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

Researchers reviewed the medical literature up to June 30, 2023 and described how a public ketamine program in Edmonton, Canada has used that evidence since 2015. They found growing support that intravenous ketamine and a similar nasal spray called esketamine can help people whose depression has not improved with usual treatments. The paper also explains how clinics can use cheaper or easier ways to give ketamine, what safety issues to watch for, and why more large and long-term studies are still needed.

Key facts:

• The paper is a literature review plus a real-world case report of a public ketamine service in Edmonton that has been running since 2015.
• Both intravenous ketamine and intranasal esketamine are reported to be effective options for people with depression that has not responded to other treatments.
• Access to these treatments is often limited because of cost, how available they are, and the need for medical monitoring during treatment.
• Demand for ongoing, or maintenance, ketamine treatments grew at the Edmonton sites and led staff to look for safer and more affordable ways to keep patients treated.
• The authors describe that sublingual (under-the-tongue) or intranasal ketamine can be used in public programs to help make treatment more sustainable and accessible.
• The review notes that evidence is growing but there are still few very large, well-controlled studies and limited information on long-term outcomes and safety.
• The paper covers practical issues clinicians face, such as who should or should not get ketamine, dosing, how to judge if it is helping, interactions with other medicines, and tolerability or side effects.

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 Poor sleep Sadness or low mood