Clinical History
Ketamine, sometimes known as the party drug Special K, is a compound made of two mirror-image molecules. It has long been approved as an anesthetic, is not covered by a patent, and is widely used — meaning it’s not going to make much money for a pharmaceutical company.
Ketamine has been an FDA approved anesthetic for decades and is the anesthesia of choice for children because of its excellent safety profile. Research also demonstrates efficacy for anxiety, PTSD, chronic pain, fibromyalgia, and more. However, IV ketamine remains “off label” for these purposes because it is not FDA indicated for this use. The FDA will most likely never approve ketamine for any indication other than anesthesia since the patent for ketamine has expired. Without a patent, pharmaceutical companies are unlikely to invest in the costly clinical trials necessary to meet the FDA’s requirements for approval, simply because they cannot monetize the drug.
Instead, Janssen Pharmaceuticals decided to patent the left part of the molecule or the “S” particle, hence “ESketamine”, and invested in clinical trials that led to the current FDA indicated use of nasal esketamine called Spravato, which, in the process, then legitimized the use of ketamine for depression.
Molecular Makeup
Esketamine is part of ketamine. In nature, many molecules exist as mirror images of each other, the only difference being the direction they spin. A mixture of these mirror-image molecules is called a racemic mixture. It is possible to separate racemic mixtures into what are called enantiomers. Esketamine is the s-enantiomer of ketamine.
1. Janssen Press Release.Janssen Submits Esketamine Nasal Spray New Drug Application to U.S. FDA for Treatment-Resistant Depression. Sep 2018).
Administration
Both ketamine and esketamine can be delivered intravenously, intramuscularly, or intranasally. However, intravenous delivery is the most effective when it comes to the absorption, accuracy, and efficacy of the dose.
FDA approval of esketamine for treating depression requires that the drug be administered as a nasal spray. In addition, patients must be taking another antidepressant at the same time, and it can only be given to patients who have unsuccessfully tried two antidepressants. Spravato is only available in certified clinics. Doctors must order medication for a patient and pick it up at a specialty pharmacy. The patient will self-administer the nasal spray in the doctor’s office, stay in the office for two hours of monitoring, and then be taken home. The Spravato never leaves the facility.
Treatment Dosage
Intranasal Spravato is given twice weekly for 4 weeks, then once weekly for 4 weeks, then
every two weeks to continue maintenance. The currently recommended doses are either 56 mg or 84 mg. Two hours of observation are required at each treatment before discharge.
Ketamine Infusions consists of 5-6 treatments over a 1-2 week period. Subsequent
maintenance occurs every 2 to 4 months. A single treatment takes approximately 40 minutes.
Side Effects
Potential side effects for both drugs include sedation and mild dissociation. On awakening from an IV infusion, patients may experience blurred vision, feelings of lightness, and, rarely, headache or nausea (prevented by including an iv anti-nausea medication with the infusion).
In addition to the same side effects from IV administration, intranasal doses may also cause vertigo, decreased sensitivity, anxiety, and vomiting.
Success Rate/Effectiveness
Some studies have shown that more than 70-80 percent of those who try IV ketamine feel better. And 45% of nasal ketamine patients find relief.
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677048/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185009/
Mechanism of Action
Ketamine/esketamine modulates glutamate NMDA receptors resulting in an increased production of neurotrophic factors (particularly BDNF) that repair damaged neurons and improve neuronal connectivity within the brain.
Costs
Johnson & Johnson list the wholesale cost of Spravato to be $590 for the 56 mg dose and $885 for the 84mg dose. In the first month that would cost $4,720 to $6,785 before facility fees.
Ketamine treatments usually cost a few hundred dollars per infusion, but the expense comes not from the generic drug, which is cheap, but from the doctors’ time and the clinic space.
Covered by Insurance
FDA approval and insurance coverage are not simultaneously guaranteed or guaranteed with the same clinical guidelines. It is yet to be determined how the insurance companies will cover the costs of Spravato, or what clinical guidelines will be required for authorization of coverage.
Ketamine Infusions or IVs are not currently covered by insurance.
Conditions Treated
Spravato is indicated, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD). Ketamine Infusion Therapy has been found effective in treating TRD, PTSD, Bipolar Depression and multiple chronic pain conditions.
Research demonstrates that ketamine is also an effective treatment for TRD when used intravenously (IV) in low doses (approximately 1/10 of anesthetic doses). More recently, research also demonstrates efficacy for anxiety, PTSD, chronic pain, fibromyalgia, and migraines.
For more information on Ketamine Therapy, contact Dr. Newman and Virginia Ketamine Therapy, 757-258-2561 or visit vaketaminetherapy.com.
