Nearly seven in ten patients in FDA trials reported some form of dissociation after a Spravato treatment session. That number sounds alarming until you understand what it actually means — and why so many people still choose this path when nothing else has worked.
Spravato, the brand name for esketamine nasal spray, isn’t a drug you take and forget about. It’s dosed in a clinical setting, under direct supervision, precisely because of how it affects the body in the short term. Side effects of Spravato tend to show up fast — usually within the first 40 minutes — and settle down within a couple of hours.
The big three are dissociation, sedation, and dizziness. Patients often describe feeling “floaty” or disconnected from their surroundings, almost like watching themselves from a slight distance. Nausea, increased blood pressure, and a spravato headache round out the list of frequently reported adverse effects. None of this is unusual for a drug built on ketamine’s chemistry, and it’s exactly why every treatment session includes a mandatory monitoring period.
What surprises a lot of new patients is how quickly it passes. Most people are cleared to leave the clinic within two hours, once a healthcare professional confirms their blood pressure and alertness have returned to baseline.
Headaches rank among the most commonly reported complaints tied to esketamine for depression side effects, and there’s a fairly simple explanation. Spravato esketamine can cause a temporary spike in blood pressure during and shortly after dosing. For some people, that shift alone is enough to trigger head pain, especially during the early weeks of treatment.
There’s also a sensory piece to it. The nasal spray delivery method, combined with the drug’s effect on brain chemistry, can produce sinus pressure or tension that mimics a typical headache. Staying hydrated before a session and avoiding caffeine right beforehand seems to help some patients, though nothing eliminates the risk entirely.
Most headaches fade within a few hours. If they don’t, or if they show up alongside vision changes or severe pain, that’s worth flagging to your provider right away rather than waiting it out.
This is one of the questions people ask most, and it deserves an honest answer. For a small subset of patients, mood can feel unstable in the first days of treatment. That doesn’t mean Spravato treatment is failing — it often means the brain is adjusting to a completely different mechanism than an oral antidepressant.
Can Spravato make depression worse? In rare cases, yes, temporarily. This is precisely why the induction phase — the first few weeks of twice-weekly dosing — is closely watched. Providers screen for suicidal thoughts before, during, and after every session, a safeguard built directly into the drug’s risk management program.
If you notice your mood dipping harder than expected, say so immediately. Depressive disorders don’t respond identically in every brain, and adjusting frequency or dose is common early on.
Here’s where the research gets more reassuring. Long-term side effects of Spravato have been studied in trials running up to a year, and no cases of bladder or urinary tract damage — a known risk with recreational ketamine misuse — turned up in that data.
That said, long-term use isn’t risk-free. Ongoing bladder or urinary symptoms should always be reported to your healthcare professional. Cognitive effects with prolonged use are still being studied, and providers typically reassess whether continued treatment remains the right treatment option every few months.
For patients with treatment-resistant depression (TRD), the calculation usually comes down to comparing these manageable risks against years of an illness that didn’t respond to anything else. Clinical trials so far suggest the trade-off favors continued treatment for most.
Timing varies by symptom. Dissociation and sedation are the most immediate — they typically start within the first 20 to 40 minutes and taper off within an hour or two. That’s the entire reason clinics require a 30-minute minimum observation window, often extending closer to two hours for new patients.
Headaches and nausea can linger a bit longer, sometimes into the next day, though this is the exception rather than the rule. Dizziness usually resolves before a patient even leaves the building. How long do Spravato side effects last is really a question of hours, not days, for the vast majority of people.
Blood pressure changes are checked before discharge every single time. If numbers haven’t normalized, patients simply stay a little longer under observation — a routine part of the process, not a red flag.
Traditional antidepressants — SSRIs and SNRIs, mainly — tend to cause gradual, chronic side effects: weight changes, sexual dysfunction, fatigue that can drag on for months. Esketamine nasal spray flips that model. The effects of Spravato are intense but brief, concentrated into the hours around each dose rather than spread across daily life.
For major depressive disorder (MDD) and treatment-resistant depression, this trade-off often matters. Patients frustrated by years of sluggish, side-effect-heavy oral medications sometimes find the short, supervised intensity of Spravato more tolerable than they expected. Feeling disconnected for an hour is different from feeling numb for a year.
The Food and Drug Administration approved esketamine specifically because its benefit-risk profile held up in patients who’d exhausted other options. That approval didn’t erase the side effect list — it just confirmed the risks were manageable within a structured treatment session.
Understanding spravato side effects explained in plain terms is one thing. Having a care team that walks you through each session is another entirely. At Scottsdale TMS, patients receive close monitoring during every dose, honest conversations about what to expect, and a treatment plan built around more than just symptom checklists.
Treatment for treatment-resistant depression trd shouldn’t feel like guesswork. Scottsdale TMS combines experienced clinical oversight with a straightforward approach to managing adverse effects, so patients know exactly what’s normal and what isn’t — before, during, and after their induction phase.
Dr. Vines has practiced psychiatry in Arizona for for over 25 years and has experience working with diverse populations that include children, adolescents, adults, geriatrics, SMI patients, and the chemically dependent.
August 24, 2026
