What are the indications and guidelines for ketamine therapy?

Ketamine Therapy: Indications and Guidelines

Ketamine therapy is primarily indicated for treatment-resistant depression (TRD) in patients who have failed at least two adequate trials of antidepressant medications, and should not be used as first-line treatment for depression. 1

Primary Indications

1. Treatment-Resistant Depression (TRD)

• Defined as failure to respond to at least two adequate trials of antidepressant medications
• Both ketamine infusion and intranasal esketamine have demonstrated efficacy in this population 1
• Typically administered as:
  • IV ketamine: 0.5 mg/kg over 40 minutes (range 0.1-0.75 mg/kg)
  • Intranasal esketamine: Twice-weekly dosing as augmentation to ongoing oral antidepressant use 1

2. Acute Suicidal Ideation with Major Depressive Disorder

• Ketamine infusions are supported as adjunctive treatment for short-term reduction in suicidal ideation 1
• Esketamine is FDA-approved for depressive symptoms in adults with MDD and acute suicidal ideation/behavior
• Important caveat: Effectiveness in preventing suicide or reducing suicidal behavior long-term has not been established 1

3. Pain Management in Specific Settings

• Critical Care Setting: Low-dose ketamine (1-2 μg/kg/hr) as an adjunct to opioid therapy to reduce opioid consumption in postsurgical ICU patients 1
• Cancer Pain: May be considered for refractory cancer pain, particularly in neuropathic pain with evidence of central sensitization 1

Administration Protocols

For Depression:

1. Dosing:

   • IV ketamine: 0.5 mg/kg (range 0.1-0.75 mg/kg) 2
   • Administration time: Typically 40 minutes (range 2-100 minutes) 2

2. Frequency:

   • Initial phase: Often every 5 days
   • Maintenance: Gradually decreasing to every 3-4 weeks 3
   • Mean of 18 total infusions over 12 months in VA system study 3

3. Routes of Administration:

   • IV (most common and studied)
   • Intranasal (esketamine FDA-approved)
   • Other routes with emerging evidence: oral, sublingual, transmucosal, intramuscular, subcutaneous 2, 4

For Pain Management in ICU:

• Low-dose ketamine: 0.5 mg/kg IV push, followed by 1-2 μg/kg/min infusion 1
• Used as adjunct to opioid therapy to reduce opioid consumption 1

Efficacy and Outcomes

Depression Treatment:

• Meta-analyses show substantial antidepressant effects with 45% response and 30% remission rates 5
• VA system study showed more modest outcomes: 26% response and 15% remission at 6 weeks 3
• Benefits typically appear within 24 hours and may persist for 3-7 days 1
• Maintenance treatment can sustain antidepressant effects 6

Pain Management:

• Reduces opioid consumption in postsurgical ICU patients 1
• Limited evidence for cancer-related neuropathic pain 1

Safety Considerations and Monitoring

1. Contraindications:

   • Patients for whom significant blood pressure elevation would be hazardous 7
   • Known hypersensitivity to ketamine 7

2. Potential Adverse Effects:

   • Hemodynamic instability (monitor vital signs) 7
   • Emergence reactions/dissociative symptoms 7
   • Risk of respiratory depression with overdosage 7
   • Tachyphylaxis, cognitive impairment, addiction concerns with long-term use 6

3. Monitoring Requirements:

   • Esketamine has risk evaluation and mitigation strategy requirements
   • Mandatory monitoring for 2 hours after treatment 1
   • Vital sign monitoring during administration 7

Key Practice Considerations

• Not First-Line: Ketamine and esketamine are not recommended as initial treatments for depression but reserved for patients who have failed or not tolerated previous therapies 1

• Limited Long-Term Data: Ketamine lacks long-term efficacy and safety trials in depression 1

• Adjunctive Use: For depression, evidence supports ketamine as augmentation to ongoing antidepressant treatment rather than monotherapy 1

• Route Selection: IV is most studied, but other routes (intranasal, sublingual, oral) may improve accessibility and reduce costs 4

• Maintenance Treatment: Evidence suggests therapeutic effect does not significantly decline with repeated treatments 5, but optimal protocols for maintenance therapy are still being established

• Monitoring for Abuse: Risk of abuse must be considered, especially with domiciliary treatment 2