Can ketamine maintenance therapy produce durable improvements in real-world settings?

How long do the benefits of maintenance ketamine actually last?

The durability of ketamine maintenance therapy varies widely by patient and treatment schedule, but the evidence shows that with regular infusions, improvements can be sustained for many months. In a large retrospective analysis of 9016 patients from 178 community clinics, those who responded to an initial course of 4-8 ketamine infusions had roughly an 80% probability of still being in response at 4 weeks and about 60% at 8 weeks, even without any maintenance treatments [4]. This suggests that the acute effect itself can persist for a short time, but the real durability comes from ongoing maintenance. Another study of 452 patients receiving intramuscular ketamine found that with maintenance treatments, average depression scores (measured by PHQ-9) improved by 38% from baseline and anxiety scores (GAD-7) by 50%, and these improvements were maintained for over 7 months [2]. Similarly, a 2025 study of 110 patients with treatment-resistant major depression and 25 with bipolar depression who continued maintenance infusions showed that depression and suicidality scores remained significantly lower than baseline for weeks to months, with no cases of suicidal behavior during treatment [7].

However, the durability is not indefinite without continued care. A small open-label study of 18 patients who completed six ketamine infusions found that 61% maintained their response immediately after the protocol, but all but one relapsed within one month after stopping treatment entirely [8]. This highlights a key point: ketamine maintenance therapy appears to work as long as it is continued, but it does not produce a permanent cure. The longest maintenance cycles reported in one study averaged 61 weeks for intravenous ketamine and 48 weeks for intranasal esketamine, with patients receiving a median of 14 and 28 treatments respectively [1]. So, for patients who stay on a regular schedule, the benefits can last a year or more.

Does maintenance ketamine work for the most severe or complex cases?

Yes, the evidence shows that even patients with highly treatment-resistant depression can benefit from maintenance ketamine, though the degree of improvement may be somewhat less for those who have failed many prior treatments. A systematic review and meta-analysis of 79 real-world studies (totaling 2665 patients) found that the overall response rate was about 45% and remission rate about 30%, with a large effect size (Hedges g = 1.44) [5]. Importantly, the analysis showed that the more treatment-resistant cases were less likely to achieve full remission, but they still showed a significant response—meaning even the most difficult-to-treat patients often get meaningful symptom reduction [5]. The same meta-analysis confirmed that the therapeutic effect does not significantly decline with repeated treatments, so maintenance therapy remains effective over time [5].

Ketamine also works for bipolar depression, which is often considered harder to treat. In a study of 66 patients with treatment-resistant bipolar I or II depression, four ketamine infusions over two weeks produced a 35% response rate and 20% remission rate, with significant reductions in suicidal thoughts and anxiety [6]. A separate maintenance study of 25 bipolar patients found that improvements persisted with ongoing infusions, and only one patient (4%) experienced a switch to hypomania, which was managed without stopping treatment [7]. For post-traumatic stress disorder (PTSD), a large analysis of 8136 patients found that ketamine infusions were associated with clinically meaningful reductions in PTSD symptoms (average 22-point drop on the PCL-5 scale by the sixth treatment) and depression symptoms (7-point drop on PHQ-9), with the biggest gains in the first three sessions [9]. So, across multiple severe and complex conditions, maintenance ketamine shows real-world effectiveness.

What are the catches and risks?

The main catch is that ketamine maintenance therapy requires a long-term commitment to regular treatments, and it does not work for everyone. Across the studies, about 30-50% of patients did not achieve a meaningful response [4][5]. Additionally, a small but real minority of patients may worsen: one large study found that 8.4% of patients experienced an increase in depressive symptoms after the initial induction phase, and 6.0% reported increased suicidal ideation [4]. This means careful monitoring is essential, especially early in treatment.

Safety is generally good but not zero. In a cohort of 452 patients receiving intramuscular ketamine, adverse events occurred during only 2.3% of 2532 treatments, and these were typically mild (e.g., transient dissociation, nausea) [2]. In the large ELEKT-D trial comparing ketamine to electroconvulsive therapy (ECT) for treatment-resistant depression, ketamine was associated with dissociation during infusion, while ECT was linked to memory problems and musculoskeletal side effects [3]. No cases of addiction or suicidal behavior were reported in the maintenance studies [7], and treatment-emergent hypomania in bipolar patients was rare (4.5% in one study, 4% in another) [6][7]. However, the evidence base is still growing, and long-term risks (e.g., bladder toxicity with very frequent use) are not fully captured in these short-to-medium-term studies.

Another practical catch is that the durability of effect depends on the route of administration. Intravenous ketamine appears to allow longer intervals between treatments (average 18.9 days) compared to intranasal esketamine (average 10.8 days) [1], meaning IV ketamine may be more convenient for maintenance. But IV infusions require clinic visits, which can be a barrier for some patients.

About These Sources

This answer is built on 9 peer-reviewed studies — published from 2022 to 2025, 4 from 2024 or later, 7 in Q1 journals, collectively cited 487 times — selected as the most relevant from 9 studies that passed quality screening, drawn from 51 papers retrieved from a database of over 500 million.

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