsens course and treatment outcomes, and complicates pharmacological strategies (for example, benzodiazepine use may attenuate ketamine’s antidepressant effects). Intravenous (IV) ketamine and intranasal (IN) esketamine have attracted clinical attention and regulatory approval for TRD, but IV approaches require medicalised settings and carry cost and access barriers. Hartelius and colleagues situate sublingual (SL) rapid‑dissolve ketamine tablets (RDT) as a pragmatic alternate delivery route with higher transmucosal bioavailability than oral dosing (approximately 30% vs 10–20%). Responding to COVID‑19–era constraints, the investigators conducted a retrospective chart review of an at‑home, clinician‑supervised SL ketamine programme to assess safety, tolerability and change in depressive and anxiety symptoms after three and six self‑administered RDT doses (300–450 mg). The study aims to evaluate whether SL ketamine delivered at home is a viable option for patients with TRD and treatment‑resistant anxiety and to extend prior prospective work in this area.