In this episode, we discuss the evidence, safety, and place in therapy of Auvelity® (dextromethorphan-bupropion), a newly approved antidepressant with a unique mechanism of action and interesting pharmacokinetic considerations.

Key Concepts

1. Auvelity® (bupropion-dextromethorphan) was FDA approved in 2022 for major depressive disorder (MDD). The bupropion component inhibits CYP2D6 metabolism and increases serum concentrations of dextromethorphan. The proposed mechanism of benefit in MDD is via dextromethorphan (as an NMDA antagonist) and possibly with bupropion (as a dopamine/norepinephrine reuptake inhibitor).
2. Although the bupropion component in Auvelity® is being used for its drug interaction, the dose is a therapeutic dose and carries several warnings and precautions, including the risk of seizure and hypertension.
3. In short (6-week) clinical trials, Auvelity® improved depression symptoms quickly (within 1-2 weeks), which is faster than many other antidepressants. Auvelity® is associated with dizziness, anxiety, hyperhidrosis, nausea, headache, diarrhea, and dry mouth.
4. As a CYP2D6 inhibitor, the bupropion component of Auvelity® will cause drug interactions with many other medications, including some antidepressants, antipsychotics, and opioid analgesics (among others).

References

• Iosifescu DV, Jones A, O'Gorman C, 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. 2022;83(4):21m14345. Published 2022 May 30. doi:10.4088/JCP.21m14345
• Tabuteau H, Jones A, Anderson A, Jacobson M, Iosifescu DV. Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. Am J Psychiatry. 2022;179(7):490-499. doi:10.1176/appi.ajp.21080800
• Kotlyar M, Brauer LH, Tracy TS, et al. Inhibition of CYP2D6 activity by bupropion. J Clin Psychopharmacol. 2005;25(3):226-229. doi:10.1097/01.jcp.0000162805.46453.e3

In this episode, we highlight important changes to the 2023 GOLD Guidelines for COPD. In particular, we discuss a revision to the GOLD group classification system and the preferred initial therapies in patients with COPD.

Key Concepts

1. The newest GOLD COPD guidelines now recognize three GOLD groups – “A”, “B”, and “E”. Group “E” (formerly groups C and D) are patients with frequent exacerbations (defined as 2 or more in the past 12 months or 1 exacerbation requiring hospitalization).
2. For group “E” patients, the preferred initial inhaler regimen is a LABA+LAMA. Triple therapy (LABA+LAMA+ICS) can be considered if blood eosinophils are elevated.
3. “Triple therapy” (LABA+LAMA+ICS) has gained traction based on the IMPACT and ETHOS trials – this regimen reduced exacerbations and mortality compared to LABA+LAMA and LABA+ICS.
4. With an exploding market of new COPD inhalers, the role of the pharmacist is even more critical to help identify affordable medications and provide patient education for proper inhaler technique.

References

• Global Strategy for Prevention, Diagnosis, and Management of COPD: 2023 Report. Global Initiative for Chronic Obstructive Lung Disease (GOLD). https://goldcopd.org/2023-gold-report-2/
• IMPACT study: Lipson DA, Barnhart F, Brealey N, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018;378(18):1671-1680. doi:10.1056/NEJMoa1713901
• ETHOS study: Rabe KF, Martinez FJ, Ferguson GT, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020;383(1):35-48. doi:10.1056/NEJMoa1916046