What clinicians need to know about intranasal esketamine for treatment-resistant depression?
Judith D. Hope, David Copolov, John Tiller, M. Galbally, Malcolm Hopwood, Richard Newton, Nick Keks
Australasian Psychiatry November 14, 2023 DOI: 10.1177/10398562231211171 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Population | Adults with treatment-resistant depression in pivotal esketamine trials |
| Interventions | Esketamine oral antidepressant |
| Duration | 4-week treatment phase; 6-month follow-up after withdrawal in stable remitters |
| Topics | Depression Esketamine Ketamine |
| Key findings | Intranasal esketamine plus an oral antidepressant produced 37% higher remission at four weeks than placebo plus antidepressant, with comparable improvement in suicidality. Relapse occurred in 45% of stable remitters after esketamine withdrawal over six months versus 25% who continued it. The authors conclude esketamine is moderately effective and acceptably tolerable, but note cost and the need for long-term use and abuse vigilance. |
Abstract
Objective: To review the usefulness of esketamine for treatment-resistant depression.
Method: Pivotal trials of intranasal esketamine in treatment-resistant depression were synthesized as a narrative review.
Results: Esketamine is postulated to act through antagonism of N-methyl-D-aspartate (NMDA) glutamate receptors, but opioidergic effects may also be involved. Unlike intravenous ketamine, esketamine is given intranasally (under clinical observation), usually in addition to an oral antidepressant. Trials compared esketamine plus antidepressant versus placebo plus antidepressant. At 4 weeks, remission was 37% higher with esketamine/antidepressant than placebo/antidepressant. Speed of response and improvement in suicidality were comparable. In stable remitters on esketamine/antidepressant, 45% relapsed when esketamine was withdrawn over the following 6 months (whereas 25% relapsed on esketamine/antidepressant). Response appears less likely in patients with multiple antidepressant failures. Adverse effects include dissociation, dizziness, nausea, sedation, and headache but no psychosis. Hypertension affected 13%, especially older patients. Dose frequency is twice-weekly for 4 weeks, then weekly/fortnightly thereafter. No abuse has been reported. Unsubsidised cost may be beyond the reach of many Australians.
Conclusion: Intranasal esketamine plus antidepressant has been approved by regulators as moderately effective and acceptably tolerable for treatment-resistant depression. Cost is a drawback. Use often needs to be long-term and vigilance for abuse is essential.
Comparable studies
Other narrative reviews on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |