After a first series, you and your clinician review how much it helped, then decide together whether to continue less often, change course or stop. Benefits can fade without a follow-up plan, so this decision matters as much as the series itself.
Part of our guide: A Patient’s Guide to Ketamine and Spravato
For Spravato, the FDA label gives a recommended schedule and calls for a benefit check. For ketamine, use for depression is off-label, with no FDA-approved maintenance schedule, so plans vary. "Integration" usually refers to therapy that helps turn any shift during treatment into changes in daily life. It is often paired with ketamine treatment, though the evidence is still early.
If you are thinking about suicide or are in danger, call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.
The first decision: did it help?
The label says evidence of benefit should be evaluated at the end of the 4-week first phase to decide whether to continue treatment for treatment-resistant depression. For depressive symptoms with acute suicidal thoughts or behavior, benefit is assessed after 4 weeks, and use beyond that has not been systematically evaluated.
A useful review looks at more than how you feel on the day:
- your scores on a depression rating scale, if your clinician uses one
- sleep, energy, appetite and concentration
- work, relationships and everyday tasks
- suicidal thoughts, if you have had them
- side effects, blood pressure and any bladder or memory concerns
- what people close to you have noticed
Not everyone responds, and no treatment should continue only out of hope. If the series did not help enough, that is useful information, and you can review other options for depression and treatment-resistant depression with your clinician.
Maintenance with Spravato
For treatment-resistant depression, the label's schedule moves from twice weekly in weeks 1 to 4 to weekly in weeks 5 to 8. From week 9 on, it is every 2 weeks or weekly. The label says frequency should be set at the least frequent schedule that maintains improvement. Your prescriber decides this with you, and every session still requires at least 2 hours of monitoring in a certified setting.
What supports this? In the label's long-term study, people who had improved and then continued Spravato with an oral antidepressant went longer before relapse than those switched to a placebo spray with an antidepressant. The estimated hazard ratio in the stable remission group was 0.49, though the label notes it did not appear constant throughout the trial.
Interim results from the SUSTAIN-3 extension study followed people for up to 4.5 years. Among those who stayed in maintenance, improvement generally persisted, 46.1% were in remission at the end of the maintenance phase, and no new safety signal appeared. Because it was open-label, had no comparison group and was run by the manufacturer, and because it reflects people who stayed in treatment, those results may look better than what a typical patient would experience.
If you miss sessions, the label says the current schedule generally continues if depression has not worsened. If symptoms worsen during maintenance, a prescriber may consider returning to the previous, more frequent schedule. Call your clinic, and do not try to make up doses in any way.
Maintenance with ketamine
Research on ketamine shows rapid effects that are often temporary. A 2022 review in Lancet Psychiatry looked at three randomized trials, eight open-label trials and 30 case reports or series. It concluded that maintenance appears to have therapeutic potential, and that side effects such as tolerance, cognitive problems, addiction and serious urinary problems seemed uncommon. The authors also stressed methodological limits and called for better long-term studies.
A 2026 expert panel reached agreement on only about a third of practical questions on ketamine and esketamine care, which shows how much remains uncertain. Questions to raise include:
- How often would sessions be, and what would allow them to be spaced out?
- How long is this expected to continue, and when is the next reassessment?
- What long-term monitoring is planned for blood pressure, bladder health, memory and misuse?
- What is the plan if the benefit fades, or if more frequent sessions are needed?
This article on how long ketamine therapy lasts discusses timing in more detail.
Long-term safety to keep watching
Some risks matter more over months and years. The label notes:
- Bladder. Ulcerative or interstitial cystitis has been reported with long-term off-label use or misuse of ketamine. No esketamine-related cases were observed in studies of up to a year, but lower urinary symptoms were more common than with placebo. Report urgency, frequent urination or pain.
- Thinking and memory. Long-term cognitive and memory impairment have been reported with repeated ketamine misuse. In 1-year and 3-year open-label trials, cognitive function remained stable on Spravato as measured.
- Misuse and dependence. Tell your clinician about cravings, wanting more frequent sessions, or using anything outside the plan.
- Blood pressure. It should be checked at every Spravato session. A substantial increase can occur after any dose.
Spravato's boxed warning continues to apply throughout maintenance:
- Sedation, dissociation and respiratory depression. Patients can become sleepy, feel disconnected, or have slowed or stopped breathing after a dose, so they must be monitored for at least 2 hours at each session and then assessed before they can leave.
- Abuse and misuse. Spravato is a Schedule III controlled substance. Risk should be weighed before prescribing and watched for during treatment.
- Suicidal thoughts and behaviors in young people. Antidepressants increased these risks in pediatric and young adult patients in short-term studies. All antidepressant-treated patients should be watched closely for worsening or new suicidal thoughts. Spravato is not approved for anyone under 18.
What integration means, and what is known
Integration has no single definition. It generally means talking through what came up during treatment and turning it into practical steps, such as re-engaging with activities, working on relationships or practicing new coping skills. It may be built into a ketamine-assisted psychotherapy program or take place with a separate therapist.
The evidence is promising in places, and it is limited:
- A 2026 systematic review of ketamine-assisted psychotherapy found 11 studies. Depressive symptoms improved across them, with some gains lasting up to six months. In the three studies with control groups, though, there were no significant differences between ketamine-assisted psychotherapy and control conditions.
- A 2026 meta-analysis of seven randomized trials of add-ons to IV ketamine found insufficient evidence for routine use. Therapy approaches involving cognitive behavioral therapy and a computer-based training showed preliminary signs of better maintenance, each in a single study.
- The 2026 expert panel also named ketamine-assisted psychotherapy as an area of continuing uncertainty.
- Separately, a 2023 review says manual-based psychotherapies offer significant relief when added to antidepressants in treatment-resistant depression, though they are not established on their own.
So integration is a reasonable thing to try and easy to value for its own sake, but no one can honestly promise that it will extend the effect of a series. Choose a therapist who can work on your actual goals and who will coordinate with your prescriber.
Building a plan beyond the sessions
- Agree on early warning signs of relapse, and write them down.
- Keep regular sleep and routines where you can, and plan for stressful periods.
- Decide who to call if your mood drops between visits.
- Review any other medicines with your prescriber, and do not stop antidepressants on your own.
- Agree on what would lead you to pause or end treatment, and how to do it safely.
This article on the role of therapy during ketamine treatment offers more background.
Where to learn more
See Mind Body Seven's pages on Spravato, ketamine therapy and psychedelic integration therapy. A consultation is a good place to discuss what follow-up would look like for you.
FAQs
How long does maintenance last?
No fixed length has been established. Your clinician should reassess regularly, using the least frequent schedule that keeps you well and revisiting whether treatment is still needed.
What happens after stopping?
Symptoms may return, and how fast varies. Plan any stop with your prescriber and agree on what to watch for. Do not stop antidepressants or other medicines on your own.
Can integration work happen with a current therapist?
Often yes, if your therapist is comfortable with it and can coordinate with your prescriber. Ask whether they have experience with people receiving ketamine or Spravato.
