Use of subcutaneous ketamine to rapidly improve severe treatment-resistant depression in a patient with Alzheimer’s disease

Rocha, Fábio Lopes; Cunha, Ulisses Gabriel de Vasconcelos; Paschoalin, Roberta Campos; Hara, Cláudia; Thomaz, Débora Pereira

doi:10.1097/yic.0000000000000334

Cited by 14 publications

(15 citation statements)

References 4 publications

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“…In this review, we found encouraging results for the SC use of ketamine in the treatment of depression. Favorable results regarding both efficacy and safety were reported in case reports (21)(22)(23)(24)(25). Data from retrospective studies (20,(26)(27)(28)(29) and two clinical trials (17,18) also confirmed efficacy and a solid tolerability profile associated with SC administration of ketamine for depression.…”

Section: Discussionmentioning

confidence: 86%

“…The third case report administered SC esketamine in a 76 year-old patient with depression and Alzheimer Disease. The patient showed improvement in depressive symptoms -dose ranged from 0.5 to 0.75 mg/kg in three sessions (eight in total, dosed twice-weekly) (25).…”

Section: Mood Outcomementioning

confidence: 99%

“…Our ability to evaluate the dose-response effect of the SC route measured in the two trials with ketamine, as well as the four retrospective studies (26)(27)(28)(29) and two case-reports (24,25) with esketamine in comparison to IV studies is limited since the latter studies used fixed doses. However, findings from dose-titration studies appear promising with patients remitting following low doses.…”

Section: Efficacymentioning

confidence: 99%

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Subcutaneous Ketamine in Depression: A Systematic Review

et al. 2021

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Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability.Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool.Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5–1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects.Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted.Systematic Review Registration: CRD42019137434

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Section: Discussionmentioning

confidence: 86%

Section: Mood Outcomementioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

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Subcutaneous Ketamine in Depression: A Systematic Review

et al. 2021

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“…Ketamine relieves depressive symptoms within hours of treatment, especially in cases where other antidepressants have failed [ 329 ]. In a case report of a 76-year-old female AD patient suffering from depression who had not responded to conventional antidepressant therapy, the patient was reported to have recovered from severe treatment-resistant depressive decline after only two doses of ketamine [ 330 ].…”

Section: Sigma Receptor Ligands For Neurological Diseasementioning

confidence: 99%

Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders

Malar,

Thitilertdecha,

Ruckvongacheep

et al. 2023

CNS Drugs

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The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in neuronal tissues. As such, they have become targets for treating neurological diseases, including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). In recent years, there have been many pre-clinical and clinical studies of sigma receptor (1 and 2) ligands for treating neurological disease. Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacological profile, are effective in treating multiple aspects of several neurological diseases. Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132. This review aims to provide a current and up-to-date analysis of the current clinical and pre-clinical data of drugs with sigma receptor activities for treating neurological disease.

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“…Comparing ketamine to memantine, the latter exhibits lower affinity to the NMDA receptors with rapid relief of its block, which allows symptomatic improvement without affecting desirable functions such as memory and learning [ 5 ]. However, ketamine showed rapid relief of major depression symptoms in patients with AD [ 31 ]. The US FDA and European Medicines Agency recently approved intranasal S-ketamine for treatment-resistant depression in conjunction with an oral antidepressant [ 32 ].…”

Section: Evidence For Ketamine Treatmentmentioning

confidence: 99%

The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease

Shehata

Masood

Nemr

et al. 2022

Neurology International

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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.

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Use of subcutaneous ketamine to rapidly improve severe treatment-resistant depression in a patient with Alzheimer’s disease

Cited by 14 publications

References 4 publications

Subcutaneous Ketamine in Depression: A Systematic Review

Subcutaneous Ketamine in Depression: A Systematic Review

Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders

The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease

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