General Literature.

Wilson (2013) wrote on “Ketamine: Old dog, new tricks” that Ketamine, an intravenous anaesthetic agent, has a long history of clinical use despite its unpleasant side effects and the advent of newer anaesthetic agents. Originally described in 1965 and approved for clinical use in 1970, ketamine's popularity waned due to its negative side effects. However, in recent years, there has been renewed interest in the drug due to its unique mechanism of action and ability to interact with various receptors, including N-methyl-D-aspartate (NMDA), opioid, monoamine, cholinergic, purinergic, and adenosine receptors. In addition to its traditional use as an anaesthetic, ketamine is now being explored for its potential in alternative clinical settings, such as the treatment of major depressive illness, potentiation of opioid analgesia, sedation and anaesthesia in traumatic brain injury, prevention of opioid-induced acute tolerance, and anti-inflammatory and anti-tumour actions. Studies have shown that ketamine's mechanism of action involves noncompetitive antagonism at the NMDA receptor and inhibition of tumour necrosis factor-alpha and interleukin-6 gene expressions in activated macrophages, in addition to its local anaesthetic effects.

 

Mion (2017), discussed the history of ketamine in anaesthesia and highlighted how concerns about its psychedelic effects, coupled with the arrival of new intravenous hypnotics such as propofol, led to a decline in the use of ketamine in affluent countries. However, in the past two decades, numerous studies have fundamentally transformed our understanding of ketamine. The finding, that the glutamate N-methyl-D-aspartate (NMDA) calcium channel receptor was responsible for inducing synaptic plasticity,  helped them appreciate how memory, thinking, and consciousness are the result of synaptic plasticity and the fine tuning of glutamatergic influences through NMDA receptor-mediated phenomena. Nowadays, ketamine is being employed to treat patients with treatment-resistant depression. Unlike ordinary antidepressants, ketamine can act within hours rather than weeks, making it a potential fast-acting antidepressant in patients with a high risk of suicide.

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Walsh et al. (2020) conducted a comprehensive systematic review on the use of ketamine for treating mental health and substance use disorders. Their findings showed that systematic reviews and meta-analyses provide evidence supporting the robust, rapid, and transient antidepressant and anti-suicidal effects of ketamine. While evidence for other indications is less robust, the results suggest similarly positive and short-lived effects. However, caution should be exercised when interpreting these conclusions due to the high risk of bias in the included studies. Further research is needed to determine optimal dosing, modes of administration, and the most effective forms of adjunctive psychotherapeutic support.

 

Ketamine has brought about a significant paradigm shift not only in the treatment of depression and suicidality but also in a range of other conditions.

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Pribish (2020) wrote a review of non-anesthetic uses of Ketamine. He found articles related to ketamine in the treatment of depression, pain syndromes including acute pain, chronic pain, and headache, neurologic applications including neuroprotection and seizures, and alcohol and substance use disorders. It can be concluded that ketamine has a potential role in the treatment of all of these conditions. However, research in this area is still in its early stages, and larger studies are required to evaluate ketamine’s efficacy for non-anesthetic purposes in the general population.

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Nowacka and Borczyk (2019) published a literature review entitled "Ketamine applications beyond anesthesia," which highlighted the growing interest in the drug's potential therapeutic uses. Recent intensive research has revealed new possible applications for ketamine, such as in acute, chronic, and cancer pain management. There are also reports highlighting the possible use of ketamine in treating addiction, asthma, preventing cancer growth, and even in animal models of schizophrenia. With numerous possible applications, the use of ketamine has once again gained popularity. However, caution must be exercised as the mechanisms by which ketamine functions and its long-term effects are not yet fully understood.

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See for more literature on Depression, Anxiety, Substance Abuse, Other Mental Health Conditions, Chronic Pain, Other Conditions.

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Other useful general articles

• Ketamine: a paradigm shift for depression research and treatment (2020)

• Ketamine—50 years in use: from anesthesia to rapid  antidepressant effects and neurobiological mechanisms (2021)

• Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature (2022)

• Toward Synergies of Ketamine and Psychotherapy (2022)