No Standard Dosing For Oral Ketamine Exists: A Systematic Audit of Oral and Sublingual Ketamine Dosing Across 26 Depression Studies and Its Implications for Patient Safety

Oral and sublingual ketamine is prescribed to tens of thousands of patients via telehealth without an FDA-approved dosing protocol or clinical guideline. A synthesis of 26 clinical studies from 2013 to 2026 found that effective doses in randomized controlled trials using standard racemic ketamine ranged from about 70 mg to 180 mg per session, while at-home users reported a 120-fold dose range from 10 mg to 1,200 mg. Three studies that failed to achieve primary endpoints attributed this to insufficient dosing. Real-world telehealth protocols use frequencies not tested in any positive placebo-controlled trial. The absence of a dosing standard creates patient safety risks: subtherapeutic doses may lead patients to abandon a potentially effective treatment, while higher doses lack controlled safety data.

Study at a glance

Abstract

Background: Oral and sublingual ketamine for depression is being prescribed to tens of thousands of patients through telehealth services with no FDA-approved dosing protocol, no clinical guideline covering this route of administration, and no publicly available synthesis of what clinical researchers have actually tested. A prior surveillance study of patient-reported experiences documented a 120-fold dose range among at-home users — from 10mg to 1,200mg per session — with no shared framework for interpreting what constitutes an appropriate dose. Objective: To identify, extract, and synthesize dosing parameters — dose amount, formulation, frequency, and duration — from all available clinical studies of oral or sublingual ketamine for depression published between 2013 and 2026, and to analyze the patient safety implications of the absence of a dosing standard. Methods: Systematic web searches were conducted across PubMed Central, medRxiv, Google Scholar, and open-access journal databases. Three sequential verification passes were conducted, supplemented by reference chasing from the most recent meta-analysis (Silberbauer et al., 2026). Studies were included if they involved human subjects, oral or sublingual administration, depression as a primary or secondary outcome, a reported dose amount, and a minimum sample size of three participants. Results: Twenty-six studies were identified spanning 2013 to 2026: 9 randomized controlled trials (RCTs), 5 open-label trials, 3 case series or retrospective studies, and 9 real-world, telehealth, or congress-abstract studies. Among RCTs using standard racemic ketamine, effective doses ranged from approximately 70mg per session (1.0 mg/kg for a 70kg individual) to 180mg per session. Three studies that failed to achieve primary endpoints or terminated early attributed their outcomes to insufficient dosing. No consensus exists across the literature on dose, frequency, duration, or formulation. Real-world telehealth protocols use frequencies — typically once weekly — not tested in any positive placebo-controlled trial. Conclusions: The absence of a dosing standard is not a theoretical concern. It creates measurable, specific patient safety risks: patients receiving subtherapeutic doses may conclude ketamine is ineffective and abandon a treatment that might have worked at an appropriate dose; patients receiving doses with no controlled safety data face unknown risk. The research evidence that does exist — though heterogeneous and underpowered — points toward a convergent effective range that has never been compiled and made publicly accessible until now.