Is it appropriate to prescribe Spravato (esketamine nasal spray) to a patient with a history of transient ischemic attack?

Spravato Should NOT Be Prescribed to This Patient

A history of TIA is an absolute contraindication to Spravato (esketamine nasal spray) due to the drug's significant blood pressure effects and the patient's underlying cerebrovascular disease. 1

Why This Is Contraindicated

FDA Label Contraindication

The FDA label for Spravato explicitly states that the medication is contraindicated in patients with cerebrovascular conditions including history of intracerebral hemorrhage and aneurysmal vascular disease 1. While TIA is not specifically listed by name, the underlying pathophysiology makes this a critical safety concern:

• Spravato causes substantial blood pressure elevations peaking at approximately 40 minutes post-dose and lasting up to 4 hours
• 3-19% of patients experience increases ≥40 mmHg systolic or ≥25 mmHg diastolic BP 1
• These increases can occur unpredictably after any dose, even if previous doses were well-tolerated

The Cerebrovascular Risk

A patient with prior TIA has demonstrated:

• Vulnerable cerebrovascular circulation
• Likely underlying atherosclerotic disease or other stroke risk factors
• Increased susceptibility to ischemic events with hemodynamic stress

The FDA label specifically warns that "before prescribing SPRAVATO, patients with cardiovascular and cerebrovascular conditions should be carefully assessed to determine whether the potential benefits outweigh its risks" 1. In the context of prior TIA, the risk clearly outweighs benefit.

Clinical Reasoning

Why the Blood Pressure Risk Is Unacceptable Here

1. Unpredictable BP surges: The substantial BP increases are not dose-dependent or predictable based on prior administrations 1

2. Duration of risk: Each treatment session creates a 4-hour window of elevated stroke risk

3. Frequency of exposure: Treatment requires twice-weekly dosing during induction, creating repeated vascular stress 2

4. Secondary stroke prevention priority: Per AHA/ASA guidelines, patients with prior TIA/stroke require aggressive risk factor management, particularly blood pressure control 3

Alternative Treatment Considerations

For treatment-resistant depression in this patient:

• Optimize oral antidepressant therapy with different classes or combinations
• Consider augmentation strategies with atypical antipsychotics or lithium
• Evaluate for ECT if appropriate, which does not carry the same cerebrovascular contraindication
• Ensure aggressive secondary stroke prevention per guidelines (antiplatelet therapy, statin, BP control) 3

Critical Pitfall to Avoid

Do not rationalize prescribing Spravato by planning "close BP monitoring." The FDA label makes clear that even with monitoring, patients can experience dangerous BP elevations requiring emergency care 1. The label specifically references risk of "hypertensive crisis" and "hypertensive encephalopathy" - both catastrophic in someone with prior cerebrovascular disease.

The one case report of esketamine use in a patient with structural brain abnormality 4 involved traumatic injury, not cerebrovascular disease, and does not override the FDA contraindication for your patient's condition.