Esketamine Nasal Spray: What You Need to Know About Dissociation, Blood Pressure, and Monitoring

When traditional antidepressants don’t work, esketamine nasal spray - brand name Spravato - offers a lifeline. Approved by the FDA in 2019, it’s the first antidepressant that works differently: instead of targeting serotonin or norepinephrine, it blocks NMDA receptors in the brain. That’s why it can lift severe depression in hours or days, not weeks. But this fast action comes with a price: intense side effects that require strict medical supervision. If you’re considering esketamine, you need to understand what happens in your body during treatment - especially the dissociation, the blood pressure spikes, and why you can’t just take it at home.

How Esketamine Works - And Why It Causes Dissociation

Most antidepressants take weeks to kick in because they slowly boost mood chemicals. Esketamine is different. It acts fast by blocking NMDA receptors, which are involved in how brain cells communicate. This isn’t just a simple on-off switch. When esketamine blocks these receptors on inhibitory neurons, it triggers a chain reaction: excitatory neurons fire more, leading to a surge in synaptic connections. That’s what helps repair damaged brain circuits in depression. But that same surge also causes dissociation - a feeling of being detached from your body or surroundings.

In clinical trials, over half of patients (56%) reported dissociation after a dose. Symptoms range from mild dizziness and blurred vision to feeling like you’re floating, watching yourself from outside your body, or hearing sounds as if they’re underwater. These aren’t hallucinations in the psychotic sense - more like a dreamlike detachment. They peak around 40 minutes after spraying and usually fade within two hours. The higher the dose (84 mg vs. 56 mg), the more likely you are to feel this. One patient described it on Reddit: “My first time felt like I was trapped in a movie. I could hear people talking, but I couldn’t move or respond. It scared me - but then it just… ended.”

Why Blood Pressure Rises - And Why It Matters

Esketamine doesn’t just affect your mind. It also triggers a stress-like response in your body. Within five minutes of spraying, your systolic blood pressure can jump 14 to 23 mmHg, and your diastolic by 7 to 16 mmHg. That’s enough to push someone with borderline hypertension into dangerous territory. In trials, 33% of users had treatment-emergent hypertension - compared to just 14% on placebo. These spikes are temporary, but they’re real. One patient with controlled high blood pressure had to stop treatment after her systolic reading hit 170 mmHg, even though she was already on medication.

That’s why screening is non-negotiable. You can’t get esketamine if your blood pressure is over 160/100 at your first visit. People with recent heart attacks, brain aneurysms, or unstable heart disease are excluded. Even if you’re cleared, your blood pressure is checked before, during, and after every dose. Clinics use automated monitors that alert staff if numbers climb too high. Most of the time, pressure returns to normal on its own. But if it doesn’t, staff are trained to act - with medications or calming techniques - before it becomes a crisis.

The REMS Program: Why You Can’t Take This at Home

Because of these risks, the FDA created the Risk Evaluation and Mitigation Strategy (REMS) - one of the strictest safety programs for any psychiatric drug. You can’t walk into a pharmacy and get a prescription filled. You must go to a certified clinic, sit in a monitored room, and be watched for at least two hours after each dose. No exceptions.

During that time, staff check your blood pressure every 5-10 minutes for the first half-hour, then every 15-30 minutes after. They also use a tool called the CADSS (Clinician-Administered Dissociative States Scale) to rate how intense your dissociation is. If it’s severe, they may offer a calming environment - dim lights, quiet music, no screens - but rarely give rescue meds like benzodiazepines. Only about 1 in 80 treatments needs them.

You also have to sign a Patient-Provider Agreement before every session. It’s not just paperwork - it’s a reminder that you’re entering a controlled medical environment, not self-medicating. The goal isn’t to scare you. It’s to make sure that if something goes wrong, help is right there.

What Patients Really Experience - And How It Changes Over Time

The first dose is often the hardest. Many patients report feeling anxious before treatment, worried about losing control. But most find that the dissociation gets milder with repeated doses. In one study, 60% of users said their dissociation was “manageable” by the fourth session. One user wrote: “I thought I’d be out of it for hours. By session three, I just felt a little spaced out for 20 minutes. I could still hear the nurse talking.”

Blood pressure spikes also tend to lessen. A survey of 347 patients found that 87% of those who had high readings during their first session saw their numbers return to normal within 90 minutes on later visits. That’s likely because the body adapts - or because patients are better prepared mentally. Still, some never adjust. People with existing heart conditions or severe anxiety often have to stop. For them, the risk outweighs the benefit.

What keeps people going? The results. In trials, nearly 70% of patients with treatment-resistant depression saw at least a 50% drop in symptoms after four weeks. Some felt better within 24 hours. That’s life-changing for people who’ve tried five or six other meds without success.

How Clinics Handle the Challenges - And What You Should Expect

Running a Spravato clinic isn’t simple. It costs an average of $18,500 to set up a dedicated room with proper monitoring gear, private space, and trained staff. Each session takes over two hours - 15 minutes to prep, 5 minutes to spray, and two full hours to monitor. That’s a lot of time and resources for one patient.

Clinics that do it well focus on three things: education, environment, and emergency readiness. Before your first visit, you’ll get detailed info on what to expect. During treatment, staff keep the room calm - no loud noises, no bright lights. Afterward, they check your vital signs and ask how you’re feeling. If you’re stable, you can leave. If not, you stay until you’re safe.

One big challenge? Access. As of 2023, there are over 2,800 certified centers in the U.S. - up from just 350 at launch. But rural areas still have only 0.8 centers per 100,000 people. Urban areas have over four times that. Insurance delays and prior authorizations also slow things down. Many patients wait weeks just to get approved.

What’s Next for Esketamine?

The FDA is already testing ways to make this safer and more accessible. In late 2023, they approved a new rule: if you’ve had two treatments without major side effects, your monitoring time can be cut from two hours to one. That’s based on data showing 63% of patients were stable after 60 minutes.

Companies are also working on alternatives - oral versions, IV infusions, or drugs that mimic esketamine’s benefits without the dissociation. But so far, nothing has matched its effectiveness in the toughest cases. Experts agree: the side effects are real, but they’re manageable. The bigger issue isn’t the drug - it’s the system. Making sure every patient who needs this treatment can actually get it, safely, is the next frontier.

If you’ve tried everything else and still feel stuck, esketamine might be worth exploring. But don’t go in blind. Know what to expect. Ask your doctor about the monitoring process. Talk to others who’ve done it. And remember - the two-hour wait isn’t a barrier. It’s the safety net that makes this treatment possible.