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Fact Checked

Could a Nasal Spray Help with Depression?

Spravato® (esketamine), related to the older drug ketamine, is a nasal spray approved in 2019 for management t of treatment-resistant depression. In August of 2020, the United States Food and Drug Administration (FDA) approved Spravato®, to be taken along with an oral antidepressant, for individuals with major depressive disorder (MDD) with acute suicidal ideation or behavior. 

What is the difference between ketamine and esketamine? Where does this drug fit in the treatment of depression? Read on to learn more! 

A Brief History of Ketamine

Ketamine is an old drug. It was originally introduced in the 1960s as an anesthetic that could rapidly be absorbed into the brain. Ketamine was desirable in this role due to its ability to provide general anesthesia and sedation while not affecting the heart and lungs of the patient. 

In fact, initial studies in the 1960s showed that ketamine worked for a limited time, and it could safely be given repeatedly to extend the effect. Some limited studies have been done to assess the effects of ketamine on depression and post-traumatic stress disorder (PTSD). 

The drug was noted to have profound hallucinogenic properties in both human and animal subjects leading to ketamine becoming a popular street drug, sometimes referred to as “Special K,” in the 1970s and 1980s.

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Getting to Esketamine from Ketamine

Spravato® (esketamine) is what is called an enantiomer of ketamine. Ketamine is a drug that is composed of molecules that are mirror images of one another. Spravato® is composed of the S-enantiomer, thus giving it the name esketamine. 

So, What’s the Difference?

Ketamine is normally required to be administered intravenously (IV). It can be taken by mouth or rectally, but the amount of medication that ultimately makes it to the bloodstream is greatly reduced. Additionally, treating patients with frequent IV infusions might not be an ideal regimen for those struggling with depression.

Spravato® is a nasal spray rather than an infusion. It is a controlled substance, but you cannot purchase it at a pharmacy. Instead, each dose must be administered at your healthcare provider’s office under their supervision

Both ketamine and Spravato® can cause short-term sleepiness and impaired thinking. They also both block N-methyl-D-aspartate (NMDA) receptors in the brain, which is a  different mechanism compared to  most other antidepressants. 

Spravato® misuse or abuse can have negative long-term effects on thinking and memory. No such effect was seen during the one-year safety study for Spravato®, but  additionallong-term data is needed. 

It should be noted that Spravato® is a brand name medication that can be expensive. In 2019, Jannsen set a cash price of $590 to $885 per treatment session. Insurance coverage cannot be guaranteed, but the company does have financial assistance options available. 

How is Spravato® Taken?

Depending on your circumstances, Spravato® should be taken while you are also taking an oral antidepressant. Spravato® comes as a nasal spray that has to be sprayed into your nostrils under the supervision of a healthcare professional. Each device contains enough solution to provide a total of 28 mg of Spravato via two sprays. Depending on your individualized therapy course, you will most likely use two or three devices in a single visit with a 5-minute wait between devices. 

Some patients will have Spravato® sessions twice a week while others are once weekly. The length of treatment depends on the individual person and their response. Because of the risk of impairment with treatment, it would be wise to have someone else drive you to and from your appointment.

What Should I Expect If I Take Spravato®?

Spravato® is only intended for people who have tried and failed multiple medications for managing their depression, or for those with major depressive disorder with suicidal ideation. This will not be a first treatment option for people newly diagnosed. Due to fetal risk, pregnant and nursing mothers should not use Spravato®.

While some hoped for rapid results, Janssen has said that patients can expect results in about four weeks when Spravato® is taken with an oral antidepressant. 

In trials, patients experienced a variety of common side effects, including: dissociation, dizziness, nausea, sedation, spinning sensation, reduced sense of touch and sensation, anxiety, lack of energy, vomiting, and feeling drunk.

Acommon concern with Spravato® administration is use in people with high blood pressure. Spravato raises blood pressure to a high point about forty minutes after the dose is taken, returning to normal levels at the two-hour mark. In trials Janssen saw no higher chances for heart-related issues as a result of this temporary increase. Expect to have your blood pressure checked before you take the medication, at forty minutes, and then as needed to track it coming down. 

Janssen does mention that there was an increase in suicidal thoughts and behaviors in people 24 years old and younger. The medication currently is not approved for anyone below the age of 18.

What is Dissociation?

The Sidran Institute defines dissociation as a “disconnection between a person’s thoughts, memories, feelings, actions or sense of who he or she is.” They describe mild examples as  daydreams or getting lost in a book.

One study of ketamine showed that individuals  experienced misperceptions of time, along with “heightened, dulled, and distorted perception.” 

Dissociation symptoms may occur after each session. The possibility of long-term effects require additional studies. 

References

1. SPRAVATO - Overview. Janssen CarePath. https://www.janssencarepath.com/hcp/spravato. Published 2020. Accessed September 14, 2020.

2. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified. Published 2020. Accessed September 14, 2020.

3. SPRAVATO® (esketamine) | SPRAVATO® HCP. SPRAVATO® (esketamine). https://www.spravatohcp.com/resources#Frequently_Asked_Questions. Published 2020. Accessed September 14, 2020.

4. Esketamine may solve depression need, but not be cost-effective - STAT. STAT. https://www.statnews.com/pharmalot/2019/03/22/antidepressants-cost-effective-johnson-and-johnson/#:~:text=Known%20as%20esketamine%20and%20marketed,which%20can%20vary%20by%20patient. Published 2020. Accessed September 14, 2020.

5. Janssenlabels.com. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf. Published 2020. Accessed September 14, 2020.

6. Fda.gov. https://www.fda.gov/media/121379/download. Published 2020. Accessed September 14, 2020.

Published September 17th, 2020 by Dr. Brady McNulty, PharmD, BCGP
Fact Checked by Chris Riley

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