Most Spravato (esketamine) side effects resolve within two hours of taking a dose, and nearly all clear by the end of the same day. The most common effects, including dissociation, drowsiness, dizziness, and nausea, are temporary and tied directly to each treatment session rather than building up over time.
The First Two Hours After a Dose
Side effects typically peak around 40 minutes after you use the nasal spray, then fade over the next hour or so. Dissociation, that feeling of being detached from your body or surroundings, is reported by roughly 25 to 31% of patients during early treatments. It almost always resolves within two hours. In a long-term safety study called SUSTAIN-3, 99.8% of all dissociation events started and resolved on the same day as dosing. The rare cases that lingered beyond that day cleared within two days.
Sedation follows a similar pattern. Over 99% of drowsiness events in the same study resolved on dosing day. This is why your provider monitors you for at least two hours after each session before letting you leave the clinic.
Blood Pressure Changes Last Longer
Spravato causes a temporary spike in blood pressure that peaks around 40 minutes after administration and can last approximately four hours. This is the longest-lasting acute side effect for most people. Your blood pressure is checked before your dose and again during the monitoring period. If you already have high blood pressure or cardiovascular concerns, your provider will watch this closely.
Nausea and Stomach Discomfort
Nausea and vomiting are common, particularly during your first few sessions. When they occur, they typically start right after dosing and go away the same day. You can reduce the chance of nausea by not eating for at least two hours before your appointment and avoiding liquids for at least 30 minutes beforehand.
Side Effects Get Milder Over Time
One of the more reassuring patterns with Spravato is that side effects tend to decrease with repeated treatments. The most intense effects usually happen during the first two sessions. After that, both the frequency and severity drop noticeably. Dissociation rates fall from around 25 to 31% during early treatment to roughly 10 to 15% with continued dosing. Severe dissociation events in the SUSTAIN-3 study occurred only during the initial induction phase and generally resolved within 90 minutes.
This doesn’t mean side effects disappear entirely for everyone, but many patients find the experience becomes more predictable and manageable as they continue treatment.
How Long Before You Can Drive or Work
You cannot drive, operate machinery, or do anything requiring full alertness on the day you receive Spravato. The restriction lasts until the following day, after a full night of restful sleep. This means treatment days are essentially half-days at minimum. Most people plan their sessions around this, scheduling them on days when they can go home and rest afterward. Someone else needs to drive you home from the clinic.
Long-Term and Lasting Effects
The long-term safety data from the SUSTAIN-3 study, which followed patients through extended maintenance treatment, did not reveal new safety concerns beyond the acute side effects described above. The same types of side effects that appear early in treatment (dissociation, sedation, dizziness, nausea) are the ones that continue to show up during maintenance, just less often and less intensely.
Each treatment session essentially resets the clock on side effects. You experience them, they clear, and you’re back to your baseline. There is no evidence that these effects accumulate or worsen with prolonged use at the doses and frequencies used in clinical settings.