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Long-term maintenance therapy with ketamine infusions for treatment-resistant depression: a retrospective chart review

E. Peters, A. Al Hasani, K. Shukla, K. Halpape

European Psychiatry June 1, 2026 DOI: 10.1192/j.eurpsy.2026.10592 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Retrospective chart review Peer reviewed
Sample size 56
Population Outpatients with treatment-resistant depression receiving intravenous ketamine therapy in Saskatchewan, Canada
Intervention Ketamine
Duration Up to 365 days of maintenance therapy
Measures 17-item Hamilton Depression Rating Scale (HAM-D)
Topics Depression Esketamine Ketamine
Key findings Long-term maintenance therapy with intravenous ketamine can be continued for up to a year alongside conventional treatment. During this time, roughly a third of patients may experience a persistent depressive symptom exacerbation of unknown clinical significance.

Abstract

Introduction: Ketamine therapy for treatment-resistant depression has a well-established rapid antidepressant effect for acute symptom management. However, there is far less research on the efficacy of long-term maintenance therapy for relapse prevention.

Objectives: To examine the utility of long-term maintenance therapy with ketamine infusions delivered in a naturalistic treatment setting.

Methods: We conducted a retrospective chart review of data from 56 outpatients with treatment-resistant depression receiving intravenous ketamine therapy in Saskatchewan, Canada. Depressive symptoms were assessed before each treatment session with the 17-item Hamilton Depression Rating Scale (HAM-D). The lowest HAM-D score after 3-6 infusions marked the start of maintenance therapy. From this point forward, Kaplan-Meier survival curves were used to estimate the probability of relapse (i.e., HAM-D score increase ≥ 25%, for two consecutive visits) over the next 365 days.

Results: Patients received, on average, 14 maintenance infusions over 253 days. The average number of days between infusions, per patient, was 25.5 ( SD = 8.86). Average HAM-D scores at the start of maintenance ( M = 17.2, SD = 7.31) did not increase by the final session ( M = 16.5, SD = 8.81; t = -0.94, p = .35). After 365 days, the estimated relapse rate was 21-36% depending on the minimum HAM-D score required to define a relapse. The average time to the start of a relapse was approximately 6 months, but individual times ranged from 14 to 328 days.

Conclusions: Long-term maintenance therapy with intravenous ketamine can be continued for up to a year alongside conventional treatment. During this time, roughly a third of patients may experience a persistent depressive symptom exacerbation of unknown clinical significance. More research is needed to determine the nature of these symptom exacerbations. Disclosure of Interest None Declared

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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