Spravato’s immediate psychoactive effects peak around 40 minutes after you take the nasal spray and largely clear within 2 hours, though some drowsiness can linger up to 4 hours. But “how long does Spravato last” has several layers: the in-office experience, how long each dose helps your mood, and how long you stay on treatment overall. Each timeline is different.
What Happens During a Session
After you self-administer the nasal spray under supervision at a clinic, the drug reaches peak levels in your blood within 20 to 40 minutes. That 40-minute mark is when dissociation, sedation, and blood pressure changes are at their strongest. Dissociation is the spacey, detached feeling some patients describe as floating or feeling slightly disconnected from their surroundings. It can range from barely noticeable to quite pronounced depending on your dose (56 mg or 84 mg).
Cognitive function, meaning your ability to think clearly and react normally, returns to baseline about 2 hours after your dose. Sleepiness tends to hang on longer, fading closer to 4 hours post-dose. Blood pressure changes follow a similar pattern, peaking at 40 minutes and normalizing over roughly 4 hours. The FDA requires that you stay at the clinic for a minimum of 2 hours after each dose so a healthcare provider can monitor your vital signs and make sure the sedation and dissociation have resolved before you leave. You cannot drive for the rest of the day after a session.
How Long the Drug Stays in Your Body
Esketamine, the active ingredient in Spravato, has a terminal half-life of 7 to 12 hours. That means the drug is mostly eliminated from your system within about two days. But the antidepressant effects outlast the drug itself by a significant margin, which is part of what makes Spravato different from a typical medication you take daily.
The current understanding is that Spravato triggers a brief burst of glutamate activity in the brain lasting minutes to hours. This burst kicks off a chain of biological changes, including the growth of new synaptic connections in the prefrontal cortex, that persist for days to weeks after the drug is gone. That’s why you don’t need to take it every day to maintain its antidepressant benefit.
The Treatment Schedule
Spravato treatment is divided into two phases, and the frequency of your visits decreases over time:
- Induction (weeks 1 through 4): You visit the clinic twice per week. Your first dose is 56 mg, and subsequent doses may be increased to 84 mg based on how you respond and how well you tolerate it.
- Maintenance (week 5 onward): During weeks 5 through 8, sessions drop to once a week. Starting at week 9, many patients move to once every two weeks, though some continue weekly if needed.
There is no fixed end date for Spravato treatment. The long-term SUSTAIN-3 study tracked patients for up to 4.5 years on intermittent dosing with no new safety concerns. Most participants in that study were receiving either the 56 mg or 84 mg dose, either weekly or every other week, to stay stable. The treatment is designed to continue as long as it’s working, and the decision to stop or adjust is made on an individual basis.
How Long the Antidepressant Effect Lasts
A single Spravato dose does not produce a permanent mood improvement. The antidepressant benefit from each dose carries you through to the next session, which is why the dosing schedule is spaced days apart rather than months. During the induction phase, depression scores drop substantially. In the SUSTAIN-3 trial, patients saw an average improvement of nearly 13 points on a standard depression scale during induction, and that improvement held steady through the maintenance phase.
By the end of the maintenance period in that trial, 46.1% of patients were in remission, meaning their depression symptoms had dropped to minimal levels. This is a notable figure given that every participant had treatment-resistant depression, meaning they had already failed to improve on multiple other antidepressants.
What Happens If You Stop
The relapse data makes a strong case for continuing treatment once it’s working. In a controlled trial, patients who had achieved stable remission on Spravato were either kept on the drug or quietly switched to a placebo spray while continuing their oral antidepressant. Among those switched to placebo, 45% relapsed. Among those who stayed on Spravato, 27% relapsed. Continuing Spravato cut the risk of relapse by 51% in patients who had achieved remission and by 70% in those who had achieved a stable response without full remission.
Relapse in these studies was defined as depression scores climbing back above a moderate threshold on two consecutive assessments, or hospitalization for worsening depression. So the stakes of stopping are not trivial, particularly for people whose depression hadn’t responded to other treatments. This doesn’t mean you can never stop Spravato, but the decision should be deliberate and closely monitored rather than abrupt.
Putting the Timelines Together
If you’re preparing for your first Spravato appointment, expect the in-office experience to take about 2 to 3 hours total, including the spray administration and mandatory monitoring. Plan to have someone drive you home, and write off driving for the rest of that day. The strongest sensations peak around 40 minutes in and fade well before you leave.
For the first month, you’ll be going to the clinic twice a week. After that, visits taper to once a week and eventually to every other week for most patients. There’s no predetermined stopping point. The long-term data supports staying on treatment for years if it continues to help, and the risk of relapse is real if you discontinue. Your provider will periodically reassess whether the benefit justifies continuing.