Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders

Ceban, Felicia; Rosenblat, Joshua D.; Kratiuk, Kevin; Lee, Yena; Rodrigues, Nelson B.; Gill, Hartej; Subramaniapillai, Mehala; Nasri, Flora; Lui, Leanna M.W.; Lipsitz, Orly; Kumar, Anil; Lee, Jung Goo; Chau, Edmond; Cao, Bing; Lin, Kangguang; Ho, Roger; Mansur, Rodrigo B.; Swainson, Jennifer; McIntyre, Roger S.

doi:10.1007/s40263-021-00846-5

Cited by 40 publications

(27 citation statements)

References 56 publications

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“…Similar to psilocybin use, significant increases in lifetime or past year use were exclusively observed in adults 26+, perhaps also due to reports suggesting therapeutic effects of ketamine for mood disorders, paired with a surge of attention in popular media to potential benefits of ketamine ( Dodge, November 4, 2021 ). While ketamine treatment for psychiatric disorders is shown to be safe under supervised use ( Serafini et al, 2014 ), illicit use may be more prone to adverse effects ( Ceban et al, 2021 ) or dissociative symptoms ( Morgan et al, 2009 ). Increases in use up to 2019 occurred simultaneously with FDA approval of esketamine, an antidepressant administered as a nasal spray derived from ketamine ( Food and Drug Administration, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Controlled Substances Act ( Belouin & Henningfield, 2018 ), empirical studies have brought a resurgence of attention to potential risks and benefits related to their use, which have recently resulted in multiple state initiatives to reevaluate their legal status ( Ballotpedia, 2020 , California Legislative Information, 2021 ). Multiple risks associated with recreational illicit use of these hallucinogens, including memory impairment ( Morgan et al, 2014 ), dysphoria or anxiety ( Bienemann et al, 2020 , Carbonaro et al, 2016 ), delusional thinking among frequent (>4x/week) ketamine users ( Morgan, Muetzelfeldt, & Curran, 2009 ), and effects that mimic psychosis ( Kapur & Seeman, 2002 ), which can lead to significant distress ( Ceban et al, 2021 ). When hallucinogenic drugs are purchased and used illicitly, individuals may lack information about safe use, including dosing, and therefore may be more at risk for these adverse effects.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Use of plant-based hallucinogens and dissociative agents: U.S. Time Trends, 2002–2019

Walsh

Livne

Shmulewitz

et al. 2022

Addictive Behaviors Reports

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use of plant-based hallucinogens and dissociative agents: U.S. Time Trends, 2002–2019

Walsh

Livne

Shmulewitz

et al. 2022

Addictive Behaviors Reports

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“…Administration of ketamine requires practitioner expertise with treatmentemergent adverse events (TEAEs) and/or related safety concerns. Short-term ketamine treatment in TRD patients may be associated with neuropsychiatric (dissociative, psychotomimetic, psychiatric, and neurologic), cardiovascular, gastrointestinal, genitourinary, and hepatic adverse events [56]. However, the discontinuation rate of ketamine due to TEAEs is moderately low in TRD patients.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review

Sukhram

Yilmaz

2022

Oxidative Medicine and Cellular Longevity

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Background. Major depressive disorder (MDD) and treatment-resistant depression (TRD) represent a global source of societal and health burden. To advise proper management of inflammation-related depression among TRD patients, it is important to identify therapeutic clinical treatments. A key factor is related to proinflammatory cytokines such as interleukin-(IL-) 1β, IL-6, and tumor necrosis factor-(TNF-) α which have been implicated in the pathogenesis of depressive symptoms in MDD patients. Ketamine may provide an anti-inflammatory therapeutic strategy by targeting proinflammatory pathways associated with depressive disorders, which may be exacerbated in the ageing population with TRD. Objective. Despite a burgeoning body of literature demonstrating that inflammation is linked to TRD, there is still a lack of comprehensive research on the relationship between proinflammatory biomarkers and ketamine's antidepressant effect on TRD patients. Method. The Cochrane Library and PubMed/MEDLINE databases were systematically searched from inception up to February 1, 2022, adopting broad inclusion criteria to assess clinical topics related to the impact of ketamine on inflammatory cytokines in TRD patients. The present work is in compliance with the World Health Organization Rapid Review Guide. Results. Five out of the seven studies examined in this review show that ketamine infusion may reduce depressive symptoms with a quick start of effect on TRD patients. Based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D) scores, the overall response rate for ketamine was 56%; that is, 56% of those treated with ketamine had MADRS/HAM-D scores decreased by at least 50%. Conclusions. While the anti-inflammatory effects of ketamine modulate specific proinflammatory cytokines, its rapid antidepressant effect on TRD patients remains inconsistent. However, our study findings can provide a reliable basis for future research on how to improve systemic inflammatory immune disorders and mental health. We suggest that ketamine infusion may be part of a comprehensive treatment approach in TRD patients with elevated levels of depression-specific inflammatory biomarkers.

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“…Ketamine is an anesthetic of N-methyl-D-aspartic acid receptor (NMDA receptor) antagonist, which can produce unique dissociative anesthesia ( 1 – 3 ). Ketamine contains equal parts of the ( S )-ketamine enantiomer (esketamine) and ( R )-ketamine enantiomer ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Both ketamine and esketamine have dissociative side effects ( 5 ). The dissociative effects include loss of self, inability to move the body, and isolation of mind from the body ( 3 ). The symptoms are similar to schizophrenia, and called schizophrenia-like changes.…”

Section: Introductionmentioning

confidence: 99%

Midazolam Attenuates Esketamine-Induced Overactive Behaviors in Mice Before the Sedation, but Not During the Recovery

et al. 2022

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Esketamine showed more potency, more rapid recovery from anesthesia, and less psychotomimetic side effects when compared with ketamine. However, the patients still experience psychotomimetic side effects of esketamine. In order to investigate whether midazolam can attenuate the esketamine-induced overactive behaviors and neuronal hyperactivities, midazolam 0, 40, 80, and 120 mg/kg combined with esketamine 50 mg/kg were administrated on Kunming mice to assess the behaviors changes during anesthesia. The indicators, including action time, duration of agitation before the sedation, duration of sedation, duration of loss of pedal withdrawal reaction (PWR), duration of loss of righting reaction (RR), duration of agitation during the recovery, and recovery time, were monitored for up to 3–4 h after intraperitoneal administration. The results demonstrated that midazolam 40, 80, and 120 mg/kg efficiently decreased the esketamine-induced overactive behaviors including ataxia, excitation, and catalepsy before sedation. Midazolam and esketamine synergically improved the anesthesia quality assessed by PWR and RR. However, even high doses of midazolam were not able to suppress the esketamine-induced psychotomimetic effects during the recovery.

show abstract

Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders

Cited by 40 publications

References 56 publications

Use of plant-based hallucinogens and dissociative agents: U.S. Time Trends, 2002–2019

Use of plant-based hallucinogens and dissociative agents: U.S. Time Trends, 2002–2019

Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review

Midazolam Attenuates Esketamine-Induced Overactive Behaviors in Mice Before the Sedation, but Not During the Recovery

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