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A Nasal Spray For Depression? Yes!

It began with a phone call from a patient.

“Are you prescribing the new nasal spray for depression?”

“Ah!” I thought. “The FDA finally released esketamine.” And then I saw two emails from patients asking the same question. I checked online and, yes indeed, Janssen Pharmaceuticals had completed all the clinical trials and received FDA approval to use very small doses of esketamine for one condition only: major depression that hasn’t responded to the usual antidepressants. The esketamine nasal spray would be marketed under the name Spravato.

Esketamine is a variation of ketamine, itself a 50-year-old anesthetic regarded by physicians worldwide as one of the safest of all medications. The doses used for depression are so low they’re termed “sub-anesthetic.”

Ketamine itself did not get this same FDA approval, not because it doesn’t work for both depression and chronic pain, but because it’s generic (in the public domain) and it would not be financially worthwhile for a pharmaceutical company to spend millions on clinical trials without a patent and exclusivity on the horizon.

Ketamine’s history
The original ketamine was discovered in 1962 and has been in continuous use around the world since 1970 (yes, almost 50 years). Because of its overall safety and effectiveness as an anesthetic for pain control, the World Health Organization placed it on their Model Lists of Essential Medicines, which are those needed in any health care system. You yourself may have had some ketamine administered by an anesthesiologist just before a surgical procedure.

Ketamine is in fact so safe that it was distributed to GIs serving in Vietnam as a so-called buddy drug, each soldier carrying a vial that could be injected into a wounded comrade to provide immediate sedation and pain relief.

It was not until 2000 that studies appeared showing that ketamine could be used for severe depression, especially in those who had tried the usual group of oral antidepressants with no results.

Every doctor has heard a patient say “I’ve tried all the antidepressants. They never work and only give me side effects.” Even more dramatic is when a patient is sinking into ever deeper depression and expressing suicidal thoughts, and the only option available is hospitalization with electroconvulsive (ECT or “shock”) therapy.

Instead of waiting weeks for an oral antidepressant like Prozac or Zoloft to take effect or enduring the possible memory losses of ECT, a quick intravenous treatment of ketamine might relieve deep depression, including suicidal thinking, in as little as a few hours.

Ketamine clinics
You may have seen or heard advertisements for ketamine clinics springing up all over the US, mainly staffed by physicians, usually psychiatrists, anesthesiologists, or nurse anesthetists. Intravenous ketamine does not have the FDA restrictions of esketamine, so ketamine clinics are allowed to offer it for conditions beyond resistant depression, including obsessive compulsive disorder, generalized anxiety, PTSD, and chronic pain, such as the pain of fibromyalgia and complex regional pain syndrome.

Certainly ketamine can be (and likely is) effective for many of these conditions, but, remember, it hasn’t garnered FDA approval just yet. There is also some controversy surrounding the clinics.

Ketamine infusion therapy is not inexpensive. Each IV treatment averages around $500 with at least six infusions recommended, so you’re looking at a potential out-of-pocket expense of $3,000. The infusions themselves are not covered by insurance, although some clinics reduce your costs by billing your insurer for a physician visit.

Although someone with severe depression will feel much better within minutes to hours after an infusion, the effect may not last long. Relapse into depression (though generally less severe than the initial episode) can occur and so-called ketamine “boosters” may be needed.

Spravato, the new nasal spray
Taking a nasal spray is obviously much easier than sitting for IV treatments. The antidepressant effect is less dramatic than an IV infusion, but the nasal spray certainly does work. However, Spravato (remember, this is esketamine) is pretty expensive as well. Without insurance the first month of treatment averages $5,000 with follow-up treatments running around $3,000.

And yes, insurers will balk at these prices, likely requesting documented evidence of multiple antidepressant failures for patients who want to try it.

The FDA has established some pretty complex guidelines for administering Spravato, far more complicated than simply going to a ketamine clinic for an infusion. The rules are so complex that I suspect Spravato treatment centers will be located in outpatient settings of hospitals that have a mental health unit (rather than being administered in a psychiatrist’s office).

The guidelines for Spravato:

–First, Spravato is sent to the doctor’s office for you to use it there. You can’t pick it up at a drugstore.

–Second, after using it, you’re required to remain in the office for two hours, in order to monitor you for any adverse reaction.

–Third, although you can come to the office yourself, someone needs to accompany you home. Because Spravato can be mildly sedating, you might feel a few minutes of out-of-body sensation. (The same is true of ketamine itself. Hence, its decades-long use as the club drug Special K.) This is called dissociation and we of the medical profession want someone other than you to get you home.

In other words, every dose of the FDA-approved esketamine Spravato nasal spray must be administered under direct medical supervision. The usual dose of Spravato is twice weekly for four weeks, with boosters as needed. It can be used at the same time as antidepressants, so if you’re taking one you need not stop. Some patients will need boosters indefinitely.

Cost comparison
Doctors dispensing generic ketamine either as IV infusions or compounded nasal sprays can use these FDA rules as a guideline, but are not required to follow them. Ketamine nasal spray prepared by a compounding pharmacy generally costs a fraction of the $5,000 Spravato will run you, and there are no studies showing that one version is superior to the other.

The low cost is, of course, because ketamine is generic and in the public domain. A good compounding pharmacist can make a month’s supply of ketamine nasal spray for about $75. Hmmm, you’re thinking. $5,000 a month for Spravato, $3000 for ketamine infusions, or $75 for generic ketamine nasal spray. What’s the catch?

None, really. The main difference between IV ketamine and either of the nasal sprays is speed of onset. When given intravenously, the antidepressant effect may occur within a few hours. The nasal spray may take a few days.

How does WholeHealth Chicago work with ketamine?
Since the FDA guidelines have been designed for patient safety, we’ve decided to follow their high points–namely that your first three doses be administered here at WholeHealth Chicago.

Here’s how it works:

–If you’re already a WholeHealth Chicago patient and are working with one of our psychotherapists (Janet Chandler, Jennifer Davis, Christine Savas), likely you already have a documented mood disorder (depression, anxiety, OCD, PTSD) and you can discuss ketamine with your therapist. If you want to proceed, your therapist will schedule you for a short visit with an MD or nurse practitioner to discuss the treatment and ask you to sign an informed-consent document, necessary because this is an FDA off-label use of ketamine.

–If you already have your own therapist outside of WholeHealth Chicago, we would need a written referral with your diagnosis and a request for intranasal ketamine. Your first appointment would be a short visit directly with an MD or nurse practitioner.

–If you’re not a WholeHealth Chicago patient and do not have a therapist, your first appointment would be with one of the three psychotherapists listed above, to confirm your mood disorder diagnosis and review your response to medications you’ve taken. You would then be scheduled to see an MD or nurse practitioner.

–We would fax your prescription for the ketamine nasal spray to the compounding pharmacy, which would contact you for payment (about $75) and mail the medication to you. You would not initiate treatment at home, but rather would bring it to our office for each of your first three treatments.

–You’d be required to remain in the office for an hour after using it (a good time to have an acupuncture treatment or a session of Healing Touch).

–You’d also be required to have someone here to take you home.

–You can self-administer treatments thereafter, but refills would require an office visit with your therapist and MD approval.

–If you’re interested in using ketamine for conditions other than depression (e.g., fibromyalgia), either discuss this with your WholeHealth Chicago physician or schedule an appointment with us, bringing a referral from your primary care physician.

I’m pretty sure you’ll be reading a lot about ketamine and Spravato over the next few months. So far, the news is good.

Be well,
David Edelberg, MD

Leave a Comment


  1. Stacey says:

    I already have a referral for the nasal spray from my neurologist. I’m not a patient there. Who should I make an appointment with?

    • cliffmaurer says:

      Hi Stacey –
      Please give a call to the office and schedule with our nurse practitioner Wendy Ploegstra. She can get you started.
      -Dr M

  2. Stacie says:

    The doctors who own and run this practice need to look into hiring some professional staff to answer the phones. Terrible experience. I would never go there for any service

    • cliffmaurer says:

      Hi Stacie –
      Thank you for your feedback, and I’m terribly sorry that you had a bad experience when calling WHC. Would you mind emailing me with some details so I can look into this for you? I’m one of the practice managers and can help rectify the problem.
      cliff@wholehealthchicago.com
      Thank you for your time,
      Dr M

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