What is the typical oral dosing of ketamine (Ketamine Hydrochloride) for a patient with a history of substance abuse or dependence, requiring treatment for chronic pain, anxiety, or depression?

Oral Ketamine Dosing for Chronic Pain, Depression, and Anxiety

Oral ketamine should be reserved for specialist use only (palliative care, pain management, or psychiatry) after other therapeutic options have failed, with starting doses of 0.5 mg/kg (approximately 25-50 mg) for ketamine-naive patients, titrated upward based on response, typically administered 3-4 times daily for chronic pain or as single doses for depression. 1, 2

Critical Context for Patients with Substance Abuse History

• Oral ketamine carries significant abuse potential and should be used with extreme caution in patients with substance abuse history, requiring close monitoring and potentially supervised administration to prevent diversion 1, 3
• The American Geriatrics Society explicitly restricts ketamine use to specialists due to serious adverse effects and psychotomimetic risks 1
• Absolute contraindications include active psychosis, uncontrolled cardiovascular disease, severe liver dysfunction, and pregnancy 1

Dosing Strategies for Chronic Pain

Starting Dose

• Begin with 0.5 mg/kg of racemic ketamine (or 0.25 mg/kg of S-ketamine) as a single oral dose in ketamine-naive patients 2
• For a 70 kg patient, this translates to approximately 35 mg of racemic ketamine 2
• The injection formulation can be taken orally 2

Dose Titration

• Increase by the same increment (0.5 mg/kg) if pain relief is inadequate, based on clinical effect and tolerability 2
• For continuous analgesia, administer 3-4 times daily 2
• Reported effective doses range from 0.25 to 7 mg/kg per session, though most patients respond to lower doses 4, 5

Conversion from Parenteral to Oral

• When switching from IV/SC ketamine to oral, maintain the same total daily dose initially, then titrate slowly based on response 2
• Account for only 20-25% oral bioavailability by using approximately 4-5 times the IV dose to achieve equivalent plasma levels 4, 5

Dosing for Depression and Suicidal Ideation

Single-Dose Strategy

• For depression, oral doses of 2.0-2.5 mg/kg (approximately 100-175 mg for a 70 kg patient) may be needed to achieve equivalence to the standard 0.5 mg/kg IV dose 5
• Fixed doses ranging from 50-300 mg per session have been used successfully in clinical trials 4, 5
• Lower doses (0.25-1 mg/kg) have shown efficacy in some patients 4

Frequency and Duration

• Dosing schedules vary from single doses to multiple daily administrations, depending on indication and response 4
• For depression maintenance, frequency should be individualized, dosing "a little before the effect of the previous session is expected to wear off" 3
• Treatment duration ranges from single sessions to weeks or years in refractory cases 3

Pharmacokinetic Considerations

• Oral ketamine has poor bioavailability (20-25%), but this is compensated by higher dosing 4, 5
• The active metabolite norketamine contributes to analgesic effects with oral administration 2
• Interindividual variations in absorption require individualized dose titration 4

Safety and Monitoring Requirements

Essential Monitoring

• Continuous cardiac monitoring and pulse oximetry during administration 1
• Regular assessment of sedation level, respiratory status, and hemodynamics 1
• Practitioners must be able to rescue patients from unintended deep sedation 1

Adverse Effects Management

• Psychotomimetic effects are the primary concern, especially at higher doses and with prolonged use 1, 2
• Consider co-administration with benzodiazepines to minimize psychotomimetic effects 1
• Common side effects include dissociation, dizziness, and nausea 4, 5

Special Precautions for Substance Abuse History

• Supervised administration is strongly recommended to prevent diversion and abuse 3
• Avoid domiciliary (home-based) treatment in patients with substance abuse history 3
• Consider more frequent follow-up and pill counts 5

Evidence Quality and Limitations

• The evidence for oral ketamine is significantly weaker than for IV administration, consisting primarily of case reports, case series, and only three small RCTs for depression 4
• For chronic pain, there is no consistent dose-response relationship, and lack of high-quality evidence does not support routine use 2
• The National Comprehensive Cancer Network found no significant difference between ketamine and placebo for cancer pain in a double-blind RCT 1

Practical Implementation

Formulation

• Use injectable ketamine solution administered orally (off-label use) 2, 6
• Flavoring can mask the bitter taste and improve palatability 6
• Compounded oral solutions (e.g., 40 mg/5 mL) have been used successfully 6

Clinical Setting

• Treatment should occur in a supervised clinical setting initially, not at home, especially for patients with substance abuse history 1, 3
• Emergency medicine, pain management, or psychiatric specialists should prescribe and monitor 1

Key Clinical Pitfalls

• Do not use oral ketamine as first-line therapy—it is reserved for complex cases where other options have failed 1, 2
• Do not prescribe for home use in patients with substance abuse history due to high diversion risk 3
• Do not assume IV dosing equivalence—oral doses must be 4-5 times higher to compensate for poor bioavailability 4, 5
• Do not ignore cardiovascular effects—ketamine increases heart rate and blood pressure through sympathetic stimulation 1