SPRAVATO® Side Effects: Common, Serious, and Long-Term

SPRAVATO side effects: what to expect and when to act

Most common SPRAVATO side effects begin during or soon after a supervised treatment session and usually resolve the same day. The current U.S. label lists feeling disconnected, dizziness, nausea, sleepiness, a spinning sensation, numbness, anxiety, low energy, increased blood pressure, vomiting, feeling drunk, and headache among the common effects. At least two hours of onsite monitoring are required because sedation, dissociation, breathing problems, and blood-pressure increases can be serious. Even if you feel better before leaving, do not drive until the next day after a restful sleep.

SPRAVATO side-effect rates: what the label's numbers show

These figures come from the pooled short-term trials in the current U.S. prescribing information (revised March 2026), which compared SPRAVATO plus an oral antidepressant against placebo nasal spray plus an oral antidepressant. Read the full label on DailyMed.

Dissociation: 41% with SPRAVATO versus 9% with placebo nasal spray.
Dizziness: 29% versus 8%. Nausea: 28% versus 9%.
Sedation: 23% versus 9%. Vertigo: 23% versus 3%.
Blood pressure: across trials, 3%–19% of SPRAVATO patients had a rise of at least 40 mmHg systolic or 25 mmHg diastolic in the first hour and a half after dosing, versus 1%–4% with placebo spray, during the first four weeks of treatment.
Dissociative or perceptual changes measured on a symptom scale occurred in 61%–84% of SPRAVATO-treated patients across trials.
Stopping because of side effects: 4.6% of SPRAVATO patients under 65 discontinued short-term treatment for adverse events versus 1.4% with placebo spray; during maintenance treatment the rates were 2.6% versus 2.1%.
Staying well: in the maintenance study, stable remitters who continued SPRAVATO with an oral antidepressant relapsed at about half the rate of those switched to placebo spray (hazard ratio 0.49; 95% CI 0.29–0.84).

Two readings of the same tables are both true: most patients notice at least one of these effects, and few stop treatment because of them. Bring the numbers to the prescriber and ask which ones matter most for your health history.

Sort the symptom by the action it requires

A symptom list alone leaves the hardest question unanswered: what should you do with the information? Use these three groups to prepare, then follow the treatment center's instructions for your specific health history.

Common does not mean “ignore it”

Feeling disconnected, dizzy, nauseated, sleepy, numb, anxious, low on energy, or “drunk” can occur. Headache, vomiting, vertigo, and a temporary blood-pressure rise are also on the label's common list.

Tell onsite staff what you feel and when it started.
Do not decide on your own that monitoring can end early.
Ask what would change the next dose or monitoring plan.

Contact the treatment team

Report an effect that is new, worsening, lasts longer than the plan described, or interferes with thinking, memory, urination, sleep, or ordinary function after the treatment day.

If a concern can safely wait, contact the treatment team when the office reopens.
Report urinary urgency, frequency, pain, or nighttime urination.
Do not start, stop, or change another medicine based on this page.

Get urgent or emergency help

The Medication Guide says to tell a healthcare provider right away about chest pain, shortness of breath, a sudden severe headache, a change in vision, or a seizure after SPRAVATO.

Call 911 for immediate danger or a medical emergency.
Call or text 988 for U.S. crisis support.
Do not wait for a scheduled treatment visit if safety is at risk.

SPRAVATO treatment-day safety map

The treatment-day plan begins before the nasal spray and continues after discharge. Bring this sequence to the center and ask what its written instructions add for you.

What the certified center checks

Stage	What the current label requires or advises	Your task
Before the dose	The center checks blood pressure. Because nausea and vomiting can occur, the label advises no food for at least two hours and no liquids for at least 30 minutes before treatment. Nasal corticosteroids or decongestants used that day are taken at least one hour before the dose.	Confirm the center's instructions, current medicines, transportation home, and what to do after leaving. Do not fast longer or change a medicine unless the treating team tells you to.
During and after dosing	Respiratory status is monitored for at least two hours, including pulse oximetry. Blood pressure is reassessed at about 40 minutes and later when clinically warranted. Staff also watch for sedation and dissociation.	Describe every new sensation, breathing change, pain, anxiety, or change in awareness. Ask what is being checked; do not use another patient's experience to judge your discharge readiness.
Leaving and the next day	The healthcare provider decides when you are clinically stable enough to leave. The label says not to drive, operate machinery, or do another hazardous activity until the next day after a restful sleep.	Use the arranged ride. Keep the written symptom and emergency plan. Contact the center when it reopens about a non-emergency effect that persists, worsens, or does not match what the team told you to expect. Use emergency services for a medical emergency rather than waiting for the office.

The day after SPRAVATO treatment

The label separates two timelines that patients often merge. Most common effects begin shortly after dosing and resolve the same day: in the trials, nausea and vomiting mostly resolved on the treatment day, and cognitive performance that declined about 40 minutes after a dose in healthy volunteers was comparable with placebo at two hours.

The driving restriction runs on the second timeline. Do not drive, operate machinery, or do another hazardous activity until the next day after a restful sleep, even when you feel normal at discharge. An effect still present the next morning—grogginess, dizziness, urinary symptoms, or trouble thinking—is worth a call to the treatment team, because the label expects the common effects to clear on the treatment day.

What the label can and cannot answer about long-term effects

“Long term” can mean a symptom that continues after one session, a change that appears during maintenance treatment, or a risk after months or years. Those questions do not have one yes-or-no answer.

Cognition: the March 2026 label says cognitive performance declined 40 minutes after one dose in healthy volunteers and was comparable with placebo at two hours. In one-year and three-year open-label SPRAVATO studies, cognitive test performance remained stable over time. Open-label data do not prove that every person is free of persistent cognitive symptoms.
Bladder and urinary symptoms: lower urinary-tract symptoms occurred more often with SPRAVATO than placebo in clinical studies. The label says no esketamine-related interstitial cystitis occurred in studies lasting up to one year, and it still directs clinicians to monitor urinary and bladder symptoms.
Ketamine is not a substitute comparison: the label discusses cognitive and bladder harms reported with repeated ketamine misuse or abuse. That is a safety signal worth understanding, but it is not evidence that supervised SPRAVATO and nonmedical ketamine exposure have identical risks.

Ask the prescriber what it will track during maintenance treatment, how benefit is weighed against side effects, and what symptom would prompt a dose, schedule, or treatment-plan review. Do not stop a prescribed treatment based only on a search result.

How long should maintenance continue, and when can treatment stop?

The FDA label does not set one stop date or maximum treatment duration. It calls for the least frequent dosing schedule that maintains response or remission. Salvatore G. Savatta, MD's clinical review recommends at least six months of continuation after meaningful improvement before a supervised stop is considered. That is clinical guidance, not a fixed FDA rule; the decision remains individual.

Continuation lowered relapse in a randomized trial: among stable remitters, continued SPRAVATO plus an oral antidepressant reduced relapse risk by 51% compared with switching to placebo spray (hazard ratio 0.49; number needed to treat 6). Among stable responders who had not reached remission, the reduction was 70% (hazard ratio 0.30; number needed to treat 4).
Stopping can reveal early vulnerability: 19 of 39 relapses among stable remitters switched to placebo occurred in the first month; 11 of those 19 people had needed weekly dosing before randomization. The trial authors interpreted this as greater relapse vulnerability, not a distinct withdrawal or rebound syndrome.
Duration depends on relapse risk: a 2026 European expert consensus placed continuation in the 6–9 months after remission and considered a supervised stop after 6–12 months of stable clinical and functional recovery. Residual symptoms, repeated episodes, worsening when frequency is reduced, and the consequences of relapse may support treatment beyond 12 months.
Long-term data are reassuring but not definitive: the open-label SUSTAIN-3 extension followed 1,148 participants for an average of 42.9 months, with some exposure lasting 79 months. No new safety signal appeared, but a single-arm extension cannot prove the right duration for one person.

A stop plan should be shared with the prescriber, usually after testing whether a less frequent schedule maintains stability. It should name the symptoms and day-to-day changes that signal relapse, the follow-up schedule, and what treatment will be reconsidered if symptoms return. Do not reduce frequency or stop SPRAVATO based on this page.

Does SPRAVATO cause weight gain?

Weight gain is not listed among the adverse reactions in the current SPRAVATO prescribing information. That absence is worth stating plainly, because weight is one of the most common reasons people abandon depression treatment. Oral antidepressants taken alongside SPRAVATO, appetite changes from depression itself, and activity changes can each move weight—so track it with the prescriber and identify the actual cause before changing any treatment.

If the stories you read online sound frightening

Accounts of intense dissociation are consistent with the label, not proof that something went wrong: dissociative or perceptual changes occurred in 61%–84% of SPRAVATO-treated patients across trials, which is exactly why every dose happens under supervision with at least two hours of monitoring. What frightening stories usually leave out is the base rate for quitting—4.6% of patients under 65 stopped short-term treatment because of adverse events. Most people who start supervised treatment continue it.

Be careful transferring stories across settings. Reports about at-home compounded ketamine, recreational ketamine, or unsupervised use describe different products, doses, and oversight. FDA has issued risk alerts specifically about compounded ketamine used for psychiatric disorders; an unsupervised product's risks are not a preview of a REMS-certified, monitored SPRAVATO session.

Five answers to get before the first treatment

1. What would make you delay today's dose?

Ask how the center uses baseline blood pressure, current symptoms, new medicines, and health changes in its decision. A page cannot calculate that risk for you.

2. What will you monitor, and when can I leave?

Confirm pulse oximetry, blood-pressure checks, sedation and dissociation monitoring, the minimum observation period, and the clinical-stability decision.

3. Which effects should I report before the next visit?

Get a written answer for persistent dizziness or nausea, thinking or memory changes, urinary symptoms, mood changes, and any center-specific concern tied to your health history.

4. What if something happens after the office closes?

A non-emergency concern that can safely wait goes to the treatment team when the office reopens. A medical emergency goes to 911 or an emergency department; an immediate mental-health crisis goes to 988 or 911. A webpage cannot decide which category a new symptom belongs in.

5. How will we decide whether treatment remains worth it?

Agree on symptom, function, tolerability, and safety measures. The label calls for evaluating benefit after the four-week induction phase before deciding whether continued treatment is appropriate.

Who reviewed this page, and what that covers

Salvatore G. Savatta, MD (Psychiatry), the platform's Clinical Review Lead, reviewed and approved this exact revision on September 1, 2026. His review corrected the after-hours guidance and added the maintenance and discontinuation guidance above. He is the sole clinical reviewer credited for this page.

The current FDA label, randomized relapse-prevention trial, final SUSTAIN-3 extension, and 2026 expert consensus are linked below. Their limits are stated where they affect a treatment decision. How reviews, updates, and corrections work is documented in the editorial policy.

What SPRAVATO is

SPRAVATO is a prescription esketamine nasal spray with FDA-labeled uses for certain adults with depression. For treatment-resistant depression, it may be prescribed alone or with an oral antidepressant.

A qualified prescriber must determine whether the diagnosis, prior treatment, current medications, blood pressure, substance-use risk, pregnancy considerations, and safety profile fit the labeled treatment pathway.

How SPRAVATO may help after other antidepressants

SPRAVATO offers an evidence-based option for adults with treatment-resistant depression when at least two adequate antidepressant trials have not helped enough.

In the current prescribing information, a controlled four-week monotherapy study found statistically greater improvement in depression-rating scores with both studied SPRAVATO doses than with placebo. The treatment difference was present at about 24 hours and remained through Day 28. A separate maintenance study found that patients who had reached stable remission or response and continued SPRAVATO with an oral antidepressant stayed well longer before relapse than patients switched to placebo nasal spray with an oral antidepressant.

Those results support real optimism without promising the same outcome for everyone. The useful question is whether symptoms and day-to-day functioning improve enough to justify continuing treatment for that individual.

What improvement should the plan measure

The goal is a meaningful reduction in depressive symptoms and better daily functioning—not a particular sensation during the monitored treatment session.

Before treatment, ask the center how it will record a baseline and measure change in mood, interest, energy, sleep, concentration, safety, and everyday function. The current label calls for evaluating therapeutic benefit at the end of the four-week induction phase before deciding whether continued treatment is worthwhile.

How a supervised treatment day supports the plan

The nasal spray is self-administered under a healthcare professional's supervision, giving the patient and clinical team a structured visit to assess response, tolerability, and next steps together.

The current prescribing information describes risks including sedation, dissociation, respiratory depression, blood-pressure increases, and abuse or misuse. Patients are monitored for at least two hours after administration, need transportation home, and should not drive or operate machinery until the next day after a restful sleep.

How the schedule may change over time

For treatment-resistant depression, the labeled schedule becomes less frequent after the initial four weeks when continued treatment is appropriate.

The label describes twice-weekly treatment during Weeks 1 through 4, once-weekly treatment during Weeks 5 through 8, and then once weekly or every two weeks from Week 9 onward. The prescriber individualizes dose and frequency to the least frequent schedule needed to maintain response or remission.

What to ask a treatment center

Confirm REMS certification, psychiatric oversight, monitoring, transportation rules, insurance requirements, and how the center coordinates the rest of your depression care.

Who confirms the diagnosis and decides whether SPRAVATO fits?
Is this location certified under the SPRAVATO REMS?
What happens during the monitoring period, and who responds if symptoms worsen?
How are other medications, psychotherapy, and follow-up coordinated?
What does insurance require, and what out-of-pocket costs should I expect?

A critical safety distinction

SPRAVATO has not been shown to prevent suicide or replace hospitalization when hospitalization is clinically warranted.

Urgent suicidal thoughts, an immediate plan, or danger to self or others require crisis or emergency care. A scheduled outpatient treatment visit is not a substitute for that response.

Common questions

Questions patients and families ask

What are the most common SPRAVATO side effects?

The current U.S. label lists dissociation or feeling disconnected, dizziness, nausea, sleepiness, vertigo, numbness, anxiety, low energy, increased blood pressure, vomiting, feeling drunk, and headache among common effects. Tell onsite staff what you feel and when it begins, even when an effect is common.

How long do common SPRAVATO side effects last?

The Medication Guide says common effects usually begin right after treatment and go away the same day. Contact the treatment team about an effect that persists, worsens, or does not match the center's instructions. Same-day improvement does not remove the next-day driving restriction.

How will I feel the day after SPRAVATO?

The label expects the common effects to resolve on the treatment day: nausea and vomiting mostly resolved the same day in trials, and cognitive performance that declined about 40 minutes after dosing in healthy volunteers was comparable with placebo at two hours. The driving restriction still runs until the next day after a restful sleep, and any effect that continues into the next morning should be reported to the treatment team.

Is weight gain a listed SPRAVATO side effect?

No. Weight gain does not appear among the adverse reactions in the current SPRAVATO prescribing information (revised March 2026). Oral antidepressants taken alongside SPRAVATO, appetite changes from depression itself, and activity changes can all affect weight, so discuss any weight change with the prescriber instead of assuming the cause.

Why does SPRAVATO monitoring last at least two hours?

Sedation, dissociation, respiratory depression, and blood-pressure increases can be serious. The certified center monitors respiratory status, including pulse oximetry, reassesses blood pressure at about 40 minutes and later when warranted, and decides when the patient is clinically stable enough to leave.

When can I drive after SPRAVATO?

Do not drive, operate machinery, or perform another hazardous activity until the next day after a restful sleep. Arrange transportation home before treatment and follow the center's discharge instructions.

What does the label say about long-term cognitive and urinary effects?

The March 2026 label reports stable cognitive test performance in one-year and three-year open-label SPRAVATO studies, but those data do not prove that every person is free of persistent symptoms. Lower urinary-tract symptoms occurred more often with SPRAVATO than placebo, so clinicians are directed to monitor urinary and bladder symptoms during treatment.

How long should SPRAVATO continue after symptoms improve?

The FDA label does not set one stop date or maximum duration. It calls for the least frequent schedule that maintains response or remission. Salvatore G. Savatta, MD's clinical review recommends at least six months of continuation after meaningful improvement before a supervised stop is considered; longer treatment may fit people with residual symptoms, prior recurrences, or a high consequence of relapse.

Primary sources

Review the evidence directly

Source links support education, not a personal treatment recommendation. Exact candidacy and risk must be assessed by a qualified clinician.