How should I manage anxiety that began three days after receiving Spravato (esketamine) treatment?

Managing Anxiety After Spravato Treatment

Anxiety occurring 3 days after Spravato treatment is likely unrelated to the acute dissociative effects of esketamine, which resolve within 2 hours post-dose, and should be managed as a potential treatment-emergent psychiatric symptom requiring clinical reassessment and supportive interventions 1.

Understanding the Timeline

The timing of your anxiety is critical to management:

• Acute anxiety (during/immediately after treatment): Esketamine causes transient dissociative symptoms and anxiety that peak around 40 minutes post-dose and resolve within 2 hours 1. This is NOT your situation.

• Delayed anxiety (3 days post-treatment): This falls outside the expected window of acute esketamine effects. The FDA label documents anxiety as a treatment-emergent adverse reaction in clinical trials, but the temporal relationship at 3 days suggests either:

  • A delayed psychiatric response to treatment
  • Anxiety related to the underlying depression
  • Coincidental timing unrelated to esketamine

Immediate Management Steps

1. Clinical Reassessment

Contact your prescribing provider immediately to evaluate:

• Severity and nature of anxiety symptoms
• Any suicidal ideation (esketamine is used in patients with suicidality, requiring ongoing monitoring) 2
• Blood pressure status (esketamine can cause delayed hypertensive effects, though typically acute) 1
• Presence of dissociative symptoms (if still present at 3 days, this is abnormal)

2. Non-Pharmacologic Interventions First

Evidence supports these as primary management:

• Music therapy during subsequent sessions: A case report demonstrated that listening to music of choice during and after esketamine administration significantly reduced anxiety and confusion associated with dissociation 3
• Reassurance and psychoeducation: Understanding that most side effects are transient and dose-dependent helps reduce anticipatory anxiety 4
• Supportive monitoring: Ensure adequate observation during the mandatory 2-hour post-treatment period 1

3. Medication Adjustments to Consider

If anxiety persists or worsens:

• Your provider may consider dose reduction (from 84 mg to 56 mg) if you're on the higher dose—approximately 19% of patients require this adjustment 1
• Adjunctive anxiolytic medications may be judiciously used, though the evidence base is limited 4
• Continue your oral antidepressant (SSRI/SNRI) as prescribed—esketamine is only approved in combination therapy 2, 5

4. Treatment Continuation Decision

Do NOT discontinue Spravato without provider consultation. Consider:

• In clinical trials, only 4.6% of patients discontinued due to adverse reactions 1
• Anxiety symptoms may actually improve with continued treatment: post-hoc analyses show esketamine reduces anxiety in patients with comorbid anxiety disorders 6
• A recent systematic review found esketamine reduces anxiety symptoms, particularly with repeated doses and maintenance treatment 7

Key Safety Monitoring

Watch for these concerning symptoms requiring immediate medical attention:

• Hypertensive crisis symptoms: Chest pain, shortness of breath, sudden severe headache, visual disturbances, seizures 1
• Severe dissociation persisting beyond 2 hours: This is abnormal 1
• Worsening suicidal ideation: Requires emergency evaluation 2
• Urinary symptoms: Dysuria, urgency, frequency (can indicate cystitis) 1

Common Pitfalls to Avoid

1. Don't assume all anxiety is drug-related: At 3 days post-dose, this may represent fluctuation in your underlying depression or comorbid anxiety disorder
2. Don't skip the 2-hour monitoring period: This is when acute adverse effects occur and can be managed 1
3. Don't drive or operate machinery until the next day after a restful sleep: Even if you feel fine 1
4. Don't discontinue your oral antidepressant: Esketamine is only effective in combination therapy 2, 5

Evidence Context

The 2022 VA/DoD guidelines support ketamine/esketamine for treatment-resistant depression after multiple failed antidepressant trials, acknowledging the balance between consistent evidence of benefit and risks of adverse effects 2. While anxiety is a documented side effect, research suggests esketamine may actually reduce pathological anxiety over time, particularly with maintenance treatment 7, 6. The majority of side effects are mild, transient, and attenuate with subsequent treatments 4.

Your next step: Contact your Spravato provider today to discuss this symptom and determine whether treatment modification is needed before your next scheduled dose.