What is the efficacy of intravenous (IV) ketamine for treatment-resistant depression?

IV Ketamine for Refractory Depression: Efficacy and Clinical Considerations

IV ketamine demonstrates rapid but transient antidepressant effects for treatment-resistant depression, with approximately 52-59% of patients achieving remission after multiple infusions, though benefits typically last only 3-7 days without maintenance treatment. 1, 2

Efficacy of IV Ketamine

Acute Treatment Response

• Single infusion efficacy:
  • Rapid onset of action (within 40 minutes to 24 hours)
  • Large effect sizes in open-label trials (d = 1.05-2.36 at 40 minutes)
  • Effects diminish over time (d = 0.45-1.27 at 230 minutes) 3
  • Approximately 67% achieve response after three infusions 1

Response Patterns

• Early response predicts eventual remission:
  • 66% of first-infusion responders achieve remission after three infusions
  • Only 40% of first-infusion non-responders achieve remission after three infusions
  • Only 20% of non-responders after two infusions achieve remission 1

Duration of Effect

• Without maintenance treatment:
  • Effects typically last 3-7 days 4
  • Approximately 70% of responders relapse by 4 weeks after final infusion 3

Maintenance Treatment

• Repeated infusions show cumulative antidepressant effects 2
• Maintenance protocols:
  • Initially more frequent (every 5 days)
  • Gradually decreasing to every 3-4 weeks over 5 months
  • Average of 18 total infusions over 12 months in VA health system 5

Anti-Suicidal Effects

• Significant reduction in suicidal ideation:
  • 67% of patients with baseline suicidal ideation experience ≥50% reduction 1
  • Effect on suicidal ideation may be independent of overall depression improvement 3
  • Particularly large effect sizes in patients with high baseline suicidal ideation (d = 2.36 at 40 minutes) 3

Administration Protocols

Standard Protocol

• Dosage: 0.5 mg/kg IV over 40 minutes 3
• Alternative protocols:
  • Extended infusions (100 minutes) show comparable efficacy and safety to standard 40-minute infusions 1
  • Lower doses (0.2 mg/kg) have been used in emergency settings 3

Treatment Course

• Initial treatment:
  • Typically 3-6 infusions over 1-2 weeks 1, 2
  • Median of 3 infusions required before achieving response 2
• Maintenance:
  • Weekly infusions can maintain response in responders 2

Clinical Considerations

Patient Selection

• Best candidates:
  • Treatment-resistant depression (failed ≥2 antidepressant trials)
  • No psychotic symptoms
  • No significant substance abuse
  • No unstable medical conditions 1

Limitations and Caveats

• Not all patients respond:
  • In VA health system, only 26% achieved response and 15% achieved remission after 6 weeks 5
• Ketamine has significant abuse potential and risk of adverse effects 6
• Repeated exposure may lead to tolerance and physical dependence 6
• Limited long-term safety and efficacy data 6

Alternative Routes of Administration

• Oral ketamine:
  • More accessible but slower onset (2-6 weeks)
  • Variable dosing (1-2 mg/kg every 1-3 days)
  • Good tolerability but less rapid effects than IV administration 7

IV ketamine represents a promising option for treatment-resistant depression with rapid onset of action, but requires careful patient selection and monitoring due to its potential for abuse and limited long-term safety data.