More than 25 systematic reviews and meta-analyses published between 2020 and 2025 on ketamine-based therapies for depression are summarized. Intravenous (IV) ketamine, esketamine nasal spray (Spravato), and oral ketamine show differences in response rates, remission rates, speed of symptom relief, and durability of results. The report also examines research on combining ketamine with psychotherapy. The evidence is drawn from high-quality peer-reviewed studies, including randomized controlled trials and observational studies, providing a clear overview of the most reliable evidence available.
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.
A synthesis of 31 studies from 2016 to 2026 finds that intravenous ketamine rapidly reduces suicidal ideation, with 63% of patients achieving full remission by Day 3 compared to 32% on placebo, effects appearing within 40 minutes. Intranasal esketamine shows inconsistent results across studies, but when confounding factors such as hospitalization floor effects, insensitive measurement, and treatment resistance are accounted for, its anti-suicidal effect becomes clear and lasts up to 18 weeks. Injection routes show promise but lack randomized trial evidence. The analysis is based on a publicly available dataset.