What is the oral dose recommendation for ketamine (Ketamine) in treating depression?

Oral Ketamine Dosing for Depression

For treating depression with oral ketamine, the recommended dosage ranges from 0.5 to 2.5 mg/kg administered every 1-3 days, with most clinical evidence supporting doses of 1-2 mg/kg. 1, 2, 3

Dosing Considerations

• Oral ketamine has poor bioavailability (approximately 20-25% reaches systemic circulation), requiring higher oral doses to achieve effects comparable to intravenous administration 1, 4
• Dosing strategies in clinical studies have included both weight-based dosing (0.5-7.0 mg/kg) and fixed dosing (50-300 mg per occasion) 1, 4
• Most studies utilize a dosing range of 1-2 mg/kg administered every 1-3 days for depression treatment 3
• Individualized dose titration is often necessary due to interindividual variations in metabolism and response 1

Efficacy Evidence

• Oral ketamine has demonstrated significant improvement in depressive symptoms across multiple studies, though effects are not as rapid as intravenous administration 2, 3
• When used as an adjunct to conventional antidepressants like sertraline, oral ketamine produces significantly greater early improvement (85.4%) compared to placebo (42.5%) 5
• Unlike IV ketamine which produces effects within 24 hours, oral ketamine's significant antidepressant effects typically emerge after 2-6 weeks of treatment 3
• Evidence suggests potential efficacy for treatment-resistant depression and depression with suicidal ideation, though this is primarily from retrospective studies rather than randomized controlled trials 1, 3

Administration Protocol

• For depression treatment, oral ketamine is typically administered:
  • As a single dose of 1-2 mg/kg every 1-3 days 3
  • In some protocols, doses up to 300 mg per occasion have been used 1, 4
  • Treatment duration varies widely across studies, from weeks to months 2

Safety and Monitoring

• Oral ketamine is generally well-tolerated with few serious adverse events reported in clinical studies 2, 3
• Dropout rates and reasons for dropout were similar between ketamine and control groups in randomized controlled trials 1
• Monitoring for psychotomimetic experiences and hypertension is recommended during administration 6
• The American Psychiatric Association indicates ketamine should be reserved for patients who have not responded to conventional depression treatments 6

Important Limitations and Caveats

• The evidence base for oral ketamine in depression is still limited, with only a few randomized controlled trials available 2, 3
• Existing RCTs have high risk of bias due to analysis methods and adverse events monitoring 2
• The VA/DoD Clinical Practice Guideline notes that ketamine lacks long-term efficacy and safety trials in major depressive disorder 7
• Ketamine is not recommended as initial treatment but is reserved for patients who have failed or not tolerated previous therapies 7
• While IV ketamine administration (0.5 mg/kg over 40 minutes) is the best-studied approach, oral administration offers greater accessibility and practicality 8, 1