What is esketamine (esketamine) session and how is it administered for treatment-resistant depression?

Esketamine Sessions: Administration and Use in Treatment-Resistant Depression

Esketamine nasal spray is administered in supervised sessions for treatment-resistant depression (TRD), requiring patients to receive treatment at certified healthcare facilities with mandatory 2-hour monitoring after administration. 1

What is Esketamine?

Esketamine is the S-enantiomer of racemic ketamine, functioning as a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor 2. While the exact mechanism by which it exerts its antidepressant effect remains unknown, it has demonstrated efficacy in treating depression when other treatments have failed.

Indications for Esketamine Sessions

Esketamine is specifically indicated for:

• Patients with treatment-resistant depression (TRD), defined as failure to respond to at least two adequate trials of antidepressant medications 1
• Adults with major depressive disorder (MDD) with acute suicidal ideation or behavior 1

It is important to note that esketamine is not recommended as an initial treatment for depression but is reserved for patients who have not responded to previous therapies 1.

Administration Protocol

Session Structure

Esketamine is administered as a nasal spray in a controlled clinical setting:

• Dosing: Available as 56 mg or 84 mg, typically administered twice weekly during the induction phase 3
• Administration: Self-administered by the patient under direct supervision of a healthcare provider
• Setting: Must be administered in a certified healthcare facility with Risk Evaluation and Mitigation Strategy (REMS) requirements 1
• Monitoring: Mandatory 2-hour monitoring period after administration to observe for potential adverse effects 1

Treatment Phases

1. Induction Phase:

   • Twice-weekly administration for 4 weeks
   • Typically consists of 8 administrations within a 45-day period 4
   • Combined with a newly initiated oral antidepressant 3

2. Maintenance Phase:

   • Frequency may be reduced based on clinical response
   • Continued in combination with oral antidepressant therapy 5

Clinical Efficacy

The evidence supporting esketamine's efficacy includes:

• Meta-analyses showing significant improvement in depressive symptoms compared to placebo when used as augmentation to ongoing antidepressant treatment 1
• Rapid onset of action, with improvements observed within 24 hours and persisting for up to 28 days of follow-up 1
• Response rates of approximately 70% and remission rates of about 60% following a second induction phase in patients who previously relapsed 5

Common Side Effects During Sessions

The most common adverse effects observed during esketamine sessions include:

• Dissociation (feeling detached from reality)
• Dizziness and vertigo
• Nausea
• Dysgeusia (taste disturbance)
• Sedation 3

These effects typically appear shortly after dosing and generally resolve within 1.5 hours 3.

Important Considerations for Esketamine Sessions

Pre-Session Requirements

• Blood pressure assessment (due to potential for transient increases)
• Fasting from food for at least 2 hours and liquids for 30 minutes before administration
• Avoidance of driving or operating machinery on the day of treatment 6

Post-Session Requirements

• Patients must be clinically assessed and deemed stable before leaving the healthcare facility
• Patients must arrange for transportation home after each session
• Monitoring for potential adverse effects such as dissociation, sedation, and blood pressure changes 6

Barriers to Esketamine Treatment

Several factors may limit access to esketamine therapy:

• Geographic barriers: Patients living more than 10 miles from treatment centers show significantly decreased initiation rates (up to 92.8% reduction for those living 50+ miles away) 4
• Insurance coverage: Medicaid coverage is associated with lower likelihood of completing induction 4
• Socioeconomic factors: Low socioeconomic status correlates with lower completion of induction phase 4

Clinical Pitfalls to Avoid

1. Inappropriate patient selection: Ensure patients have truly failed at least two adequate antidepressant trials before considering esketamine 1

2. Inadequate monitoring: The 2-hour post-administration monitoring period is mandatory, not optional 1

3. Monotherapy use: Esketamine should be used in conjunction with an oral antidepressant, not as monotherapy 1

4. Discontinuing too early: Patients may need to complete the full induction phase before determining efficacy 5

5. Transportation planning: Patients must not drive after receiving esketamine and need pre-arranged transportation 6

Esketamine represents an important treatment option for patients with TRD, offering rapid symptom improvement when traditional antidepressants have failed. However, the structured administration requirements and monitoring protocols are essential to ensure patient safety and maximize treatment efficacy.