At-Home Telehealth-Supported Subcutaneous Ketamine Therapy for Safety, Feasibility, and Clinical Outcomes in Adults With Moderate to Severe Depression, Anxiety, or Posttraumatic Stress Disorder in a Large, Heterogeneous Cohort in the United States: Retrospective Cohort Study.

BACKGROUND: Depression, anxiety, and posttraumatic stress disorder (PTSD) are leading global causes of disability. Standard interventions have slow mechanisms of action, high attrition, and significant accessibility barriers. While intravenous and intranasal ketamine are rapid-acting alternatives, high cost and intensive logistical requirements limit adoption. Sublingual at-home ketamine addresses some gaps but is constrained by low bioavailability and variable absorption. Subcutaneous administration offers high bioavailability and precise dosing, potentially bridging the gap between in-clinic effectiveness and at-home accessibility.

OBJECTIVE: This study evaluated the safety, feasibility, and clinical outcomes of a telehealth, at-home subcutaneous ketamine protocol using a convenience sample of deidentified health records collected through Mindbloom's telehealth platform across 38 states.

METHODS: This retrospective cohort study analyzed deidentified health records from 3870 patients with moderate to severe symptoms of depression (Patient Health Questionnaire-9 [PHQ-9] score≥10), anxiety (Generalized Anxiety Disorder-7 Scale [GAD-7] score≥10), or PTSD (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition; PCL-5] ≥33). Participants completed a structured program involving clinical assessment, mandatory peer monitoring, remote physiological screening, mailed injection kits and blood pressure monitors, and clinician-guided subanesthetic dosing starting at 0.5 mg/kg. 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 analyzed symptom trajectories and accounted for time-varying assessments. Statistical significance was defined as α=.05; effect sizes were reported. Sensitivity analyses used multiple imputation and last observation carried forward.

RESULTS: Patients (mean age 44.7, SD 10.8 years; 1592/3041, 52.4% female) demonstrated high adherence, with 0.5% (16/3041) switching from subcutaneous to sublingual administration. After 6 sessions (approximately 44 days), adjusted marginal means showed significant declines: PHQ-9 scores dropped from 14.64 (95% CI 13.99-15.29) to 6.30 (95% CI 5.90-6.70), GAD-7 from 13.06 (95% CI 12.45-13.67) to 6.09 (95% CI 5.72-6.47), and PCL-5 from 46.7 (95% CI 43.30-50.10) to 27.5 (95% CI 25.40-29.70) with large effect sizes (1.35-1.58). Minimal clinically important difference was achieved by 81.8% (603/737) patients with major depressive disorder, 80% (475/594) with generalized anxiety disorder, and 84.6% (203/240) with PTSD (P<.001 for all). Adverse events were low (2.8%-3.2%), with no serious complications related to subcutaneous administration.

CONCLUSIONS: This study is the first large-scale evaluation of at-home subcutaneous ketamine. Results suggest that at-home subcutaneous ketamine is a safe, feasible intervention associated with high rates of symptom reduction in depression, anxiety, and PTSD. It differs from existing literature by using a high-bioavailability (93%) subcutaneous route in a remote setting, whereas patients typically receive infusions of this potency in-clinic. Patients achieved clinical outcomes comparable to or exceeding traditional and intranasal therapies, potentially closing the access gap for treatment-resistant populations and supporting the expansion of supervised telehealth models in mental health care.