Oral Dosing Recommendations for Ketamine (NMDA Receptor Antagonist)
For chronic pain management, the recommended starting oral dose of ketamine is 0.5 mg/kg racemic ketamine or 0.25 mg/kg S-ketamine given 3-4 times daily, with careful titration based on clinical response and side effects. 1
General Dosing Guidelines
- For ketamine-naïve patients with chronic pain, begin with 0.5 mg/kg racemic ketamine or 0.25 mg/kg S-ketamine as a single oral dose, increasing by the same amount if required 1
- For maintenance of analgesia, ketamine is typically administered 3-4 times daily to maintain continuous analgesic effect 1
- When converting from parenteral to oral ketamine, the daily dosage can initially be kept equal and then slowly increased based on clinical effect and/or adverse effects 1, 2
- Due to low oral bioavailability (20-25%), oral doses of approximately 2.0-2.5 mg/kg may be needed to achieve equivalence to intravenous administration 3
Specific Clinical Applications
For Pain Management
- In cancer pain management, low (subanesthetic) doses of ketamine may be considered for intractable pain that is unresponsive to conventional analgesics 4
- For perioperative pain management, ketamine can be administered at 0.5 mg/kg for breakthrough pain in post-anesthesia care units 4
- When using ketamine as an adjuvant to opioids for cancer pain management, careful monitoring is required as evidence for efficacy is limited 4
For Depression
- Oral ketamine doses ranging from 0.25 to 7.0 mg/kg in weight-based dosing or 25 mg to 300 mg in fixed dosing have been used in depression treatment 3
- For treatment-resistant depression, doses may need to be individualized through a dose discovery process 5
Special Considerations
- When using S-ketamine (the S-enantiomer), the dose should be reduced to 0.25-0.5 mg/kg due to its approximately four-fold higher affinity for the NMDA receptor compared to R-ketamine 6
- Continuous monitoring of vital signs, including ECG, pulse oximetry, and regular blood pressure measurements, is essential during initial administration 6, 7
- For patients with chronic neuropathic pain, some clinicians start with a divided dose of 100 mg/day and titrate upwards by 40 mg/day until efficacy is reached or side effects become limiting 8
Safety and Monitoring
- The risk of psychotomimetic side effects can be reduced by concurrent administration of a benzodiazepine, particularly when initiating ketamine therapy 2
- Lack of robust evidence regarding long-term efficacy and safety does not support routine use of oral ketamine in chronic pain management 1
- Oral ketamine should be considered as an add-on therapy only in complex chronic pain patients when other therapeutic options have failed 1
- When considering domiciliary (home) treatment, the risk of abuse must be carefully evaluated 5
Practical Administration
- Injectable ketamine solution can be taken orally when oral formulations are unavailable 1
- For long-term treatment, the frequency is best individualized with dosing scheduled before the effect of the previous dose is expected to wear off 5
- The pharmacologically active metabolite norketamine contributes to the analgesic effect of oral ketamine, which may influence dosing strategies 1