The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease
Islam Mohammad Shehata, Waniyah Masood, Nouran Nemr, Alexandra Anderson, Kamal Bhusal, Amber N. Edinoff, Elyse M. Cornett, Adam M. Kaye, Alan D. Kaye
Neurology International June 23, 2022 DOI: 10.3390/neurolint14020025 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Keywords | Alzheimer’s disease Dementia Ndma antagonists |
| Citations | 41 |
| Key findings | Ketamine may provide neuroprotection and reduce neuropsychiatric symptoms associated with Alzheimer's disease. |
Abstract
Depression is a leading cause of disability globally, with a prevalence of 3.8% among the whole population, 5% of the adult population, and 5.7% of the elderly population over 60 years of age. There is evidence that depression is linked to certain neurodegenerative diseases, one being Alzheimer’s disease (AD). The efficacy of conventional antidepressants to treat depression in AD is conflicting, especially regarding selective serotonin reuptake inhibitors (SSRIs). A recent systemic review and meta-analysis of 25 randomized controlled trials including fourteen antidepressant medications showed no high efficacy in treating AD patients’ symptoms. However, ketamine, a nonselective N-methyl-D-aspartate (NMDA) receptor antagonist, can mediate a wide range of pharmacological effects, including neuroprotection, anti-inflammatory and anticancer properties, multimodal analgesia, and treatment of depression, suicidal attempts, and status epilepticus. Esketamine, which is ketamine formulated as a nasal spray, was approved by the Federal Drug Administration (FDA) in March 2019 as an adjuvant drug to treat treatment-resistant depression. NMDA receptor antagonists treat AD through offsetting AD-related pathological stimulation of subtypes of glutamate receptors in the central nervous system. Recent clinical findings suggest that ketamine may provide neuroprotection and reduce neuropsychiatric symptoms associated with AD. In the present investigation, we evaluate the potential role of ketamine and its postulated mechanism in AD management.
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 | |
| Personalized use of ketamine and esketamine for treatment-resistant depression. | 2024 | Review |
Citations in the library
Cited by 16
- Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. International Journal of Molecular Sciences December 5, 2024
- The diverse effects of ketamine, jack-of-all-trades: a narrative review. British Journal of Anaesthesia March 1, 2025
- A Brief Review on the Potential of Psychedelics for Treating Alzheimer’s Disease and Related Depression International Journal of Molecular Sciences August 7, 2023
- Is there evidence for using ketamine among individuals with dementia? Journal of International Medical Research June 1, 2024
- Repurposing Ketamine in the Therapy of Depression and Depression-Related Disorders: Recent Advances and Future Potential. Aging and disease April 29, 2024
and 11 more in the library
Cites 9
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. American Journal of Psychiatry January 5, 2021
- Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochemical Pharmacology July 1, 2020
- Ketamine: Neuroprotective or Neurotoxic? Frontiers in Neuroscience September 10, 2021
and 4 more in the library