In a patient with a prior ischemic stroke and remote stable cardiac disease, can Spravato (esketamine) nasal spray be initiated if blood pressure is controlled (<140/90 mmHg) and there is no evidence of aneurysmal disease, arteriovenous malformation, or recent intracerebral hemorrhage?

Spravato Cannot Be Initiated in This Patient

Spravato (esketamine) nasal spray is absolutely contraindicated in patients with a history of ischemic stroke, regardless of blood pressure control or timing since the event. The FDA drug label explicitly lists "history of intracerebral hemorrhage" as a contraindication, and more broadly contraindicates use in patients for whom blood pressure increases pose a serious risk 1.

Why This Is Contraindicated

Direct FDA Contraindications

The Spravato label specifically contraindicates use in patients with 1:

• Aneurysmal vascular disease (including intracranial vessels)
• Arteriovenous malformation
• History of intracerebral hemorrhage

While your patient had an ischemic stroke (not hemorrhagic), the label also states that Spravato is contraindicated "in patients for whom an increase in BP or intracranial pressure poses a serious risk" 1. A history of ischemic stroke definitively places patients in this high-risk category.

The Blood Pressure Problem

Spravato causes predictable and substantial blood pressure elevations 1, 2:

• Peak increases occur ~40 minutes post-dose
• Mean maximum increases: 13-16 mmHg systolic / 8-10 mmHg diastolic (even higher in elderly patients)
• Effects last approximately 4 hours
• 3-19% of patients experience increases ≥40 mmHg systolic or ≥25 mmHg diastolic
• These increases occur even when baseline BP is controlled (<140/90 mmHg)

Why Prior Stroke Makes This Dangerous

Cerebral autoregulation is permanently impaired after ischemic stroke, making the brain vulnerable to blood pressure fluctuations 3, 4, 5. Current stroke guidelines emphasize 6, 4, 5:

• In acute ischemic stroke (first 72 hours), BP should generally not be lowered unless extremely elevated (>220/120 mmHg)
• Even modest BP reductions can worsen ischemia in stroke patients
• The brain relies on systemic BP for perfusion when autoregulation is impaired
• Rapid BP changes in either direction are harmful

The concern with Spravato is the reverse problem: inducing acute hypertensive episodes in a patient whose cerebral vasculature has already been damaged. This creates risk for:

• Hemorrhagic transformation of prior infarct
• New ischemic events
• Hypertensive encephalopathy (for which the label warns patients with prior stroke are at "increased risk") 1

What the Evidence Shows

Clinical Trial Exclusions

All major Spravato trials explicitly excluded patients with cardiovascular disease, including those with uncontrolled hypertension (>140/>90 mmHg) or "clinically significant ECG abnormalities" 2. Patients with prior stroke would have been excluded from these trials, meaning there is no safety data for this population.

Cardiovascular Safety Data

In the clinical development program 2:

• 12.8% experienced BP-related adverse events
• Three serious cardiovascular events related to BP increases occurred
• One fatal cardiac event (though deemed unrelated)
• Patients with established cardiovascular disease were excluded, so these rates underestimate risk in your patient

Long-term Safety Concerns

Even in the carefully selected trial populations without cardiovascular disease 7:

• 9.5% discontinued due to adverse events
• 6.9% experienced serious adverse events
• Dissociative symptoms and BP elevations occurred with each dose

The "Stable Cardiac Disease" Consideration

You mention the patient has "remote stable cardiac disease." This is another relative contraindication. The FDA label states: "patients with other cardiovascular and cerebrovascular conditions should be carefully assessed to determine whether the potential benefits of SPRAVATO outweigh its risks" 1.

In a patient with BOTH prior stroke AND cardiac disease, the risk-benefit calculation clearly favors avoiding Spravato.

Clinical Bottom Line

Do not initiate Spravato in this patient. The combination of:

1. Prior ischemic stroke (impaired cerebral autoregulation)
2. Cardiac disease
3. Predictable significant BP elevations with each dose
4. No safety data in this population
5. FDA contraindication for patients at risk from BP increases

...makes this an unacceptable risk, even with controlled baseline BP.

Alternative Approaches

For treatment-resistant depression in this patient, consider 8:

• Optimizing oral antidepressant therapy (different classes, combinations)
• Augmentation strategies (lithium, thyroid hormone, atypical antipsychotics)
• Psychotherapy (especially cognitive-behavioral therapy)
• Electroconvulsive therapy (ECT) - which has established safety data in cardiovascular disease
• Transcranial magnetic stimulation (TMS)

The absence of aneurysmal disease, AVM, or recent hemorrhage does not make Spravato safe in this patient - the history of ischemic stroke alone is disqualifying.