How to Structure Maintenance Ketamine Treatment for TRD
How did this clinic start, taper, and reassess maintenance ketamine or esketamine treatment for adults with treatment-refractory depression?
After acute improvement with ketamine-based treatment, clinicians need a practical way to decide who should enter maintenance, how fast to space treatments, and when to stop or restart an acute series. This article describes a real-world symptom-guided maintenance workflow used for both intravenous ketamine and intranasal esketamine.
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Identify patients eligible to enter maintenance
Offer maintenance treatment after the acute phase only to patients who showed at least a partial response or clinically meaningful improvement. In this clinic, partial response was defined as more than 25% reduction in QIDS from baseline, or the patient could subjectively report significant improvement supported by clinical evaluation during the acute phase. Only patients who progressed to maintenance were included in the analysis.
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Begin with four weekly maintenance treatments
After an initial positive response, most patients transitioned to the next phase with 4 weekly treatments. This served as the starting maintenance schedule before attempting to widen intervals. The goal was to determine the optimal frequency needed to sustain antidepressant benefit.
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Gradually extend intervals if response is maintained
If the patient maintained a positive response, progressively reduce treatment frequency rather than stopping abruptly. In this protocol, treatments were initially spaced to every 2 weeks, then every 3 weeks, then every 4 weeks, and then every 5 to 6 weeks if response continued. Once a clinical response was established at an optimal interval, patients continued treatment at that frequency.
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Adjust frequency based on symptom recurrence
Personalize the maintenance interval according to depressive symptoms during follow-up. If symptoms recurred or the response was being lost, increase treatment frequency to maintain symptom stability. The article summarizes the approach as progressively extending intervals when symptoms improved and tightening them again when symptoms returned.
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Periodically review whether further tapering is possible
Conduct periodic collaborative reviews to see whether the frequency can be reduced further. If patients were able to maintain their response at 6-week intervals, discontinuation of treatment was considered after 2 cycles. This makes tapering and discontinuation an active, planned part of maintenance care rather than a one-time decision.
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Reassess after two consecutive maintenance treatments with loss of response
If a patient lost positive response status after 2 consecutive maintenance treatments, trigger a formal case review. In this clinic, at least 2 ketamine clinic clinicians reviewed the case to decide whether ongoing treatment remained appropriate. If continued treatment was judged inappropriate, ketamine treatment under this protocol was stopped and the patient was referred back to the primary health care team.
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Modify the plan or repeat an acute series when appropriate
For patients considered appropriate to continue ketamine therapy after review, clinicians collaboratively determined the dose and frequency of ongoing treatment and the number of additional infusions before the next review. If response was completely lost, the clinic offered a repeat acute series using the same procedural review process. In this study, a new cycle was considered when more than 60 days had passed since the previous infusion.
Clinical Considerations
- This was a real-world clinic protocol rather than a randomized tested maintenance algorithm.
- The maintenance approach was individualized, so it should be understood as a symptom-guided framework rather than a fixed schedule proven superior by trial evidence.
- The findings are not generalizable to patients without treatment-refractory depression.
- The study also reported 3 suicide attempts during IV ketamine maintenance, underscoring that maintenance scheduling does not remove the need for ongoing suicide risk assessment.
Bottom Line
A practical maintenance workflow after acute ketamine response is to start with 4 weekly treatments, then widen intervals stepwise according to symptoms, with formal multidisciplinary review after loss of response across 2 consecutive maintenance sessions.
