At-Home Telehealth-Supported Subcutaneous Ketamine Therapy for Depression, Anxiety, and PTSD: A Real-World Observational Study of Safety, Feasibility, and Effectiveness in a Large Cohort (Preprint)

BACKGROUND Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and Post-Traumatic Stress Disorder (PTSD) are leading global causes of disability. Standard interventions often suffer from slow mechanisms of action, high attrition, and significant accessibility barriers. While intravenous (IV) and intranasal ketamine have emerged as rapid-acting alternatives, their high cost and intensive logistical requirements limit widespread adoption. Sublingual (SL) at-home ketamine has addressed some of these gaps but is constrained by low bioavailability and variable absorption. Subcutaneous (SC) administration offers high bioavailability and precise dosing, potentially bridging the gap between in-clinic effectiveness and at-home accessibility. OBJECTIVE This retrospective observational chart review study evaluated the safety, feasibility, and effectiveness of a telehealth-mediated, at-home SC ketamine protocol. METHODS A sample of N=3,870 patients with moderate-to-severe symptoms of depression (Patient Health Questionnaire-9 [PHQ-9] ≥10), anxiety (General Anxiety Disorder-7 [GAD-7] ≥10), or PTSD (The Posttraumatic Stress Disorder Checklist for DSM-5 [PCL-5] ≥33) participated in a structured program involving clinician assessment and education, mandatory peer monitoring, and remote physiological screening. Dosing followed a subanesthetic protocol starting at 0.5 mg/kg, with clinician-guided titration. Primary outcomes were measured at baseline and after weeks 2, 4, and 6 using the PHQ-9, GAD-7, and PCL-5. Linear mixed-effects models with cubic splines were used to analyze symptom trajectories. RESULTS Patients (mean age 45.6 years; 52.4% female) demonstrated high adherence, with only 0.5% electing to switch from SC to SL administration. Rapid and robust symptom reductions were observed across all symptom domains assessed. After 6 weekly treatment sessions (approximately 44 days), adjusted marginal means showed significant declines from symptomatic to mild to subthreshold ranges: PHQ-9 scores dropped from 14.64 to 6.30, GAD-7 from 13.06 to 6.09, and PCL-5 from 46.7 to 27.5 with large effect sizes (dz) ranging from 1.35 to 1.58. Minimal Clinically Important Difference (MCID) was achieved by 81.8% of MDD patients, 80% of GAD patients, and 84.6% of PTSD patients. The incidence of adverse events was low (2.8%−3.2%), with no reported serious complications related to SC administration. CONCLUSIONS At-home SC ketamine administration is a safe, feasible, and highly effective intervention for depression, anxiety, and PTSD. This model provides a low-cost, high-bioavailability alternative to in-clinic infusions, achieving clinical outcomes comparable to or exceeding traditional and intranasal therapies. These findings support the continued expansion of supervised telehealth models to close the gap in mental health care access. CLINICALTRIAL n/a