Oral Ketamine for Depression, 2: Practical Considerations

The oral route of administration is probably the least expensive and most convenient way to administer ketamine in indicated contexts in depressed patients. Because only 20%-25% of orally administered ketamine reaches systemic circulation, oral doses of about 2.0-2.5 mg/kg may need to be administered to achieve equivalence to intravenously administered ketamine. In case reports, case series, standard operating practice in ketamine facilities, and randomized controlled trials, oral ketamine has been administered through weight-based dosing and as fixed doses, and the dosing strategy has been one-size-fits-all or individualized through a dose discovery process. Administered doses have ranged from 0.25 to 7.0 mg/kg in weight-based dosing sessions and from 25 mg to 300 mg in fixed dosing sessions. This article reviews strategies for dosing with oral ketamine, dose discovery procedures, rates of dosing during a session, the frequency of dosing sessions and the duration of treatment, treatment in the clinic vs domiciliary treatment, adverse effects and risks, and safety issues. Finally, this article provides a detailed account of practices and experiences with oral ketamine so that readers may know what to expect when the treatment is orally administered. Whereas oral ketamine appears to be a safe and effective treatment and could make ketamine an accessible and affordable intervention in less privileged medical facilities, readers are warned that the literature on oral ketamine is thin and that there are many areas that need more investigation, especially matters related to pharmacokinetics, physiologic effects, abuse potential and strategies to mitigate illicit use, and adverse effects and efficacy relative to other routes of administration. Until studies of a sufficiently high quality become available, the use of oral ketamine to treat depression must be considered experimental.