Who is most likely to benefit from ketamine maintenance therapy?

Who benefits most from ketamine maintenance therapy?

The clearest answer from the evidence is that people with treatment-resistant depression (TRD) who are younger and have had depression for a shorter time are the strongest candidates. A 2025 systematic review found that patients under age 45 and those with depression lasting less than 2 years had better response rates to maintenance ketamine [3]. This suggests that intervening earlier in the course of illness, before the depression becomes entrenched, may maximize the benefit.

For people with TRD who do respond to an initial course of ketamine, sticking to a regular maintenance schedule is critical. The same review reported that regular maintenance dosing led to a relapse rate of only 27.3%, compared to 45.6% with variable or inconsistent dosing [3]. This means nearly half of those on irregular schedules relapsed, versus just over a quarter on regular schedules — a substantial difference that underscores the importance of consistency.

Another group that appears to benefit is people with chronic pain who also misuse substances like opioids or benzodiazepines. A 2026 observational study of 20 chronic pain patients found that monthly intramuscular ketamine (0.25 mg/kg) improved pain from severe to moderate, mood from moderately severe to mild, and reduced substance dependence severity to satisfactory levels [4]. While this is a small study, it points to a potential dual benefit for this complex population.

Does the dose and type of ketamine matter?

Yes, and the evidence is consistent: higher doses and racemic ketamine (the standard form) outperform lower doses and esketamine (a purified version). A large 2023 meta-analysis of 49 randomized controlled trials with 3,299 participants found that high-dose racemic ketamine produced the strongest antidepressant effects immediately after the first dose (standardized mean difference -0.73), and these effects persisted during repeated dosing and even after treatment stopped [1]. In contrast, esketamine's effects were weaker and did not last as long — its ongoing effects during repeated dosing were not significantly better than placebo [1].

This pattern was confirmed in a naturalistic study of 77 hospitalized patients with multiple treatment-resistant depression. High-dose intravenous ketamine (0.75-1 mg/kg) produced the most pronounced clinical effects, with 28.9% of patients responding and 15% achieving remission after five weeks of twice-weekly treatment [2]. Importantly, the initial response to the first few doses was highly predictive of the final outcome, meaning that if a patient responds early, they are likely to continue benefiting [2].

For chronic pain conditions like fibromyalgia, a case report described a 60-year-old woman who achieved over 50% pain relief after a series of nine IV ketamine infusions, and then maintained that relief with two monthly maintenance infusions [6]. While this is only a single case, it suggests that maintenance therapy may also be viable for pain, though standardized protocols are still lacking.

Is ketamine maintenance therapy safe and practical?

Overall, the evidence indicates that ketamine maintenance therapy is safe and well-tolerated when properly monitored. Across the studies, side effects were generally mild to moderate, and discontinuation rates were low — just 7.2% in one systematic review [3]. In the inpatient study of 77 patients, none of the reported side effects required medical intervention [2]. Serious problems like addiction, cognitive impairment, or urinary issues appear to be uncommon [5].

However, the practical challenge is that protocols are not yet standardized. The 2022 systematic review noted that while intravenous, intranasal, oral, and even intramuscular routes have all been used successfully, there is no consensus on the optimal dose, frequency, or duration of maintenance therapy [5]. The 2025 review echoed this, calling for standardized protocols and careful patient selection [3]. For now, treatment is often individualized, and patients need to work closely with a specialist to find what works for them.

One promising finding is that combining ketamine maintenance with psychotherapy may improve outcomes. The 2025 review found that concurrent psychotherapy reduced the risk of relapse by 28% (hazard ratio 0.72) [3]. This suggests that ketamine may open a window of neuroplasticity that therapy can then capitalize on, making the combination more effective than either alone.

About These Sources

This answer is built on 6 peer-reviewed studies — published from 2022 to 2026, 3 from 2024 or later, 3 in Q1 journals, collectively cited 273 times — selected as the most relevant from 6 studies that passed quality screening, drawn from 45 papers retrieved from a database of over 500 million.

Sources used in this answer

Related research questions