The People's Perspective on Medicine

Will FDA Approve Esketamine Nasal Spray for Depression?

FDA is considering whether to approve esketamine nasal spray as a treatment for severe depression. An advisory panel recommends approval.
Man uses a nasal spray for treatment

An FDA advisory panel voted this week that a new form of an old compound is sufficiently safe and effective to be considered for approval. The old compound is ketamine, which has been used as an intravenous anesthetic since 1970. The new formulation is esketamine nasal spray. Janssen, a division of Johnson & Johnson, hopes that the FDA will approve this as a new antidepressant. That would make it the first new type of antidepressant since 1984.

What Did the Panel Think About Esketamine Nasal Spray?

The advisory panel voted overwhelmingly that the drug is safe and effective and that its benefits outweigh its risks. However, the experts based their evaluation on relatively short-term clinical trials. At least one of those did not show that the drug is more effective than placebo.

J&J is developing esketamine nasal spray to treat people with severe depression who have not responded well to other treatments. The drug can cause side effects such as a metallic taste, vertigo and dizziness, drowsiness, headache, nausea, and most worrisome, mind-body dissociation. FDA’s approval decision is scheduled for March 4.

What Do We Already Know About Ketamine for Severe Depression?

This is not the first we have heard of ketamine acting against depression. Back in 2012, we heard from one reader who had severe chronic depression.

Q. I participated in two clinical trials of ketamine for depression. The infusion was not pleasant, but a few hours later my depression was mysteriously lifted. I felt as though someone carefully cleaned, polished and rejuvenated every cell in my brain. It was not a feeling of being high; it was completely different from anything I had ever experienced in my entire life.

Unfortunately, it only lasted a few days. When it went away, I returned to life as I had always known and felt even more horrible. They told me up front it is a clinical trial and the drug is not available for depression treatment. But it is an FDA-approved medication. Any MD could prescribe it, but no one has been willing to administer it.

I have felt closer to suicide at times since I found out how good other people feel every day. Hopefully, ketamine will soon be approved for severe depression.

Frustrations in Treating Major Depression:

A.  Psychiatrists find it challenging to treat major depression like yours. Current antidepressants may take weeks to start working. Clinical trials reveal that only about a third of patients achieve good results, even after optimal therapy (Rush et al, American Journal of Psychiatry, Nov. 2006).

Ketamine (Ketalar) is a unique injectable anesthetic that has been used in surgery since the early 1970s. More recently, scientists have been studying ketamine infusions for the treatment of major depression.

Preliminary studies suggested that intravenous ketamine might relieve severe depression rapidly even for those with treatment-resistant depression (Covvey et al, Annals of Pharmacotherapy, Jan. 2012). This is still very much an experimental approach, however.

Why Turn to Esketamine Nasal Spray?

Many doctors have been somewhat reluctant to prescribe ketamine for depression because the effect is short lived. In fact, some people report that relief lasts only a few days. Moreover, ketamine has been abused as the club drug “Special K.”  In addition, oral or intravenous ketamine can cause hallucinations and changes in heart rate and blood pressure. That is probably why J&J is counting on esketamine nasal spray to provide help for depression while limiting side effects and potential for abuse. 

For more information on intravenous ketamine for treating depression, listen to this report from NPR.

You may also find our Guide to Dealing with Depression of value.

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About the Author
Terry Graedon, PhD, is a medical anthropologist and co-host of The People’s Pharmacy radio show, co-author of The People’s Pharmacy syndicated newspaper columns and numerous books, and co-founder of The People’s Pharmacy website. Terry taught in the Duke University School of Nursing and was an adjunct assistant professor in the Department of Anthropology. She is a Fellow of the Society of Applied Anthropology. Terry is one of the country's leading authorities on the science behind folk remedies. .
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If for some reason this does not make it to market, it’s now possible to get Ketamine as a nasal spray as a compounded drug . It’s used in the pain community, and just recently they decided a higher dose was more effective.

Wow. Interesting. So ‘could’ it possibly help those in real need? Yet the side effects? Dependency? Too scary to risk in my opinion. If indeed an RX might help, in my opinion it needs to be used for a minimum 5 years by many or by taking it as part of a clinical trial. Would be interesting to learn if any of the judges ever tried it.

Ketamine is also employed for other neuropathic conditions, including PTSD, and is said to be helpful for a limited number of pain conditions that include fibromyalgia. The way I would describe its potential effect is like a total neuro-endocrine “reset.”

It is currently offered in low dose protocols in a few locations around the country, though not enough to make it widely convenient without major travel plans for many. Offerings vary somewhat from practice to practice. I am currently making plans for first-time treatment at a satellite office of a practice based in NY.

Ketamine infusion therapy is not covered directly by insurance because of its off-label use but with a referral some people may qualify for partial reimbursement or more, and/or travel costs. A nice thing about it is that it doesn’t usually require a referral.

My personal experience with ketamine as an incidental after-effect of two outpatient surgeries mirrors that of the person quoted in the article who participated in a trial for depression, except that my problem was not depression, although there are a number of crossover symptoms. After my first experience with it, chronic, hyper-reactive palpitations that had become a near daily experience for more than two years disappeared forever. My CFS/ME energy deficit felt improved also — but only for several days. I would describe the two conditions it improved as longstanding post-viral CFC/ME and PTSD of a mostly physical nature.

My second experience was about 7 years after that and I felt normal for the first time in about 15 years — much more than after my previous experience with ketamine. This lasted for 2-3 weeks and then it was a fairly rapid crash down to my debilitated “normal.”

Low dose infusion protocols vary somewhat from practice to practice and I believe differ between pain and other conditions. The first set of infusions, spread over so many days, is not intended to last forever. Single follow-up booster infusions are the norm but fewer are expected to be required over time, especially after the first year. How many and when varies by condition and patient. My understanding is that some doctors are sometimes prescribing the nasal form as a booster now.

The most effective medicine for clinical depression is Vitamin D3 supplements or daily doses of sunshine, at least in the summer months in these latitudes.

My sister-in-law says ketamine changed her life. She had several infusions for depression, and it made such a difference she’s preaching the gospel of ketamine to everyone who suffers from unrelenting depression. My husband and I could both probably benefit, but we’re wary of the side effects. A nasal version might be just the ticket. We’ll be keeping an eye on this.

I think patients should think about what they are taking. As difficult as life is, a drug that is used for anesthetic purposes has too many problems. A doctor should be aware of the complications. I have depression too. There must be something that will not further deplete my health, yet provide some relief. This is not for me. Reading about these harmful pharmaceuticals is depressing.

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