Spravato (Esketamine) Side Effects Explained

If two or more antidepressants haven't worked for you, you're not alone. There are 2.8 million American adults living with treatment-resistant depression right now, cycling through medications that don't move the needle.

People with treatment-resistant depression are 7x more likely to attempt suicide than the average person with depression.

Spravato (esketamine) is different. It's a nasal spray. It works in 24 hours. It's FDA-approved as a standalone treatment for adults with treatment-resistant depression whose symptoms haven't responded to oral antidepressants. And its side effects are very different than traditional antidepressants.

Here's what those side effects actually feel like, how long they last, and why typically less than 5% of patients stop treatment because of them.

The Most Common Spravato Side Effects

The FDA recognizes several Spravato side effects when used for treatment-resistant depression. The following side effects showed up at least 5% of the time:

• Dissociation — feeling disconnected from your body, thoughts, or surroundings
• Dizziness and vertigo
• Nausea and vomiting
• Sedation and lethargy
• Numbness — usually around the mouth or throat
• Headache
• Anxiety
• Feeling drunk
• Increased blood pressure

Nearly every Spravato patient experiences some version of these. They're predictable, well-understood, and almost entirely confined to the treatment session itself. They nearly all dissipate with 1-2 hours

How Often Spravato Side Effects Actually Happen

In the clinical trials behind the FDA approval for treatment-resistant depression:

• Dissociation: 41% of Spravato patients vs. 9% on placebo
• Dizziness: 29% vs. 8%
• Nausea: 28% vs. 9%
• Sedation: 23% vs. 9%
• Vertigo: 23% vs. 3%
• Headache: 20% vs. 17%
• Numbness: 18% vs. 2%
• Increased blood pressure: 10% vs. 3%
• Vomiting: 9% vs. 2%

These numbers held up in the real world. The most recent five-year safety analysis tracked more than 58,000 patients with treatment-resistant depression across 1.48 million treatment sessions. Sedation showed up in 34.7% of sessions, dissociation in 41.0%, and elevated blood pressure in less than 1%. Serious adverse events occurred in fewer than 0.2% of sessions. No new safety concerns emerged.

How Long Spravato Side Effects Last

Here's the part the FDA label doesn't communicate well: Spravato side effects typically don't linger.

85% of side effects happen on dosing days, and roughly 90% of those resolve the same day. Dizziness, dissociation, nausea, blood pressure changes, and sedation are most intense in the first week of treatment and taper from there. Nausea and vomiting fade after the first few sessions.

The two-hour observation period isn't there in case something goes wrong later. It's there because the side effects happen during those two hours — and then they're usually done.

What Ketamine Dissociation Actually Feels Like

Dissociation is the side effect people worry about most, and the hardest to describe in advance.

Patients describe it as a dream-like state. Time slows down. Your body feels lighter. Music sounds different. Colors look brighter. You might feel like you're watching yourself from a slight remove. It can feel different than normal consciousness. It rarely feels frightening when you're prepared for it and supported through it.

It also passes. Dissociation peaks in the first 40 minutes after dosing and fades during the observation window. By the time you leave the clinic, it should be gone.

Blood Pressure and Sedation from Ketamine

Your blood pressure goes up briefly after dosing — usually around 7 to 10 mmHg systolic, peaking at 40 minutes, back to baseline within four hours. Most patients don't feel it. Your clinic checks before and after every session. Patients with certain cardiovascular conditions can't receive Spravato at all.

Sedation is part of the experience for most patients. You won't drive yourself home, and you shouldn't drive or operate machinery until the next day after a full night's sleep.

How Often Spravato Side Effects Stop Treatment

This is the question that matters most: do these side effects actually make Spravato unworkable for people with treatment-resistant depression?

In trials, 4.6% of patients stopped Spravato because of side effects, compared to 1.4% on placebo. Across the entire clinical program, fewer than 7% discontinued for any side effect reason. The most common reasons — anxiety, dizziness, blood pressure — each accounted for around 1% or less.

More than 93% of patients tolerate Spravato well enough to keep going.

Why the Ketamine Clinic You Choose Matters

Spravato side effects are predictable and time-limited. What's not predictable is the clinic.

A high-volume clinic with rushed intake and minimal preparation can make dissociation feel disorienting. A clinic that prepares you carefully, paces the experience, and stays with you the whole time makes the same side effects feel manageable — sometimes even meaningful.

At Clarus Health in downtown San Francisco, every Spravato session happens in a private treatment room with compassionate clinical support throughout the full two-hour window. Our doctors advocate that the setting matters as much as the medication. You're prepared for what to expect, monitored continuously, and discharged only when you're fully ready.

We treat treatment-resistant depression with a full range of evidence-based therapies beyond Spravato — including IV ketamine, stellate ganglion block, and root-cause workups that identify what's actually driving the depression in the first place.

Spravato Treatment for Treatment-Resistant Depression in San Francisco

If you've been told you have treatment-resistant depression and you're considering Spravato — or if you're in treatment elsewhere and want a more supported experience — we'd be glad to talk.

Book a free consultation or call 415-237-3007.