Effects of Repeated Intravenous Ketamine in Treatment-Resistant Geriatric Depression

Abstract

Purpose There is an immediate need for more sustainable, effective therapies for treatment-resistant depression in patients who do not respond to traditional psychopharmacology. The aim of this study was to determine the efficacy and safety of intravenous ketamine infusions on the elderly population by using a case series of 6 geriatric patients with treatment-resistant depression. Methods Eligible patients aged 65 to 82 were given a subanesthetic ketamine hydrochloride dose of 0.5 mg/kg delivered intravenously over 40 minutes twice weekly for an acute series. If patients reported a 50% decrease in depression symptoms after the acute series of 2 to 4 infusions, they would be moved to a maintenance series of infusions, which would occur every 2 to 6 weeks on an individual basis. Results Of the 6 patients given ketamine, 1 failed to respond to the acute treatment phase, 4 responded to the acute infusion phase but failed to sustain a response after a range of 8 to 22 maintenance infusions, and 1 responded to the infusions but relapsed into alcohol use; therefore, treatment was discontinued. Conclusions The relative safety of intravenous ketamine in the elderly was demonstrated by the mild, transient adverse effects seen by this patient group. The geriatric population is unable to maintain an antidepressant response to intravenous ketamine over time, signifying that ketamine has low efficacy for the elderly.

Current Understanding of the Neurobiology of Agitation

“…Of note, the efficacy and safety of ketamine in geriatric patients and in individuals with neuropsychiatric disorders are still being investigated and need further study, although some small studies suggest lack of significant adverse effects in these populations. 54 , 55 Finally, because doses of ketamine used to control behavior are more likely to lead to considerable sedation, with arguably less leeway to titrate to a minimal effective dose to reach a more measured state of calmness, it could be posited that this drug should not be considered as a first-line strategy, but rather reserved for refractory cases in which a rescue or second-line medication is needed.…”

Safety of Repeated Administration of Parenteral Ketamine for Depression

“…Bryant et al [ 31 ] reported on six geriatric patients (65‒82 years old) who received 8‒22 ketamine IV infusions (0.5 mg/kg over 40 min) every 2‒6 weeks, based on individual maintenance interval needs. They noted only mild, transient adverse effect.…”

Repurposing Potential of Ketamine: Opportunities and Challenges

“…[25] However, ketamine has shown low antidepressant efficacy in elderly, with mild and transient adverse effects. [26] Pro b a b l e m e c h a n i s m s re s p o n s i b l e f o r r a p i d antidepressant effects of ketamine are increase in the signalling of mammalian target of rapamycin (mTOR), increased protein synthesis via dephosphorylation of eukar yotic translation elongation factor 2, and increase in brain-derived neurotrophic factor (BDNF). Various pathways associated with the action of ketamine are tropomyosin-related kinase B (TrkB) pathway, associated downstream phosphatidylinositol-3-kinase (P13K)-Akt pathway, and glycogen synthase kinase-3 (GSK-3)-associated pathways.…”