Seizures Are NOT a Contraindication for Spravato
Seizures are not listed as a contraindication for Spravato (esketamine) nasal spray according to the FDA-approved prescribing information. The only contraindications are aneurysmal vascular disease, arteriovenous malformation, history of intracerebral hemorrhage, and hypersensitivity to esketamine or ketamine 1.
FDA-Approved Contraindications
The official FDA label explicitly states that Spravato is contraindicated only in patients with 1:
- Aneurysmal vascular disease (thoracic/abdominal aorta, intracranial, peripheral arterial vessels)
- Arteriovenous malformation
- History of intracerebral hemorrhage
- Hypersensitivity to esketamine, ketamine, or excipients
Seizures or epilepsy are notably absent from this list.
Clinical Context and Considerations
While seizures are not a contraindication, several important clinical points warrant attention:
Psychogenic Non-Epileptic Seizures (PNES)
Emerging evidence suggests esketamine may actually be beneficial for functional seizures. A 2025 case report documented successful resolution of both treatment-resistant depression and psychogenic non-epileptic seizures with intranasal esketamine therapy 2. This suggests potential therapeutic effects beyond antidepressant properties.
True Epileptic Seizures
For patients with epilepsy, there is no evidence that esketamine increases seizure risk or worsens seizure control. In fact, ketamine (the parent compound) is routinely used as an anesthetic agent during electroconvulsive therapy, where seizure induction is the therapeutic goal 3.
Practical Management Algorithm
For patients with a seizure history being considered for Spravato:
- Differentiate seizure type: Determine if seizures are epileptic or psychogenic/functional
- Ensure adequate seizure control: If epileptic, confirm patient is on appropriate antiepileptic medications
- Proceed with standard Spravato protocols: Follow REMS requirements including 2-hour post-administration monitoring 4
- Monitor closely during initial doses: Watch for any neurological changes during the mandatory observation period
Common Pitfall to Avoid
Do not confuse the dissociative and perceptual disturbances commonly seen with Spravato (occurring in 28-48% of patients) 1 with seizure activity. These dissociative symptoms are expected adverse effects, not contraindications, and typically resolve within the monitoring period.
Bottom line: Proceed with Spravato in patients with seizure disorders, ensuring appropriate seizure management is in place, but recognize that seizures themselves do not preclude treatment.