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

When traditional antidepressants don’t work, people with treatment-resistant depression often face a long, exhausting road. For many, esketamine nasal spray (brand name Spravato) has become a turning point - not because it’s easy, but because it works when nothing else does. But it’s not a simple pill you pick up at the pharmacy. Esketamine requires strict monitoring, and two major side effects - dissociation and blood pressure spikes - are part of the process. Understanding these risks isn’t scary if you know what to expect.

How Esketamine Works Differently

Most antidepressants target serotonin, norepinephrine, or dopamine. Esketamine doesn’t. It blocks NMDA receptors in the brain, which are involved in how glutamate, a key brain chemical, communicates between nerve cells. This is a completely different pathway. By doing this, esketamine can trigger rapid changes in brain connectivity, sometimes lifting depression within hours or days. That’s why it’s used for people who haven’t responded to at least two other antidepressants. It’s not a first-line treatment - it’s a last-resort option with real power.

Dissociation: Feeling Unattached from Reality

Dissociation is the most common side effect of esketamine. In clinical trials, over half of patients (56%) reported feeling detached from their body or surroundings, as if they were in a dream. Some described it as floating, blurred vision, or feeling like time slowed down. These feelings aren’t hallucinations in the psychotic sense - they’re more like being mentally disconnected from your environment.

The intensity depends on the dose. At 84 mg, about 61% of patients experience dissociation. At 56 mg, it’s around 54%. Symptoms usually start within 20 minutes, peak at 40 minutes, and fade by 1.5 to 2 hours. In rare cases (about 6%), the dissociation is severe enough to meet clinical criteria for a dissociative state. But here’s what most patients find: it gets better with time. Many report that after the third or fourth treatment, the feeling is much milder - sometimes just a slight dizziness or foggy head.

Clinics use a tool called the Clinician-Administered Dissociative States Scale (CADSS) to measure this. Staff check in with you at 40 minutes and again before you leave. You’re never left alone during this time. The environment is kept calm - dim lights, no loud noises, minimal distractions. If you feel overwhelmed, staff can offer a blanket, water, or gentle reassurance. Benzodiazepines are kept on hand as a backup, but they’re rarely needed.

Blood Pressure Spikes: A Temporary but Real Risk

Esketamine causes your blood pressure to rise. Not a little - a noticeable jump. In trials, 33% of patients saw their systolic blood pressure climb above 140 mmHg. For some, it went as high as 170 or even 180. Diastolic pressure often rose by 10 to 16 points. These spikes start within 5 minutes of dosing, peak around 40 minutes, and almost always return to normal within 90 to 120 minutes.

This isn’t dangerous for most healthy people. But if you already have high blood pressure, heart disease, or a history of stroke or aneurysm, this can be risky. That’s why clinics screen you before every session. If your blood pressure is above 160/100 before treatment, you won’t get the spray that day. You’ll be rescheduled, and your doctor may adjust your blood pressure meds first.

Monitoring is strict. Your blood pressure is checked before the treatment, then every 5 to 10 minutes for the first 30 to 40 minutes, then every 15 to 30 minutes after that. Most clinics use digital monitors connected to a central system that alerts staff if numbers go too high. You’ll be asked to sit quietly, avoid talking or moving suddenly, and breathe slowly. Many patients say the monitoring itself helps them feel safe - knowing someone is watching keeps anxiety low.

The Monitoring Protocol: Why It’s So Strict

Esketamine is only available through a government-mandated program called REMS (Risk Evaluation and Mitigation Strategy). This means you can’t get it at home. You must go to a certified clinic, sit in a monitored room, and stay for at least two hours after each dose. This isn’t optional. It’s the law.

The process looks like this:

1. Arrive 15 minutes early for a check-in and vital signs check.
2. Sign a consent form confirming you understand the risks.
3. Administer the spray yourself under staff supervision - two sprays, one in each nostril.
4. Wait in a quiet room with staff nearby for 2 hours.
5. Get your blood pressure and dissociation assessed at key intervals.
6. Only leave once your numbers are stable and you’re fully alert.

Clinics spend about $18,500 to set up a dedicated room with proper lighting, seating, oxygen, and emergency equipment. Staff go through 2 hours of initial training and must renew it yearly. Over 2,800 clinics in the U.S. are certified. But access is still uneven - urban areas have more options than rural ones. Many patients drive over an hour for treatment.

What Patients Really Say

Online forums like Reddit’s r/Spravato and Healthgrades have thousands of posts from people using esketamine. The tone isn’t all positive, but it’s honest. One user wrote: “My first session felt like I was watching myself from the ceiling. Terrifying. But by the fourth time, I just felt a little floaty. Worth it.” Another said: “My BP hit 172. They paused, waited 20 minutes, and it came down. I was scared, but the staff knew exactly what to do.”

The most common complaint isn’t the side effects - it’s the time commitment. Taking off two hours every week or two isn’t easy if you work, have kids, or live far away. Insurance delays add to the stress. But 91% of people who rate Spravato positively say the clinic staff made all the difference. “They didn’t rush me. They explained everything. That’s why I kept going,” one reviewer said.

Is It Worth It?

For people who’ve tried five, six, or more antidepressants with no relief, esketamine offers something rare: hope. In trials, about 60% of patients saw a meaningful drop in depression scores within 28 days. That’s faster than any other treatment for treatment-resistant depression. And the effects can last weeks after the last dose - especially when combined with talk therapy and oral antidepressants.

The side effects? They’re real, but they’re temporary. Dissociation fades. Blood pressure normalizes. The monitoring isn’t a punishment - it’s protection. Every clinic that follows the protocol has a safety record nearly as clean as any standard psychiatric treatment.

The biggest barrier isn’t the medicine. It’s access. If you live in a small town, finding a certified center might be hard. But the number of clinics is growing fast. And in 2023, the FDA approved a trial allowing some patients to reduce their monitoring time from two hours to one - if they’re stable after the first session. That could change everything for rural patients.

What Comes Next

Researchers are already working on the next generation of rapid-acting antidepressants - pills or IV drugs that work like esketamine but without the dissociation. Companies like Sage Therapeutics and Allergan are testing alternatives. But so far, nothing has matched esketamine’s effectiveness in the hardest-to-treat cases.

Long-term data from the RECOVER study shows no worsening of blood pressure or dissociation with repeated use. That’s important. It means this isn’t a one-time fix with growing risks. It’s a treatment you can use safely over months.

The future of esketamine isn’t about eliminating side effects - it’s about making monitoring smarter. Digital tools are being tested to let patients track their own dissociation at home using apps. Wearables could monitor blood pressure remotely. But for now, the human presence in the room still matters most.

Final Thoughts

Esketamine nasal spray isn’t a miracle. It’s a tool - powerful, precise, and demanding. It asks you to sit with discomfort so you can move past depression. The dissociation, the blood pressure spikes, the two-hour waits - they’re not bugs. They’re features of a drug that works differently than anything else.

If you’re considering it, go in with eyes open. Talk to your doctor. Ask about the clinic’s protocol. Find out how they handle dissociation. Ask if they’ve ever had to stop a session because of high blood pressure. Most importantly, ask yourself: have I tried everything else? If the answer is yes, then esketamine might not be the easy path - but it could be the one that brings you back.