When people with commercial insurance first learn about esketamine, a second question tends to follow the first. Should I go through my plan, with the forms and approvals and waiting? Or should I pay myself and just get started? And what about the ketamine programs that promise to ship something to my door?

This comparison lays out those routes side by side. It is not a recommendation. Which treatment suits you, if any, is a question for your clinician. But knowing how the routes differ can make that conversation, and the decision after it, much clearer.

Where most people are starting from

Very few people start this with any background knowledge. In our commissioned survey of 443 Midwest adults, most, 73 percent, had never come across Spravato, an esketamine nasal spray. One in five knew the name without the meaning, and only 6 percent could explain it.

We also asked people to choose between two paths: a treatment covered by insurance but with more hoops, or paying yourself for a simpler process. Just over half, 51 percent, chose the covered path. Twenty-three percent chose to pay. The other 26 percent were unsure.

These top-line figures are final; the panel data behind them has been validated. Commercially insured respondents, the largest payer group at 39 percent, number 173; half of them, 50 percent, took the covered path. The comparison below is practical, based on how these routes generally work.

Route 1: Esketamine through your commercial plan

What it is. FDA-approved Spravato, given at a certified treatment center, billed to your insurer.

Getting started. Your doctor or the center requests prior authorization. Expect to document the antidepressants you have tried. Approval can take days to weeks, and a first denial is not unusual.

What you pay. Your normal cost sharing: deductible, copays, or coinsurance, depending on whether it is billed under your medical or pharmacy benefit. Costs are often heaviest early in the plan year. The manufacturer's support program has at times helped commercially insured patients with costs.

Oversight. High. Dosing happens under direct observation, followed by monitoring, under a federal safety program.

Logistics. Frequent visits early on. You need a ride home each time.

Best fit for. People who want an FDA-approved treatment and are willing to handle the paperwork to keep costs down. A plain explanation of Spravato covers the treatment itself.

Route 2: Esketamine, paying out of pocket

What it is. The same FDA-approved treatment at the same kind of certified center, but paid for directly.

Getting started. Potentially faster, since you skip prior authorization. Some centers may still require a referral and evaluation.

What you pay. The full cost of the drug and the visits. Esketamine is a brand-name medication, and the early phase involves frequent sessions, so this can be expensive. Ask for a written estimate before starting.

Oversight. The same as Route 1.

Logistics. The same as Route 1.

Best fit for. People with the means who value speed, or who have been denied coverage and are pursuing an appeal at the same time. Paying out of pocket while you have commercial coverage deserves a careful conversation with the center and your insurer first, since some costs may not count toward your deductible.

Route 3: IV ketamine infusions

What it is. Generic ketamine given by IV at a clinic. It is not FDA-approved for depression, so this is off-label use.

Getting started. Often quick. Many clinics take self-referrals, though good ones will want records from your doctor.

What you pay. Usually cash. Commercial plans cover off-label ketamine less often, though some may reimburse parts of the visit.

Oversight. Varies by clinic. Infusions happen in a medical setting with monitoring, but the standards are set by each clinic rather than an FDA safety program specific to depression.

Best fit for. A conversation with your clinician. It is a real treatment some psychiatrists use, but it is a different decision from esketamine.

Route 4: At-home ketamine through telehealth

What it is. Ketamine prescribed by a remote clinician, often as lozenges or tablets, for use at home. Off-label for depression.

Getting started. Often the fastest. Sometimes a video visit is all it takes.

What you pay. Typically a cash subscription or package.

Oversight. The lowest of any route here. No clinician is present while you dose, and monitoring is often left to you or a family member.

Best fit for. Proceed with real caution, and only after your regular clinician has weighed in. Do not confuse this with FDA-approved esketamine.

How the routes stack up on what people said mattered

Respondents picked the two things they would weigh most in choosing a provider. Here is how the routes relate to the leading answers:

Covered by insurance (85 percent): Route 1 is designed for this. Routes 2 through 4 largely are not.
Close to home (43 percent): Route 4 wins on convenience. Routes 1 and 2 depend on where certified centers are. Route 3 depends on local clinics.
FDA-approved (27 percent): Only Routes 1 and 2 involve an FDA-approved treatment for depression.
Fast results (24 percent): No route can promise speed of response. Routes 2 through 4 may start sooner, but how quickly any treatment helps varies by person.

Respondents' delivery preferences leaned toward clinics: in-person care drew 44 percent, clinic-then-home 23 percent, and at-home telehealth 22 percent. Put together, two-thirds wanted a clinic involved at some point.

A sensible order of operations

Talk to your doctor first. 74 percent of respondents would be swayed toward a new treatment by their own doctor's recommendation.
Ask whether your history qualifies as treatment-resistant depression.
Call your insurer about esketamine coverage and in-network centers.
If coverage is denied, ask about an appeal before deciding to pay.
If you consider an off-label route, get your regular clinician's input first.

No matter which route you are weighing, a crisis comes first. Anyone thinking about suicide can get the Suicide and Crisis Lifeline immediately at 988, by phone or text, free and regardless of coverage; veterans can press 1.

Methodology

This comparison uses top-line results from our Pollfish consumer panel survey, which 443 adults, ages 18 to 64, finished by June 23, 2026, in Minnesota, Indiana, Iowa, Oklahoma, Missouri, Wisconsin, Illinois, Ohio, Kansas, and Nebraska. The one group figure is for commercially insured respondents. Payer and priority questions were multi-select. Every figure has passed Pollfish's final validation. Commissioning and funding the study both fell to our publisher. Route descriptions are general; this is not medical, financial, or insurance advice.

Your plan or your wallet: comparing routes to esketamine care