Ketamine and esketamine (Spravato) have been breakthrough treatments for depression, but unfortunately many people cannot afford ketamine or esketamine (more on the differences in a moment). This is the tragic reality of many new treatments (especially in the US) — they exist, but are out of reach for the people who need them most. However, I recently learned about an antidepressant, dextromethorphan/bupropion, that works like ketamine or esketamine, which may be an option for those looking for a new, unique depression treatment, especially for treatment-resistant depression. Learn more about dextromethorphan and ketamine as treatments for depression.

Ketamine and Esketamine? How do they work?

This was reported by Medscape:

Ketamine is a dissociative anesthetic approved in the United States for induction and maintenance of anesthesia by intravenous infusion or intramuscular injection. It is not indicated for major depressive disorder (MDD) or TRD (treatment-resistant depression), although it is often used off-label for these indications.

Ketamine a N-methyl-D-aspartate (NMDA) receptor agonist. This results in an increase in the release of glutamate, which causes many downstream effects. (This is interesting because I have spoken how glutamate can be beneficial for depression over the years.)

Esketamine (Spravato) is an enantiomer of racemic ketamine (S). Esketamine is the active enantiomer of ketamine in terms of NMDA receptor antagonism. It also increases glutamate levels. It is approved by the Food and Drug Administration (FDA) for adults with treatment-resistant depression and major depression with suicidal thoughts or actions in combination with an oral antidepressant.

Ketamine Vs Esketamine – To simplify

I know it's a bit confusing, but it was explained to me that ketamine is made up of two mirror image compounds: esketamine and archetamine. These two halves have the same properties and modes of action as ketamine. Currently, esketamine is manufactured and sold in an intranasal form as Spravato. It is used to treat depression and is FDA approved. Ketamine is used as an intravenous (IV) infusion to treat depression. (I suspect Arketmaine may come in the future.)

Ketamine and Esketamine (Spravato) are Expensive

Ketamine is very expensive because, while the drug itself is cheap (it's a generic drug that's been around since the 1960s), it requires medical personnel to administer the IV infusion and then monitor people. Esketamine (Spravato) is expensive because it is a brand-name drug for which the company makes a fortune, and the patient must be observed in the doctor's office for hours after administration.

Some people can get one or both of these drugs through insurance, but many people do not. I think it's a great shame. I hate knowing that there are things that can help people, but because of money, they are out of reach. (If you are trying to get your hands on esketamine (Spravato)), See here for cost support.)

Ketamine Vs Dextromethorphan/Bupropion (Auvelity)?

This brings me to my point. There is an antidepressant called Auvelity that was approved for use in August 2022. It is a combination of dextromethorphan (Robitussin) and bupropion (Welbutrin). If you recognize the name “Robitussin”, it may be because it is a cough suppressant and is available over the counter at various locations. It was first approved by the FDA in 1958 and has since been used in numerous combinations for various treatments. Welbutrin, of course, is a generic antidepressant that was originally approved by the FDA in 1985, although there were problems with the formulation and a sustained-release version was approved in 1996. He became famous at that time.

Dextromethorphan acts on NMDA receptors and modulates glutamate. Bupropion is combined with dextromethorphan to increase its bioavailability. In other words, bupropion allows dextromethorphan to be in your body long enough to have a chance to work. A very brilliant company realized all these things, put them together and made the Auvelity brand.

Why Is Alternative Depression Treatment Dextromethorphan Important For Ketamine Seekers?

If you've been paying attention (I know it's a bit heavy), you may have noticed that dextromethorphan and ketamine have a similar mode of action (they work in a similar way). You can think of dextromethorphan as a weak cousin of ketamine. In other words, if ketamine works for you, dextromethorphan may work too.

This is great for several reasons:

• You can take dextromethorphan/bupropion pills at home and you do not need to be monitored.
• Dextromethorphan/bupropion is widely available.
• Dextromethorphan is cheaper (and may even have a better chance of being covered by your insurance).

According to Amazon Pharmacy, Auvelity costs $657.60 without insurance, or about $35 a month with insurance. It is much less than esketamine (Spravato) or ketamine.

But you can buy Dextromethorphan and Burprion for less!

But there is more to the story. Auvelity is a combination of two over-the-counter medications because you can get bupropion (which your insurance will likely cover since it's generic) and dextromethorphan separately. You may have to get the correct dose of dextromethorphan made for you at a pharmacy, so I can't tell you what that might cost, but I suspect it's a lot less than $657.60 a month.

Evidence for Dextromethorphan/Bupropion in the Treatment of Depression and Treatment-Resistant Depression

Of course, everyone is different, but when it comes to major depressive disorder, a lot of research say things like that:

These data indicate that dextromethorphan-bupropion is an effective, fast-acting, and well-tolerated option for the treatment of depression, producing remission in a large proportion of patients.

Note that it is said fast moving. This is good news for people suffering from depression. (But I'm not saying it won't take longer for some people)

Dextromethorphan/bupropion for bipolar depression

Now, when it comes to bipolar depression specifically, there are all of these concerns that may be associated with treatment with any antidepressant. Regarding the evidence, the use of dextromethorphan/bupropion showed mixed results in the treatment of bipolar depression. Personally, I don't feel it's worth writing, especially if you're on the fence about treatment.

Also, other studies have combined dextromethorphan with compounds other than bupropion and looks like there is some promise therealso.

What you need to know about dextromethorphan as an antidepressant

Here's the long and short of it: dextromethorphan, especially with bupropion, is worth considering as an antidepressant, especially if you're resistant to treatment. It works in a unique way, which means that if many other treatments fail, you can only respond to this. Ketamine or esketamine can also work in this situation, but they are more expensive.

Remember that you should only take medications that you and your doctor think are right for you. You may find some strange side effects with this drug because it is different from other antidepressants. You should also understand the risks before starting any treatment. I do not take or recommend this drug; I'm just giving you some information so you can be more informed when you go to your next doctor's appointment. I hope this alternative can help people who cannot turn to some other treatments.

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