In SUSTAIN-1, patients in stable remission who continued Spravato had a 51 percent lower relapse risk than those switched to placebo. Maintenance is weekly or every two weeks at the lowest frequency that holds remission. One-year data show no cognitive decline. Tapering is possible after sustained stability, but relapse risk is highest in the weeks after stopping.
This page covers what those studies found, how we set the maintenance schedule at Stedfast Psychiatry, what the long-term safety data show and do not show, and how we approach tapering. The honest summary: continuing Spravato roughly halves the risk of relapse, most people who respond stay well on every-one-to-two-week dosing, a year of continuous use has not shown cognitive or organ harm, and stopping is possible for some patients but carries a real relapse risk.
Who it is for
Patients finishing Spravato induction who responded and want to know what comes next; patients on maintenance wondering whether to continue, space out or stop; and patients deciding whether to start, who want to understand the long-term commitment. It also addresses patients who relapsed after stopping and are considering restarting.
How it works
The antidepressant effect of esketamine comes from synapse regrowth in stressed brain circuits. Those new connections are reinforced by repeated dosing and by the activity that follows, including therapy, sleep and engagement. Without reinforcement, they can be pruned back if the underlying stress biology is still active, and depression returns. Maintenance dosing supplies the reinforcement at the longest interval that holds. The interval is individual: in SUSTAIN-1 about half of stable remitters could stretch to every two weeks, and the rest needed weekly dosing. We use rating scale scores at each visit to find your interval and to catch early drift before it becomes a relapse.
In SUSTAIN-1, 26.7 percent of stable remitters who continued esketamine relapsed over the follow-up period versus 45.3 percent on placebo, a 51 percent reduction in relapse risk; among stable responders, 25.8 percent versus 57.6 percent relapsed, a 70 percent reduction.
Source: Daly et al., JAMA Psychiatry, 2019
In SUSTAIN-2, an open-label study of 802 patients treated for up to one year, 76.5 percent of patients in the maintenance phase were responders and 58.2 percent were in remission at endpoint, and 6.9 percent discontinued because of adverse events.
Source: Wajs et al., Journal of Clinical Psychiatry, 2020
Across SUSTAIN-2, there was no evidence of decline on a computerized cognitive battery over 52 weeks, and urinary tract symptoms were infrequent and resolved.
Source: Wajs et al., Journal of Clinical Psychiatry, 2020
In SUSTAIN-1, most relapses in the placebo arm occurred within the first several weeks after esketamine was withdrawn, and about half of remitters could be maintained on every-two-week dosing.
Source: Daly et al., JAMA Psychiatry, 2019
What to expect
From week 9, sessions are weekly or every two weeks, each with the same preparation, dosing, two-hour monitoring and ride home. We measure the PHQ-9 at every session and the MADRS periodically. If you have been in remission for at least four weeks on weekly dosing, we try every two weeks. If scores rise, we go back to weekly. Every few months we discuss whether to continue, space further or taper. Insurance reauthorization typically happens every three to six months and requires documented response, which the scores provide. Most patients settle into a stable rhythm by month three or four and describe the sessions as a scheduled reset rather than a burden.
Benefits
- Relapse risk roughly halved by continuing Spravato in stable remitters, and reduced about 70 percent in stable responders, in a randomized trial
- More than three quarters of patients who entered a one-year maintenance study were still responding at the end
- No cognitive decline on standardized testing through 52 weeks
- Interval individualized with rating scales, so many patients need only two sessions a month
- Tapering is an option with a plan, not a cliff
Risks and side effects
Session side effects do not accumulate but do recur at every dose: dissociation, dizziness, nausea, sedation and blood pressure rise. Long-term concerns specific to maintenance: urinary symptoms (ulcerative cystitis is documented in chronic ketamine misuse; rare, mild urinary symptoms were seen in the one-year study and resolved); cognitive effects (none found through one year); and dependence (not seen in the REMS structure, but we monitor for craving or escalating requests). The main clinical risk of maintenance is spacing too fast; the main risk of stopping is relapse, which was most frequent in the first weeks after discontinuation in SUSTAIN-1.
Cost and insurance
Maintenance is covered by most commercial plans and Medicare, usually with reauthorization every few months based on documented response. The manufacturer savings program has an annual cap that patients on weekly maintenance may reach late in the year. Moving to every-two-week dosing halves the annual drug cost and visit count. See our cost and insurance page.
The maintenance evidence in detail
SUSTAIN-1: does continuing matter?
SUSTAIN-1 enrolled patients who had responded to esketamine plus an oral antidepressant during induction and stabilization, then randomized them to continue esketamine or switch to a placebo spray while continuing the antidepressant. Among those in stable remission, 26.7 percent relapsed on continued esketamine versus 45.3 percent on placebo, a 51 percent reduction in relapse risk. Among those who were stable responders but not in full remission, the numbers were 25.8 versus 57.6 percent, a 70 percent reduction. The trial was stopped early because the benefit was clear. Two points from the data shape how we practice: relapses in the placebo arm clustered in the first weeks after withdrawal, and about half the remitters could be held on every-two-week dosing.
SUSTAIN-2: is a year safe?
SUSTAIN-2 followed 802 patients on open-label esketamine for up to 52 weeks. Of those who entered the maintenance phase, 76.5 percent were responders and 58.2 percent were in remission at the end. Side effects were the familiar session effects, with 6.9 percent discontinuing because of them. A computerized cognitive battery showed no decline. Urinary symptoms were uncommon and resolved. Blood pressure effects did not increase over time.
SUSTAIN-3: beyond a year
The long-term extension followed more than 1,100 patients for several years. Response and remission rates stayed stable, and no new safety signals emerged. This is open-label data without a control group, so it cannot prove efficacy, but it is the longest safety follow-up for any ketamine-based antidepressant.
Maintenance decision table
| Situation | What we usually do |
|---|---|
| Remission for 4 or more weeks on weekly dosing | Move to every 2 weeks |
| Scores rise meaningfully at every 2 weeks | Return to weekly for 4 to 8 weeks, then retry |
| Stable remission 6 to 12 months, first or second episode, no prior relapse on stopping | Discuss a gradual taper |
| Stable remission but history of multiple relapses or chronic depression | Continue every 2 weeks long term |
| Partial response plateau | Dose increase to 84 mg; consider adding TMS; reassess diagnosis and other factors |
| Loss of response after prior remission | Review sleep, alcohol, stress, medications; dose increase; if persistent, move to next option |
| New urinary or cognitive symptoms | Evaluate; lengthen interval or pause |
What makes maintenance work better
- Keep the oral antidepressant. The maintenance trials used esketamine plus an antidepressant; monotherapy maintenance data are shorter.
- Therapy during the plastic window. The days after a session appear to be a period of heightened learning. CBT or behavioral activation scheduled then may take better.
- Sleep, alcohol and stress. All three directly affect synaptic maintenance. Alcohol in particular undermines the response.
- Track scores. A rising PHQ-9 two sessions in a row is the signal to tighten the interval, before you feel fully unwell.
Realistic expectations
Most patients who respond to Spravato stay well on maintenance. A minority relapse despite it, and a minority can stop and stay well without it. We cannot tell in advance which group you will be in, and the only way to find out whether you still need it is a careful taper with a plan to restart. Spravato is a treatment for a chronic illness, and like most treatments for chronic illness, it works for as long as you use it in most people. That is not a failure of the drug; it is what depression is.
Spravato at Stedfast Psychiatry
We offer Spravato at three Palm Beach County offices, each with a dedicated monitoring room and staff trained under the Spravato REMS program:
- Boynton Beach: 10301 Hagen Ranch Rd, Suite D720, Boynton Beach, FL 33437
- Palm Beach Gardens: 11641 Kew Gardens Ave, Suite 209, Palm Beach Gardens, FL 33410
- Royal Palm Beach: 420 South State Road 7, Suite 112, Royal Palm Beach, FL 33414
Call the office nearest you or request an appointment online. The first step is an evaluation, in person or by telehealth, to confirm you are a candidate and to start insurance authorization.
Frequently asked questions
How long do you stay on Spravato?
There is no fixed limit. Many patients continue every-two-week maintenance for a year or more; some taper after six to twelve months of stability and remain well on an oral antidepressant and therapy; some stop, relapse and restart. We revisit the question every few months based on your scores, your history of relapse and your preference. Patients with a long history of recurrent episodes usually do better staying on maintenance.
What happens if I stop Spravato?
In the SUSTAIN-1 trial, people in stable remission who were switched to placebo relapsed at nearly twice the rate of those who continued, with most relapses in the first weeks. Not everyone relapses; roughly half stayed well for the length of the study without the drug. If you want to stop, we taper rather than stop abruptly, keep your oral antidepressant and therapy in place, and schedule check-ins so that a relapse is caught early and Spravato can be restarted.
Is long-term Spravato use safe?
Through one year of continuous use in SUSTAIN-2, and in longer follow-up from the SUSTAIN-3 extension, there was no cognitive decline, no new safety signals and infrequent, resolving urinary symptoms. That is reassuring but not the same as decades of data. We minimize exposure by using the longest interval that holds remission, and we monitor cognition and urinary symptoms in maintenance patients.
Can Spravato be done every two weeks?
Yes. Every two weeks is one of the two labeled maintenance intervals, and about half of stable remitters in SUSTAIN-1 were maintained on it. We move you to every two weeks after at least four weeks of remission on weekly dosing. If scores drift upward, we return to weekly for a stretch and try again later.
Does Spravato stop working over time?
Tolerance has not been a consistent finding. In the one-year and long-term extension data, response rates were stable over time rather than fading. Some individual patients do find the effect lessening; when that happens we look for other explanations first (sleep, alcohol, stress, medication changes), consider a dose increase to 84 mg if on 56, and reassess the diagnosis. A small number of patients do lose response, and for them we move to TMS or other options.
How do you taper off Spravato?
Gradually, from your stable interval. A typical taper goes from every two weeks to every three weeks for two or three sessions, then every four weeks, then stop, with PHQ-9 checks at each step and for several months afterward. Your oral antidepressant and therapy continue. If scores rise meaningfully at any step, we hold or step back. The goal is to find out whether you still need it without risking a full relapse.
Can I restart Spravato after stopping?
Yes. Patients who relapse after tapering generally respond again when Spravato is restarted, and prior response is one of the better predictors of future response. Depending on how long you have been off and how severe the relapse is, we may restart at maintenance frequency or repeat a shortened induction. Insurance usually reauthorizes a restart with documentation of the relapse.
Where this treatment is offered
- Boynton Beach, FL
10301 Hagen Ranch Rd, Suite D720 and Suite B710 - Palm Beach Gardens, FL
11641 Kew Gardens Ave, Suite 209 - Royal Palm Beach, FL
420 South State Road 7, Suite 112
Conditions this treats
If you are in crisis, call or text 988 or go to the nearest emergency room. Educational content; individual results vary. Reviewed by Dr. David Husted, board-certified psychiatrist.