Ketamine Clinical Studies
Ketamine was developed in 1962 by Dr. Calvin Stevens, a researcher for Parke-Davis. Scientists were looking for a rapid-onset anesthetic that was safer than PCP (phencyclidine). PCP worked well but had some adverse effects such as hallucinations and violent behavior.
Ketamine was approved by the FDA (Federal Drug Administration) in 1970. Due to its rapid onset and safety profile, it has continued to be a ‘go-to’ drug for anesthesia in emergency situations. It is still one of the most used sedation medications in emergency rooms today.
Ketamine became popular as a recreational drug known as ‘special k’. People liked its dissociative effects, meaning they were detached from reality. It was also a relatively safe party drug compared to the other options available.
This is a graph of PHQ-9 scores from one of our patients. The vertical lines indicate ketamine infusion days.
Ketamine’s main, immediate action is as an NMDA receptor antagonist. The NMDA receptor is one of the targets of glutamate, a powerful and abundant excitatory neurotransmitter. By antagonizing the action of glutamate at this site, neurons are calmed and the patient ‘dissociates’. Another receptor target of glutamate is the AMPA receptor. As ketamine blocks glutamate action at the NMDA site, glutamate stimulation at the AMPA receptor site ensues, which is thought to be the mechanism of ketamine’s anti-depressant effects. Another action of ketamine is increased protein synthesis of BDNF (brain-derived neurotrophic factor) in neurons. This is part of the ‘neuroplasticity’ that is one of the benefits of ketamine use in depression, anxiety, PTSD, fibromyalgia, and other conditions. There are multiple additional mechanisms of ketamine that are under investigation to determine how ketamine affects patients.
Ketamine can be delivered intravenously, intramuscularly, intranasally, epidurally, orally, rectally, and sublingually. The following is a list of bioavailabilities of ketamine by different modes of administration:
- Intravenously: 100%
- Intramuscularly: 93%
- Epidurally: 77%
- Intranasally: 45-50%
- Sublingually: 24-30%
- Rectally: 25-30%
- Orally: 16-20%
Ketamine has an elimination half-life of 2.5-3 hours. Norketamine, a ketamine metabolite, has an elimination half-life of 12 hours. Most of the ketamine is metabolized and then excreted by the kidneys, with a small amount excreted in the feces.
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Ketamine & Depression
Effectiveness and Safety of Ketamine for Unipolar Depression: a Systematic Review
Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression
Efficacy of ketamine therapy in the treatment of depression
Cognitive changes in patients with unipolar TRD treated with IV ketamine: A systematic review
A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression
Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review
Effectiveness and Safety of Ketamine for Unipolar Depression: a Systematic Review
Ketamine and PTSD
Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression
Ketamine and Migraines
Ketamine for Refractory Headache: A Retrospective Analysis
Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series
Ketamine and Chronic Pain
Ketamine for the Treatment of Chronic Pain: A Comprehensive Review
Systematic Review of the Use of Intravenous Ketamine for Fibromyalgia
Ketamine and Eating Disorders
Ketamine and Safety
Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions
Effectiveness and Safety of Ketamine for Unipolar Depression: a Systematic Review
Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression