Spravato Safety, Warnings, and Contraindications

The Spravato boxed warning is titled: sedation; dissociation; respiratory depression; abuse and misuse; and suicidal thoughts and behaviors. Its themes are: [FDA label]

• patients are at risk for sedation after administration;
• patients are at risk for dissociative or perceptual changes after administration;
• respiratory depression has been observed in postmarketing experience;
• Spravato has the potential to be abused and misused;
• because of these risks, Spravato is available only through a restricted program under a Risk Evaluation and Mitigation Strategy;
• antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients.

The last item is a class-wide warning that applies to antidepressants generally. It sits alongside the labeling’s statement that the effectiveness of Spravato in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated.

The prescribing information lists three:

• Aneurysmal vascular disease, including of the thoracic and abdominal aorta, intracranial vessels, and peripheral arterial vessels, or arteriovenous malformation.
• History of intracerebral hemorrhage.
• Hypersensitivity to esketamine, ketamine, or any of the excipients.

[FDA label]

The first two contraindications share a logic. Spravato raises blood pressure at all recommended doses, and in a vessel that is already aneurysmal or malformed — or in someone who has previously bled into the brain — a sudden pressure increase carries risk that cannot be justified for this treatment. [FDA label]

“Aneurysmal vascular disease” in the labeling explicitly includes the thoracic and abdominal aorta, intracranial vessels, and peripheral arterial vessels. If you have ever been told you have an aneurysm or an arteriovenous malformation anywhere, or have had a brain bleed, say so during screening even if it was years ago and is considered resolved.

Known hypersensitivity to esketamine, ketamine, or any of the excipients in the product is a contraindication. [FDA label] Any prior reaction to ketamine — including during surgery or a procedure — is relevant history worth reporting.

Spravato causes increases in systolic and/or diastolic blood pressure at all recommended doses. The increase peaks approximately 40 minutes after administration and lasts approximately four hours. [FDA label]

Elevated baseline blood pressure is not a contraindication, but the labeling directs that its risks be weighed against the benefit of treatment, and that patients with cardiovascular or cerebrovascular conditions warrant particular consideration. Blood pressure is measured before dosing and again around 40 minutes afterward, then monitored until it declines and the patient is stable.

Practically, this means blood pressure control is part of the treatment conversation, and readings may influence whether a given session goes ahead.

The prescribing information states that Spravato is not recommended during pregnancy. Human data are insufficient, and animal studies of ketamine in pregnant animals showed fetal neuronal cell death and skeletal malformations at maternally toxic doses. Women of reproductive potential are advised to consider pregnancy planning and prevention during treatment. [FDA label]

Breastfeeding is not recommended during treatment, because esketamine is present in human milk and published studies have shown potential neurotoxicity in juvenile animals.

If you are pregnant, may become pregnant, or are breastfeeding, this belongs at the front of the conversation rather than in a form.

Esketamine is a Schedule III controlled substance, and the labeling directs that the risk of abuse or misuse be assessed before prescribing and that patients be monitored during treatment for signs and symptoms. [FDA label]

A history of substance use disorder is not listed as a contraindication. It is information that shapes how treatment is planned and monitored, and withholding it makes that harder rather than easier. The prohibition on take-home dispensing under the REMS program is itself part of how this risk is managed. [SPRAVATO REMS]

The labeling addresses cognitive impairment and impaired ability to drive and operate machinery. Short-term declines in measured cognitive performance occurred around 40 minutes after dosing and returned toward baseline by two hours in the studies described; longer-term open-label data showed generally stable cognitive performance over time. [FDA label]

The instruction that follows is fixed: do not drive or operate machinery until the next day, after a restful sleep.

Two interaction categories in the labeling have direct practical consequences:

• Central nervous system depressants — including alcohol and benzodiazepines — may increase sedation when used with Spravato.
• Psychostimulants and monoamine oxidase inhibitors may increase blood pressure when used with Spravato.

[FDA label] Provide a full medication list, including over-the-counter products, supplements, and medications taken only occasionally. Nasal corticosteroids and decongestants are not prohibited but should be taken at least one hour before a dose.

Everything above describes categories. Applying them to a person requires knowing that person’s history: prior imaging findings, blood pressure trends, current medications, reproductive plans, other diagnoses, and how previous treatments went.

This page cannot tell you whether Spravato is safe for you, and nothing here is personalized medical advice. That determination belongs to a clinician who has evaluated you — at Innerbloom Medical, that begins with a clinical evaluation of eligibility.

Spravato’s safety framework has three layers: a boxed warning describing the risks that shaped the program, three absolute contraindications, and a set of precautions — blood pressure, pregnancy and reproductive planning, substance use history, cognitive effects, and interactions — that are weighed case by case.

The contraindications are checkable facts about your medical history. The precautions are judgments. Both require a clinician with your full history in front of them, which is why no page can tell you whether treatment is safe for you.