
Auvelity is a medication that combines dextromethorphan and bupropion, and it is used to treat depression. This article will provide information on how Auvelity works, its potential benefits, and whether it may be a suitable option for individuals seeking treatment for depression.
Currently, there is a greater need for further therapy choices for major depressive disorder. The first rapidly acting oral therapy for MDD, Auvelity from Axsome Therapeutics, has received FDA approval.
The capacity of Auvelity to act swiftly sets it apart from the current crop of antidepressants available on the market. Let’s get into further detail about Auvelity and its efficacy.
Depression is a common mental health disorder that affects millions of people worldwide. Persistent feelings of sadness, loss of interest or pleasure in activities, changes in appetite or sleep patterns, and difficulty concentrating or making decisions can occur with depression.
There are several treatment options available for depression, including therapy, medication, and lifestyle changes. However, not all individuals respond to these treatments, and there is a need for alternative options. This article will explore the potential of Auvelity, a medication that combines dextromethorphan and bupropion, as a treatment for depression.
Auvelity is a medication that combines dextromethorphan and bupropion, two substances that have shown promise in treating depression. Dextromethorphan is a cough suppressant that also has antidepressant properties. It increases levels of certain chemicals in the brain associated with mood regulation. Bupropion, on the other hand, is an antidepressant that works by inhibiting the reuptake of certain neurotransmitters, such as dopamine and norepinephrine.
By combining these two substances, Auvelity aims to provide a more effective and comprehensive treatment option for individuals with depression. However, it is important to consult with a healthcare professional to determine if Auvelity is the right choice for you, as it may not be suitable for everyone. Contraindications include history of previous seizures, eating disorders, severe kidney or liver issues, or alcohol misuse.
Dextromethorphan is a sigma-1 receptor agonist and an N-methyl-D-aspartate (NMDA) receptor antagonist, which blocks the receptor (meaning it attaches to the receptor). Dextromethorphan increases glutamate and monoamine levels in the brain by blocking or activating specific receptors. The modulation of these neurotransmitters exerts its anti-depressant effects.
Bupropion increases levels of two mood-enhancing substances in your brain (norepinephrine and dopamine). Additionally, it prolongs the half-life of dextromethorphan in your body. The exact mechanism of how it improves depression is unclear.
On August 19, the U.S. Food and Drug Administration approved Auvelity, a medication used to treat adults with major depressive disorder, also known as clinical depression.
According to the pharmaceutical company Axsome Therapeutics, it is the first rapid-acting medication to treat major depressive disorder that works within a week of use and the first new medication to treat depression utilizing a new mechanism of action in more than 60 years.

The FDA approval was based on a clinical trial conducted in more than 1,100 depressed individuals. This includes the GEMINI placebo-controlled and ASCEND studies, which compared Auvelity with bupropion sustained-release tablets as supporting evidence.
The GEMINI study, a double-blind placebo-controlled clinical trial, demonstrated Auvelity’s effectiveness in treating MDD in adults.
Adult patients meeting DSM-5 criteria for MDD are randomized to receive Auvelity twice daily for six weeks or a placebo. The major outcome metric was the MADRS score change from baseline to week six. In terms of reducing depression symptoms, as indicated by a drop in MADRS score at week 6, Auvelity was discovered to be statistically superior to placebo.
In patients between 18 and 65 with a diagnosis of a major depressive disorder of moderate or greater severity, this randomized, double-blind, multicenter, parallel-group trial compared dextromethorphan bupropion to the active comparator sustained-release bupropion.
On the significant outcome measure in the ASCEND research, Auvelity outperformed bupropion sustained-release tablets 105 mg twice daily statistically substantially. The MADRS total score change from baseline from Week 1 to Week 6 was evaluated, and the average of those scores determined the ASCEND study’s primary outcome measure.
Auvelity (AXS-05) considerably reduced depressive symptoms in patients with major depression when compared to bupropion, and it was typically well tolerated.
The only fast-acting oral medication for MDD, this novel antidepressant has a distinctive mode of action. Dextromethorphan increases glutamate levels by acting as an uncompetitive NMDA receptor antagonist.
Dextromethorphan also acts as a sigma-1 receptor agonist, raising serotonin levels. Norepinephrine and dopamine availability are increased by bupropion’s reuptake inhibition. Dextromethorphan is thus present in higher concentrations due to its ability to inhibit CYP2D6.
By inhibiting cytochrome P450 2D6, which catalyzes a significant biotransformation pathway for dextromethorphan, competitively, bupropion raises the levels of dextromethorphan in the blood. Bupropion does not inhibit monoamine oxidase or the reuptake of serotonin and only has a somewhat mild inhibitory effect on norepinephrine and dopamine neuronal reuptake.
Dextromethorphan is metabolized in 3 hours by most people, however when combined with bupropion, the metabolism is reduced. As a result, dextromethorphan’s effects last longer and the risk of adverse consequences from taking a higher dose is diminished. When SSRI or SNRI drugs have failed to relieve the symptoms of depression in a patient, Auvelity is an option.

Auvelity mechanism of action makes it different from other drugs. The FDA stated in the Axsome press release from August 19, 2022, that the quick-acting medication could treat clinical depression in as little as one week. Its action is fast.
This brief treatment period contrasts sharply with the four to six weeks most depression drugs require to provide relief.
Patients who must wait longer than expected for a drug to take effect find it annoying. The fact that something would function more quickly is actually highly significant because the majority of our antidepressants don’t.
By acting on NMDA receptors, Auvelity attempts to alter glutamate levels in the brain. Currently, available antidepressants alter neurotransmitters like serotonin and noradrenaline. According to researchers, Auvelity is the first-of-its-kind drug.
Drugs in this class, including ketamine. are referred to as glutamate modulators. This drug is a result of research on ketamine as a treatment for clinical depression. Over the past ten years, research has shown that ketamine has an immediate, potent antidepressant impact.
The use of ketamine in treatment marked a significant shift since it was the first time in many years that researchers had access to an antidepressant that operated differently from all the others.
Auvelity is a pharmaceutical that combines the effects of two different drugs. An earlier medication called dextromethorphan has some modifying properties. Bupropion, the other medication in the combination, is an effective antidepressant on its own. Bupropion’s role in this drug is to slow dextromethorphan metabolism, though.
A new therapeutic option for patients whose illness has proven resistant to other types of therapy is provided by the novel drug combination, which holds promise for the future of treating depression.
The first NMDA antagonist for depression licensed by the FDA, which can be given orally as opposed to intravenously, intramuscularly, or intranasally, is Auvelity (sprayed intranasally). Although these various methods of administration offer benefits, some people might feel that a pill taken at home is more convenient.
Standard antidepressants can have side effects that cause patients to stop taking them even when they are therapeutically helpful.
Auvelity is not linked to weight gain or sexual dysfunction, two of the most frequent side effects, because of its new action method. Dextromethorphan-bupropion did not result in temporary psychotomimetic effects, unlike ketamine or Spravato (intranasal esketamine), according to the clinical trials.

Some children, adolescents, and young adults may have an increase in suicidal thoughts and behaviors while taking Auvelity and other antidepressant medications, particularly during the first few months of treatment or when the dose is altered. Children are not supposed to use Auvelity.
If you have any fresh or unexpected changes in mood, behavior, thoughts, or sensations, or if you start to have suicidal thoughts or deeds, you should pay particular attention. This is crucial to remember while beginning or altering the dosage of an antidepressant.
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Serious side effects are possible with Auvelity. Inquire with your HCP if you experience the following severe side effects and what to do if you suspect you have one:
Seizures might happen while receiving Auvelity therapy. If you use Auvelity at larger doses, have specific medical conditions, or combine it with other medications, your risk becomes elevated.
If you experience a seizure while taking Auvelity, stop taking it immediately and contact your HCP. If you experience a seizure, do not retake Auvelity.
While receiving treatment with Auvelity, some patients may develop high blood pressure. Your HCP should perform blood pressure checks before and during your Auvelity treatment.
Those who use Auvelity Dextromethorphan/Bupropion for bipolar disorder may experience manic episodes. Some signs could be:
In those with specific additional eye diseases, auvelity may lead to an eye ailment known as angle-closure glaucoma. If you experience eye pain, altered vision, eye swelling, or redness, call your doctor immediately.
Your risk of falling may rise if you experience quality-related vertigo.
When you take Auvelity with specific other medications, you risk developing the potentially fatal condition known as serotonin syndrome. If you have any symptoms or signs mentioned below, immediately contact your HCP.
Before beginning treatment, it is critical to understand the hazards of using Auvelity. Auvelity can still be utilized in patients with impaired renal function and erratic liver metabolism; however, it may be used at lower doses. Patients should refrain from drinking alcohol while receiving therapy with Auvelity in the same effort to prevent liver damage.
Below are other instances of people who are more likely to experience side effects with Auvelity. Anyone thinking about using it should discuss their medical history with their doctor:
Despite Auvelity’s benefits, pricing and reimbursement issues will arise for this new pharmaceutical, as they do for the majority of newly licensed medications in classes with several (less expensive) therapy options.
Given its anticipated high cost, payers might limit Auvelity’s use to second and subsequent lines of therapy.
A recently licensed drug for treating depression in adults is called Auvelity Dextromethorphan/Bupropion. Auvelity combines dextromethorphan and bupropion, two previously used medications to treat depression. The drug Auvelity modulates NMDA receptors, a recently recognized probable source of depression.
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