Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing
Jennifer Swainson, L. Klassen, Stefan Brennan, P. Chokka, M. Katzman, Robert Tanguay, Atul Khullar
CNS Drugs February 14, 2022 DOI: 10.1007/s40263-022-00897-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | sublingual |
| Topics | Addiction Depression Esketamine Ketamine |
| Citations | 42 |
| Key findings | Ketamine misuse risks appear similar to those of stimulants or benzodiazepines, and non-parenteral ketamine is a reasonable treatment option for select treatment-resistant depression cases. |
Abstract
Intravenous (IV) ketamine is increasingly used off-label at subanesthetic doses for its rapid antidepressant effect, and intranasal (IN) esketamine has been recently approved in several countries for treating depression. The clinical utility of these treatments is limited by a paucity of publicly funded IV ketamine and IN esketamine programs and cost barriers to private treatment programs, as well as the drug cost for IN esketamine itself, which makes generic ketamine alternatives an attractive option. Though evidence is limited, use of non-parenteral racemic ketamine formulations (oral, sublingual, and IN) may offer more realistic access in less rigidly supervised settings, both for acute and maintenance treatment in select cases. However, the psychiatric literature has repeatedly cautioned on the addictive potential of ketamine and raised caution for both less supervised and longer-term use of ketamine. To date, these concerns have not been discussed in view of available evidence, nor have they been discussed within a broader clinical context. This paper examines the available relevant literature and suggests that ketamine misuse risks appear not dissimilar to those of other well-established and commonly prescribed agents with abuse potential, such as stimulants or benzodiazepines. As such, ketamine prescribing should be considered in a similar risk/benefit context to balance patient access and need for treatment with concern for potential substance misuse. Our consortium of mood disorder specialists with significant ketamine prescribing experience considers prescribing of non-parenteral ketamine a reasonable clinical treatment option in select cases of treatment-resistant depression. This paper outlines where this may be appropriate and makes practical recommendations for clinicians in judicious prescribing of non-parenteral ketamine.
Comparable studies
Other narrative reviews on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| Can psychedelic compounds play a part in drug dependence therapy? Patients with substance dependency | 2015 | Review | |
| Therapeutic potential of ketamine for alcohol use disorder. | 2021 | Review | |
| Ketamine, an Old–New Drug: Uses and Abuses | 2023 | Review | |
| The therapeutic use and efficacy of ketamine in alcohol use disorder and alcohol withdrawal syndrome: a scoping review Humans with alcohol use disorder or alcohol withdrawal syndrome | 2023 | Scoping review |