Psychiatric safety of ketamine in psychopharmacology research

Perry, Edward; Cramer, Joyce A.; Cho, Hyun Sang; Petrakis, Ismene L.; Karper, Laurence P.; Genovese, Angelina; O’Donnell, Elizabeth; Krystal, John H.; D’Souza, Deepak Cyril

doi:10.1007/s00213-007-0706-2

Cited by 108 publications

(91 citation statements)

References 42 publications

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“…Future treatment strategies need to be developed to decrease the risk of adverse events associated with long-term ketamine treatment for depression. Impairment of learning and memory [36] 50 and 100 ng/mL Impairment of episodic memory and recognition memory [37] 0.23 and 0.5 mg/kg Impairment of executive function [45] 0.54 mg/kg Mild increases in blood pressure [52] 0.23 mg/kg Adverse events related to mental status [47] 0.5 mg/kg Psychotomimetic effects [40,78] 0.3 and 0.5 mg/kg Cardiovascular side-effects [8,49] 18.5 g/week Uropathy [56] …”

Section: Discussionmentioning

confidence: 99%

“…There is no evidence that repeated ketamine exposure increases psychotic, perceptual, euphoric, or anxiogenic responses [46]. Ketamine administration at sub-anesthetic doses has been consistently shown to present an acceptable level of risk in healthy individuals throughout their participation in a study [47].…”

Section: Cognitive Effects Of Ketaminementioning

confidence: 99%

“…Ten significant adverse events associated with mental status were documented in 833 healthy individuals who received sub-anesthetic doses of ketamine intravenously [47]. These events included self-reported sensations of ''very unpleasant,'' ''no control, not a good feeling,'' ''weird,'' ''panicky,'' and ''too high, walls closing in,'' nightmares, insomnia, a lower ability to concentrate, tearfulness, and no response to verbal and painful stimuli [47]. Most of these events resolved within minutes after the cessation of ketamine administration, and they all improved within 4 days and were not present after 2 weeks.…”

Section: Effects Of Ketamine On Adverse Events Associated With Mentalmentioning

confidence: 99%

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Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

et al. 2016

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Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive Nmethyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fastacting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related sideeffects. Future treatment strategies should consider using Rketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

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Section: Discussionmentioning

confidence: 99%

Section: Cognitive Effects Of Ketaminementioning

confidence: 99%

Section: Effects Of Ketamine On Adverse Events Associated With Mentalmentioning

confidence: 99%

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Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

et al. 2016

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“…In healthy volunteers, ketamine reliably results in acute impairments in learning and memory (Krystal et al, 1994;Krystal et al, 1999;Krystal et al, 2005;Morgan et al, 2004;Parwani et al, 2005;Perry et al, 2007). Most studies of neurocognition in healthy volunteers have utilized a dosing strategy distinct from what has been utilized in clinical trials for depression to date.…”

Section: Introductionmentioning

confidence: 99%

Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

Murrough

Burdick

Levitch

et al. 2014

Neuropsychopharmacol

116

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The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current study, 62 patients (mean age ¼ 46.2 ± 12.2) with TRD free of concomitant antidepressant medication underwent neurocognitive assessments using components of the MATRICS Consensus Cognitive Battery (MCCB) before and after a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in a 2:1 fashion under double-blind conditions and underwent depression symptom assessments at 24, 48, 72 h, and 7 days post treatment using the Montgomery-Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment was conducted once at 7 days. Neurocognitive performance improved following the treatment regardless of treatment condition. There was no differential effect of treatment on neurocognitive performance and no association with antidepressant response. Slower processing speed at baseline uniquely predicted greater improvement in depression at 24 h following ketamine (t ¼ 2.3, p ¼ 0.027), while controlling for age, depression severity, and performance on other neurocognitive domains. In the current study, we found that ketamine was devoid of adverse neurocognitive effects at 7 days post treatment and that slower baseline processing speed was associated with greater antidepressant response. Future studies are required to further define the neurocognitive profile of ketamine in clinical samples and to identify clinically useful response moderators.

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“…Intravenous ketamine, a dissociative anaesthetic, has been reported to alleviate major depression [1] and chronic pain [2] with minimal adverse effects [3,4], although perceptual disturbances are not uncommon [5]. Hallucinogen persisting perception disorder (HPPD) is an illness arising from the abuse of hallucinogens in which individuals suffer visual pseudohallucinations for months to years following exposure to LSD and similar drugs [6].…”

Section: Introductionmentioning

confidence: 99%