SPRAVATO can cause dissociation, dizziness, nausea, sedation, vertigo, numbness, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk, and headache. Serious risks include sedation, dissociation, respiratory depression, abuse or misuse, and suicidal thoughts or behaviors.
SPRAVATO® is a prescription esketamine nasal spray used for specific depression indications in adults. Esketamine is related to ketamine, but SPRAVATO is not the same as racemic ketamine nasal spray.
Understanding both expected SPRAVATO side effects and medically important warning signs helps patients know what may occur during treatment. Most acute effects occur around the treatment session, while cognition, urinary symptoms, and longer-term tolerability require separate context.
The current U.S. prescribing information, revised in March 2026, identifies dissociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk, and headache among common adverse reactions in treatment-resistant depression.
The following overview shows how the main SPRAVATO side effects differ.
| Side effect | What it may feel like | Typical context | Why it matters |
| Dissociation | Feeling detached from yourself, surroundings, thoughts, or time | Around treatment | Requires clinical observation |
| Sedation | Sleepiness or reduced alertness | After dosing | Affects alertness and driving |
| Dizziness | Lightheadedness or unsteadiness | Around treatment | Can affect balance |
| Vertigo | Spinning or movement sensation | Around treatment | Differs from general dizziness |
| Nausea or vomiting | Stomach upset or vomiting | Often on the dosing day | Affects treatment tolerability |
| Increased blood pressure | Often no noticeable sensation | Peaks during post-dose monitoring | Requires blood-pressure checks |
| Other reactions | Headache, anxiety, numbness, lethargy, feeling drunk | Around treatment | Requires symptom-specific interpretation |
SPRAVATO adverse-event rates vary by study, indication, dose, age, and whether treatment is used alone or with an oral antidepressant. One study percentage should therefore not be treated as a universal rate.
What Are the Most Common Spravato Side Effects?
The most common SPRAVATO side effects include dissociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk, and headache.
The current U.S. label defines common adverse reactions within specific clinical-trial populations. The label uses a threshold of at least 5% incidence and at least twice the placebo rate for its highlighted common reactions.
In one short-term treatment-resistant depression study using SPRAVATO with an oral antidepressant, dissociation occurred in 41% versus 9% with placebo. Dizziness occurred in 29% versus 8%, while nausea occurred in 28% versus 9%. These percentages apply to that specific study population.
What Does Spravato Dissociation Feel Like?
SPRAVATO dissociation is a temporary perceptual change that can make you feel detached from yourself, your thoughts, surroundings, body, or sense of time.
Dissociation can include derealization and depersonalization. Derealization describes surroundings feeling unreal or altered. Depersonalization describes feeling detached from yourself.
SPRAVATO studies also assessed perceptual changes such as altered time or space perception and illusions. Clinical-trial assessments found dissociative or perceptual changes in 61% to 84% of SPRAVATO-treated patients in the specified studies.
MedlinePlus describes dissociation in patient language as feeling disconnected from your body, thoughts, emotions, space, or time.
Dissociation is not the same as sedation. Dissociation changes perception and connectedness, while sedation primarily affects alertness.
Dissociation is also not the same as dizziness. Dizziness primarily describes lightheadedness, unsteadiness, or balance-related sensations.
What Are Sedation and Drowsiness With Spravato?
SPRAVATO sedation can involve unusual sleepiness, reduced alertness, or, less commonly, a deeper reduction in consciousness.
Sedation includes related experiences such as somnolence and drowsiness. Clinically measured sedation can be more significant than ordinary tiredness.
The current label reports sedation on a standardized alertness scale in 48% to 61% of SPRAVATO-treated patients across specified clinical trials. Loss of consciousness occurred in 0.3% to 0.4%.
SPRAVATO sedation can also become more concerning when another central nervous system depressant is involved. Examples include benzodiazepines, opioids, and alcohol.
Medication review, post-dose monitoring, and assessment of clinical stability help manage sedation risk during treatment.
How Are Dizziness and Vertigo Different?
Dizziness and vertigo are related SPRAVATO side effects, but vertigo specifically describes a spinning or movement sensation.
Dizziness can feel like lightheadedness, instability, or feeling off balance. Vertigo creates a more specific sensation that you or your surroundings are moving.
The SPRAVATO label treats dizziness and vertigo as separate adverse reactions. In one TRD study with an oral antidepressant, dizziness occurred in 29% of SPRAVATO-treated patients versus 8% with placebo. Vertigo occurred in 23% versus 3%.
Balance-related symptoms are monitored during the supervised treatment period, along with overall clinical stability before discharge.
Can Spravato Cause Nausea and Vomiting?
Yes. SPRAVATO can cause both nausea and vomiting, particularly on the treatment day.
Nausea and vomiting are related gastrointestinal reactions, but they describe different experiences. Nausea is the sensation of needing to vomit. Vomiting is the physical event.
In one fixed-dose TRD study, nausea occurred in 27% of patients receiving 56 mg and 32% receiving 84 mg. Vomiting occurred in 6% and 12%, respectively.
SPRAVATO trial data show that most nausea and vomiting occurred and resolved on the dosing day. Median duration did not exceed one hour for most participants across treatment sessions.
Patients are instructed to avoid food for at least two hours and liquids for at least 30 minutes before treatment. MedlinePlus provides the same preparation guidance.
How Does Spravato Affect Blood Pressure?
SPRAVATO can temporarily increase systolic and diastolic blood pressure after administration.
SPRAVATO-related blood-pressure increases generally peak around 40 minutes after dosing. Elevated values can persist for approximately four hours.
The current label reports that approximately 3% to 19% of SPRAVATO-treated patients experienced an increase of at least 40 mmHg systolic or 25 mmHg diastolic at least once during the first four weeks. The corresponding placebo range was 1% to 4%.
These percentages come from specific clinical studies rather than one universal patient population.
Blood pressure is checked as part of the treatment process. Cardiovascular, cerebrovascular, and other relevant medical factors also require review when they affect treatment safety.
SPRAVATO is contraindicated when increased blood or intracranial pressure poses a serious risk. Current labeling includes aneurysmal vascular disease, arteriovenous malformation, and previous intracerebral hemorrhage among those contraindications.
What Other Common Spravato Side Effects Can Occur?
SPRAVATO can produce additional neurological, psychiatric, sensory, and general adverse reactions.
Other reported effects include:
- Headache
- Anxiety
- Hypoesthesia or numbness
- Lethargy or fatigue
- Feeling drunk
- Altered taste
- Nasal discomfort
- Throat irritation
SPRAVATO labeling groups anxiety with related experiences such as agitation, fear, jitteriness, irritability, nervousness, and panic symptoms in some trial tables.
Hypoesthesia means reduced sensation or numbness. SPRAVATO studies include oral and throat-area hypoesthesia within this adverse-event category.
Anxiety is a recognized adverse reaction. Anxiety is not an FDA-approved indication for SPRAVATO.
What Serious Side Effects and Warning Signs Can Spravato Cause?
SPRAVATO carries serious warnings for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.
The current U.S. boxed warning includes these five safety areas. SPRAVATO is therefore available only through the restricted SPRAVATO REMS program.
Common side effects and serious risks should not be treated as equivalent. A common reaction is not automatically dangerous, while a serious reaction is not necessarily common.
The following framework separates treatment-session effects from symptoms requiring further action.
| Situation | What it means | What to do |
| Expected during monitored treatment | A known acute effect occurs within the supervised setting | Tell the treatment team and remain monitored |
| Persistent or concerning | A symptom becomes severe, unusual, worsening, or slow to resolve | Contact the treating clinician |
| Urgent | Serious respiratory, cardiovascular, neurological, or psychiatric warning signs occur | Seek urgent or emergency medical care |
When Can Sedation or Dissociation Become Concerning?
SPRAVATO sedation or dissociation becomes more concerning when symptoms are severe, prolonged, or affect consciousness, breathing, or clinical stability.
Expected dissociation during supervised treatment does not automatically represent an emergency. Clinical assessment focuses on whether symptoms remain within an expected monitored pattern and resolve sufficiently for discharge.
Current patient guidance instructs patients to report being unable to stay awake or feeling as though they may pass out.
The required two-hour observation period is a minimum. Discharge depends on clinical stability rather than the passage of time alone.
What Is Respiratory Depression From Spravato?
Respiratory depression is slowed or impaired breathing and is a serious SPRAVATO safety risk included in the current boxed warning.
Postmarketing reports have identified respiratory depression after SPRAVATO use, including rare respiratory arrests. Postmarketing data cannot provide a reliable incidence rate.
The SPRAVATO REMS program therefore requires respiratory monitoring with pulse oximetry during the post-dose observation period. Pulse oximetry measures blood-oxygen saturation.
Respiratory risk is one reason SPRAVATO cannot be taken home for unsupervised administration.
Can Spravato Worsen Depression or Suicidal Thoughts?
Yes. New or worsening depression or suicidal thoughts can occur during treatment and require prompt assessment, although their occurrence does not prove SPRAVATO caused the change.
Current labeling carries a warning concerning suicidal thoughts and behaviors associated with antidepressant treatment in adolescents and young adults. SPRAVATO is not approved for pediatric patients.
SPRAVATO is also approved, with an oral antidepressant, for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior. However, its effectiveness in preventing suicide has not been demonstrated.
Sudden mood changes, emerging suicidal thoughts, unusual behavior, or worsening psychiatric symptoms require clinical attention rather than being assumed to be expected treatment effects.
What Is the Abuse and Misuse Risk With Spravato?
SPRAVATO contains esketamine, a Schedule III controlled substance with recognized potential for abuse and misuse.
Current labeling directs clinicians to assess abuse and misuse risk before prescribing SPRAVATO and monitor for relevant behaviors during treatment.
The boxed warning does not mean every patient develops dependence. The warning identifies a clinically important risk requiring controlled distribution and direct supervision.
SPRAVATO should also not be described as ordinary “ketamine nasal spray.” Esketamine is the S-enantiomer of racemic ketamine. The two entities are related but not interchangeable.
When Should You Seek Urgent Medical Help?
Seek urgent medical assessment when symptoms suggest a serious respiratory, cardiovascular, neurological, or psychiatric complication.
Examples include:
- Severe breathing difficulty
- Inability to remain awake
- Loss of consciousness
- Chest pain
- Severe shortness of breath
- Sudden severe headache
- Sudden vision changes
- Seizures
- New focal neurological symptoms
- Immediate suicidal intent or another acute safety crisis
Expected dizziness, dissociation, nausea, or sleepiness during monitored treatment belong to a different clinical category from these urgent warning signs.
Patients should report symptoms during treatment rather than deciding independently whether an effect is medically important.
How Long Do Spravato Side Effects Last?
Many acute SPRAVATO side effects begin during or shortly after treatment and improve within the observation period or later that day, but duration varies by reaction.
SPRAVATO research shows different timelines for dissociation, sedation, nausea, blood-pressure changes, and cognitive effects. The required driving restriction continues until the next day after restful sleep.
The following timeline separates acute, same-day, next-day, and longer-term considerations.
| Time point | What patients may experience |
| During administration | Acute perceptual, neurological, or gastrointestinal effects may begin |
| Early post-dose period | Dissociation, sedation, dizziness, nausea, or perceptual changes may become noticeable |
| Around 40 minutes | Blood-pressure and short-term cognitive changes are especially relevant |
| First 2 hours | Acute side effects and clinical stability remain under observation |
| Later that day | Many acute reactions improve or resolve |
| Next day | Driving restrictions remain until after restful sleep |
| Repeated treatment | Cognition, urinary symptoms, and long-term tolerability require separate assessment |
When Do Spravato Side Effects Usually Start?
SPRAVATO acute side effects usually begin during or soon after administration, although different reactions do not share one exact onset time.
Esketamine reaches its average maximum blood concentration approximately 20 to 40 minutes after the final nasal spray. Blood-pressure increases also tend to peak near 40 minutes.
Dissociation, sedation, dizziness, nausea, and perceptual changes therefore receive particular attention during the early post-dose period.
Long-term urinary or cumulative safety concerns follow a different timeline and should not be combined with immediate treatment-session effects.
What Happens to Spravato Side Effects During the First Two Hours?
SPRAVATO side effects can emerge, peak, and begin improving during the first two hours while the patient remains under observation.
Dissociation in clinical trials was transient and occurred on dosing days. Nausea and vomiting also usually resolved on the treatment day. Sedation can occasionally be delayed or prolonged.
Short-term cognitive testing found reduced performance around 40 minutes after one dose. Cognitive performance and mental effort were comparable with placebo by two hours in that study.
The two-hour period is therefore a minimum observation window rather than a promise that every side effect disappears within exactly two hours.
Can Spravato Side Effects Last Into the Next Day?
Yes. SPRAVATO-related tiredness, dizziness, reduced alertness, or cognitive effects can persist after discharge, so driving remains restricted until the next day after restful sleep.
The driving restriction applies even when a patient has been clinically stable enough to leave the treatment setting.
Patients need to arrange transportation home after each SPRAVATO treatment session.
The restriction does not mean every patient remains impaired throughout the night. Individual recovery differs, which is why the next-day rule provides a consistent safety boundary.
When Should Lingering Side Effects Be Reviewed?
Discuss lingering SPRAVATO side effects with the treating clinician when symptoms remain severe, unusual, worsening, or interfere significantly with normal functioning.
SPRAVATO side effects do not share one universal duration. Arbitrary time limits should not replace individual clinical assessment.
Persistent dizziness, unusual confusion, excessive sedation, breathing changes, significant blood-pressure symptoms, or urinary problems deserve individualized review.
How Are Spravato Side Effects Monitored and Managed?
SPRAVATO side effects are monitored through supervised administration, REMS requirements, vital-sign checks, respiratory monitoring, observation, and a clinical-stability assessment before discharge.
Supervised treatment allows the healthcare team to observe acute reactions when they are most likely to occur. The federal REMS framework requires at least two hours of observation after each dose.
What Is the SPRAVATO REMS Program?
The SPRAVATO REMS is a Risk Evaluation and Mitigation Strategy requiring supervised administration and post-dose monitoring in certified healthcare settings.
The program exists because of sedation, dissociation, respiratory depression, abuse, and misuse risks.
SPRAVATO REMS requirements include direct healthcare-provider supervision and at least two hours of post-dose monitoring.
SPRAVATO cannot be dispensed directly to patients for home use.
What Is Monitored During the Two-Hour Observation Period?
SPRAVATO monitoring includes alertness, dissociation, breathing, oxygen saturation, blood pressure, other vital signs, and overall clinical stability.
The REMS program requires monitoring for respiratory depression with pulse oximetry.
Blood pressure is checked before treatment and reassessed after administration. The current label uses approximately 40 minutes as an important post-dose assessment point because blood-pressure effects peak around that time.
The minimum two-hour period does not function as an automatic discharge time. The healthcare provider determines whether the patient is clinically stable before leaving.
What Can Make Spravato Side Effects More Concerning?
Certain medications and medical conditions can increase specific SPRAVATO safety concerns.
Important examples include:
- CNS depressants such as benzodiazepines, opioids, and alcohol, which can increase sedation
- Psychostimulants such as amphetamines or methylphenidate, which can increase blood pressure
- MAO inhibitors, which can increase blood pressure
- Cardiovascular or cerebrovascular conditions that increase the consequences of blood-pressure changes
- A history of substance misuse, which affects abuse-risk assessment
The current prescribing information identifies these medication interactions and monitoring concerns.
Patients should provide complete medication and medical histories so the treating clinician can assess treatment risks accurately.
Can You Drive After Spravato Treatment?
No. Do not drive or operate machinery until the next day after a restful night’s sleep.
SPRAVATO can temporarily affect attention, thinking, judgment, reaction speed, and motor coordination. Current labeling therefore requires transportation home after each session.
Patients should arrange transportation before treatment rather than planning to drive themselves home.
Clinical discharge and driving clearance are separate concepts. Leaving the treatment setting after monitoring does not cancel the next-day driving restriction.
What Are the Long-Term Side Effects of Spravato?
Current long-term SPRAVATO evidence has not identified a new overall safety signal, but the available data do not prove that indefinite treatment carries zero risk.
Long-term safety differs from acute treatment reactions. Current evidence particularly informs repeated-exposure tolerability, cognition, urinary symptoms, and adverse events over extended treatment.
What Does Long-Term Research Show About Spravato Safety?
The final SUSTAIN-3 dataset provides multi-year evidence from adults with treatment-resistant depression.
Zaki and colleagues published the final extension results in 2025. The study included 1,148 adults and 3,777 cumulative patient-years of esketamine exposure. Treatment exposure extended to 79 months, or approximately 6.5 years.
SUSTAIN-3 reported headache in 36.9%, dizziness in 33.9%, nausea in 33.6%, dissociation in 25.5%, and somnolence in 23.1% of participants. Adverse events led 6.4% to discontinue the study.
SUSTAIN-3 identified no new safety signal during long-term intermittent treatment. However, the study was an open-label, single-arm extension rather than a long-term randomized placebo-controlled trial.
The correct conclusion is therefore limited:
No new safety signal was identified in SUSTAIN-3, but this does not establish that indefinite SPRAVATO treatment is risk-free.
Can Spravato Cause Memory Problems or Brain Fog?
Yes. SPRAVATO can temporarily impair cognitive performance after dosing, but chronic SPRAVATO-caused memory decline is not established in current clinical evidence.
A controlled study in healthy volunteers found reduced cognitive performance approximately 40 minutes after one dose. Performance was comparable with placebo at two hours.
SPRAVATO labeling also reports stable cognitive functioning over time in one-year and three-year open-label studies using standardized cognitive assessments.
The current label separately notes long-term cognitive and memory impairment associated with repeated ketamine misuse or abuse.
SPRAVATO and repeated high-exposure ketamine misuse are not equivalent exposure conditions.
Brain fog is also an informal term rather than one specific diagnosis. Patients may use it to describe concentration difficulty, slowed thinking, sedation, or other cognitive sensations.
New memory, concentration, or thinking changes should be reported to the treating clinician so their timing and clinical context can be reviewed.
Can Spravato Cause Bladder Problems or Frequent Urination?
Yes. Lower urinary-tract symptoms have occurred more often with SPRAVATO than placebo in clinical studies.
Current labeling identifies urinary symptoms including:
- Frequent urination
- Urinary urgency
- Painful urination
- Nighttime urination
- Cystitis
The label reports no esketamine-related interstitial cystitis cases in studies containing treatment for up to one year.
The same label distinguishes these findings from ulcerative or interstitial cystitis reported with long-term off-label ketamine use or misuse.
The bladder-risk profile of prolonged ketamine misuse should therefore not be transferred directly to supervised SPRAVATO treatment.
New or persistent urinary symptoms should be reported during ongoing treatment.
How Do We Approach Spravato Safety and Monitoring at Lotus Psychiatry & Wellness?
At Lotus Psychiatry & Wellness, we provide SPRAVATO in a supervised psychiatric setting with clinical evaluation, treatment planning, blood-pressure assessment, observation, and transportation planning.
Our SPRAVATO treatment service is available through our South Florida psychiatric practice, including our Boca Raton and Coral Springs locations. Treatment includes supervised self-administration, interval blood-pressure checks, at least two hours onsite, and transportation home.
What Happens Before Spravato Treatment?
Before SPRAVATO treatment, we review treatment fit, psychiatric history, medical factors, medications, and relevant safety concerns.
Our evaluation can include:
- Reviewing current depression symptoms
- Reviewing diagnosis
- Reviewing previous treatment
- Reviewing current medications
- Reviewing medical and psychiatric history
- Reviewing blood-pressure concerns
- Reviewing vascular or neurological risk factors
- Reviewing substance-use history when relevant
- Discussing side-effect concerns and treatment expectations
Current March 2026 U.S. labeling allows SPRAVATO for adult treatment-resistant depression as monotherapy or with an oral antidepressant.
SPRAVATO remains used with an oral antidepressant for depressive symptoms in adults with MDD and acute suicidal ideation or behavior.
Our clinical information follows current U.S. prescribing guidance.
How Do We Monitor Patients During and After Spravato Treatment?
We supervise SPRAVATO administration and keep patients onsite for at least two hours after treatment.
Our monitoring includes blood-pressure assessment, observation for treatment effects, and transportation planning after the session.
The SPRAVATO REMS framework also requires monitoring for sedation, dissociation, respiratory depression with pulse oximetry, and clinically relevant changes in vital signs.
The goal is not simply to complete a two-hour timer. We assess whether the patient is clinically stable before discharge.
When Should You Discuss Spravato Side Effects With Our Team?
Discuss SPRAVATO side effects with our team when symptoms are new, persistent, severe, unusual, or different from previous treatment sessions.
Helpful details include:
- Describe what the symptom feels like.
- State when the symptom began.
- State how long the symptom lasted.
- Explain whether it began during or after treatment.
- Explain whether it continued into the next day.
- Describe whether it affected breathing, alertness, balance, mood, thinking, blood pressure, or urination.
- Tell us about recent medication or health changes.
Specific symptom information helps us interpret timing, severity, possible contributing factors, and appropriate next steps.
Patients considering SPRAVATO treatment in Boca Raton or Coral Springs can discuss treatment expectations, side effects, medical history, and individual safety considerations with our clinical team.
What Are Common Questions About Spravato Side Effects?
The following questions address narrower treatment concerns that often arise after patients understand SPRAVATO’s immediate and long-term side-effect profile.
How Long Do People Stay on Spravato?
SPRAVATO treatment duration is individualized according to diagnosis, response, tolerability, and ongoing clinical need. Treatment duration is different from side-effect duration. Current TRD labeling reduces treatment frequency after the initial treatment phases, but individual maintenance decisions require clinician-guided assessment.
Can You Stop Spravato, and Why Do People Discontinue It?
Yes. SPRAVATO treatment can be discontinued, but patients should make that decision with their treating clinician. Reasons can include side effects, insufficient benefit, changing clinical needs, or personal circumstances. In SUSTAIN-3, 6.4% discontinued because of adverse events, but that rate applies specifically to that long-term extension study.
What Should You Remember About Spravato Side Effects?
SPRAVATO side effects range from expected acute reactions to less common but clinically serious risks.
SPRAVATO common adverse reactions include dissociation, dizziness, nausea, sedation, vertigo, numbness, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk, and headache in current TRD labeling.
SPRAVATO serious warnings include sedation, dissociation, respiratory depression, abuse or misuse, and suicidal thoughts or behaviors. These risks explain why treatment occurs under direct supervision rather than at home.
SPRAVATO side effects often occur during or shortly after treatment. The REMS program requires at least two hours of monitoring, including respiratory assessment and observation for acute treatment effects.
SPRAVATO long-term data now extend to approximately 6.5 years in SUSTAIN-3. The study identified no new safety signal, but its open-label, single-arm design does not establish zero risk from indefinite treatment.
Patients should understand what expected treatment reactions can look like and which symptoms require further evaluation.
Patients considering treatment can learn more about Lotus Psychiatry & Wellness’s SPRAVATO treatment evaluation process.