Spravato Side Effects: What to Expect and How We Monitor

The most common side effects of SPRAVATO® (esketamine) are dissociation (feeling detached from yourself or your surroundings), dizziness, nausea, sleepiness, a spinning sensation called vertigo, and a temporary rise in blood pressure. In the trials behind the FDA label, these usually started soon after the dose and faded the same day, often within the 2 hours you are required to stay at the clinic. Here is what the label reports about Spravato side effects, and when to call your care team.

What are the most common Spravato side effects?

Unless a specific study is named, the figures in this article come from the SPRAVATO prescribing information as revised in April 2025, the version posted by the FDA. Its main side-effect table comes from short-term trials in adults with treatment-resistant depression (TRD) who started Spravato with a new oral antidepressant: 346 people on Spravato and 222 on a placebo spray plus an oral antidepressant. The most common side effects, Spravato vs placebo, were:

• Dissociation: 41% vs 9%
• Dizziness: 29% vs 8%
• Nausea: 28% vs 9%
• Sedation (sleepiness): 23% vs 9%
• Vertigo (spinning sensation): 23% vs 3%
• Numbness or reduced sensation: 18% vs 2%
• Increased blood pressure: 10% vs 3%
• Vomiting: 9% vs 2%

In the same label's safety data for Spravato used on its own in adults with TRD (226 on Spravato, 250 on placebo), the most common were dissociation (28% vs 4% on placebo), nausea (25% vs 8%), dizziness (22% vs 7%) and headache (19% vs 9%). The trials had different designs, so don't compare their rates directly.

Those are side effects people reported. When researchers measured dissociation with a rating scale, the label's dissociation warning reports that 61% to 84% of people on Spravato showed some dissociative or perceptual change, and sedation measured the same way appeared in 48% to 61%. Few stopped because of side effects in the short-term trials with an oral antidepressant: 4.6% of adults under 65 with TRD, compared with 1.4% on placebo.

What does dissociation feel like, and how long does it last?

People describe dissociation as feeling disconnected from their body, thoughts or surroundings, or noticing that time, sights or sounds seem different. It is a side effect, not the goal of treatment.

The label describes dissociation as transient, occurring on dosing days. In the TRANSFORM-2 trial, common side effects began shortly after dosing and had resolved by 1.5 hours. If it feels distressing, tell the staff member monitoring you.

What happens to blood pressure after a dose?

Spravato's effect on blood pressure peaks about 40 minutes after the dose and lasts about 4 hours. In the trials summarized in the April 2025 label's blood-pressure warning, 3% to 19% of people on Spravato had a rise of at least 40 mmHg in the top (systolic) number or at least 25 mmHg in the bottom (diastolic) number, compared with 1% to 4% on placebo, within the first 1.5 hours after a dose.

That's why your blood pressure is checked before each dose and again at around 40 minutes. The prescribing information gives 140/90 as a general guide: if your reading before the dose is above that, it advises the prescriber to weigh the short-term risk against the benefit of treating that day, and the dose may be delayed. In SUSTAIN-3, the longest study, average systolic pressure rose about 9.5 mmHg at 40 minutes during the first weeks of treatment, and markedly elevated readings were more common in people with a history of hypertension. Stimulants and MAOI antidepressants can also raise blood pressure, so tell your team if you take either.

What about nausea and vomiting?

Nausea affected 28% and vomiting 9% of people in the label's TRD trials, compared with 9% and 2% on placebo. The label reports that most episodes happened on the day of dosing and resolved the same day, with a median duration of an hour or less for most people. If nausea keeps coming back for you, your care team may discuss options.

What can I do before a session to reduce side effects?

A few steps in the label are aimed directly at the side effects above:

• No food for at least 2 hours before your dose, and no liquids for at least 30 minutes before. This precaution is tied to nausea and vomiting. Can't fast for medical reasons? Ask your team first.
• Use any nasal steroid or decongestant spray at least 1 hour before Spravato.
• Tell your team about benzodiazepines, opioids and alcohol, which can add to sleepiness during the monitoring window.
• Plan for someone to drive you home. You can't drive or operate machinery until the next day, after a restful sleep.

For everything else about the visit itself — scheduling, what the room is like, how the appointment flows — see our walkthrough of what to expect before your first Spravato session.

What is the 2-hour monitoring for?

Spravato is given only in healthcare settings certified in the SPRAVATO REMS, a restricted FDA safety program. You give yourself the nasal spray under the direct supervision of a healthcare provider, and you are monitored for at least 2 hours at every session, until the provider decides you are ready to leave.

During that time, staff watch for:

• Sedation. Loss of consciousness was rare in trials (0.3% to 0.4%).
• Dissociation, which usually fades within the window.
• Breathing. Slowed breathing (respiratory depression) has been reported since approval, including rare cases of respiratory arrest. A REMS update now requires certified settings to keep a pulse oximeter on site.
• Blood pressure, with the recheck around 40 minutes.

MindVibe offers Spravato treatment in REMS-certified settings, and our guide on who may qualify for Spravato covers eligibility.

What do the long-term studies show?

The longest data come from SUSTAIN-3, an extension study that followed 1,148 adults with TRD for an average of 42.9 months, and up to 79 months, totaling 3,777 patient-years. The authors reported "no new safety signals."

• 94.9% had at least one side effect at some point, and 97% of dosing-day side effects resolved the same day.
• 6.4% stopped because of side effects.
• 18.8% had a serious adverse event of any kind during the study.

SUSTAIN-3 was open-label with no control group, so it can't show which events esketamine caused. It also includes only people who stayed on treatment.

Does Spravato affect memory or thinking?

Briefly, yes. In a label study of healthy volunteers, performance dipped about 40 minutes after a single dose and was comparable to placebo by 2 hours.

Over the long term, cognitive testing in the 1-year and 3-year open-label studies "remained stable over time," and SUSTAIN-3 found no clinically meaningful decline in any age group. Those studies had no placebo group.

Can Spravato cause bladder problems?

Long-term misuse or off-label use of ketamine has been linked to severe bladder inflammation called interstitial or ulcerative cystitis. In Spravato studies lasting up to a year, no esketamine-related interstitial cystitis was seen, and SUSTAIN-3 reported no treatment-related interstitial or ulcerative cystitis.

People on Spravato did report more urinary symptoms than people on placebo, such as frequent or urgent urination, pain when urinating, or waking at night to urinate. For how Spravato differs from other ketamine treatments, see Spravato vs ketamine infusions.

Can Spravato be misused?

Yes, and the label says so. Spravato is a Schedule III controlled substance with a Boxed Warning for abuse and misuse. In a lab study of 34 people who used drugs recreationally, "drug liking" scores for Spravato were similar to IV ketamine and higher than placebo. In the clinical trials, no withdrawal symptoms were seen in the 4 weeks after people stopped treatment.

The risk is managed by in-clinic dosing: every dose is taken at the clinic under supervision. A past history of substance use doesn't automatically rule you out, but tell your prescriber so they can weigh it with you.

Who shouldn't take Spravato?

Spravato is approved only for adults 18 and older, for the uses listed in the safety information.

You should not take it if you have:

• Aneurysmal blood-vessel disease (in the brain, chest, abdomen, arms or legs)
• An arteriovenous malformation (an abnormal connection between arteries and veins)
• A history of bleeding in the brain
• An allergy to esketamine, ketamine or any ingredient in the spray

It is not recommended during pregnancy or breastfeeding. The prescriber will also look carefully at any history of psychosis or substance use, heart or blood-vessel conditions, liver problems (moderate impairment may mean longer monitoring) and your other medicines. If another clinician manages your medications, our questions to ask your current prescriber may help.

When should I call my care team?

Call your care team if:

• You have new or worsening depression, unusual changes in mood or behavior, or thoughts of suicide. Antidepressants may increase suicidal thoughts and behaviors in people 24 and younger.
• A side effect lasts past the treatment day or keeps getting worse.
• You notice urinary urgency, pain or frequent urination.
• You've started or changed any other medicine.

Call 911 for chest pain, shortness of breath, a sudden severe headache, sudden vision changes, a seizure or trouble breathing. If you are having thoughts of suicide, call or text 988, the Suicide & Crisis Lifeline. Our article on feeling worse on a new psychiatric medication explains what to report.

Important safety information

Spravato (esketamine) nasal spray, CIII, is a prescription medicine. It's approved for adults with treatment-resistant depression — alone or with an oral antidepressant — and, used with an oral antidepressant, for depressive symptoms in adults who have major depressive disorder with suicidal thoughts or actions. It isn't approved as an anesthetic, and it hasn't been shown to prevent suicide.

Spravato carries a Boxed Warning: it can cause sedation, dissociation — a sense of being disconnected from yourself, your thoughts or your surroundings — and respiratory depression (slowed breathing). After each dose, a healthcare provider monitors you for at least 2 hours. Spravato carries a potential for abuse and misuse. In people 24 and younger, antidepressants may increase suicidal thoughts and behaviors — if you notice new or worsening depression or suicidal thoughts, call your provider right away. Spravato is available only through a restricted program, the SPRAVATO REMS, and it's given solely in certified healthcare settings. Don't drive or operate machinery until the next day — and only after a restful sleep. See the full Prescribing Information, including the Boxed Warning, and the Medication Guide.

To talk with a MindVibe psychiatric clinician about whether Spravato or another depression treatment fits your situation, start with our booking process.

If you are in crisis: call or text 988 to reach the Suicide & Crisis Lifeline, available 24/7, or call 911 or go to the nearest emergency room if you or someone else is in immediate danger.

Sources

• SPRAVATO Prescribing Information, revised April 2025 (FDA) — the source of all label figures cited in this article: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s019lbl.pdf
• SPRAVATO (esketamine) full current Prescribing Information, Janssen Pharmaceuticals / Johnson & Johnson: https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf
• FDA REMS modification letter (pulse oximeter requirement): https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/211243Orig1s013ltr.pdf
• Zaki N et al. Long-term extension study of esketamine in TRD (SUSTAIN-3). Int J Neuropsychopharmacol 2025: https://academic.oup.com/ijnp/article/28/6/pyaf027/8124703
• Popova V et al. Flexibly dosed esketamine nasal spray with a new oral antidepressant (TRANSFORM-2). Am J Psychiatry 2019: https://psychiatryonline.org/doi/10.1176/appi.ajp.2019.19020172

Frequently asked questions

How long do Spravato side effects last?

The common side effects, including dissociation, dizziness, nausea and sleepiness, usually begin soon after the dose and fade the same day. In the TRANSFORM-2 trial the most common ones had resolved by 1.5 hours, and in the long-term SUSTAIN-3 study 97% of dosing-day side effects resolved that day. Blood pressure increases last about 4 hours. You stay at the clinic for at least 2 hours, until a provider decides you are ready to leave.

Can I drive after a Spravato treatment?

No. Per the prescribing information, you shouldn't drive or operate machinery until the next day, after a restful sleep — so arrange for someone to drive you home after every session. In a label driving study, lane-keeping 18 hours after a single 84 mg dose was similar to placebo.

Why do I have to stay at the clinic for 2 hours after my dose?

Spravato is given only in healthcare settings certified in the SPRAVATO REMS, a restricted FDA safety program, and monitoring for at least 2 hours is part of it. During that window, staff watch for sedation, dissociation, slowed breathing and the blood pressure rise that peaks around 40 minutes after the dose. You leave when the provider decides you are ready, not automatically at the 2-hour mark.

What happens if my blood pressure is high before my dose?

Your blood pressure is checked before every dose. The prescribing information gives 140/90 as a general guide: if your reading is above that, it advises the prescriber to weigh the short-term risk of a further rise against the benefit of treating that day, and the dose may be delayed. If you do receive the dose, your pressure is rechecked at around 40 minutes, when the effect peaks.

Does Spravato affect memory long term?

Thinking dips briefly after a dose: in a study of healthy volunteers, performance declined about 40 minutes after dosing and was comparable to placebo by 2 hours. In the 1-year and 3-year open-label studies, cognitive testing remained stable over time, and the SUSTAIN-3 extension found no clinically meaningful decline in any age group. Those studies had no placebo group, so they offer reassurance rather than proof.

Can Spravato cause bladder damage like street ketamine?

Severe bladder inflammation has been linked to long-term misuse or off-label use of ketamine. In Spravato studies lasting up to a year, no esketamine-related interstitial cystitis was seen, and the multi-year SUSTAIN-3 study reported none related to treatment. Urinary symptoms such as urgency, frequent urination or pain were more common than on placebo, so tell your care team if you notice them.

Can I take my other medicines on a treatment day?

Tell your care team about everything you take. Use any nasal steroid or decongestant spray at least 1 hour before your dose. Benzodiazepines, opioids and alcohol can add to sleepiness, and stimulants and MAOI antidepressants can raise blood pressure, so your team may monitor you more closely. Don't stop or change a prescribed medicine on your own.

This article is for educational purposes only and is not medical advice, a diagnosis, or a treatment recommendation. Talk with your own clinicians before making any change to your care.