Spravato (Esketamine) Nasal Spray Protocol and Administration Guidelines

Spravato administration requirements include in-clinic dosing at a certified treatment center, direct supervision while the patient uses the nasal spray, and at least two hours of monitoring before discharge. Spravato is the brand name for esketamine, a prescription nasal spray approved by the U.S. Food and Drug Administration for specific depressive-disorder indications when used with an oral antidepressant.

These requirements differ from an ordinary prescription pickup because Spravato is available only through the Spravato Risk Evaluation and Mitigation Strategy, or REMS, program. The program is designed to address risks including sedation, dissociation, respiratory depression, misuse, and temporary blood-pressure increases. This guide summarizes the labeled protocol, what patients can expect on treatment day, and questions to discuss with a qualified prescriber.

What the Spravato REMS program requires

The Spravato REMS program is an FDA-required restricted distribution program for esketamine nasal spray. A patient cannot take Spravato home for self-treatment. The healthcare setting, prescriber, pharmacy, and patient must participate in the program as applicable.

According to the Spravato REMS program, Spravato is administered only in certified healthcare settings, and patients must be monitored for at least two hours after each dose. The treatment setting must be able to monitor patients and manage symptoms that may occur after dosing.

Before leaving, the patient should be assessed to confirm that clinical stability is present. The FDA-approved Spravato prescribing information is the primary source for the current requirements, contraindications, dosing, and monitoring instructions.

Approved uses and dosing schedules

Spravato is approved for adults with treatment-resistant depression and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. It is used with an oral antidepressant, not as a stand-alone replacement for ongoing depression care.

Treatment-resistant depression

For treatment-resistant depression, the labeled schedule has an induction phase followed by maintenance treatment. During weeks 1-4, patients generally receive 56 mg or 84 mg twice weekly. Treatment is typically started at 56 mg, and the dose may be increased to 84 mg based on tolerability and clinical judgment.

During weeks 5-8, treatment is generally once weekly at 56 mg or 84 mg. From week 9 onward, the frequency may be once weekly or once every two weeks. The prescriber should individualize the schedule to the lowest frequency needed to maintain response or remission.

Major depressive disorder with acute suicidal ideation or behavior

For this indication, the labeled dose is 84 mg twice weekly for four weeks, used with standard-of-care oral antidepressant treatment. The prescribing information states that the effectiveness of Spravato in preventing suicide or reducing suicidal ideation or behavior has not been demonstrated. A patient with acute safety concerns needs an urgent, individualized care plan from their treatment team or emergency services when appropriate.

Each nasal spray device contains 28 mg. A 56 mg dose uses two devices, and an 84 mg dose uses three devices. The dose should not be changed without the prescribing clinician's direction.

How Spravato is administered

Patients administer Spravato themselves while a healthcare provider supervises the process. The clinician provides the device instructions and observes each dose. Patients should not attempt to copy a clinic protocol at home or use a different ketamine product as a substitute.

Before treatment, the prescribing information advises patients to avoid food for at least two hours and liquids for at least 30 minutes. If an intranasal corticosteroid or nasal decongestant is needed, it should be used at least one hour before Spravato.

Blood pressure is measured before dosing. The label advises considering the risks and benefits of delaying treatment when pre-dose blood pressure is elevated, generally above 140/90 mmHg. A clinician may decide not to administer Spravato if an increase in blood pressure would pose a serious risk for that patient.

During dosing, the patient uses one nasal spray device at a time, with a brief rest period between devices. The care team will explain positioning, alternating nostrils, and how to handle nasal discomfort. Patients should tell staff about congestion, nosebleeds, medication changes, or symptoms that may affect the visit.

Post-dose monitoring and discharge

The two-hour observation period is a core part of Spravato administration requirements. Blood pressure is typically reassessed at about 40 minutes after dosing, when increases commonly peak, and again as clinically warranted. If blood pressure remains elevated or the patient has concerning symptoms, the clinic may continue observation and provide appropriate evaluation or treatment.

Dissociation can involve feeling detached from oneself, altered perception, or changes in time sense. Sedation can range from sleepiness to reduced alertness. Staff assess these effects and determine whether the patient is ready for discharge. The Clinician-Administered Dissociative States Scale, or CADSS, may be used as one clinical assessment tool, but use varies by practice.

A patient should leave only when the clinician determines they are clinically stable. They should plan for transportation home and avoid driving, operating machinery, or other activities requiring full alertness until the following day after a restful sleep. For broader context on expected effects, see how long ketamine effects can last and this guide to ketamine safety and side effects.

Safety issues to review before treatment

Spravato is contraindicated for patients with aneurysmal vascular disease, arteriovenous malformation, or a history of intracerebral hemorrhage. It is also contraindicated for people with known hypersensitivity to esketamine, ketamine, or the product's excipients. A clinician must assess individual risks, including cardiovascular history and psychiatric symptoms, before treatment.

Central nervous system depressants, including benzodiazepines, opioids, and alcohol, may increase sedation. Psychostimulants and monoamine oxidase inhibitors may increase blood-pressure effects. Patients should provide a complete medication and substance-use history at every visit and follow their prescriber's treatment-day instructions. Read more about ketamine drug interactions and ketamine and alcohol safety risks.

For longer-term treatment, clinicians may track depressive symptoms with measures such as the PHQ-9 or MADRS, assess tolerability, and periodically reassess whether continued dosing is appropriate. Urinary symptoms, cognitive concerns, psychotic symptoms, or persistent perceptual changes should be reported promptly so the prescriber can evaluate the next step.

Questions to ask a Spravato treatment provider

A useful consultation should make the protocol clear before the first dose. Ask whether the site is certified in the Spravato REMS program, how it handles elevated blood pressure or prolonged sedation, what transportation is required, and how the clinician will assess response over time. Also ask how your current medications, alcohol use, nasal medicines, cardiovascular history, and mental health history may affect eligibility or monitoring.

Spravato is not interchangeable with other ketamine formulations. Readers comparing treatment approaches can review the site's comparison resources and ketamine research and evidence guide before discussing options with a licensed clinician.