Auvelity is a new, oral medication approved by the US Food and Drug Administration (FDA) for treatment of major depressive disorder (MDD) in adults. Auvelity combines two medications, dextromethorphan and bupropion, into one pill taken by mouth.
Dextromethorphan is an NMDA receptor antagonist and is commonly used as a cough syrup. NMDA receptors have been connected to the pathophysiology of various neurologic and psychiatric diseases such as Alzheimer’s disease, epilepsy, chronic pain syndrome, schizophrenia Parkinson’s disease, Huntington’s disease major depression, substance use disorders and anxiety. Another NMDA receptor antagonist recently approved by the FDA is esketamine (brand name Spravato), which is a nasal spray for treatment-resistant depression or depressive symptoms in adults with MDD with acute suicidal ideation or behavior.
Bupropion alone is available as a generic medication that can be used to treat depression or help quit smoking. Bupropion works by increasing the amount of norepinephrine and dopamine available in the brain. However, bupropion also effects as enzyme in the liver that break down other medications, including dextromethorphan. If you think of enzymes in the liver as Pac-Man eating up dots, bupropion makes Pac-Man move slower, so it takes longer for Pac-Man to get all the dots. In the same way, bupropion makes it take longer for the enzyme to metabolize dextromethorphan. Typically the effects of dextromethorphan last for only 3-8 hours, but with the addition of bupropion that time is prolonged.
Read our blog about other depression treatments here.
Both the GEMINI placebo-controlled study and the ASCEND study (which compared Auvelity to bupropion sustained-release tablets), looked at improvement in depression scores after 6 weeks. Depression scores began improving as early as week 1 in all groups, with Auvelity having a significant difference by week 2 when compared to both placebo and bupropion alone. The results are promising for Auvelity as a treatment option that may provide quicker results since it typically takes 4-5 weeks before noticeable changes in motivation and energy start to occur with other types of antidepressants. The most common side effects included dizziness, headache, diarrhea, sleepiness, dry mouth, sexual dysfunction, and excessive sweating.
Before prescribing Auvelity your doctor will need to assess your blood pressure, screen for history of bipolar disorder, mania, or hypomania, and make sure you are not receiving any other medications that contain bupropion or dextromethorphan. It is important to note that if someone has moderate to severe depression it is recommended to use both medications and psychotherapy, not just medications.
Auvelity will likely be available in late 2022. Auveltiy is also being studied for Alzheimer’s disease agitation and smoking cessation.