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Dextromethorphan-Bupropion: A New Way to Treat Depression. By Our Student Pharmacist, Samantha Steele.

Auvelity Image

Major depressive disorder (MDD) is a leading cause of disease, both in the United States and globally. In 2021, an estimated 21 million adults in the US had at least one major depressive episode, with 61% of those diagnosed receiving treatment in the past year.

Symptoms of MDD include:

  • depressed mood
  • decreased interest in pleasurable activities
  • feelings of worthlessness or guilt
  • lack of energy
  • poor concentration
  • changes in appetite
  • agitation
  • sleep disturbances
  • suicidal thoughts

The goal for treatment of MDD is full remission, meaning minimal or no residual symptoms. However, the majority of patients do not achieve this with first line therapies.

In one study, only about one-third of patients achieved remission after a treatment trial with a selective serotonin reuptake inhibitor (SSRI), a commonly used type of antidepressant. About 10-30% of patients do not find depression relief after trying two different antidepressants. Given the significant decline in quality of life, functional impairment, and financial costs associated with MDD, the development of safe, effective, and fast-acting treatments is in high demand.

In August 2022, dextromethorphan-bupropion was approved for MDD by the Food and Drug Administration (FDA), marketed under the brand name Auvelity. Auvelity works differently than other oral antidepressants on the market. The unique way it works makes it an effective and fast-acting oral antidepressant treatment option. One clinical trial demonstrated improvement in patients’ depression in as early as one week. This is different from most other oral antidepressants, which can take up to four weeks before they begin to show symptom improvement.

One key thing for patients to note is that Delsym cough syrup, an over-the-counter medication that contains dextromethorphan, cannot be used to self treat depression at home. Without the bupropion, dextromethorphan does not last long enough in the body for depression treatment.

Dextromethorphan-bupropion also has good effectiveness compared to other oral antidepressants. One study showed that 53% of patients achieved clinical remission at six weeks. At twelve months, remission was sustained at 69%.

Studies have also shown that the medication is well tolerated, with the most common adverse events including:

  • dizziness
  • nausea
  • dry mouth
  • headache

The introduction of dextromethorphan-bupropion marks a significant advancement in the treatment of MDD. With a favorable safety profile, it may be a promising oral option for those who have not had success with other antidepressants. Every person is different, and every treatment option has pros and cons. If you notice you are experiencing symptoms of depression, make sure to talk with your doctor to find the right treatment options for you.


1. National Institute of Mental Health. Major Depression. National Institute of Mental Health. Published July 2023. https://www.nimh.nih.gov/health/statistics/major-depression
2. Stahl SM. Dextromethorphan/Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity [published correction appears in CNS Spectr. 2020 Dec;25(6):803]. CNS Spectr. 2019;24(5):461-466. doi:10.1017/S1092852919001470
3. Diagnostic and statistical manual of mental disorders. Arlington, VA, USA: American Psychiatric Publishing, 2013.
4. Trivedi MH, Daly EJ. Treatment strategies to improve and sustain remission in major depressive disorder. Dialogues Clin Neurosci. 2008;10(4):377-384. doi:10.31887/DCNS.2008.10.4/mhtrivedi
5. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. doi:10.1176/ajp.2006.163.11.1905
6. Akbar D, Rhee TG, Ceban F, et al. Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials. CNS Drugs. 2023;37(10):867-881. doi:10.1007/s40263-023-01032-5






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