What we know now: Ketamine maintenance can work, but only under specific conditions
Regular, scheduled maintenance dosing is far more effective than ad-hoc or variable dosing. A 2025 systematic review of 11 studies found that patients on a fixed maintenance schedule had a relapse rate of 27.3%, compared to 45.6% for those on variable protocols — a difference of nearly 20 percentage points [1]. This means that if you're going to use ketamine long-term, consistency in timing and dose matters a lot.
Younger patients and those with a shorter history of depression respond best. The same review found that being under 45 years old and having had depression for less than 2 years predicted better outcomes [1]. This suggests that maintenance therapy is not a one-size-fits-all solution and that patient selection is critical.
Combining ketamine with psychotherapy improves the odds of staying well. The systematic review reported that concurrent psychotherapy reduced the risk of relapse by 28% (hazard ratio 0.72) [1]. This is a key practical point: ketamine is not a standalone fix — it works best as part of a broader treatment plan.
Intranasal ketamine is a feasible and well-tolerated maintenance option, though data are very preliminary. A 2025 pilot study of 5 patients found that intranasal racemic ketamine spray (mean dose 220 mg) maintained or improved depressive symptoms and quality of life over up to 192 days, with no serious adverse events [3]. However, the sample is tiny, so effectiveness conclusions cannot be drawn yet.
What was previously believed: Ketamine was a quick fix with no long-term role
Earlier thinking held that ketamine's antidepressant effects were too short-lived to justify maintenance therapy. A 2022 Canadian health technology review confirmed that while ketamine works rapidly, the effects fade after a few weeks, and guidelines from Denmark and Canada recommend against routine use or only as a third-line option because of the lack of long-term efficacy data and abuse risk [4]. This caution remains valid — the new evidence doesn't overturn it, but it does suggest that with careful patient selection and regular dosing, maintenance may be viable for some.
Another old assumption was that ketamine maintenance was too risky or impractical for public health systems. A 2024 Australian report from the first public hospital ketamine clinic in the country acknowledges that delivering these treatments is resource-intensive and perceived as difficult in the public sector, which has historically limited access to the private sector and worsened mental health inequity [5]. The report shows that public implementation is possible, but it requires dedicated infrastructure and careful planning.
The catch: Safety is reassuring in the short term, but long-term risks are not well understood
Adverse effects are generally mild to moderate, but they are real. The systematic review found a discontinuation rate of only 7.2% due to side effects [1], and the intranasal pilot study reported no serious adverse events [3]. Common side effects include anxiety, nausea, and transient increases in blood pressure [3][4]. These are manageable in a clinical setting, but they mean patients need monitoring.
The bigger unknown is long-term safety. The Canadian review specifically flags the risk of abuse and the lack of strategies for relapse prevention after stopping ketamine [4]. The systematic review also notes that standardized protocols and optimal maintenance duration are still unknown [1]. So while the short-term safety profile is good, we don't yet know what happens after a year or more of regular use.
Evidence for conditions other than depression is even thinner. A 2023 case report on fibromyalgia found that a 60-year-old patient achieved >50% pain relief with a maintenance regimen of two monthly IV infusions [2]. But this is a single case — not enough to guide clinical practice.
About These Sources
This answer is built on 5 peer-reviewed studies — published from 2022 to 2025, 3 from 2024 or later, 1 in Q1–Q2 journals — selected as the most relevant from 5 studies that passed quality screening, drawn from 47 papers retrieved from a database of over 500 million.
Sources used in this answer
Efficacy and safety of ketamine maintenance therapy in treatment-resistant depression: A systematic review of treatment protocols and clinical outcomes.
A 2025 systematic review of 11 studies found that regular maintenance ketamine dosing reduced relapse rates to 27.3% versus 45.6% for variable dosing, and that younger age (<45) and shorter depression duration (<2 years) predicted better response; concurrent psychotherapy reduced relapse risk by 28% (HR 0.72).
Maintenance IV Ketamine Therapy in the Fibromyalgia Patient: A Case Report
A 2023 case report on a 60-year-old fibromyalgia patient found that a 9-session IV ketamine induction followed by maintenance infusions (two monthly, one day apart) provided >50% pain relief, suggesting higher doses and longer infusions may be needed for pain.
Intranasal racemic ketamine maintenance therapy for patients with treatment-resistant depression: a naturalistic feasibility study.
A 2025 pilot study of 5 patients with treatment-resistant depression found that intranasal racemic ketamine maintenance (mean 220 mg) was feasible and well tolerated over up to 192 days, with no serious adverse events and stable or improved depressive symptoms and quality of life.
Ketamine for Adults With Treatment-Resistant Depression or Post-Traumatic Stress Disorder
A 2022 Canadian health technology review found mixed evidence for repeated IV ketamine in PTSD and short-lived antidepressant effects; Danish and Canadian guidelines recommend against routine use or only as third-line due to insufficient long-term efficacy and abuse risk.
Implementation of a ketamine programme for treatment-resistant depression in the public health system: Lessons from the first Australian public hospital clinic.
A 2024 Australian report from the first public hospital ketamine clinic describes the resource-intensive nature of delivering ketamine treatment in the public sector, highlighting that it is possible but requires dedicated infrastructure and careful planning to avoid worsening mental health inequity.