What is Ketamine?

About Ketamine

Ketamine is on the World Health Organization’s list of essential medications and is approved by the US Food and Drug Administration. It’s been used regularly in emergency departments and operating rooms for anesthesia and pain relief since the 1970s. It’s a selective agonist of the N-methyl-D-aspartate (NMDA) receptor that’s similar in structure to phencyclidine, or PCP. Ketamine is also known as Ketaset, Ketanest or Ketalar. It’s regularly referred to as ketamine treatment or ketamine theraputics.
In recent years, ketamine has grown in popularity as a treatment option for patients with a variety of conditions, from PTSD to migraines.

How Ketamine Works

The mechanism by which ketamine produces it’s antidepressant effects are hypothesized to include the blocking of the NMDA Receptor, interacting with the AMPA Receptor, activating mTor molecule in the cell, which in turns releases G proteins that instruct the nerve cell to grow additional dendritic spines and increase the amount of glutamate produced. Ketamine also reduces the production of nitric oxide and interacts with the opioid receptors which decreases the sensations of pain.
Some other effects ketamine has on the body include:
  • Bronchodilation, which increases airflow to the lungs
  • Occasionally nausea and rarely vomiting – these appear to be dosage-dependent
  • Cardiovascular changes that may include an increased heart rate and blood pressure

Routes of Ketamine Administration

Ketamine may be administered in the form of a pill, nasal spray, intramuscular injection, or intravenous infusion. When used in the hospital for anesthetic or pain control purposes, ketamine is usually administered intravenously. Ketamine infusions and nasal sprays are also used to treat other conditions in an outpatient setting, often as an off-label (Non FDA Sanctioned) use.

Ketamine Side Effects

Ketamine is a very safe medication, but side effects may occur. To ensure your safety, a physician and registered nurse will be present and will monitor you during the entire course of the infusion. If you experience any side effects during or after your infusion, report them to your doctor or nurse right away.
Some possible side effects of ketamine include:
  • Spasm of the vocal cords (laryngospasm)
  • Airway obstruction
  • Respiratory arrest
  • Blood pressure changes
  • Rapid heart rate
  • Slow heart rate
  • Abnormal heart rhythm
  • Increased intracranial pressure
  • Rash
  • Nausea and vomiting
  • Increased salivation
  • Low appetite
  • Visual changes
  • Pain at the injection site
All of the side effects listed above are more common when ketamine is taken in higher doses. In rare cases, ketamine may cause a serious allergic reaction known as anaphylaxis.

Discovery and History of Ketamine

Ketamine was first discovered in 1962 when it was synthesized in a laboratory. After two years of successful tests on animals, researchers began testing the drug on human subjects in 1964. The FDA first approved ketamine for use as an anesthetic in 1970, and doctors began using this drug on soldiers injured during the Vietnam War.
Because of its hallucinogenic and dissociative properties, ketamine quickly became a recreational drug as well. Following FDA approval, recreational use continued to increase, and it was classified as a controlled substance in the US in the 1990s.

Uses of Ketamine

In sub-anesthetic doses, ketamine can successfully treat mood disorders, including depression, PTSD and OCD, as well as anxiety and chronic pain syndromes including central sensitization syndrome, fibromyalgia, and reflex simplex dystrophy. For the greatest chance of prolonged remission from symptoms, a series of infusions are scheduled over a two-to-three-week period. Some studies have also shown that ketamine therapy can relieve migraine headaches. In 2019, a form of ketamine was approved to treat depression.
Multiple studies have shown promising results when ketamine is used to treat different conditions involving pain or mood disturbances. According to the World Health Organization, potential new therapeutic uses include treatment for depression and refractory status epilepticus. The use of ketamine for treating depression is under evaluation in Phase III clinical studies. As noted in the report, levels of ketamine abuse appeared to be declining in many countries worldwide. As a result, the FDA approval for the treatment of these conditions may face less resistance in the future.
Research into the efficacy of ketamine continues today. As more data is produced, it is likely that ketamine will become more widely available for patients.

Studies on Ketamine

Ketamine is being studied for several other possible uses.

Ketamine for Pain

Ketamine’s efficacy as an anesthetic is well established. However, a review published by Leiden University Medical Center found that ketamine could effectively relieve pain during infusion and for up to three months following prolonged infusion. These results indicate that ketamine could be effective in the treatment of both acute and chronic pain. Other studies have found that ketamine can be especially useful in the treatment of postoperative pain, and may reduce patients’ needs for opioids.

Ketamine for Depression

Ketamine is already being used off-label to treat depression and other mood disorders, but researchers continue investigating this issue in hopes of gaining FDA approval. Multiple research studies on the efficacy of ketamine in the treatment of depression have been conducted.
Researchers have found that ketamine works as a fast-acting antidepressant – even in cases of treatment-resistant depression. It can have an effect within hours, which offers a huge advantage over other available treatments that may take several weeks or months to work. To determine how ketamine works in the treatment of depression, researchers analyzed mice who had been exposed to substantial long-term stress. These mice exhibited loss and decreased formation of dendritic spines in the prefrontal cortex. After a single dose of ketamine, the affected mice showed evidence of new functional neuronal dendritic spines and a regression of abnormal behaviors related to depression.
According to a review published in World Psychiatry, several randomized trials have supported the use of ketamine for the treatment of depression, including bipolar depression. Additional studies mentioned in this review showed that ketamine can rapidly reduce suicidal thinking. Furthermore, the data from these studies indicates that ketamine is relatively safe and well-tolerated by most patients, making it an ideal treatment option.

Considerations for Patients with Chronic Pain and Mood Disorders

The Food and Drug Administration has approved ketamine for both anesthesia and pain control. In March 2019, a form of ketamine was even approved for the treatment of treatment-resistant depression. However, the FDA has not yet approved ketamine for the treatment of other mood disorders or chronic pain alleviation. Ketamine infusions for these indications are considered an “off label” usage of the medication. Because of this, insurance companies and government insurance programs like Medicaid and Medicare do not reimburse physicians for these infusions. However, if you need treatment with ketamine for one of these off-label purposes, you can pay for the treatment yourself.
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