What are the guidelines for using intranasal (IN) ketamine for medical treatment?

Guidelines for Intranasal Ketamine Use in Medical Treatment

Intranasal ketamine is recommended for treatment-resistant depression and procedural sedation, with specific dosing protocols based on indication, but is not recommended as first-line therapy for most conditions. 1, 2

Approved Indications and Dosing

Treatment-Resistant Depression

• Intranasal esketamine is FDA-approved for treatment-resistant depression (TRD) in patients who have failed at least two adequate trials of antidepressants 1, 2
• Recommended dosing for esketamine is twice-weekly administration as an adjunctive therapy to ongoing oral antidepressants 2
• Intranasal esketamine has demonstrated improvement in depressive symptoms and remission rates for up to 28 days of follow-up 1, 2
• Intranasal esketamine is also approved for treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior 1, 2

Procedural Sedation in Pediatrics

• Ketamine is effective for procedural sedation in children, though the intranasal route is less commonly used than IV or IM administration 1, 3
• For pediatric procedural sedation, ketamine has demonstrated 100% efficacy for "adequacy of sedation" in clinical studies 1
• When used for procedural sedation, continuous monitoring of vital signs and airway status is required 3

Safety Considerations

Monitoring Requirements

• Risk evaluation and mitigation strategy requirements exist for esketamine, including mandatory monitoring for 2 hours after treatment 2
• Patients should be monitored for signs of somnolence, dissociation, and changes in vital signs during and after administration 2, 3
• Continuous monitoring of oxygen saturation, heart rate, and blood pressure is required during ketamine administration 3

Side Effects

• Common side effects of intranasal ketamine include:
  • Dissociative symptoms (transient) 2, 4
  • Increased blood pressure 2, 3
  • Nausea 2, 5
  • Dizziness 4, 5
• Recovery agitation occurs in approximately 17.6% of patients (mild) and 1.6% (moderate-to-severe) 3
• Emesis without aspiration is reported in 6.7% of cases 3

Contraindications

• Ketamine should be avoided in patients with:
  • Ischemic heart disease 3
  • Cerebrovascular disease 3
  • Uncontrolled hypertension 3
  • History of psychosis 2, 6

Practical Administration Guidelines

Dosing for Depression

• For intranasal ketamine in depression, doses range from 0.5-0.75 mg/kg 4, 7
• Esketamine nasal spray is administered under direct healthcare provider supervision 1, 2
• Treatment frequency is typically twice weekly initially, then individualized based on response 2, 4

Dosing for Acute Pain

• For acute pain management in emergency settings, intranasal ketamine at 0.7 mg/kg with an additional 0.3 mg/kg if needed after 15 minutes has shown efficacy 5
• Pain reduction of ≥20mm on visual analog scale was achieved in 80% of patients within 15 minutes 5

Abuse Potential and Long-term Considerations

• Intranasal ketamine has abuse potential, particularly with racemic (R,S)-ketamine and (S)-ketamine 8
• Long-term safety and efficacy of ketamine/esketamine as antidepressants require further study 6
• The risk of abuse must be considered, especially if domiciliary treatment is contemplated 4

Comparison to Other Administration Routes

• While intravenous administration is most commonly studied, intranasal delivery offers advantages of:
  • Non-invasive administration 4, 7
  • Potentially lower resource requirements compared to IV administration 7
  • Rapid onset of action 4, 5
• Cost considerations: compounded intranasal racemic ketamine may be significantly less expensive than commercial esketamine preparations 7

Efficacy Considerations

• Intranasal ketamine is not recommended as first-line therapy for depression 1, 2
• For treatment-resistant depression, efficacy has been demonstrated with repeated administrations and concurrent standard antidepressant therapy 2, 6
• For acute pain, intranasal ketamine provides rapid analgesia with effects lasting approximately 60 minutes 5