This post was written by Hannah Davis, PharmD, Parkview Health.
Ketamine was first developed in 1962 and became widely used in the 1970s. During the Vietnam War, doctors used it to help wounded soldiers with pain. Later, in the 1980s, recreational misuse of the drug increased due to its ability to induce a "dream-like" state. In 1999, ketamine was classified as a controlled substance, meaning it can only be used under a doctor's supervision due to its illicit use and potential for addiction. Even with these restrictions, ketamine remains a beneficial drug. In this post, we will review what ketamine is and explore some of its modern treatment applications.
What is Ketamine?
Ketamine is a fast-acting general anesthetic that, when used properly, can help patients heal and feel better. It is currently approved by the U.S. Food and Drug Administration (FDA) to provide sedation before surgeries, dental procedures and diagnostic testing. This medication works by intercepting certain signals in the brain, like N-methyl-D-aspartate (NMDA) receptors, which block glutamate, an excitatory neurotransmitter.
In addition to ketamine's uses as an anesthetic, it's frequently prescribed off-label for the treatment of chronic conditions such as pain management, depression, epilepsy and headaches.
Uses within the hospital
Doctors may administer ketamine alone or with other medications to induce the loss of consciousness before surgery or medical procedures.
They may also give it to patients on ventilators to help manage pain and keep them comfortable.
At lower doses, providers may prescribe ketamine for acute pain relief in cases such as traumatic pain, sickle cell pain and musculoskeletal pain. Sometimes, patients receive the medication as a continuous infusion into the veins for chronic pain conditions, including nerve pain and pain associated with cancer treatments.
Emerging therapies
Treatment-resistant depression
Finding relief from depression can be frustrating, as symptoms may not improve or may improve temporarily but continue to return despite counseling or standard treatments. These are hallmark signs of treatment-resistant depression for which there are limited medication options available. However, extensive research shows ketamine and its derivative, esketamine, may offer some patients relief.
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Ketamine: Ketamine works differently than other medications for depression. Some studies show that ketamine creates more connections, or synapses, between brain cells, which eases depression. People living with depression usually have fewer of these connections. Research published by the National Institutes of Health Library of Medicine indicates that ketamine delivered as an IV infusion at low doses can provide rapid relief in treatment-resistant depression lasting for days to weeks. It's typically given in decreasing frequency over several weeks, starting with two doses a week for 2-3 weeks, then once weekly, then once monthly. Patient response rates have been as high as 70%. Ongoing studies continue to investigate ketamine as a treatment for other mental health issues such as post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and in patients with a history of psychosis. However, more research is required before it can be recommended for those conditions.
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Esketamine: Esketamine, also known by the brand name Spravato®, was approved by the FDA in 2019 as a nasal spray for adults diagnosed with treatment-resistant depression and depressive symptoms in adults diagnosed with major depressive disorder in conjunction with an oral antidepressant. It's administered in a clinic as a squirt in each nostril, followed by a two-hour monitoring period. Its rapid delivery system can ease symptoms within several hours. It is given twice weekly for 5 weeks and then reduced to once weekly, then once every two weeks. Research has shown that esketamine can significantly reduce depression symptoms and provide relief that can last weeks after treatment ends.
Migraines
Ketamine may also reduce the length and severity of migraines when given intranasally or intravenously. For migraines and most indications, it is a second – or third-line treatment when headaches or migraines do not respond to conventional treatments.
Intranasal ketamine has been found to improve the quality of life of up to 49% of patients with chronic migraines. Another study showed that it could reduce pain intensity in cluster headache patients within 30 minutes.
Intravenous ketamine may provide short-term pain relief in patients with chronic migraines and cluster headaches. One study showed that 77% of patients experienced immediate pain relief, and 40% maintained that relief for another month.
Caveats to consider
Both ketamine and esketamine are classified as Schedule III drugs, meaning they have the potential for misuse and a moderate to low potential for physical and psychological dependence. While these medications present promising options for patients with treatment-resistant depression and headaches, understanding potential side effects and using them under medical supervision is crucial.
Some side effects are more common and occur in about 1 to 10 out of 100 people and may include:
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Higher blood pressure
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Blurry vision
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Dizziness
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Nausea or vomiting
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Trouble with balance
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Difficulty focusing
More serious side effects are likely to occur in approximately 1 in 100 to 1 in 1,000 people. These include:
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Sudden jerking or shaking movements
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Hallucinations (seeing or hearing things that aren't real)
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Dissociation (feeling detached from the body or experiencing time differently)
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Confusion
Due to the potential for these side effects, ketamine and esketamine are only administered in a clinical setting, where a healthcare provider can observe patients for adverse reactions. In most cases, side effects typically arise within 2 hours of administration. Patients remain in the clinic during this time, and a provider will monitor them, checking blood pressure, heart rate and overall well-being.
Not everyone is an ideal candidate for these drugs. Patients who have been diagnosed with schizophrenia, uncontrolled or elevated blood pressure or who are pregnant or breastfeeding should not receive either medication.
Patients considering ketamine or esketamine for the treatment of a chronic condition should speak with their primary care provider or pharmacist for guidance.
References
Practical Neurology - Ketamine for intractable headaches
Harvard Health Publishing - Ketamine for treatment-resistant depression: When and where is it safe?
