Spravato Side Effects: What to Expect, Session by Session
The most common side effects of esketamine (Spravato), such as dissociation, dizziness, nausea, and a temporary rise in blood pressure, tend to appear during the session itself and resolve within the same day. This is precisely why every Spravato session includes two hours or more of on-site monitoring before you leave. This is not because the side effects are dangerous in most people, but because they deserve attention, measurement, and a clinical team nearby while they run their course.
If you are weighing whether to begin Spravato, or if you have already had a session or two and want to understand what you felt, this article walks through the side-effect profile organized the way you actually experience it, including during the dose, the hours after, the following day, and across weeks of treatment. Every side effect listed here comes from the FDA-approved prescribing information or from peer-reviewed clinical trial data. Nothing is rounded or invented.
What Are the Most Common Side Effects of Spravato?
In the pivotal clinical trials that led to FDA approval, the side effects reported most often during esketamine (Spravato) treatment were dissociation, dizziness, nausea, sedation, a spinning sensation (vertigo), reduced sense of touch (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting, and a feeling of intoxication. The majority of these occurred shortly after the nasal spray was administered and resolved on the same day. Most clear within the monitoring window of two hours or more.
Esketamine is FDA-approved for adults with treatment-resistant depression and major depression with suicidal thoughts. It carries a boxed warning for sedation, dissociation, respiratory depression, and the potential for abuse and misuse. This is the same boxed warning that applies to all antidepressant medications regarding suicidal thoughts and behaviors, particularly in the early weeks of treatment or during dose changes. These warnings are serious, and they are the reason Spravato is administered exclusively under medical supervision.
During the session (0–40 minutes after the dose)
Spravato is a self-administered nasal spray. You spray it while seated in a private treatment room, and within roughly 15 to 30 minutes, you may begin to notice changes. The most commonly described effects during this window include:
- Dissociation: A feeling of being detached from your surroundings, your body, or your usual stream of thought. Some people describe it as watching themselves from a slight distance. Others notice that time seems to stretch or that the room feels unfamiliar. Dissociation was reported by a meaningful proportion of patients in clinical trials and is usually the most talked-about side effect of Spravato.
- Dizziness and vertigo: A sense of lightheadedness or the room seeming to rotate. This can feel disorienting but rarely lasts beyond the monitoring period.
- Sedation and drowsiness: Some patients feel profoundly sleepy. Others describe it more as a heaviness in the limbs. The clinical team monitors your oxygen saturation and responsiveness throughout.
- Nausea: Stomach discomfort or queasiness is common and often peaks around 30 to 40 minutes. It usually passes without intervention, though medication can be provided if it becomes bothersome.
- Increased blood pressure: Esketamine can cause a temporary rise in both systolic and diastolic blood pressure. This is why blood pressure is checked before the dose and again during and after it. In clinical trials, blood pressure typically peaked about 40 minutes post-dose and returned to pre-treatment levels within roughly 90 minutes.
"The blood pressure goes up a little bit, the heart rate goes up a little bit. To the mind of the explorer and the curious, it's like listening to a good song and you're starting to get excited and your body is responding to the music."
— Dr. Ben Yudkoff, Chief Medical Officer, Lumin Health
During the monitoring period
After the spray is administered, you remain in your treatment room for two hours or more. This is a federal requirement under the Spravato REMS (Risk Evaluation and Mitigation Strategy) program. During this window, your care team checks blood pressure, oxygen levels, and your overall state at regular intervals.
For most people, the dissociative and sedative effects are strongest between 20 and 60 minutes after the dose, then gradually fade. By the end of the monitoring period, most patients describe feeling "more like themselves." Some residual drowsiness or a dreamlike quality may linger, but the acute effects have usually cleared.
This monitoring period is not idle time. It is a structured safety interval. At Lumin Health, it happens in a private room with a trained mental health team nearby rather than a crowded waiting area. The environment is designed so that the unusual perceptual shifts feel contained and manageable rather than alarming.
The rest of the day
After you are cleared to leave, you cannot drive, operate heavy machinery, or perform tasks requiring full mental alertness until the following day after a restful sleep. We make sure you have a safe way home arranged in advance, and we suggest activities to further decompress and take stock of the experience. For a detailed discussion of driving restrictions, see our article on driving after Spravato or ketamine treatment.
Some patients describe feeling tired or slightly foggy for the rest of the afternoon. Others feel an unexpected sense of calm or emotional openness. Mild headache and fatigue are not uncommon. Most people find that by evening, they feel largely returned to baseline, though rest is still encouraged.
How Long Do Spravato Side Effects Last?
Most esketamine side effects resolve within the same day as treatment. In clinical trials, the median duration of dissociation was approximately 40 to 60 minutes, and the majority of adverse events had cleared by the time the monitoring period of two hours or more ended. Blood pressure changes followed a similar arc: an increase that peaked around 40 minutes post-dose and returned to near-baseline within about 90 minutes.
By the next morning, after a full night of sleep, most patients report no lingering side effects from the session itself. Some describe a mild residual fatigue, particularly in the first few sessions, but this tends to diminish as the body acclimates to the medication.
A subtler question that patients ask thoughtfully is whether there are side effects that accumulate across months of treatment. For a thorough discussion of what the peer-reviewed literature currently shows on longer-duration use, including cognitive, urinary, and cardiovascular considerations, see our dedicated article on long-term side effects of ketamine treatment. The short answer is that at the doses and frequencies used in clinical psychiatric treatment, the data to date are reassuring, but ongoing monitoring remains an important part of responsible care.
A systematic review examining the long-term safety of ketamine and esketamine in depression treatment found that therapeutic dosing, delivered under medical supervision, carries a side-effect profile that is meaningfully different from patterns seen in heavy recreational misuse. Cognitive impairment, for instance, has not been a consistent finding at clinical doses.
Does Spravato Cause Weight Gain?
Weight gain is not listed among the common side effects of esketamine (Spravato) in the FDA prescribing information. In the clinical trials that supported approval, weight changes were not flagged as a significant or frequently reported adverse event.
This matters because weight gain is one of the reasons many patients become frustrated with certain oral antidepressants, particularly some SSRIs, SNRIs, and atypical antipsychotics sometimes prescribed as augmentation. For patients who have already had difficulty tolerating those medications, knowing that Spravato works through a different mechanism (glutamate modulation rather than serotonin or norepinephrine reuptake) and carries a different metabolic side-effect profile can be relevant to the treatment decision.
That said, depression itself, changes in appetite, sleep disruption, and concurrent medications can all influence weight. If you are concerned about weight changes during any course of treatment, it is worth discussing with your prescriber so the full picture is considered rather than just one medication.
Can You Drink Alcohol While Taking Spravato?
You should not consume alcohol before a Spravato session. Both esketamine and alcohol affect the central nervous system, and combining them increases the risk of excessive sedation, slowed breathing, impaired judgment, and nausea. At Lumin Health, patients are asked to avoid alcohol for at least 24 hours before their appointment.
Beyond the acute safety concern, alcohol also has downstream effects on the very mechanisms that make ketamine therapy and Spravato treatment potentially effective. Alcohol impairs neuroplasticity (the brain's ability to form and strengthen new synaptic connections), which is thought to be one of the central ways esketamine exerts its antidepressant effect. In other words, heavy or frequent drinking may erode the benefit you are working to build.
Occasional, moderate alcohol use on non-treatment days is not an automatic disqualifier, but regular or heavy drinking is something your care team will want to discuss before beginning a course of treatment. This is less about moral judgment and more about optimizing what the medication can do for you.
How Often Do You Take Spravato?
The FDA-labeled dosing schedule for esketamine (Spravato) follows a structured progression, though frequency is always tailored in partnership with your prescribing provider:
- Weeks 1–4 (induction): Twice per week.
- Weeks 5–8 (optimization): Once per week.
- Week 9 onward (maintenance): Once weekly or once every other week, depending on your response and clinical judgment.
In practice, some patients eventually extend to less frequent sessions, such as once every three or four weeks, once they have established a durable response. Others find that a consistent weekly or biweekly rhythm is what keeps their symptoms managed. There is no single correct maintenance frequency; the right schedule is the one that sustains your improvement while remaining practical for your life.
Each session involves a visit to a REMS-certified treatment location, the nasal spray administration, and two hours or more of post-administration monitoring. Total time on site is typically two and a half to three hours per visit. It is a meaningful time commitment, especially during the induction phase, and one worth understanding clearly before you begin.
How Long Does Spravato Take to Work?
One of the reasons esketamine generated such interest in the psychiatric community is the speed of its onset. In the TRANSFORM-2 pivotal trial (a flexibly-dosed, randomized, controlled study of esketamine as adjunctive treatment for treatment-resistant depression), patients receiving Spravato plus an oral antidepressant showed statistically significant improvement in depressive symptoms by the end of the four-week induction period compared to placebo nasal spray plus an oral antidepressant. Notably, much of the separation between groups was already observable within the first 24 hours after the initial dose.
That early signal does not mean everyone feels dramatically better after a single session. Some people notice a subtle shift, such as a slightly softer mood, marginally better sleep, or a loosening of the relentless self-critical inner dialogue, within the first week or two. Others require the full induction course before the effect becomes clear. And for some, the medication does not produce a meaningful response, and the clinical team works with them to reassess the plan.
A useful frame: if you have seen no improvement at all after four weeks of twice-weekly treatment, the probability of a delayed response is low, and it is appropriate to discuss alternatives. But if you are seeing gradual, incremental gains, staying the course through the optimization and early maintenance phases is usually recommended.
"Ketamine acts on glutamate, which is entirely different from the serotonin system that SSRIs target. That's why it can work for people who haven't responded to traditional antidepressants."
— Dr. Ben Yudkoff, Chief Medical Officer, Lumin Health
This mechanistic distinction matters for understanding the timeline. Oral antidepressants that modulate serotonin, norepinephrine, and dopamine can take four to six weeks to begin working. This delay is rooted in the slow process of receptor-level adaptation. Esketamine, by acting on the glutamate system and triggering downstream release of Brain-Derived Neurotrophic Factor (BDNF), may promote more rapid synaptic reconnection in brain circuits that depression has weakened. That faster pharmacological cascade is what enables the shorter timeline to initial response, even though the full therapeutic benefit still unfolds over weeks of treatment.
Why Is Spravato Given Only in a Certified Treatment Center?
Esketamine (Spravato) is classified as a Schedule III controlled substance and is available only through a restricted distribution system called the REMS (Risk Evaluation and Mitigation Strategy). Under REMS, every dose must be administered in a healthcare setting that has been certified to meet specific safety requirements, and every patient must be monitored on site for two hours or more after administration.
The REMS program exists because of the specific side-effect profile discussed throughout this article. Dissociation, sedation, and blood pressure changes are common enough that unsupervised use at home would create real safety risks, including falls, cardiovascular events in vulnerable individuals, and impaired judgment during the acute window. The in-office monitoring requirement ensures that vital signs are tracked, that medical staff are available to intervene if needed, and that no patient drives or operates machinery while still under the medication's influence.
At Lumin Health, every treatment session happens in a private room with dedicated staff specifically trained in ketamine and esketamine care. Blood pressure, heart rate, and oxygen saturation are measured at structured intervals. If side effects arise, whether physical discomfort like Spravato nausea or perceptual shifts like dissociation, staff are there to provide reassurance, grounding support, or medication as appropriate.
The REMS framework also addresses the boxed warning concerning abuse and misuse. By restricting dispensing to certified locations, the system limits diversion and ensures that every dose is accounted for. Patients do not take Spravato home. They do not self-administer in unmonitored settings. This structure is a feature, not a limitation. It is what allows a medication with this pharmacological profile to be used safely as a psychiatric treatment rather than as something patients have to navigate alone.
For a complete overview of how Lumin Health meets and exceeds REMS requirements, visit our page on Spravato REMS safety standards at Lumin Health.
Understanding Spravato Side Effects in the Bigger Picture
One of the quieter truths about esketamine side effects is that the profile is, by design, manageable precisely because of the setting in which the medication is given. The dissociation, the dizziness, and the temporary blood pressure increase are not hidden risks. They are expected, measured, and attended to in real time. The monitoring period of two hours or more exists so that every session has a beginning, a middle, and a supervised resolution.
This is fundamentally different from the side-effect experience of oral antidepressants, where adverse effects (weight gain, sexual dysfunction, emotional blunting) may develop slowly over weeks and are often endured at home with little clinical oversight between appointments. With Spravato, the acute side effects are front-loaded and time-limited, and your care team is present for the entire arc.
That does not mean the experience is trivial. Dissociation can feel strange, even unsettling, particularly in the first few sessions. Nausea is genuinely unpleasant. The driving restriction requires logistical planning. These are real costs of treatment, and any honest discussion of Spravato should name them clearly rather than minimizing them.
What the data also show, from a long-term safety perspective, is that the side effects tend to be most pronounced in the first few sessions and often diminish over time as the body acclimates to the medication. A long-term open-label safety study (SUSTAIN-2) followed patients through extended treatment courses and found the safety profile to be consistent with what was observed in the initial trials, without new or unexpected concerns emerging at scale.
Frequently Asked Questions
Can Spravato cause long-term side effects?
At the doses and frequencies used for depression treatment, long-term cognitive impairment has not been observed in clinical studies. Urinary and bladder issues, which are a concern with heavy recreational ketamine misuse, have not been a significant finding in the clinical Spravato data. Ongoing cardiovascular monitoring is standard. For a full discussion, see our article on long-term side effects of ketamine treatment.
What does Spravato dissociation actually feel like?
People describe it in different ways: a sense of distance from one's own thoughts, the room feeling unfamiliar, time seeming to slow down, or a feeling of floating. It is temporary, usually peaking within the first hour and resolving within the monitoring period. It is not the same as losing consciousness. You remain aware and responsive throughout.
Is Spravato addictive?
Esketamine is a Schedule III controlled substance, and the REMS program is specifically designed to reduce abuse and misuse risk. Patients do not take the medication home. Every dose is administered in a certified treatment location and accounted for. While psychological dependence is a theoretical concern with any substance that alters mood, the structured clinical delivery and close psychiatric care significantly mitigate this risk.
What if I have high blood pressure — can I still take Spravato?
Pre-existing hypertension does not automatically disqualify you from treatment, but it does require careful evaluation. Your blood pressure is checked before every dose, and if it is elevated beyond a safe threshold, the session may be postponed. Patients with uncontrolled cardiovascular disease, aneurysmal vascular disease, or a history of intracerebral hemorrhage should not receive esketamine. This is a conversation to have with your prescribing psychiatrist, who can evaluate your specific cardiovascular picture.
How is Spravato different from ketamine for depression?
Esketamine (Spravato) is the S-enantiomer of ketamine (one of ketamine's two mirror-image molecular forms) and the one that binds the NMDA receptor more strongly. It is FDA-approved and typically covered by insurance. Ketamine therapy, administered off-label via intramuscular injection or other routes, uses the racemic mixture containing both the S- and R-enantiomer. The side-effect profiles are largely the same. For a detailed comparison, visit our page on esketamine (Spravato) for depression.
If you are evaluating whether Spravato may be appropriate for your depression, understanding the side-effect profile is an important part of that decision. Lumin Health provides esketamine (Spravato) and intramuscular ketamine treatment at locations across Massachusetts and in Bethesda, Maryland, with academically-affiliated, psychiatrist-led care teams specifically trained in these treatments. If you would like to explore whether this may be a fit, we would be grateful to walk with you toward clarity. Learn more about Spravato at Lumin Health.
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