|
1
|
Mario A, Ivana L, Claudia MM, Antonello B, Francesco P, Tommaso C, Madia L. Can ketamine therapy overcome treatment-resistant depression in Alzheimer's disease and older adults? Preclinical and clinical evidence. Biomed Pharmacother 2025; 188:118199. [PMID: 40412361 DOI: 10.1016/j.biopha.2025.118199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2025] [Revised: 05/11/2025] [Accepted: 05/21/2025] [Indexed: 05/27/2025] Open
Abstract
Treatment-resistant depression (TRD) presents substantial clinical challenges, particularly in patients with Alzheimer's disease (AD) and older adults experiencing late-life depression. Traditional monoaminergic therapies often fail in this population due to neurodegenerative changes that impact receptor dynamics and neurotransmitter systems. Emerging evidence suggests that N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, esketamine, and arketamine, may offer new avenues for treatment. This review examines the potential of ketamine and its derivatives in treating TRD in older adults and individuals with AD, focusing on their mechanisms of action, clinical efficacy, and limitations in the context of neurodegenerative pathology. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic search of PubMed, Google Scholar, and Web of Science databases up until January 2025, with no year restrictions. Nineteen human clinical studies and eight preclinical studies met the inclusion criteria. Evidence suggests that ketamine may offer advantages over standard treatments for AD, potentially due to its broader mechanism of action compared to the NMDA antagonist memantine, as observed in animal models of AD. Clinical findings have demonstrated the rapid and robust antidepressant effects of ketamine and esketamine, alleviating depressive symptoms in both AD patients and older adults with TRD, indicating their potential as effective therapeutic options for these complex conditions.
Collapse
Affiliation(s)
- Altamura Mario
- Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy.
| | - Leccisotti Ivana
- Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
| | | | - Bellomo Antonello
- Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
| | - Panza Francesco
- Cesare Frugoni" Internal and Geriatric Medicine and Memory Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Cassano Tommaso
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Lozupone Madia
- Department of Translational Biomedicine and Neuroscience "DiBrain", University of Bari Aldo Moro, Bari, Italy
| |
Collapse
|
|
2
|
Caliman-Fontes AT, Vieira F, Leal GC, Carneiro BA, Quarantini-Alvim Y, Andrade TV, Mello RP, Gadelha A, Lacerda ALT, Quarantini LC. Ketamine for catatonia: A novel treatment for an old clinical challenge? A systematic review of the evidence. Schizophr Res 2024; 271:355-370. [PMID: 39098303 DOI: 10.1016/j.schres.2024.07.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 07/27/2024] [Accepted: 07/29/2024] [Indexed: 08/06/2024]
Abstract
INTRODUCTION Catatonia, documented since the 19th century, remains a significant challenge in terms of recognition and treatment. Over the last two decades, ketamine has brought new perspectives to psychiatry, sparking widespread interest. Concurrently, catatonia has attracted heightened scientific attention. Preliminary evidence suggests the therapeutic potential of ketamine for catatonia. METHODS We systematically searched Medline/PubMed, Embase, PsycINFO, Lilacs, and Cochrane Library databases, as well as Google Scholar, for studies with ketamine or its enantiomers as intervention for catatonia, with no restrictions to underlying diagnosis, date, language, or study design. RESULTS Twenty articles were included, encompassing a total of 25 catatonic patients receiving ketamine or esketamine. Predominantly female (61.9 %), with a mean age of 44.4 years, patients mostly exhibited manifestations compatible with the retarded subtype of catatonia. Mood disorders were the most prevalent underlying diagnoses. Ketamine was primarily administered intravenously over a 40-minute period and in multiple-dosing schemes. Mean response and remission rates of catatonic manifestations for the whole sample were 80 % and 44 %, respectively, with no reports of worsening catatonic features or psychotic symptoms. Only one patient discontinued treatment due to intolerable dissociative effects. CONCLUSION Challenging the conventional contraindication of ketamine in psychotic disorders, current evidence highlights its potential efficacy, particularly in treating catatonia. Pending further research, we advocate reevaluating this contraindication, as it may offer a promising therapeutic option, especially for challenging cases. Preliminary evidence suggests potentially greater benefits for catatonic patients with underlying mood disorders compared to primary psychotic disorders.
Collapse
Affiliation(s)
- Ana Teresa Caliman-Fontes
- Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Flávia Vieira
- Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Gustavo C Leal
- Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Beatriz A Carneiro
- Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Yana Quarantini-Alvim
- Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Taiane V Andrade
- Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Rodrigo P Mello
- Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Ary Gadelha
- Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Acioly L T Lacerda
- Programa de Transtornos Afetivos, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Lucas C Quarantini
- Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
| |
Collapse
|
|
3
|
Kapoor A, Peguero Estevez T, Chan C, Yamagata N, Doumlele K, Tampi R. Is there evidence for using ketamine among individuals with dementia? J Int Med Res 2024; 52:3000605241258473. [PMID: 38907362 PMCID: PMC11193926 DOI: 10.1177/03000605241258473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 05/13/2024] [Indexed: 06/23/2024] Open
Abstract
The aim of this short narrative review was to evaluate the existing literature regarding the clinical use of ketamine among individuals with dementia, especially those with behavioral disturbances. PubMed, Cochrane, and Ovid (Embase, APA PsycINFO, and MEDLINE) databases were searched for abstracts using the search terms "ketamine" AND "dementia." Only articles describing the use of ketamine in individuals with dementia were included. Articles that did not include individuals with dementia, did not use ketamine, were published in a non-English language, primarily described animal studies, or were reviews were excluded. Three case reports met the inclusion criteria. One described the use of subcutaneous ketamine for depression, one described the use of intramuscular ketamine for acute agitation, and one described the use of S-ketamine as anesthesia during electroconvulsive therapy for depression and catatonia. No significant adverse effects were reported in any of the cases. Although the use of ketamine in the treatment of depression and agitation associated with dementia has potential, the current evidence remains limited. High-quality prospective studies are needed to confirm the observations of these case reports before ketamine can be used to treat behavioral disturbances in individuals with dementia.
Collapse
Affiliation(s)
- Arushi Kapoor
- University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America
| | | | - Carol Chan
- Case Western Reserve University School of Medicine, Cleveland, United States of America
| | - Natsuko Yamagata
- Lake Erie College of Osteopathic Medicine, Seton Hill, Greensburg, United States of America
| | - Kyra Doumlele
- Dartmouth-Hitchcock Medical Center, Lebanon, United States of America
| | - Rajesh Tampi
- Creighton University School of Medicine, Omaha, United States of America
| |
Collapse
|
|
5
|
Jaimes-Albornoz W, Ruiz de Pellon-Santamaria A, Nizama-Vía A, Isetta M, Albajar I, Serra-Mestres J. Catatonia in older adults: A systematic review. World J Psychiatry 2022; 12:348-367. [PMID: 35317341 PMCID: PMC8900590 DOI: 10.5498/wjp.v12.i2.348] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 07/27/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Catatonia is a complex psychomotor syndrome that often goes unrecognized and untreated, even though its classification has evolved in recent years. Prompt and correct identification of catatonia allows for highly effective treatment and prevention of possible complications. The underrecognition of catatonia in older patients is also frequent, and research in this population is scarce.
AIM To conduct a systematic review of the literature on catatonia in older people to ascertain its clinical characteristics across settings.
METHODS Following the PRISMA guidelines, MEDLINE, EMBASE, and PsycINFO databases were searched from inception to December 2021, with a strategy aimed at identifying all articles published on catatonia in older adults. Titles and abstracts were scanned and selected independently by two authors. Papers investigating issues related to catatonia and/or catatonic symptoms in older people, with English abstracts available, were included. References of selected articles were revised to identify other relevant studies.
RESULTS In total, 1355 articles were retrieved. After removing duplicates, 879 remained. Of the 879 identified abstracts, 669 were excluded because they did not meet the inclusion criteria. A total of 210 articles underwent full text review, and 51 were eliminated for various reasons. Fourteen more articles were selected from the references. Overall, 173 articles were reviewed: 108 case reports, 35 case series, 11 prospective cohort studies, 6 case-control studies, 3 retrospective cohort studies and 10 reviews. We found several particular aspects of catatonia in this population. Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology. Older patients, compared to younger patients, have a higher risk of developing catatonia with benzodiazepine (BZD) withdrawal, in bipolar disorder, and in the general hospital. Age, together with other risk factors, was significantly associated with the incidence of deep venous thrombosis, neuroleptic malignant syndrome poor outcome, other complications and mortality. Treatment with BZDs and electroconvulsive therapy is safe and effective. Prompt treatment of its cause is essential to ensure a good prognosis.
CONCLUSION Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology. The risk of developing catatonia in some settings and conditions, as well as of developing complications, is high in this population. Symptomatic treatment is safe and effective, and timely etiologic treatment is fundamental.
Collapse
Affiliation(s)
- Walter Jaimes-Albornoz
- Psychiatry Service, Hospital Universitario Donostia, Basque Health Service - Osakidetza, San Sebastian 20014, Gipuzkoa, Spain
| | - Angel Ruiz de Pellon-Santamaria
- Psychiatry Service, Hospital Universitario Donostia, Basque Health Service - Osakidetza, San Sebastian 20014, Gipuzkoa, Spain
| | - Ayar Nizama-Vía
- Psychiatry Service “Virgen del Cisne” Mental Health Community Center, Regional Health Directorate, Tumbes 24002, Peru
| | - Marco Isetta
- Library and Knowledge Services, Central & North West London NHS Foundation Trust, St Charles’ Hospital, London W10 6DZ, United Kingdom
| | - Ines Albajar
- Neurology Service, Hospital Universitario Donostia, Basque Health Service - Osakidetza, San Sebastian 20014, Gipuzkoa, Spain
| | - Jordi Serra-Mestres
- Old Age Psychiatry Service, Cardinal Clinic, Windsor SL4 5UL, United Kingdom
| |
Collapse
|