Use of ketamine for treatment resistant depression: updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada

Summary & key facts

This paper reviews research up to mid-2023 on using ketamine to treat people whose depression did not get better with usual medicines. The authors describe how two public hospitals in Edmonton have given intravenous ketamine since 2015 and how rising demand for ongoing (maintenance) treatment led them to create safer, cheaper ways to care for patients. They found growing evidence that ketamine can help some people, but noted that big, long-term studies are still missing, so programs should use ketamine carefully and watch patients closely.

Key facts:

• Two forms of ketamine treatment—intravenous (given into a vein) ketamine and intranasal (spray) esketamine—have been shown to help people with depression that did not respond to other treatments.
• Access to these treatments is often limited by cost, how easy they are to get, and the need for medical monitoring during treatment.
• Since 2015, two public hospitals in Edmonton have offered intravenous ketamine, and demand for ongoing maintenance treatments has grown over time.
• The paper is a literature review of studies up to June 30, 2023 and also describes a community case study showing how evidence can be used in real clinics.
• The authors say the evidence for ketamine use is growing, but large, long-term comparison studies and long-term outcome data are still lacking.
• To make treatment more affordable and sustainable, public programs may add lower-cost options such as sublingual (under-the-tongue) or intranasal ketamine for maintenance care; the paper describes three such program models.
• The authors caution about prescribing ketamine outside of settings where patients can be properly monitored, because safety and long-term effects are not yet fully known.

Abstract

Background: Though intravenous (IV) ketamine and intranasal (IN) esketamine are noted to be efficacious for treatment-resistant depression (TRD), access to each of these treatments within healthcare systems is limited due to cost, availability, and/or monitoring requirements. IV ketamine has been offered at two public hospital sites in Edmonton, Canada since 2015. Since then, demand for maintenance ketamine treatments has grown. This has required creative solutions for safe, accessible, evidence-based patient care. Objectives: Aims of this paper are twofold. First, we will provide a synthesis of current knowledge with regards to the clinical use of ketamine for TRD. Consideration will be given regarding; off-label racemic ketamine uses versus FDA-approved intranasal esketamine, populations treated, inclusion/exclusion criteria, dosing, assessing clinical response, concomitant medications, and tolerability/safety. Second, this paper will describe our experience as a community case study in applying evidence-based treatment. We will describe application of the literature review to our clinical programming, and in particular focus on cost-effective maintenance treatments, long-term safety concerns, routes of ketamine administration other than via intravenous, and cautious prescribing of ketamine outside of clinically monitored settings. Methodology: We conducted a literature review of the on the use of ketamine for TRD up to June 30, 2023. Key findings are reviewed, and we describe their application to our ketamine program. Conclusion: Evidence for the use of ketamine in resistant depression has grown in recent years, with evolving data to support and direct its clinical use. There is an increasing body of evidence to guide judicious use of ketamine in various clinical circumstances, for a population of patients with a high burden of suffering and morbidity. While large-scale, randomized controlled trials, comparative studies, and longer-term treatment outcomes is lacking, this community case study illustrates that currently available evidence can be applied to real-world clinical settings with complex patients. As cost is often a significant barrier to accessing initial and/or maintenance IV or esketamine treatments, public ketamine programs may incorporate SL or IN ketamine to support a sustainable and accessible treatment model. Three of such models are described.

Topics

Mental Health Treatment and Access Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Adverse effect Depression (economics) Dosing Economics Intensive care medicine Ketamine Macroeconomics Major depressive disorder Medicine Mood Pharmacology Psychiatry Tolerability Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood