Ketamine and esketamine (Spravato) were breakthrough treatments for depression, but unfortunately, many people can’t afford ketamine or esketamine (more on the differences in a moment). That’s the sad reality of so many new treatments (especially in the United States) — they exist but aren’t available to the people who need them most. However, I recently learned of an antidepressant, dextromethorphan/bupropion, that works similarly to ketamine or esketamine, which may be an option for those looking for a new, unique depression treatment, particularly for treatment-resistant depression. See more about dextromethorphan vs. ketamine as a depression treatment.
Ketamine vs. Escetamine? How do they work?
Ketamine is a disruptive anesthetic approved in the United States for the induction and maintenance of anesthesia by intravenous infusion or intramuscular injection. Not indicated for major depressive disorder (MDD) or TRD [treatment-resistant depression]although it is often used off-label for these indications.
Ketamine is a N-Methyl-hey-aspartate receptor agonist (NMDA). This results in an increase in glutamate release, which leads to many downstream effects. (This is interesting because for years I’ve been talking about how helpful glutamate can be for depression.)
Escetamine (Spravato) is the (S) enantiomer of racemic ketamine. Esketamine is the active enantiomer of ketamine in terms of antagonizing the NMDA receptor. It also increases glutamate levels. It is approved by the Food and Drug Administration (FDA) for adults with treatment-resistant depression and severely depressed adults with suicidal thoughts or actions in combination with an oral antidepressant.
Ketamine vs. Escetamine — To simplify
I know it’s a little confusing, but it’s been explained to me that ketamine is made up of two mirror-like compounds: esketamine and nicamine. These two halves have many of the same properties and modes of action as ketamine. Escetamine is currently manufactured and marketed in intranasal form as Spravato. It is used to treat depression and is FDA approved. Ketamine is used as an intravenous (IV) infusion off-label to treat depression. (I suspect arketmaine may come in the future.)
Ketamine and esketamine (Spravato) are expensive
Ketamine tends to be very expensive as while the drug itself is cheap (it’s been a generic since the 1960s), it requires medical staff to administer the IV and monitor people afterwards. Esketamine (Spravato) is expensive because it is a brand-name drug for which the company charges a fortune, and the patient must be monitored for hours after administration in the doctor’s office.
Some people have access to one or both of these drugs through their insurance, but many people do not. I think this is a great shame. I hate to know that there are things that could help people but are out of reach because of money. (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 approved for use in August 2022 called Auvelity. 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 in various formulations. It was first approved by the FDA in 1958 and has since been put into many combinations for various treatments. Welbutrin, of course, is a common antidepressant that was originally approved by the FDA in 1985, although there were problems with the formulation and an extended-release version was approved in 1996. It became popular at that point.
Dextromethorphan acts on NMDA receptors and modulates glutamate. Bupropion is combined with it to increase the bioavailability of dextromethorphan. In other words, bupropion allows dextromethorphan to be available in your body long enough for it to have a chance to work. A pretty brilliant company has figured all this out, packaged it together, and called it Auveity.
Why Does Alternative Depression Treatment Dextromethorphan Matter For Ketamine Cravings?
If you’ve been paying attention (I know it’s been a bit heavy), you may have noticed that dextromethorphan and ketamine have a similar mode of action (they work in similar ways). You can think of dextromethorphan as ketamine’s weaker cousin. In other words, if ketamine works for you, then dextromethorphan might work too.
This is great for a few reasons:
- You can take dextromethorphan/bupropion in pill form at home and you do not need to be supervised.
- Dextromethorphan/bupropion is widely available.
- Dextromethorphan is much less expensive (and you may be more likely to have it covered by your insurance).
According to Amazon Pharmacy, Auvity costs $657.60 without insurance or about $35 with insurance per month. This is much less than esketamine (Spravato) or ketamine.
But you can probably get Dextromethorphan and Burprion for less!
But there is more to the story. Because Auvelity is a combination of two over-the-counter medications, you may be able to get bupropion (which your insurance will probably pay for since there is a generic) and dextromethorphan separately. You may have to get the dextromethorphan made up for you in the correct dose at a compounding pharmacy, so I can’t tell you what that might cost, but I strongly suspect it’s a lot less than $657.60 a month.
Evidence for dextromethorphan/bupropion in depression and treatment-resistant depression
Of course, everyone is different, but when it comes to major depressive disorder, multiple studies say such things:
These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well-tolerated option for the treatment of depression and has induced remission in a large proportion of patients.
Note that it says fast acting. For people with depression, this is welcome news. (I’m not saying it doesn’t take longer for some people, though)
Dextromethorphan/Bupropion for Bipolar Depression
Now, when it comes to bipolar depression specifically, there are all the concerns that one might have with treatment with any antidepressant. In terms of evidence, the use of dextromethorphan/bupropion has shown mixed results in the treatment of bipolar depression. Personally, I don’t think that means it’s worth deleting, especially if you’re on a healing roadblock.
Also, other studies combine dextromethorphan with compounds other than bupropion and there seems to be some promise therealso.
What you need to know about dextromethorphan as an antidepressant
The long and short of it is this: dextromethorphan, especially with bupropion, is worth considering as an antidepressant, especially if you are resistant to treatment. It works in a unique way, which means that if you have failed many other treatments, you just might respond to this one. Ketamine or esketamine may also work in such a situation, but they are much more expensive.
Keep in mind that you should only take a medication that you and your doctor think is right for you. You may find some strange side effects with this drug precisely because it is different from other antidepressants. You also need to understand the risks before starting any treatment. I do not endorse 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 access some other treatments.
