Objective: To critically evaluate the available evidence for low-dose oral ketamine for analgesia and provide summary recommendations for clinicians on its use in practice. Data sources: A search of the primary literature was performed in PubMed from 2010 through 2025 using the following keywords: “Administration, oral,” “Administration, sublingual,” “ketamine,” and “pain.” Study selection and data extraction: All studies and case reports involving the use of oral or sublingual ketamine for analgesia as the primary focus were included. Data synthesis: Oral ketamine was well tolerated in dose ranges from 25 to 300 mg/day, which were associated with reduced pain scores, improved quality of life, and decreased opioid requirements in line with low-dose infusions for pain management. Weight-based doses above 6 mg/kg corresponded with an increase in adverse effects. Optimal parenteral-to-oral dose conversions are not known; however, dose reductions by 75% from the daily infusion dose maintained analgesia in a small number of cases. Treatment durations ranged from single doses up to 12 years but were predominantly studied in less than 2 years of use. Relevance to patient care and clinical practice: There remains a dearth of safe and effective pharmacologic pain management options which serve as alternatives to opioids. Low-dose ketamine is an oft-overlooked analgesic with evidence dating back over 50 years, but clinical uptake is poor. Oral ketamine presents a pragmatic formulation, and this review uses the current evidence to address pertinent clinical queries raised by clinicians in practice. Conclusions: Subanesthetic oral ketamine is an analgesic with continually growing evidence investigating use in a variety of acute and chronic pain syndromes. Based on the current evidence, ketamine may be helpful for refractory pain, as a component of multimodal analgesia, or in patients with high opioid requirements. Adverse effects are typically mild, but the risks of long-term use ultimately remain unclear.
Phan et al. (Thu,) studied this question.