Can Ketamine Be Administered Intranasally?
Yes, ketamine can be administered intranasally, and this route has been successfully used for sedation and analgesia, particularly in children in pre-hospital and emergency settings, though tolerability and absorption variability remain significant concerns.
Clinical Evidence for Intranasal Ketamine
Pre-Hospital and Emergency Use
- The intranasal route has been successfully used for pre-hospital sedation and analgesia, particularly in pediatric patients 1
- Intranasal ketamine is considered when intravascular access is difficult, such as in combative patients or those with a history of intravenous drug abuse 1
Comparative Efficacy in Pediatric Sedation
- Intravenous ketamine/midazolam (1 mg/kg and 0.1 mg/kg) was superior to intranasal midazolam (0.5 mg/kg) for laceration repair, with better sedation scores at 30 minutes (2.4 vs 3.5, P<.001) and higher physician satisfaction (88% vs 54% rated "excellent or good", P=.006) 1
- Low-dose intramuscular ketamine (2.5 mg/kg) was superior to intranasal midazolam for laceration repair, with 100% vs 70% rated as "cooperative" or "intermittently crying" during repair (P<.01) 1
Significant Limitations and Safety Concerns
Poor Tolerability Profile
- A 2018 randomized controlled trial using 100 mg intranasal ketamine for treatment-resistant depression was stopped early due to poor tolerability 2
- Significant acute cardiovascular, psychotomimetic, and neurological side effects occurred at doses <100 mg 2
- No participants could self-administer all 10 ketamine sprays due to incoordination, and treatment time occasionally had to be extended beyond 45 minutes due to acute side effects 2
Variable Absorption
- There is approximately two-fold variation in ketamine and norketamine plasma concentrations between individuals receiving intranasal ketamine 2
- The drug formulation, delivery device, insufflation technique, and individual patient factors all play important roles in tolerability and efficacy 2
Evidence for Efficacy in Depression
- The pooled effect size for intranasal ketamine/esketamine at 24 hours was g = 1.247 (95% CI: 0.591-1.903, p<0.01) in adults with treatment-resistant depression 3
- At 7-20 days, intranasal ketamine had a pooled effect size of g = 1.018 (95% CI: 0.499-1.538, p<0.01) 3
Alternative Routes with Better Evidence
- Intravenous ketamine remains the best-studied approach with the most robust safety and efficacy data 4, 5
- Oral ketamine is the most practical route for mainstream psychiatry, with bioavailability of 20-25% that can be compensated by higher dosing 4
- Subcutaneous and intramuscular routes have demonstrated safety and efficacy with bolus administration 5
Clinical Recommendation
While intranasal ketamine is feasible and has been used successfully in pediatric emergency settings, the route demonstrates significant tolerability issues and variable absorption in adults, making intravenous, intramuscular, or oral routes preferable for most clinical applications 2, 5, 6. The intranasal route should be reserved for situations where other routes are not accessible, particularly in pediatric pre-hospital or emergency settings 1.