Ketamine: Used at Cook Children's for Treatment of Migraines, While Derivative Recently Approved for Depression

The rest of the world may soon learn what neurologists and clinical pharmacists at Cook Children’s have known for almost three years – intranasal ketamine is a groundbreaking drug with the potential to help people from all walks of life.

Cook Children’s has been utilizing intranasal ketamine as a rescue treatment to break unrelenting migraine attacks in the emergency room and inpatient setting since December 2016. Originally, the drug was utilized out of necessity due to a shortage of dihydroergotamine – the medication previously used most frequently for persistent migraine attacks which failed to respond to outpatient therapy. The team presented their findings at the International Headache Conference in 2017.

“Until that time, little to no experience with nasal ketamine had been reported in pediatric patients,” said Adrian Turner, a clinical pharmacist at Cook Children’s. “However, our institution’s experience is broadening the horizon of potential treatment options.”

Now the U.S. Food and Drug Administration has approved esketamine, a chemical compound similar to the anesthetic ketamine, to relieve depression in hours instead of weeks. The drug, the first to be approved to fight depression since 1988, is believed to help patients who have been treatment resistant to other depression therapies.

Esketamine, developed by Johnson & Johnson, will be marketed under the name Spravato® and is a nasal spray that allows the drug to be absorbed through the lining of the nose, directly to the blood stream.

Patients using Spravato® will also be required to enroll in a Risk Evaluation and Mitigation Strategy (REMS) program to monitor for serious side effects related to sedation, dissociation, abuse/misuse and to support its safe use. Patients will be required to self-administer the drug under direct observation of a healthcare provider.

“This is potentially a game changer for millions of people,” Dr. Dennis Charney, dean of the Icahn School of Medicine at Mount Sinai in New York, told NPR. “It offers a lot of hope.”

At this time, no plans have been made at Cook Children’s to use ketamine for depression, but intranasal ketamine has been vital for helping patients with severe migraines.

Intranasal ketamine for migraines not only worked for a majority of Cook Children’s patients (almost 70 percent of patients between December 2016 and October 2017), but was safe and well tolerated. Any side effects seen, some dizziness and very mild dissociative effects (i.e. feeling funny, out of body experience) were mild and didn’t last longer than one hour after administration.

No patient had to stop due to side effects.

Turner said using ketamine for migraine offers many benefits:

1. Patients don’t need an IV or injection to receive treatment.
2. The number of medications needed to treat the pain may be reduced.
3. The time needed to treat the pain may be reduced.
4. It provides patient with a wider variety of options to treat their migraine.

Ketamine was first created in the 1960s and was largely used as a battlefield anesthetic and veterinary medicine. By the 1980s, hospitals were using the drug for sedation and severe pain.

Until recently, the FDA approved the drug in patients 16 and older for general anesthesia (dental procedures, outpatient surgery, intubation). Compared to other medications used for sedation/anesthesia, ketamine is relatively safe due to less effects on breathing and blood pressure.

In the past few decades, ketamine became the focus of studies for the treatment of depression. The Department of Health and Human Services reported an estimated 16.2 million adults and 3.1 million adolescents aged 12 to 17 in the United States had at least one major depressive episode. This is especially important when considering the rates of suicide. In 2016, the Centers for Disease Control and Prevention (CDC) reported suicide as the number 10 overall cause of death with more than 44,000 deaths attributed to suicide reported. Even more troubling, suicide was reported to be the number 2 overall cause of death for people aged 10-34, number 4 for people aged 35-54, and number 8 for people aged 55-64.

“Expanding treatment options is not only beneficial to improve the quality of lives of patients with depression, but it may also help save many lives in the future. Depression can be very difficult to treat,” Turner said. “Compared to other diseases and diagnoses, depression is not a one-size fits all treatment. Expanding the treatment options is a huge benefit to patients who have exhausted several treatment options with little to no relief.”

Aside from the new indication for depression, ketamine and esketamine both have potential use in post-traumatic stress disorder (PTSD), migraines, refractory/chronic pain conditions, and seizures. There are active studies underway in the U.S. and internationally examining the use of ketamine to treat PTSD, status epilepticus, and oral ketamine to treat chronic pain in adults and children. Cook Children's Pain team is currently treating patients with chronic/refractory pain with a ketamine IV and oral ketamine.

Some may know ketamine as a party drug. Ketamine (also known as Special K, Super K, and Vitamin K among other street names) is known as a potential drug of abuse and a drug used to facilitate sexual assault crimes. When taken illegally, users often inject, snort, or smoke the drug to feelings of calmness and out of body experiences.

Unfortunately, because these are often taken in very large doses, users also experience complications such as hallucinations, immobility, amnesia, and unconsciousness. It’s especially dangerous when given in very high doses or mixed with other drugs and/or alcohol because this greatly increases the chances of serious health problems and/or death. The World Health Organization notes that ketamine is a potential drug for abuse, but the actual incidence of dependence or overdose is rare. Chronic abuse has been linked to urinary tract problems.

But under the guidance of health care providers, ketamine has been highly beneficial.

“Our experience with ketamine has been positive,” Turner said. “The success we have seen at Cook Children’s combined with the approval of esketamine for refractory depression is very exciting. As a health care professional, it is invigorating to see years of research produce positive outcomes for our patients. I look forward to seeing Cook Children’s on the forefront of contributing to this new frontier. ”