This newsletter includes information regarding the recent approval of dextromethorphan combined with bupropion for treating MDD in adults.
We also share practical tips on using psychotropic drugs in lactation, key points from a presentation on atypical psychopharmacologic strategies for youth, and our practical research summaries (Quick Takes).
Dextromethorphan HBr + Bupropion HCI (Auvelity) for Treating MDD
Auvelity is a combination of dextromethorphan—a cough suppressant, which acts as an NMDA receptor antagonist—and bupropion, which increases and prolongs the blood levels of dextromethorphan, thereby modulating glutamatergic neurotransmission.
This combination is the first oral nonmonoamine antidepressant approved in 60 years for treating MDD.
- What do we know about its efficacy?
- The GEMINI study compared the efficacy of dextromethorphan–bupropion vs placebo for 6 weeks.
- Dextromethorphan–bupropion was superior to placebo in improving MADRS scores at all times, including weeks 1 and 2.
- Remission was achieved by 39.5% of patients with dextromethorphan–bupropion vs 17.3% with placebo and clinical response by 54% vs 34%, respectively. Learn more here.
- Is the combination more effective than bupropion alone?
- The ASCEND study assessed the efficacy of dextromethorphan–bupropion vs sustained-release bupropion.
- The mean change from baseline in MADRS score was significantly greater with dextromethorphan–bupropion.
- Response rates at week 6 were 60.5% with dextromethorphan–bupropion vs 40.5% with bupropion. Learn more here.
- What is the recommended dose of Auvelity?
- The studied dose is dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg.
- The starting dosage is 1 tablet once daily in the morning. After 3 days, it is recommended to increase the dose to 1 tablet twice daily.
- For which patients is Auvelity indicated?
- For now, it is indicated only for the treatment of MDD in adults. Auvelity is not approved for pediatric patients.
- What are the most common side effects?
- Dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis
- How is it different from existing antidepressants?
- It improves depressive symptoms as early as week 1.
- Unlike intranasal esketamine—another medication that can improve depressive symptoms quickly—Auvelity is administered orally.
- When will it be available?
- Dextromethorphan and bupropion extended-release tablets are expected to be available by the end of 2022.
Understanding the Use of Psychotropic Drugs in Lactation, With Lauren Osborne, M.D.
In this interview, Dr. Lauren Osborne highlights practical considerations regarding the use of psychotropic medications during lactation. She guides clinicians through the process of medication selection using evidence-based research for patients with psychiatric conditions who wish to breastfeed.
Interview highlights include the following:
- When prescribing antipsychotics for women who breastfeed, consider molecular size and effect on prolactin.
- Valproate is safer to use during lactation compared with during pregnancy. When using lithium, always consider hydration status, and watch out for possible lithium toxicity.
- Clozapine is best avoided in lactation due to the risk of agranulocytosis for both the mother and child.
Learn more and earn 0.75 CME credits here.
Atypical Psychopharmacologic Strategies for Children and Adolescents
In this presentation, Dr. David Rosenberg discusses the use of atypical psychopharmacologic strategies in children and adolescents. He reviews potential indications of nonstandard psychoactive drugs, such as opiate antagonists, glutamate modulators, anticonvulsants, and exogenous hormones, providing prescription and monitoring guidelines for these medications. At the end of the presentation, he highlights valuable concepts with a clinical vignette.
Naltrexone: Potential Indications and Administration in Children and Adolescents
- There are no FDA-approved pediatric indications for naltrexone.
- Off-label use regularly occurs in conditions associated with abnormalities of the endogenous opioid system.
- Current evidence supporting the use of naltrexone in children and adolescents is limited and conflicting.
- Low-dose naltrexone effectively blocks opioid receptors and is well tolerated.
- Mild hepatic toxicity has been reported at high doses.
- Consider liver function tests before initiation and periodically during chronic treatment.
Learn more and earn 1.25 CME credits here.
Quick Takes: Informing Your Practice
The Potential Use of Folate and Its Derivatives in Treating Psychiatric Disorders: A Systematic Review
- At minimum, this review helps remind us of the metabolic pathways that folic acid and dietary folate travel before the potential bottleneck posed by inefficient versions of the methyltetrahydrofolate reductase (MTFR) enzymes. Learn more.
Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-Analysis
- Self-reported physical activity is inversely associated with risk of developing depression—no big surprise.
- But the surprise is, it doesn’t take even reaching the WHO-recommended “dose” of 30 minutes 5 times a week if this relationship is causal. Half of that yields most of the benefit. Learn more.
Listen to or read the full volume, and earn 0.5 CME credits here.
Listen to Our Podcast: Psychopharm Updates
Don’t miss out on the latest updates in psychopharmacology! Each episode showcases one of our products on a regular basis: Video lectures, Quick Takes, and Expert Consultations. We update our feed every 5 days.
References
- Tabuteau, H., Jones, A., Anderson, A., Jacobson, M., & Iosifescu, D. V. (2022). Effect of AXS-05 (dextromethorphan-bupropion) in major depressive disorder: A randomized double-blind controlled trial. American Journal of Psychiatry, 179(7), 490-499.
- Iosifescu, D. V., Jones, A., O’Gorman, C., Streicher, C., Feliz, S., Fava, M., & Tabuteau, H. (2022). Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder. The Journal of Clinical Psychiatry, 83(4).
- Axsome Therapeutics. (2022, August). Highlights of prescribing information. Expanding Treatment for CNS Conditions – Axsome Therapeutics. https://www.axsome.com/auvelity-prescribing-information.pdf
