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 feel trapped. No matter how many pills they try, the fog doesn’t lift. That’s where esketamine nasal spray comes in - a breakthrough treatment that can shift the needle in days, not weeks. But it’s not a simple prescription. It comes with intense side effects, strict rules, and a monitoring process unlike any other antidepressant. If you’re considering it, or just trying to understand why it’s so tightly controlled, you need to know what really happens when you use it.

How Esketamine Works - And Why It’s Different

Most antidepressants target serotonin, norepinephrine, or dopamine. Esketamine doesn’t. It works on glutamate, the brain’s main excitatory chemical. Specifically, it blocks NMDA receptors, which are like gates that control how much calcium flows into brain cells. By blocking these gates on certain inhibitory neurons, esketamine actually increases activity in other parts of the brain. This sudden surge in neural communication is thought to help rebuild connections that depression has broken.

It’s fast. Within hours, some people feel a shift. That’s why it’s used for severe, treatment-resistant depression - when people have tried at least two other antidepressants and still can’t get better. The FDA approved it in 2019, and since then, over 125,000 people in the U.S. have received it. But this speed comes with a cost: strong, immediate side effects that demand careful oversight.

Dissociation: Feeling Unreal - And Why It’s Normal

If you’ve never heard the word “dissociation,” you’re not alone. But if you’ve ever felt like you were watching yourself from outside your body - like you were in a dream - you’ve experienced it. That’s exactly what happens with esketamine.

In clinical trials, more than half of patients (56%) reported dissociation after their first dose. That’s compared to just 14% in the placebo group. Symptoms include:

• Feeling detached from your body or surroundings
• Time feeling slowed down or stretched out
• Blurred vision or seeing colors differently
• Feeling like you’re floating or disconnected from reality

These aren’t hallucinations in the psychotic sense. You usually know you’re in a clinic, you know you’re being treated. But your mind feels like it’s on pause. It peaks around 40 minutes after spraying and fades by 1.5 to 2 hours.

The dose matters. At 84 mg, 61% of people report dissociation. At 56 mg, it’s 54%. Many patients say it gets easier over time. One user on Reddit wrote: “My first two sessions felt like I was underwater. By the fourth, I was just a little dizzy. I didn’t even need to close my eyes.”

Clinics use tools like the CADSS scale to measure how bad it is. If it’s severe - which happens in about 6% of cases - staff are trained to help. Most often, they just dim the lights, turn on calming music, and sit quietly with you. Benzodiazepines are kept on hand, but they’re rarely needed.

Blood Pressure Spikes: The Silent Risk

While dissociation is obvious, the blood pressure spike is silent - and just as dangerous.

Within 5 minutes of spraying, your systolic pressure (the top number) can jump 14 to 23 points. Diastolic (the bottom number) can rise 7 to 16. For most people, it’s harmless. But for someone with high blood pressure, heart disease, or a history of stroke, it’s risky.

In trials, 33% of patients had a blood pressure reading over 140/90 - the clinical definition of hypertension. That’s more than double the placebo group. These spikes aren’t symptoms - you won’t feel dizzy or have a headache. That’s why checking it is non-negotiable.

You can’t take esketamine if your blood pressure is above 160/100 at the time of your appointment. If you have an aneurysm, a recent heart attack, or uncontrolled hypertension, you’re excluded. Even if you’re on blood pressure meds, some people still spike too high. One patient on PatientsLikeMe stopped after two sessions when their systolic hit 170.

That’s why clinics check your blood pressure before, during, and after treatment - every 5 to 10 minutes for the first half hour, then every 15 to 30 minutes after. They’re watching for anything above 180/120, which requires immediate intervention.

The 2-Hour Monitoring Rule: Why It’s Not Optional

You don’t just walk in, spray, and leave. Esketamine is only available through the FDA’s REMS program - a strict safety system designed to prevent misuse and manage acute risks.

Here’s what happens during your visit:

1. You arrive 15 minutes early for a health check - blood pressure, heart rate, mental status.
2. You self-administer the spray under direct supervision. The nurse watches you closely.
3. You sit in a quiet, calm room. No phones, no TV, no distractions.
4. Staff monitor your vitals every 5-10 minutes for the first 30-40 minutes.
5. Dissociation is assessed at the 40-minute mark using a standardized scale.
6. You stay for at least 2 hours - no exceptions. Even if you feel fine.
7. You must have someone drive you home. You can’t drive or operate machinery for the rest of the day.

This isn’t just bureaucracy. It’s life-saving. In 95% of certified centers, the 2-hour rule is followed exactly. Only 5% ever let patients leave early - and even then, only if vital signs are rock-solid and dissociation is gone.

Clinics spend an average of $18,500 to set up a dedicated room with proper lighting, emergency equipment, and staff training. Each session takes over two hours - and that’s just one patient. That’s why there are only about 2,800 certified centers in the U.S., and rural areas have barely one per 100,000 people.

What Patients Really Say - The Good, the Bad, the Real

On Healthgrades, Spravato has a 3.7 out of 5 rating. The reviews are split, but the patterns are clear.

People who say it changed their life often mention:

• “I felt like myself again after two weeks - something no other drug did.”
• “The dissociation was scary at first, but the staff made me feel safe.”
• “I was suicidal. Now I’m not. That’s worth the hassle.”

Those who say it didn’t work or was too hard to handle often say:

• “The blood pressure spikes scared me. I couldn’t risk it.”
• “I had to take the whole day off. My job didn’t understand.”
• “I felt worse after the first dose - like I was losing my mind.”

The most consistent theme? The quality of the clinic matters more than the drug. Patients who felt heard, calm, and supported were far more likely to continue treatment - even through the worst dissociation.

What’s Next? Shorter Visits, Better Tools

The system isn’t perfect. But it’s changing.

In September 2023, the FDA approved a new option: for patients who have stable vitals and mild dissociation after their first few treatments, the monitoring time can be cut from 2 hours to 1. This is based on data from the SUSTAIN-2 trial, which showed 63% of patients were safe to leave after 60 minutes.

Companies are also working on digital tools - apps and wearables that can track dissociation and blood pressure remotely. But here’s the catch: the FDA still says you need to be in a certified center. Why? Because dissociation can turn dangerous fast. You need someone physically there to help if you panic, vomit, or have a seizure.

Experts agree: the side effects aren’t going away. They’re built into how the drug works. But with better screening, smarter monitoring, and more centers opening up, access is improving.

Is It Right for You?

Esketamine isn’t for everyone. But for people with severe, treatment-resistant depression who’ve run out of options, it’s a lifeline.

Ask yourself:

• Have I tried at least two antidepressants without lasting improvement?
• Do I have uncontrolled high blood pressure or heart disease?
• Can I take off 2.5 hours for each treatment, twice a week for the first month?
• Is there a certified clinic nearby - and can I get there safely?

If you answered yes to the first and no to the rest, you might be a good candidate. But don’t decide alone. Talk to a psychiatrist who’s trained in esketamine. Bring your full history. Ask about the clinic’s monitoring protocol. Ask what they do if dissociation gets too intense.

This isn’t a miracle cure. It’s a powerful tool - with real risks and real rules. But for many, it’s the only thing that’s brought them back from the edge.