Most Spravato side effects begin during the dose and fade before you go home. In the FDA trials, dissociation affected 41 percent of patients, dizziness 29 percent, and nausea 28 percent. Serious risks exist too. That’s why every dose is given in a certified clinic, with 2 hours of monitoring afterward.
This guide walks through the real numbers from the prescribing information, how long each effect tends to last, and what our Richmond team does during a treatment session to keep you steady.
What Are the Most Common Spravato Side Effects?
Spravato is an esketamine nasal spray approved for treatment resistant depression. Because it acts on the NMDA receptor rather than on serotonin, its side effect profile looks nothing like the profile of traditional antidepressants.
The FDA prescribing information lists adverse reactions from 346 adults who took Spravato plus an oral antidepressant, compared with 222 who took a placebo nasal spray plus an oral antidepressant. We compared the two columns below, because the placebo column is what makes the medication column readable.
| Side effect | Spravato plus oral antidepressant | Placebo nasal spray plus oral antidepressant |
|---|---|---|
| Dissociation | 41% | 9% |
| Dizziness | 29% | 8% |
| Nausea | 28% | 9% |
| Sedation | 23% | 9% |
| Vertigo | 23% | 3% |
| Headache | 20% | 17% |
| Altered taste | 19% | 14% |
| Numbness in mouth or throat | 18% | 2% |
| Anxiety | 13% | 6% |
| Raised blood pressure | 10% | 3% |
| Vomiting | 9% | 2% |
| Feeling drunk | 5% | 0.5% |
Two details make that table easier to read. Every rate covers reactions that appeared in at least 2 percent of patients and more often than on placebo, so mild complaints that matched placebo aren’t listed. The label also groups related terms, meaning dissociation covers everything from altered time perception to ringing in the ears.
That first column looks scary until you read the placebo column beside it. Headache and altered taste barely separate from placebo. But dissociation, numbness, and vertigo? Those clearly belong to the medication.
Two of the common side effects deserve a plain-language translation. Dissociation means a sense of distance from yourself or the room, sometimes with distorted time or sound. Hypoesthesia, listed above as numbness, usually shows up as a dead feeling in the mouth, teeth, or throat from the spray itself.
How Long Do Spravato Side Effects Last?
Short answer: the day of the dose, and usually less than that.
Nausea and vomiting occurred on dosing day and resolved the same day in the clinical trials, with a median duration under 1 hour in most patients across sessions. Dissociation was described in the label as transient, appearing on the treatment day only. Sedation follows the same arc.
Blood pressure runs on its own clock. Increases peak around 40 minutes after the dose and last roughly 4 hours. Mean placebo-adjusted rises were about 7 to 10 mmHg systolic and 4 to 6 mmHg diastolic at 40 minutes, then 2 to 5 mmHg systolic by 1.5 hours.
Taste changes deserve a mention because they surprise people. Dysgeusia, the label’s term for a distorted sense of taste, was reported by 19 percent of patients, and numbness in the mouth or throat by 18 percent. Both come from the spray landing on nasal and throat tissue, and both clear within the visit.
Cognitive fog is brief as well. In a study of healthy volunteers, one dose slowed cognitive performance at 40 minutes, but performance matched placebo again by 2 hours. Sleepiness matched placebo by 4 hours.
Here’s the encouraging part, and our patients in Richmond, VA notice it. Thankfully, reported nausea and vomiting dropped across dosing sessions from the first week onward, and kept dropping with longer treatment. Week 1 is often the roughest week you will have.
Why Do You Stay 2 Hours After a Spravato Dose?
Look, the 2-hour rule isn’t clinic policy. The label requires that patients be “monitored by a healthcare provider for at least 2 hours at each treatment session”, and it exists because of three specific risks: sedation, dissociation, and slowed breathing.
Sedation is measured in trials with a scale called the MOAA/S. In a fixed-dose study, 50 percent of patients on 56 mg and 61 percent on 84 mg showed some sedation, against 11 percent on placebo. Loss of consciousness was rare, at 0.3 to 0.4 percent of Spravato treated patients.
Dissociation is measured with the CADSS scale. Rates ran from 61 to 84 percent depending on the study and dose, against 5 to 16 percent on placebo. Higher doses produced more of it.
So the monitoring window covers the hours when those effects peak. Your team watches your breathing with pulse oximetry, checks blood pressure at about 40 minutes, and then decides when you are steady enough to leave. If your readings are still climbing, you stay longer. You aren’t rushed out at the 2-hour mark for the sake of the clock.
What Does the Spravato Boxed Warning Cover?
Every Spravato Medication Guide carries a boxed warning, the strongest warning the FDA issues. It covers four things.
- Sedation, including diminished breathing in some patients.
- Dissociation and perceptual changes during and after the dose.
- Abuse and misuse, since esketamine is a Schedule III controlled substance.
- Suicidal thoughts and behaviors, a warning shared across antidepressant medication labels.
We know how that list reads. Four serious-sounding risks in a row, and you’re being asked to sign up anyway. Fair enough. The fourth item confuses patients most, so here’s the precise version. Pooled antidepressant trials covering roughly 77,000 adults and 4,500 pediatric patients found more suicidal thoughts and behaviors in people aged 24 and under, and fewer in adults aged 25 to 64. Spravato has not been shown to prevent suicide on its own. Put another way, it treats the depression, not the emergency. It sits inside a wider mental health treatment plan, alongside therapy and a safety plan, rather than replacing either.
Because of these risks, esketamine treatment runs under a restricted program called the Spravato REMS, short for risk evaluation and mitigation strategy. Clinics must be certified, pharmacies must be certified, and patients treated in an outpatient office must be enrolled. You cannot take the spray home.
Which Spravato Side Effects Are Serious?
Most reactions are uncomfortable rather than dangerous. A few deserve real attention.
We’d rather write “this part is safe” and move on. The label doesn’t allow it, so here’s the short list of what to actually watch for.
Raised blood pressure. Roughly 3 to 19 percent of Spravato treated patients had a rise of at least 40 mmHg systolic or 25 mmHg diastolic. That happened within the first 1.5 hours, at least once during the first 4 weeks. A large jump can happen at any session, even after mild ones before it. Which is unsettling, honestly, and worth naming rather than glossing over. Chest pain, breathlessness, sudden severe headache, or vision changes after a dose mean emergency care, not a wait-and-see.
Respiratory depression. Slowed breathing has been reported after approval, with rare reports of respiratory arrest. Pulse oximetry during the monitoring window exists for this reason.
Bladder symptoms. Ulcerative or interstitial cystitis has been reported with long-term ketamine misuse. In the Spravato studies, patients reported more urinary frequency, urgency, and painful urination than placebo patients, though no esketamine-related interstitial cystitis appeared in trials that ran up to a year. Report burning or urgency early. Pollakiuria, the medical term for needing to urinate often, showed up in 3 percent of Spravato patients against 0.5 percent on placebo.
Allergic reaction. Spravato is contraindicated if you are hypersensitive to esketamine, ketamine, or any ingredient in the spray.
Adverse effects severe enough to stop treatment were uncommon. In short-term studies of adults under 65, 4.6 percent of patients discontinued because of an adverse reaction, against 1.4 percent on placebo. Anxiety led that list at 1.2 percent.
How Do You Lower the Risk on Treatment Day?
Small habits change how a treatment session feels. And the label asks for some of them directly.
- Skip food for at least 2 hours before your dose, which cuts the nausea risk.
- Stop drinking liquids 30 minutes before.
- Take any nasal steroid or decongestant at least 1 hour ahead of the spray.
- Arrange your ride before the appointment, since driving waits until the next day.
- Bring headphones or a podcast, because a quiet distraction settles most people.
- Tell your provider about every medication you take, including sleep aids.
Drug interactions matter more than patients expect. Benzodiazepines, opioids, and alcohol deepen sedation. Stimulants such as amphetamines or modafinil raise blood pressure further, as do MAOIs. Severe liver disease matters too, because hepatic impairment changes how your body clears the drug, and there is no clinical experience with severe impairment.
Our team reviews that list at the start of every course of Spravato treatment. In our experience the two problems we head off most often at the Richmond, VA clinic are a missing ride home and a forgotten breakfast.
How Do Spravato Side Effects Compare With Antidepressant Pills?
Patients who’ve spent years on conventional antidepressants often expect a similar experience, and it isn’t one.
A daily pill spreads its adverse effects thin. Nausea, sleep changes, weight change, and sexual side effects arrive quietly, stay for weeks or months, and get managed with dose tweaks. The antidepressant effect builds slowly on the same timeline, which is why a fair trial of traditional antidepressants runs 4 to 8 weeks before anyone judges it.
Spravato does the opposite. It packs its side effects into a supervised 2-hour window twice a week during induction, then tapers that frequency down. Between sessions, there’s no daily dose to feel. You’re not carrying dizziness or dissociation around with you on a Tuesday afternoon.
That trade has real consequences for daily life. Twice-weekly clinic visits of 2 to 3 hours each are a heavy month, and you lose driving for the rest of each treatment day. Against that, esketamine treatment acts on the NMDA receptor and mood regulation pathways rather than serotonin, which gives some patients a response after conventional antidepressants have failed them.
One more difference matters for anyone tracking their own mental health. Because Spravato is a nasal spray given under observation, a nurse sees your reaction each time. With a pill at home, a side effect gets noticed when you happen to mention it at your next visit, sometimes weeks later.
Neither pattern is better in the abstract. If you’re weighing a fifth antidepressant medication against esketamine, the honest comparison is between a slow, quiet risk and a short, watched one.
What If a Spravato Side Effect Is Too Much to Handle?
Tell your care team, and tell them during the session rather than afterward. Actually, scratch that. Tell them the moment you notice it, even mid-dose. Most reactions have a straightforward answer.
Dose reduction is the first lever. The label allows 56 mg or 84 mg, and dropping a step is a normal move. In one study of patients with acute suicidal ideation, about 19 percent of patients had their dose cut from 84 mg to 56 mg because they couldn’t tolerate the higher one.
Nausea usually responds to the food and liquid rules, and it fades across sessions anyway. Patients who feel nervous before a dose respond to a calmer room, familiar staff, and a clear description of what’s about to happen. Blood pressure that runs high before the spray may mean delaying that session rather than pushing through.
Missing a session isn’t a crisis either. If your depressive symptoms are stable, the label says to continue the current schedule. If symptoms worsen after missed doses during maintenance, your provider may step back to the previous, more frequent schedule.
Long-term safety data offers some reassurance here. Across the completed phase 3 studies, 479 patients received at least 6 months of Spravato treatment and 178 received at least 12 months. In 1-year and 3-year open-label trials, cognitive function stayed stable on formal testing. Sense of smell showed no difference against placebo.
Discontinuation because of an adverse reaction was also uncommon during longer treatment. In the maintenance phase of a long-term study, 2.6 percent of Spravato patients stopped for that reason, against 2.1 percent on placebo nasal spray.
Who Should Not Take Spravato?
The label rules out three groups entirely. Spravato is contraindicated in patients with aneurysmal vascular disease, in patients with a history of bleeding in the brain, and in anyone hypersensitive to esketamine or ketamine.
Other health conditions call for a careful look rather than a flat no. Heart and blood vessel disease, a history of hypertensive encephalopathy, psychosis, and a history of substance misuse all change the risk calculation. Pregnancy is a separate conversation, since Spravato is not recommended during pregnancy.
One note on access before that. Spravato has to be given in a certified clinic, so it runs from our Richmond, VA office. The Dallas, Texas, Decatur, Georgia, and American Fork, Utah clinics offer psychiatry and medication management instead. Where esketamine is a poor fit, other options remain. TMS therapy uses magnetic pulses instead of medication and carries a different risk profile. A change of oral antidepressant, or an added one, may still have room to work. Your provider weighs all of it during a psychiatric evaluation.
More Questions About Spravato Side Effects
Does Spravato feel like IV ketamine therapy?
Patients who have tried both often describe a milder, shorter experience with the nasal spray. Dosing is fixed by the label, the setting is certified, and the monitoring is standardized, which is not true across IV ketamine clinics.
Will the side effects stop me from working?
Plan on losing the rest of the day, especially early on. Most patients return to normal activity the next morning after a full night of sleep. Two subjects in a driving study stopped the test at 8 hours post-dose, which is exactly why the label sets a next-day rule.
Do side effects mean the medication is working?
No. Dissociation intensity has not been shown to predict who improves. Some patients feel very little during a session and still see depressive symptoms ease.
What should I report between visits?
Call about new urinary symptoms, ongoing anxiety, worsening depression symptoms, or any thought of self-harm. Also call if a home blood pressure reading looks unusually high.
Key Takeaways
- Dissociation, dizziness, nausea, and sedation are the most common Spravato side effects, at 41, 29, 28, and 23 percent in the trials.
- Nearly all of them begin during the dose and clear the same day.
- Blood pressure peaks near 40 minutes and settles over about 4 hours.
- The boxed warning covers sedation, dissociation, abuse and misuse, and suicidal thoughts.
- Monitoring for at least 2 hours is a label requirement under the Spravato REMS, not a clinic preference.
- Only 4.6 percent of patients stopped treatment because of an adverse event in short-term studies.
- Skipping food for 2 hours and liquids for 30 minutes lowers nausea.
- Severe hypertension symptoms, slowed breathing, or bladder pain need prompt medical attention.
- Nausea and vomiting reports fell across sessions, so week 1 is often the hardest.
Talk With Foundation Medical Group in Richmond
Reading a list of adverse reactions can be unsettling, particularly when you’re already worn down by severe depression. Our physician-led team in Richmond, Virginia will walk you through your own risk, check your blood pressure history, and say plainly whether Spravato nasal spray fits your situation. If it doesn’t, we’ll tell you that too.
Learn more about how Spravato works, what Spravato costs, and whether insurance covers it. When you’re ready, our Richmond Spravato team will take it from there.