Spravato side effects: what the label reports

The FDA prescribing information (revised 04/2025) lists the adverse reactions observed in the clinical trials. For adults with treatment-resistant depression treated with Spravato plus an oral antidepressant, the most commonly observed reactions — incidence ≥5% and at least twice that of placebo nasal spray plus oral antidepressant — were:

• Dissociation
• Dizziness
• Nausea
• Sedation
• Vertigo
• Reduced sensation or numbness (hypoaesthesia)
• Anxiety
• Lethargy
• Increased blood pressure
• Vomiting
• Feeling drunk

Two framings matter. First, these are trial-recorded rates in selected participants, not personal odds. Second, most of these effects are exactly what the REMS monitoring period is designed around: they tend to begin shortly after dosing, peak in the first forty minutes or so, and ease over the two-hour window while a healthcare professional is watching.

Blood pressure is the effect with the most clinical weight. The label requires blood pressure to be assessed before dosing and reassessed after (around the 40-minute mark and as needed). If baseline blood pressure is elevated, the clinician may postpone that day's dose. A substantial rise can occur after any dose, even when earlier sessions were mild. This is also why the label contraindicates the drug in certain vascular conditions — covered on the eligibility page.

The full list, including less common reactions and the complete boxed warnings, is in the prescribing information linked in the sources below. It is a better primary source than any summary, including this one.

People searching "long-term side effects of Spravato" are usually looking for a clear answer. The honest one is that long-term data on esketamine is limited, and that limit should not be papered over with either reassurance or alarm.

What exists. The Phase 3 programme included long-term studies. In the open-label SUSTAIN-2 safety study (Wajs et al., Journal of Clinical Psychiatry 2020), adults with treatment-resistant depression received esketamine nasal spray plus an oral antidepressant for up to a year under open-label conditions — useful for describing adverse events over that horizon, not for predicting any one person's future. Across completed Phase 3 studies, about 30% of Spravato-treated patients received at least six months of treatment and about 11% at least twelve months (as of the FDA label revised 04/2025). SUSTAIN-1 (Daly et al., JAMA Psychiatry 2019) studied relapse prevention in people who had already responded, which is a different question from first-use safety.

Cognitive function. The label notes that long-term cognitive and memory impairment have been reported with repeated ketamine misuse or abuse. In 1-year and 3-year open-label clinical trials of Spravato in adults, cognitive functioning remained stable over time on the measures used (Cogstate battery and Hopkins Verbal Learning Test-Revised). That is not the same as "no long-term cognitive risk ever" — it is what those trials measured, in those participants, over those periods.

Withdrawal. In the clinical programme, no withdrawal symptoms were captured up to four weeks after stopping esketamine treatment. Withdrawal symptoms have been reported after frequent large-dose ketamine use over long periods; the label says similar withdrawal would be expected if esketamine were abused in that pattern. That is not the same as stopping a supervised REMS regimen after a normal course — but monitoring for signs of physical dependence on discontinuation is still part of the label's guidance.

Bladder and urinary symptoms. Cases of ulcerative or interstitial cystitis have been reported with long-term off-label use or misuse of ketamine. In Spravato clinical studies, lower urinary tract symptoms (including pollakiuria, dysuria, urgency, nocturia, and cystitis) occurred at a higher rate than with placebo. No cases of esketamine-related interstitial cystitis were observed in those studies, which included treatment for up to a year. The label still recommends monitoring for urinary and bladder symptoms during treatment.

Where evidence is thin, this page stops. It does not invent a multi-year safety narrative the trials did not produce.

Searches like "spravato ruined my life" and "spravato horror stories" are not noise. They are often people who had a frightening session, a lasting adverse effect, or a treatment that did not help — and who are looking for language that matches what they felt. That search deserves a careful answer, not dismissal and not a click-farm of worst-case anecdotes.

Why individual online accounts can still be valuable. Clinical trials capture a defined list of adverse events in a selected population under protocol. Real people sometimes experience things trials under-capture: intensity that felt unmanageable, anxiety that outlasted the session, or a sense that the treatment made depression worse. Listening carefully to those reports is part of honest safety culture.

Why they are unreliable as base rates. People with bad experiences are more likely to post than people with uneventful ones. Forums and social media select for drama. Without knowing the dose, the setting, other medications, whether monitoring was proper, or whether the product was even Spravato (as opposed to off-label IV ketamine), a single story cannot tell you how often something happens.

Transient session effects vs lasting harm. Dissociation, anxiety, and feeling "out of it" during the monitored window are common and usually temporary — they are a large part of why the two hours exist. A lasting bad outcome (worsening depression, suicidal thoughts, a medical complication) is a different category and needs clinical attention, not internet triage. This site cannot tell which category a particular experience falls into.

What this page will not do. It will not quote, reproduce, or link specific Reddit threads or user stories. Aggregating horror content is not a public service for a treatment-resistant depression audience.

If you are in distress right now — whether related to Spravato or not — contact the 988 Suicide & Crisis Lifeline↗ (opens in a new tab) (call or text 988) or text HOME to 741741 (Crisis Text Line). If something felt wrong during or after a session, tell the treatment site and your prescriber; they need the report, and dissociation intensity in particular informs dosing decisions. What a session is like hour by hour is on the what-to-expect page.

This is not dosage advice and not a substitute for your site's instructions. It is the practical layer that sits next to the label.

Nausea and food timing. Nausea and vomiting are common enough that sites often advise limiting food for a couple of hours before dosing and fluids shortly before. Follow your site's guidance over any general summary. Anti-nausea medication, if used, is a clinical decision.

The ride home. The label instructs that you must not drive or operate machinery until the day after the dose, following a restful sleep. Arrange the lift before the appointment, for every session. This is not optional even when you "feel fine" at two hours.

The rest of the day. Most people plan the remainder of the day as unproductive. That is not weakness; the sedation and residual effects can outlast the felt peak even though esketamine clears the plasma relatively quickly — how long it stays in your system covers the pharmacokinetics separately from the driving restriction.

Session logistics. What to expect walks through the hour-by-hour visit: check-in, baseline BP, dosing, the first 40 minutes, monitoring, and discharge. Pair that page with this one: one is the schedule, one is the safety profile.

There is no honest way for a website to promise a side-effect-free course. The useful goal is a prepared visit, a reported experience, and a care team that hears the hard parts.