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

When you’ve tried multiple antidepressants and still feel stuck in deep depression, the idea of a treatment that works in hours instead of weeks can feel like a lifeline. Esketamine nasal spray - sold under the brand name Spravato - is one of the first antidepressants in decades that doesn’t work on serotonin or norepinephrine. Instead, it targets the brain’s glutamate system, offering rapid relief for people with treatment-resistant depression. But it’s not a simple pill you pick up at the pharmacy. It comes with intense side effects, strict monitoring rules, and a level of oversight you won’t find with any other depression medication.

How Esketamine Works - And Why It’s Different

Most antidepressants, like SSRIs or SNRIs, take weeks to kick in. They slowly adjust brain chemicals tied to mood. Esketamine works differently. It blocks NMDA receptors, which are part of the glutamate system - the brain’s main excitatory signaling pathway. This isn’t just a tweak. It’s a reset. Within hours, some patients report feeling less numb, more connected, even hopeful. That’s why it’s used only when other treatments have failed - typically after at least two antidepressants didn’t help.

The drug is delivered as a nasal spray, not an injection or pill. You self-administer it under the watch of a healthcare provider in a certified clinic. It’s absorbed quickly: peak levels hit your bloodstream in 20 to 40 minutes. That’s when the effects - both good and bad - start to show.

Dissociation: The Most Common Side Effect

If you’ve never heard of dissociation, you’re not alone. But if you’ve taken esketamine, you probably have now. Dissociation means feeling detached from yourself or your surroundings. It’s not hallucinating, but it can feel like it: time slows down, your body feels unreal, sounds seem muffled, or you feel like you’re floating. In clinical trials, over half of patients (56%) reported dissociation after their first dose. That’s compared to just 14% in the placebo group.

It’s not the same as being high on ketamine - though they’re chemically related. The experience is usually milder and more predictable. Most people describe it as “dreamlike” or “out of body.” It peaks around 40 minutes after spraying and fades within two hours. By the fourth or fifth treatment, many say it’s much less intense - sometimes barely noticeable.

Clinics use a tool called the CADSS (Clinician-Administered Dissociative States Scale) to measure how strong it is. If your score hits 3 or higher, it’s considered severe. That happened in about 6% of patients during trials. But even then, most people don’t panic. They’re in a calm, quiet room with trained staff nearby. Soft lighting, no phones, no distractions. That’s part of the protocol.

Blood Pressure Spikes - And Why They Matter

Esketamine doesn’t just change how you feel mentally. It changes your body too. Blood pressure rises - sometimes sharply. In trials, 33% of patients saw their systolic pressure jump above 140 mmHg. For someone with high blood pressure, that’s dangerous. Diastolic pressure (the bottom number) can climb 7 to 16 points. These spikes start within 5 minutes, peak at 40 minutes, and drop back down by the end of the 2-hour monitoring window.

That’s why you can’t just take this at home. You need to be monitored. Your blood pressure is checked before the spray, then every 5 to 10 minutes for the first half hour, then every 15 to 30 minutes after that. If your pressure goes above 180/110, treatment stops. You’re not allowed to get esketamine if you have uncontrolled high blood pressure, a history of stroke, aneurysm, or recent heart attack.

Most people don’t feel anything during the spike. No headache, no dizziness. But the risk is real. One patient on PatientsLikeMe stopped treatment after two sessions because his systolic pressure hit 170 - even though he was already on blood pressure meds. That’s why screening is so strict.

The 2-Hour Monitoring Rule - And Why It Exists

You don’t leave the clinic until at least two hours after your spray. That’s not optional. It’s part of the FDA’s Risk Evaluation and Mitigation Strategy (REMS), a safety program designed to prevent misuse and manage acute side effects. The clinic must be certified, staff must be trained, and they need emergency equipment on hand - oxygen, benzodiazepines for severe reactions, and tools to monitor your vitals.

The 2-hour window isn’t arbitrary. It’s based on when side effects peak and fade. Dissociation and blood pressure changes usually resolve by then. But some clinics are starting to test shorter times. A 2023 trial found that 63% of patients were stable after just one hour. Based on that, the FDA approved a new option: if you’ve had several treatments and your side effects stay mild, you might be able to leave after 60 minutes. It’s not universal yet - but it’s a step toward making access easier.

What the Clinics Are Doing Right (and Where They Struggle)

There are now over 2,800 certified Spravato clinics in the U.S. That’s up from just 350 in 2019. But setting one up isn’t cheap. The average cost to equip a room - with private space, monitoring gear, staff training, and emergency supplies - is around $18,500. Staff spend about 2 hours and 15 minutes per patient: 15 minutes for prep, 5 minutes to spray, and two full hours of monitoring.

The biggest challenges? Patient anxiety, scheduling conflicts, and insurance delays. Many people are scared of dissociation before they even try it. Clinics that spend time explaining what to expect see 32% less anxiety. Others use calming techniques: dim lights, headphones with soothing music, no talking unless needed.

Only 1.2% of treatments need emergency drugs like benzodiazepines. Most patients just sit quietly, breathe, and wait it out. And that’s where the system works: trained staff know exactly what to do. In fact, 91% of positive reviews on Drugs.com mention that the staff made them feel safe.

Real People, Real Experiences

On Reddit’s r/Spravato, users share stories that mirror the data. One person wrote: “My first treatment felt like I was watching myself from the ceiling. I was terrified. By my fourth, I just felt a little spaced out - and then I cried for the first time in months.”

Another said: “I have hypertension. My doctor said no. But I begged for a trial. My pressure went to 165. They watched me for two hours. It came down. I did two more sessions and stopped. It helped my depression - but not worth the risk.”

On Healthgrades, the average rating is 3.7 out of 5. People who benefit most are those who’ve tried everything else. Those who respond well often say it’s life-changing. Those who don’t tolerate it say the side effects outweigh the relief.

Is It Worth It?

Esketamine isn’t for everyone. It’s not a first-line treatment. It’s not a magic cure. But for people with treatment-resistant depression - those who’ve lost hope after years of failed meds - it offers something rare: a chance to feel human again, quickly.

The dissociation and blood pressure spikes are real. They’re not minor. But they’re predictable. And they’re managed. The monitoring system isn’t perfect - it’s expensive, time-consuming, and hard to access in rural areas. But it’s designed to keep you safe while giving you a shot at recovery.

The future might bring easier versions: oral pills, fewer clinic visits, digital monitoring tools. But for now, esketamine works because it’s controlled. The side effects are part of the treatment. And the monitoring? That’s what makes it possible.