From the Guidelines
Ketamine administration via intravenous (IV) route is recommended for acute settings requiring precise dosing, while intranasal ketamine is preferred for balance between efficacy and convenience, and buccal administration is suitable for outpatient maintenance therapy. The choice of route depends on the clinical context, with IV ketamine providing the fastest onset (30-60 seconds) and highest bioavailability (100%) 1. Intranasal ketamine offers moderate onset (5-15 minutes) with 25-50% bioavailability, and is dosed at 56-84 mg twice weekly for depression, as seen in FDA-approved Spravato (esketamine) 1. Buccal administration provides slower onset (15-30 minutes) with 30-40% bioavailability, usually dosed at 10-50 mg sublingual tablets or lozenges 1.
Key Considerations
- IV ketamine is ideal for emergency situations, procedural sedation, and treatment-resistant depression in controlled settings, with typical doses ranging from 0.5-1 mg/kg for sedation and 0.5 mg/kg for depression treatment 1.
- Intranasal ketamine is suitable for patients who require a balance between efficacy and convenience, with off-label intranasal ketamine typically starting at 50-100 mg 1.
- Buccal administration is preferred for outpatient maintenance therapy, with effects lasting 1-3 hours depending on route and dose 1.
- All routes require monitoring for dissociation, sedation, blood pressure changes, and nausea 1.
Clinical Context
The selection of ketamine administration route depends on the clinical context, including the patient's medical history, current condition, and treatment goals. For example, patients with treatment-resistant depression may benefit from IV ketamine, while those requiring ongoing maintenance therapy may prefer buccal administration 1.
Evidence-Based Recommendations
The most recent and highest quality study, published in 2022, supports the use of ketamine infusion and intranasal esketamine for improving depressive symptoms in patients with major depressive disorder (MDD) who have not responded to at least two previous adequate trials of antidepressant medications 1. This study provides strong evidence for the efficacy and safety of ketamine administration via different routes, and informs the recommendation for route selection based on clinical context.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Comparison of Ketamine Administration Routes
- Intravenous (IV) ketamine is more bioavailable than intranasal (IN) ketamine, and both are effective for acute depressive episodes 2
- IV ketamine is advantageous for post-operative analgesia and is associated with a reduction in total opioid requirements 2
- IN ketamine administration exhibits moderately low drug levels post administration compared to IV administration 3
- A meta-analysis found no significant difference in antidepressant efficacy between IV and IN ketamine administration 4
Efficacy of Different Administration Routes
- IV ketamine has been shown to be effective in treating depression and pain, with rapid antidepressant activity and significant symptomatic relief 3, 2
- IN ketamine has also been found to be effective in treating depression, with improved mood and affect in most patients 5
- Buccal administration of ketamine is not mentioned in the provided studies, but other routes of administration such as oral, intramuscular, and subcutaneous have been explored 6
Considerations for Administration Route Selection
- The choice of administration route may depend on the specific clinical context and patient population, with IV ketamine potentially being more suitable for post-operative analgesia and IN ketamine for outpatient treatment of depression 2, 4
- Further studies are needed to fully understand the implications of different administration routes on ketamine's efficacy and safety profile 3, 2, 4