Low-Dose Oral Ketamine for Pain Management: A Primer for Clinicians

Area of Science:

• Pharmacology
• Pain Management
• Clinical Therapeutics

Background:

• Opioid-sparing analgesics are crucial due to the opioid crisis.
• Ketamine, an N-methyl-D-aspartate receptor antagonist, has demonstrated analgesic properties.
• Oral ketamine presents a convenient formulation for pain management.

Purpose of the Study:

• To critically evaluate evidence for low-dose oral ketamine in analgesia.
• To provide clinical recommendations for oral ketamine use in practice.
• To address clinician queries regarding oral ketamine for pain.

Main Methods:

• Literature search of PubMed (2010-2025) using keywords: "Administration, oral," "Administration, sublingual," "ketamine," and "pain."
• Inclusion of all studies and case reports focusing on oral or sublingual ketamine for analgesia.

Main Results:

• Oral ketamine (25-300 mg/day) was well-tolerated, reducing pain scores, improving quality of life, and decreasing opioid requirements.
• Doses exceeding 6 mg/kg were associated with increased adverse effects.
• Optimal parenteral-to-oral dose conversions are unknown; however, a 75% reduction from daily infusion dose maintained analgesia in some cases.

Conclusions:

• Low-dose oral ketamine is an underutilized analgesic with growing evidence for acute and chronic pain.
• It may benefit patients with refractory pain, those requiring multimodal analgesia, or high opioid users.
• While generally safe in the short term, long-term risks of oral ketamine remain unclear.