The FDA Just Approved a Ketamine-Like Nasal Spray for People With Treatment Resistant Depression

September 11, 2018

On Monday, the maker of Spravato, a nasal spray previously approved by the FDA as a treatment for patients with major depression, was approved for patients experiencing “acute suicidal ideation or behavior,” said Janssen, the manufacturing company. The nasal spray is used in conjunction with an oral antidepressant.

The antidepressant was first approved by the FDA in March 2019, achieving several firsts in the process. It’s the first new antidepressant to be approved in decades, the first antidepressant to work in an entirely new way, the first to come in the form of a nasal spray, and the first to work in a short period of time, rather than in weeks or even months. And for people suffering from major depression, where no other medication has worked, it has the potential to offer a new chance at recovery.

The news brings a lot of hope and excitement – but there are a few caveats.” People are saying it’s a game-changer because it seems to work well for refractory depression, meaning people who don’t respond to traditional antidepressants and behavioral treatments,” Dr. Soonjo Hwang, a psychiatrist at the University of Nebraska Medical Center, told Health when the drug was originally approved.” Additionally, it seems to work within 24 to 48 hours, so there’s a very quick solution to symptoms.”

Timothy B. Sullivan, M.D., chair of psychiatry and behavioral sciences at Northwell Health at the University Hospital of Staten Island, echoed these thoughts.” There are a significant number of people suffering from major depression who either partially respond or do not respond well to currently available treatments. Anything that promises to help address the needs of this population is very exciting.”

The drug was originally approved for treating patients with drug-resistant depression, meaning those who did not respond to “at least two antidepressant treatments given at a dose of sufficient duration in the current episode,” according to the FDA. as with any new drug, it comes with a number of issues, as the clinical studies conducted prior to FDA approval were limited in the number and type of patients it included.

In the case of esketamine (sold as Spravato), one of those concerns is that it is related to ketamine, which has been used as an anesthetic and to get high in the form of the once-popular party drug Special K. There is a concern that this new antidepressant may carry the risk of addiction and substance abuse.

Esketamine appears to help alleviate depression by acting on NMDA/glutamate receptors, unlike the more recent popular antidepressants. But Esketamine also seems to have an effect on the opiate system. It’s not a direct effect, but a “downstream” effect, Dr. Sullivan said, yet there is a clear potential impact on public health.

“My concern is that we don’t really understand how it keeps people from being depressed,” Dr. Mark George, a psychiatrist and neurologist at the Medical University of South Carolina in Charleston, told Health.” There are complex interactions with different neurotransmitter systems. If this works through NMDA and glutamate mechanisms, that’s great, but if it works through the opiate system, we need to be prepared.”

According to the study published in the journal Science, ketamine works by restoring the microcircuitry portion of the brain’s prefrontal cortex. The new technique allowed researchers to access the brains of living mice. Their findings suggest that ketamine speeds up the healing process after a depressive state.

The data so far suggests that esketamine is safe to use, “but it must be used in a very well regulated manner to prevent problems associated with addiction/substance use,” says Dr. Huang.

This includes obtaining the drug at a certified doctor’s office or clinic. According to the U.S. Food and Drug Administration, nasal sprays are used by patients themselves under the supervision of a medical professional. Nasal sprays never leave the office and must be taken along with oral antidepressants. Patients can only leave the medical facility after the nursing staff says it is okay (usually about two hours).

The FDA’s official approval also warns of possible side effects such as sensory sedation and problems with attention, judgment and thinking (called “dissociation”). Patients are required to sign a form stating that they understand they need to make arrangements to return home safely and that they cannot drive or use heavy machinery on the day they receive the medication.

About 16 million people in the U.S. suffer from major depression, a third of whom do not respond well to available treatments and therefore may be considered to have treatment-resistant depression.

“We definitely need better treatments,” says Dr. Hwang.” I don’t think this is going to be a miracle cure for depression. There are a lot of areas we need to address.” But he added that the FDA’s approval is a step toward having another viable and safe treatment for major depression.