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What is Ketamine?
Ketamine is a medication used regularly in both Emergency Departments and Operating rooms for both anesthesia and pain relief. It is a medication that is on the World Health Organization’s list of essential medications. In recent years, however, ketamine has grown in popularity as a treatment option for patients with a variety of conditions, from PTSD to migraines. Below is some information about ketamine, as well as its potential to provide pain relief.
Ketamine is a United States Food and Drug Administration-approved medication that has been used as an anesthetic since the 1970s. It is a selective agonist of the N-methyl-D-aspartate (NMDA) receptor that is similar in structure to phencyclidine, or PCP. Ketamine may also be called Ketaset, Ketanest or Ketalar.
Ketamine has a number of different effects on the body. It acts as an anesthetic, and it also produces transient memory loss. In addition, doses of ketamine can produce dissociative effects and alteration of perceptions, which is why it has been abused recreationally.
How Does Ketamine Work
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 of the other effects ketamine has on the body include:
- Bronchodilation, which increases airflow to the lungs.
- Occasionally Nausea and rarely vomiting, which 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 via virtually any route into the body. This drug can 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 via an Intravenous route. Ketamine infusions and nasal sprays are also used to treat other conditions in an out patient setting, often as an “off-label (Non FDA Sanctioned)” use of the drug.
Ketamine Side Effects
Like all medications, ketamine has certain side effects. Some of the 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
- 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 completing 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. Its use for this purpose continued to increase over the years after its approval by the FDA, causing it to eventually become a controlled substance in the United States at the end of the 1990s.
Uses of Ketamine
Ketamine can be used for more than just anesthesia and pain control. Since its discovery in 1962, it has been discovered that in sub-anesthetic doses ketamine can be a successful treatment of mood disorders including depression, PTSD and OCD, as well as anxiety and chronic pain syndromes including central sensitization syndrome, fibromyalgia and reflex simplex dystrophy. To provide 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 can be used to relieve migraine headaches. In 2019, a form of ketamine was approved for the treatment of depression.
Researchers are not sure exactly how ketamine produces its effects at lower dosages. However, 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, on May 27, 2016, updates on ketamine were presented in which new potential medical applications were identified. 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. Additionally, 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
In addition to its approved uses, ketamine is being studied for several other possible uses as well. Below is some information about the research that has been conducted and published thus far.
Ketamine for Pain
Ketamine’s efficacy as an anesthetic is well established. However. One review published by Leiden University Medical Center found that ketamine could effectively relieve pain during infusion and/or 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 it may reduce patients’ need for opioids.
Ketamine for Depression
Ketamine is already being used “off-label” to treat depression and other mood disorders, but researchers are continuing to investigate this issue in hopes of eventually gaining FDA approval. Multiple research studies on the efficacy of ketamine in the treatment of depression have been conducted. Many of these studies focused specifically on treatment-resistant depression, which is of particular interest to patients who haven’t found relief with other conventional antidepressant treatments.
Researchers have found that ketamine works as a fast-acting antidepressant even in cases of treatment-resistant depression. This drug can produce its effects in 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 indicate that ketamine is relatively safe and well-tolerated by most patients, making it an ideal treatment option.
Ketamine is a very safe medication, but like all medications, side effects may occur. To ensure your safety, a physician and a 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, be sure to report them to your doctor or nurse right away.
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 of 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. Therefore, ketamine infusions for these indications is considered to be an “off label” usage of the medication. Due to this fact, it is important to note that insurance companies and government insurance programs such as Medicaid and Medicare have not started to reimburse physicians for these infusions. Nonetheless, if you need of treatment with ketamine for one of these off-label purposes, you may pay for the treatment personally.