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.

Summary

At-home subcutaneous (SC) ketamine treatment showed significant effectiveness in reducing symptoms of depression, anxiety, and PTSD among 3,870 patients over approximately 44 days. After six sessions, PHQ-9 scores decreased 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 between 1.35 and 1.58. Most patients achieved clinically meaningful improvements, and adverse events were low, indicating this method is safe and feasible.

Study at a glance

Abstract

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.