Auvelity vs. Spravato: 5 Differences Between These Fast-Acting Antidepressants
Key takeaways:
Auvelity (dextromethorphan / bupropion) and Spravato (esketamine) are fast-acting antidepressants. They work differently than most other antidepressants.
Auvelity is an oral tablet that begins working in about 1 week. Spravato is a nasal spray that typically works 2 to 4 hours after being administered. However, Spravato must be administered by a healthcare provider because of its potential risks.
There are ways to save on Auvelity and Spravato. If you’re eligible, manufacturer savings cards can help make your prescription more affordable.
Access savings on related medications
Table of contents
If you or a loved one have depression, you know all about the good days and bad days. And how it can sometimes feel like there’s nothing you can do on your own to cope with your symptoms. The bright side is that many treatment options are available for you to try, if and when you’re ready.
Prescription antidepressant medications are effective for many people. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are popular antidepressants you may have heard of or take yourself. These serotonin-boosting medications are beneficial, but they can take 1 to 2 months to make a difference.
More recently, the FDA approved two newer antidepressants that work differently than these traditional ones. They’re called Auvelity (dextromethorphan / bupropion) and Spravato (esketamine). Each one is known for their fast-acting effects, but they have some differences worth exploring. We’ll discuss five such differences below.
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1. Auvelity and Spravato have different active ingredients
Auvelity is a combination tablet that contains two medications, dextromethorphan and bupropion. Each component of Auvelity plays a role in helping manage your symptoms.
Dextromethorphan works by affecting receptors (chemical binding sites) in your brain, specifically the N-methyl-D-aspartate (NMDA) receptor. This leads to higher levels of glutamate and monoamines — chemical messengers that are linked to a positive mood.
Bupropion is an antidepressant in its own right, but it plays more of a supportive role in Auvelity. It works by blocking a protein (enzyme) that breaks down dextromethorphan. This allows dextromethorphan to last longer and be more effective for your symptoms. Bupropion may also have a small effect on other chemical messengers in the brain, such as norepinephrine and dopamine.
Spravato also targets NMDA receptors in the brain to help raise glutamate levels. But it has a different active ingredient — esketamine. Spravato is used to treat treatment-resistant depression and depression associated with thoughts of suicide.
Good to know: The primary ingredient in Spravato is esketamine, which is derived from ketamine, a similar medication used for anesthesia and depression. Both medications are Schedule III controlled substances that have a low-to-moderate risk of dependence.
2. They’re both fast acting, but Spravato works more quickly
Auvelity and Spravato don’t start working at the same time. This difference is due to how each medication is administered.
Spravato is a nasal spray. It’s able to get into your bloodstream and start working quickly. Research has shown that Spravato reaches its highest concentration in your body within 20 to 40 minutes of receiving your dose. This translates to feeling a noticeable difference in your depression symptoms within 2 to 4 hours.
Auvelity, on the other hand, is an oral tablet. It needs to be broken down by the body before it reaches the bloodstream where it has its effect. This means that it takes a bit longer to kick in. You can start to feel the effects of Auvelity within roughly 1 week of starting treatment.
3. Auvelity is an oral tablet, while Spravato is a nasal spray
One major difference between these fast-acting antidepressants is how you take them. As mentioned earlier, Auvelity is a tablet that’s taken by mouth. Spravato is a nasal spray.
Each Auvelity tablet contains 45 mg of dextromethorphan and 105 mg of bupropion. When you first start taking Auvelity, it’s recommended to take 1 tablet daily for the first 3 days of treatment. This will help your body get used to the medication. After this, you can take 1 Auvelity tablet twice daily. These doses should be taken at least 8 hours apart. This is your “maintenance” dose of Auvelity that you’ll take on a daily basis.
Spravato comes in a nasal spray device that contains 2 sprays, 1 for each nostril. Two sprays contain 28 mg of esketamine. But unlike Auvelity, Spravato isn’t used daily. It’s administered less frequently.
During your first 4 weeks of receiving Spravato, it’s recommended to have two treatments every week. After this, you and your healthcare provider will discuss whether you should continue taking Spravato. If you think it’s helping and want to keep receiving it, you’ll likely receive it once weekly for the next 4 weeks. After that, Spravato may be given once weekly or once every other week.
4. You can’t receive Spravato at home
One drawback to Spravato is that you can’t use it at home. It must be administered by a healthcare provider.
This is because Spravato can cause several serious side effects. Because of these risks, Spravato is only available through a Risk Evaluation and Mitigation Strategies (REMS) medication safety program. This program helps make sure Spravato’s benefits outweigh its risks. In order to receive the medication, your healthcare provider will enroll you in the Spravato REMS program.
Another factor to consider with Spravato is the logistics of your appointments. You’ll need to be monitored at your treatment center for at least 2 hours after each dose. This can be a problem if you have a really busy schedule. It can also cause sleepiness, so you'll need to arrange for transportation home from your appointment.
5. Both medications may cause side effects, but their risks are different
Spravato and Auvelity both have their own side effects to keep in mind.
Spravato side effects
The most common Spravato side effects include:
Dissociation (feeling detached)
Dizziness
Nausea
Blood pressure changes
Anxiety
Spravato can also cause more serious side effects. Spravato carries few boxed warnings, the FDA’s most serious type of medication warning:
Suicidal thoughts and behaviors
Sedation
Dissociation
Respiratory depression (slowed breathing)
Abuse and misuse
Many side effects may get better over time as your body adjusts to Spravato. But since you’ll receive each dose from your healthcare provider, they’ll always be a handy resource for answering questions about side effects that you experience.
Auvelity side effects
Auvelity can also cause side effects. The most common Auvelity side effects are dizziness, nausea, and headache.
Rare but serious side effects are also possible. Similar to Spravato and other antidepressants, Auvelity carries a boxed warning about the potential risk of suicidal thoughts and behaviors while taking it. Other serious side effects include seizures, high blood pressure, and changes in mental health.
If you’re experiencing any bothersome side effects while taking Auvelity, contact your healthcare provider right away. It’s especially important to report any sudden changes in thoughts or behavior.
How to save on Auvelity and Spravato
Auvelity and Spravato are only available as brand-name medications. But GoodRx can help you navigate ways to save on your prescription.
If you have commercial insurance and meet eligibility requirements, Auvelity’s price is as little as $10 per prescription if you use the manufacturer’s savings card. Spravato’s price is also as little as $10 per treatment if you use the manufacturer’s savings card.
The bottom line
Auvelity (dextromethorphan / bupropion) and Spravato (esketamine) are two fast-acting antidepressants. Auvelity is an oral tablet that’s taken daily. Spravato is a nasal spray that’s only used twice a week at most, but you’ll need to receive each dose from a healthcare provider.
Auvelity and Spravato’s effects can be felt significantly faster than other antidepressants. You can typically feel the effects of Auvelity within 1 week, while Spravato usually works within 2 to 4 hours. But both medications have their own risks and side effects to consider. Your healthcare provider can help you decide which treatment is right for you.
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References
Axsome Therapeutics, Inc. (2022). Auvelity - dextromethorphan hydrobromide, bupropion hydrochloride tablet, multilayer, extended release [package insert].
Iosifescu, D. V., et al. (2022). Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: A Phase 3 randomized clinical trial (GEMINI). The Journal of Clinical Psychiatry.
Janssen Pharmaceuticals, Inc. (2023). Spravato - esketamine hydrochloride solution [package insert].
Krystal, J. H., et al. (2020). A new rapid-acting antidepressant. Cell.
Pereira, S., et al. (2021). Managing dissociative symptoms following the use of esketamine nasal spray: A case report. International Clinical Psychopharmacology.
Spravato. (2020). What is the Spravato REMS (Risk Evaluation and Mitigation Strategy)?
Wang, S. M., et al. (2021). Rapid onset of intranasal esketamine in patients with treatment resistant depression and major depression with suicide ideation: A meta-analysis. Clinical Psychopharmacology and Neuroscience.
For additional resources or to connect with mental health services in your area, call SAMHSA’s National Helpline at 1-800-662-4357. For immediate assistance, call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.
