The clinical case for considering esketamine in a given patient is a conversation for the prescriber. The logistics are a different matter, and they are where referrals most often stall. This explainer covers the mechanics a referring physician needs to understand: where the treatment happens, what the patient commits to, and what the paperwork usually requires.

Context comes from our ten-state Midwest poll of 443 adults, which points to primary care as the place most of these conversations will start. Pollfish has completed validation, so the figures are final.

Why the logistics land on you

Our respondents' likely path into esketamine care starts in your office: 56 percent chose their primary doctor as a first stop, and only 12 percent a solo online search. The most persuasive voice, for 74 percent, was their own physician.

That makes the referring physician the person patients will look to for a realistic picture of what the treatment involves. Knowing the mechanics lets you set expectations before the patient is surprised by them.

The approved indications

Spravato, the esketamine nasal spray, carries FDA approval in adults with treatment-resistant depression; check the current label for its full indications. It has no approval for PTSD or anxiety disorders. It is also distinct from IV racemic ketamine, which is off-label for depression, and from at-home ketamine prescribed through telehealth services.

The REMS framework

Esketamine is distributed under a Risk Evaluation and Mitigation Strategy. In practical terms:

  • Certified settings only. The drug can only be dispensed to and administered in healthcare settings certified in the program.
  • Patient enrollment. Patients are enrolled in the program before treatment begins.
  • Supervised administration. A healthcare provider watches while the patient uses the spray.
  • Post-dose monitoring. Patients remain on site for a required observation period after each dose, because of risks including sedation, dissociation, and respiratory depression, and blood pressure is checked before and after dosing.
  • No driving. Driving and machinery are off limits until the following day, after a night's sleep.

Most primary care practices are not certified sites. Your role is typically to identify a patient who may be a candidate, document the history, and refer to psychiatry or directly to a certified treatment center, depending on local arrangements.

What the patient is signing up for

Patients are often surprised by the time commitment. Treatment begins with an induction phase of twice-weekly sessions, after which frequency tapers based on response. Each session includes dosing, observation, and time for vitals, so it takes a meaningful block of the day. Every session requires a ride home.

For some patients, the transportation requirement alone determines feasibility. Ask early who would drive them, and how far the nearest certified site is. Among our respondents, 43 percent listed nearness among their two chief provider priorities. For patients, the Brain Recovery Centers site offers a readable summary of Spravato treatment logistics that can go home with the referral.

Contraindications and cautions worth screening early

The label lists contraindications including aneurysmal vascular disease or arteriovenous malformation, a history of intracerebral hemorrhage, and hypersensitivity to esketamine or ketamine. Uncontrolled hypertension, cardiovascular and cerebrovascular conditions, substance use history, and a history of psychosis all warrant attention. Noting these in the referral saves the receiving clinician time and spares the patient an avoidable dead end.

Prior authorization: what usually gets asked

Requirements vary by payer, but documentation commonly requested includes:

  • A diagnosis of major depressive disorder.
  • A record of prior antidepressant trials: drug, dose, duration, and response. Adequacy of dose and duration is often scrutinized.
  • A standardized severity measure, such as the PHQ-9, ideally with serial scores.
  • Whether the patient is on a concurrent oral antidepressant, where relevant to the indication.
  • Confirmation that treatment will occur at a certified site.

A clean medication history in the referral is the single most useful thing a referring physician can contribute. Coverage decides a great deal for patients: 65 percent of our respondents rated insurance a deciding or big factor, and half would put up with extra hoops to use it instead of paying cash.

Medical versus pharmacy benefit

Depending on the payer and the site's arrangements, esketamine may be covered under the medical benefit, with the site acquiring the drug, or under the pharmacy benefit, with the drug shipped from a specialty pharmacy to the site. The observation visit is billed separately. Patients rarely understand this distinction, and it affects their out-of-pocket cost. Pointing them to ask the treatment center about it helps.

Payer mix to plan around

Coverage among our respondents, multiple answers allowed, ran commercial plans at 39 percent and Medicaid at 37 percent, nearly a tie, then Medicare at 23, uninsured at 9 and TRICARE at 5 percent. Build your referral list for either of the big two alone and you will miss a large share of patients. Knowing which local certified sites accept Medicaid and Medicare is worth the phone calls.

What to tell the patient at the referral

  • This is an approved treatment with specific requirements, not a casual prescription.
  • Every dose is at a certified site, observed afterward, and someone else drives home.
  • Early treatment involves frequent visits.
  • Insurance will likely ask for records of past treatment, which we will provide.
  • The treating clinician will decide whether it is appropriate after their own evaluation.

Scope

This article summarizes publicly available information about the esketamine program and our own survey findings. It is not prescribing guidance; consult the current label and REMS materials. Suitability for any patient is a clinical judgment.

Any patient in acute crisis should leave knowing the number 988, the Suicide and Crisis Lifeline's number, which takes a spoken call or a typed text day and night. Including it on after-visit instructions is simple and worthwhile.

Methodology

Figures come from Pollfish survey 395586438, open to consumer-panel members through June 23, 2026: 443 completes, adults 18 to 64, in Minnesota, Kansas, Ohio, Iowa, Missouri, Nebraska, Wisconsin, Indiana, Illinois and Oklahoma. Multi-select results exceed 100 in sum. Figures are whole-sample and validated. The publisher commissioned the survey and met its cost.