Spravato in practice: what I tell patients before their first session

Spravato is the first genuinely new mechanism for depression to reach my prescription pad in my career, and it comes with more rules than any other treatment I offer. I oversee the Spravato program at Stedfast Psychiatry, and before a patient's first session I have a conversation that covers the same ground every time. This is that conversation, written down.

What Spravato is and who it is for

Spravato is the brand name for esketamine, a nasal spray derived from ketamine. The FDA approved it in March 2019 for adults with treatment-resistant depression, taken together with an oral antidepressant, and in August 2020 for adults with major depressive disorder who have acute suicidal thoughts or behavior. In January 2025 the FDA also approved it on its own, without a daily antidepressant, for treatment-resistant depression in adults.

Treatment-resistant depression, for this purpose, means a current episode that has not responded adequately to at least two different antidepressants given at an adequate dose for an adequate time. That definition matters because insurers hold to it and because the evidence was gathered in that population. I review every prior medication trial before I call a patient treatment-resistant.

The mechanism is different from every other antidepressant. SSRIs and SNRIs act on serotonin and norepinephrine. Esketamine blocks the NMDA glutamate receptor, which sets off a cascade that appears to restore synaptic connections in prefrontal circuits. The practical consequence is speed. Some patients notice a change within hours of the first dose, rather than the weeks a conventional antidepressant takes.

What the evidence shows

The pivotal trial, TRANSFORM-2, was published by Vanina Popova and colleagues in the American Journal of Psychiatry in 2019. Patients with treatment-resistant depression were started on a new oral antidepressant plus either esketamine or a placebo spray. At four weeks the esketamine group had improved significantly more, and a larger share had reached remission. A second trial, SUSTAIN-1, published by Ella Daly and colleagues in JAMA Psychiatry in 2019, followed patients who had responded and found that continuing esketamine cut the risk of relapse by about half compared with stopping it.

I give patients those numbers and I also give them the honest version: a meaningful minority of patients do not respond, the placebo response in these trials was substantial, and the long-term data beyond a few years are still accumulating. Spravato is a real treatment with real evidence. It is not a cure for everyone.

The rules, and why they exist

Spravato is dispensed under an FDA program called a REMS, a Risk Evaluation and Mitigation Strategy. The rules are not negotiable, and I explain each one.

• You take it in our office, never at home. Spravato is administered only in a certified treatment center. Our Jupiter and Palm Beach Gardens offices are certified. You self-administer the spray under observation, and the medication never leaves the building.
• You stay for two hours. A staff member monitors you for at least two hours after each dose. We check blood pressure before the dose and again about 40 minutes after, because esketamine raises blood pressure temporarily in most people. We treat a sustained rise seriously.
• You do not drive until the next day. Not after lunch, not after a nap. The next day, after a full night's sleep. Someone else drives you home, and that person needs to be arranged before the first visit, not found afterward.
• No food for two hours and no liquids for 30 minutes before the dose. Nausea is a common side effect and an empty stomach reduces it.
• Tell me about every other medication, including benzodiazepines, sleep aids, stimulants and anything from outside a pharmacy. Sedatives compound the drowsiness. Stimulants raise blood pressure.

What the first session feels like

I tell patients to expect dissociation, and I describe it rather than naming it. For about 30 to 60 minutes after the spray many people feel detached from their surroundings or their body, as if watching themselves from a short distance. Sounds and colors may seem different. Some people find it unsettling the first time; most find it tolerable, and it fades well within the monitoring period. It is also the reason you are in a quiet room with a reclining chair and a staff member checking on you, not a waiting room.

Other common effects are dizziness, nausea, drowsiness, a feeling of numbness and a temporary sense of being intoxicated. Blood pressure goes up for an hour or so. Nearly all of this resolves before you leave. I ask patients to bring something to listen to, to skip caffeine that morning, and to plan nothing for the rest of the day.

The schedule

The induction phase runs four weeks with two sessions a week. The first dose is 56 milligrams; after that we use 56 or 84 milligrams depending on response and tolerability. Weeks five through eight are once a week. After that, most patients move to a session every week or every two weeks, and we taper the frequency to the lowest that keeps them well. Including the monitoring time, each visit takes about two and a half hours.

That is a significant commitment and I say so. A patient who cannot arrange eight visits in the first month, each with a ride home, should not start. We will find another approach.

Who should not take it

Spravato is not appropriate for people with aneurysmal vascular disease, a history of bleeding in the brain, or uncontrolled high blood pressure. I am cautious in patients with a history of psychosis and in anyone with a current substance use disorder, because esketamine is a controlled substance with abuse potential, and I screen for both. Pregnancy is a contraindication. Patients with these conditions get a different plan.

How we judge whether it is working

We take a PHQ-9 at every visit and track it against the baseline. I look for a clear response by the end of the four-week induction. If there is none, we stop, and I say that in advance so no one feels they have failed. If there is a response, the maintenance phase is where the SUSTAIN-1 data become relevant: continuing treatment protects the gain. We also keep working on the oral antidepressant, therapy and the functional goals we set at the start, because esketamine opens a window and the rest of the plan is what gets built in it.

What I ask of patients

Arrange your ride before the first session. Eat early. Be honest about alcohol and other substances, because I cannot keep you safe with incomplete information. Tell the monitoring staff how you feel during the session, not afterward. And tell me plainly if the dissociation was more than you can live with, because that is a real reason to reconsider and I will not talk you out of it.

Spravato has given some of my most treatment-resistant patients their first real improvement in years. It has also failed for others. I offer it the way I offer everything else: with the evidence on the table, the rules explained, and the decision left to a patient who understands both.

More from Dr. Husted

• Why I measure depression treatment by function, not just mood2026-06-11
• When to consider Deep TMS: how I decide with my patients2026-07-09
• Anxiety that does not respond to the first medication: my next steps2026-08-27

Educational content and not a substitute for evaluation. If you are in crisis, call or text 988.