At-Home Telehealth-Supported Subcutaneous Ketamine Therapy in Adults With Moderate to Severe Depression, Anxiety, or PTSD: A Real-World Observational Study of Safety, Feasibility, and Clinical Outcomes in a Large, Heterogeneous Cohort in the United States.

Background: Depression, anxiety,, and PTSD are leading global causes of disability. Standard interventions utilize slow mechanisms of action, high attrition, and significant accessibility barriers. While intravenous (IV) and intranasal ketamine are rapid-acting alternatives, high cost and intensive logistical requirements limit adoption. Sublingual (SL) at-home ketamine addresses some 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 study evaluated the safety, feasibility, and clinical outcomes of a telehealth, at-home SC ketamine protocol using a convenience sample of de-identified health records collected via Mindbloom's telehealth platform across 38 states.

Methods: A sample of N=3,870 patients with moderate-to-severe symptoms of depression (PHQ-9 ≥ 10), anxiety (GAD-7 ≥ 10), or PTSD (PCL-5 ≥ 33) participated in a structured program involving clinical assessment, mandatory peer monitoring, and remote physiological screening. Injection kits and blood pressure monitors were mailed home. 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 via online survey. Linear mixed-effects models with cubic splines analyzed symptom trajectories and accounted for time-varying assessments. Statistical significance was defined as alpha = .05; effect sizes were reported. Sensitivity analyses utilized multiple imputation and LOCF.

Results: Patients (mean age 44.7 years; 52.4% female) demonstrated high adherence, with 0.5% switching from SC to SL administration. After 6 sessions (approximately 44 days), adjusted marginal means showed significant declines: PHQ-9 scores dropped from 14.64 (13.99-15.29) to 6.30 (5.90-6.70), GAD-7 from 13.06 (12.45-13.67) to 6.09 (5.72-6.47), and PCL-5 from 46.7 (43.30-50.10) to 27.5 (25.40-29.70) with large effect sizes ($d_z$) ranging from 1.35 to 1.58. Minimal Clinically Important Difference (MCID) was achieved by 81.8% of MDD, 80% of GAD, and 84.6% of PTSD patients ($p < .001$ for all). Adverse events were low (2.8%-3.2%), with no serious complications related to SC administration.

Conclusions: This study is the first large-scale evaluation of at-home SC ketamine. Results suggest at-home SC ketamine is a safe, feasible intervention associated with high rates of symptom reduction in depression, anxiety, and PTSD. It differs from existing literature by utilizing a high-bioavailability (93%) SC 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.