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

Zhu, Weili; Ding, Zengbo; Zhang, Yinan; Shi, Jie; Hashimoto, Kenji; Lu, Lin

doi:10.1007/s12264-016-0081-2

Cited by 80Treatment of Major DepressionElectroconvulsive Therapy StudiesTryptophan and brain disorders

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

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Zhu, Weili, Ding, Zengbo, Zhang, Yinan, Shi, Jie, Hashimoto, Kenji, Lu, Lin·2016·Neuroscience Bulletin

DOI 10.1007/s12264-016-0081-2PMC PMC5567488

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Abstract

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 N-methyl-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 fast-acting 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 side-effects. Future treatment strategies should consider using R-ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

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PSSD is a sexual dysfunction caused by both SSRIs and SNRIs.
“that is a sexual dysfunction, caused by both SSRIs and SNRIs, characterized by a decrease or absence of libido, genital anesthesia, numbness in nipples, orgasmic disorders (i.e., anorgasmia or anhedonic orgasm), erectile dysfunction, delayed or premature ejaculation, testicular pain or atrophy (in males), lack of lubrication (in females) and by psychological symptoms such as anhedonia, diff”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [125]
The Introduction (page not available) mentions SSRIs and SNRIs only as conventional antidepressants with a delayed therapeutic response. Searches for PSSD, persistent sexual dysfunction, and the claimed symptoms found no passage in our copy linking either drug class to PSSD. (LLM, conf=0.76)
Experimental — accuracy not yet measured
These sexual manifestations have been identified as a syndrome called post-SSRI sexual dysfunction (PSSD).
“These sexual manifestations have been rapidly identified as a syndrome called post-SSRI sexual dysfunction (PSSD) [125]”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [125]
The Introduction mentions SSRIs only as conventional antidepressants, while the paper’s discussion of adverse effects concerns ketamine. Searches for “post-SSRI sexual dysfunction,” “PSSD,” and persistent sexual symptoms after SSRI use found no passage identifying the claimed syndrome in our copy. (LLM, conf=0.78)
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Adverse reactions to ketamine Anaesthesia
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Ulcerative Cystitis Associated with Ketamine
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Eide PK, Stubhaug A, Breivik H, Oye I. Reply to S.T. Meller: Ketamine: relief from chronic pain through actions at the NMDA receptor. Pain 1997, 72: 289-291.

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“These effects, together with a risk of abuse and misuse, made ketamine a widespread street drug, also known as ‘Special K’ (Zhu et al., 2016).”
Background
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The Role of Ketamine in Depression #384
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Real-world patient characteristics, treatment patterns, efficacy and safety of intramuscular ketamine treatment: a retrospective cohort studyPreprint
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Special Topic on Mental Health and Addiction
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Authors: Zhu, W., Ding, Z., Zhang, Y., Shi, J., Hashimoto, K., & Lu, L.
Affiliations: Peking University (CN)
Chiba University (JP)
ORCID: Zhu, Weili
Zhang, Yinan
Shi, Jie
Hashimoto, Kenji
Venue: Neuroscience Bulletin
Publisher: Springer Science and Business Media LLC
Published: 2016-11-22
Volume: 32
Issue: 6
Pages: 557-564
ISSN: 1995-8218 (ISSN-L)
1673-7067
DOI: 10.1007/s12264-016-0081-2
PMC: PMC5567488
OpenAlex: W2554276897
Cited by: 80
References: 80
Citations by year: 2026: 2 · 2025: 6 · 2024: 4 · 2023: 7 · 2022: 13 · 2021: 9 · 2020: 11 · 2019: 14 · 2018: 8 · 2017: 5 · 2016: 1
FWCI: 1.07
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (unspecified)
Locations: Neuroscience Bulletin (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Agency for Medical Research and Development
National Natural Science Foundation of China
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: ketamine, esketamine, rapid-acting antidepressants, major depressive disorder, antidepressant safety, neurotoxicity, cognitive impairment, psychotomimetic effects, cardiovascular adverse events, enantiomers, NMDA receptor antagonists, suicide risk
MeSH terms: Animals, Antidepressive Agents, Cognition Disorders, Depressive Disorder, Major, Major Depressive Disorder, Humans, Ketamine, Substance-Related Disorders

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

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