Release date 2024.8.26
Characteristics
Auvelity was approved in the United States in August 2022 as a treatment for depression 1)、(Figure 1).
（Fig 1）The dosage from of Auvelity
It is a combination drug consisting of two medications: dextromethorphan, an antitussive, and bupropion, an antidepressant (Figure 2).
（Fig 2）Composition of Auvelity
Bupropion has norepinephrine reuptake inhibition and dopamine reuptake inhibition actions and is classified as an NDRI (Noradrenaline-Dopamine Reuptake Inhibitor) among antidepressants.
Dextromethorphan has serotonin and norepinephrine reuptake inhibition actions, as well as NMDA glutamate receptor antagonist actions and sigma-1 receptor agonist actions, which have been shown to possess antidepressant effects.
By combining these two drugs, Auvelity was developed by Axsome Therapeutics as a fast-acting treatment that exerts antidepressant effects within one week 2）、(Figure 3).
（Fig 3）Antidepressant Effects of Auvelity
In June 2024, it was reported that comparative analysis showed that Auvelity was significantly more effective than placebo and bupropion alone 3).
Mechanism of Action
The antidepressant effects of Auvelity are primarily due to the NMDA glutamate receptor antagonist actions and sigma-1 receptor agonist actions of dextromethorphan.
It has been reported that dextromethorphan has a relatively high affinity for sigma-1 receptors compared to other antidepressants 4)、(Figure 4).
（Fig 4）Comparison of the Affinity for Sigma Receptors between Dextromethorphan and Antidepressants
The NMDA receptor antagonism is reported to be relatively weaker than that of ketamine, for example 3)、(Figure 5).
（Fig 5）Inhibition Rate of Glutamate NMDA Receptors by Dextromethorphan
Dextromethorphan is metabolized by the liver enzyme CYP2D6. Bupropion, which inhibits CYP2D6, extends the duration of dextromethorphan in the bloodstream from about 4 hours to 22 hours.
As a result, dextromethorphan, with its enhanced action, exerts a rapid antidepressant effect 1)、(Figure 6).
（Fig 6）Mechanism of Action of Auvelity
Dosage and Administration
Before starting oral administration, the following screenings are required:
- Blood pressure measurement and regular monitoring
- Screening for a history or family history of bipolar disorder, mania, or hypomania
- Screening to ensure the patient is not receiving other prescription medications containing bupropion or dextromethorphan
The dosage and administration are as follows: take one tablet once a day in the morning for the first three days, then take one tablet twice a day, with an 8-hour interval.
Side Effects
The following conditions are contraindications:
- History of seizures
- Current or past history of bulimia nervosa or anorexia nervosa
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
- Hypersensitivity to dextromethorphan, bupropion, or any component of Auvelity
The following warnings are noted:
- Suicidal thoughts and behaviors in children and young adults
- Seizures
- Elevated blood pressure and hypertension
- Mania
- Psychosis and other neuropsychiatric reactions
- Angle-closure glaucoma
- Dizziness
- Serotonin syndrome
- Fetal toxicity
In a Phase 3 clinical trial, side effects were observed in 100 out of 162 patients (61.7%), with the main ones listed below (Figure 7).
（Fig7）Main Side Effects of Auvelity
References
- 1） Keam SJ.: Dextromethorphan/Bupropion: First Approval. CNS Drugs, 36: 1229-1238, 2022.
- 2） Iosifescu DV, et al.: Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). J Clin Psychiatry, 83: 21m14345, 2022.
- 3） Gaca Z, et al.: Network meta-analysis (NMA) of dextromethorphan-bupropion (AXS-05) efficacy and safety in major depressive disorder. Eur Neuropsychopharmacol, 86: 18-19, 2024.
- 4） Taylor CP, et al.: Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta) clinical use. Pharmacol Ther, 164: 170-82, 2016.
Column list
- Characteristics, Mechanism of Action, and Side Effects of Zuranolone
- Characteristics, Mechanism of Action, and Side Effects of Auvelity
- Characteristics, Mechanism of Action, and Side Effects of Esketamine
- Latest Comparison of Weight Changes Due to Antidepressants
- Comparison of the Efficacy of Long-Acting Injectable Antipsychotics in Acute Schizophrenia: Latest Report
- Comparison of Efficacy and Tolerability of Drug Treatments in Acute Manic Episodes of Bipolar Disorder: Latest Report
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