February 22, 2023
One of the problems with starting traditional antidepressants in hospice patients is that they might take too long to start working (typically a few weeks) and/or reach their full effect (up to 8 weeks). To get around this, some hospice clinicians will prescribe methylphenidate or ketamine to treat depression more rapidly; the onsets are about 1 day for methylphenidate and a few hours for ketamine. However, not all are comfortable prescribing these drugs off-label for this purpose and not all patients are suitable candidates.
Soon, folks will have access to a new antidepressant that might represent the best of both worlds, i.e., FDA-approved and rapid onset. Twice-daily Auvelity (dextromethorphan-bupropion) can be titrated to its maximum dose after 3 days and antidepressant effects might be evident in as little as 7 days.
Auvelity is a combination of two drugs that have been widely available for many years. Dextromethorphan, commonly used as a cough suppressant, is an NMDA antagonist and sigma-1 receptor agonist, though the exact mechanism of its antidepressant effect isn’t clear. Bupropion is used to treat a variety of conditions including depression and tobacco dependence, but is noted to be less effective than other types of antidepressants. Besides being an antidepressant when used as monotherapy, bupropion also happens to strongly inhibit CYP2D6, the enzyme primarily responsible for dextromethorphan metabolism.
This isn’t the first time that dextromethorphan has been combined with a CYP2D6 inhibitor (see our previous blog post on Nuedexta). In the case of Nuedexta, dextromethorphan is combined with subtherapeutic doses of quinidine (another strong CYP2D6 inhibitor) to prevent rapid metabolism of dextromethorphan. Without 2D6 inhibition, dextromethorphan is rapidly metabolized to dextrorphan, an antitussive (but not antidepressant) metabolite. Excessive 2D6 inhibition would occur if Auvelity is prescribed for patients who receive other 2D6 inhibitors like paroxetine, fluoxetine, or quinidine and it should only be taken once daily in these cases.
73% of patients who received Auvelity in a clinical trial experienced at least one adverse event, most commonly dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and sweating. Older adults, who represent the majority of hospice patients and are more prone to adverse drug effects, were excluded from the trial.
While it would be nice to have another option to treat depression quickly, tolerability, drug interactions, and, last but not least, cost (AWP $1,258 per month), will undoubtedly be a barrier to use in the hospice setting.
Melissa Corak, PharmD, BCGP
Melissa Corak is the Senior Clinical Pharmacist at OnePoint Patient Care, primarily supporting the needs of pharmacy staff and hospice partners in OnePoint’s Western Division. She has worked closely with the clinical team since joining OnePoint as a staff pharmacist in 2012 and transitioned to working with the team full-time in 2018. Melissa earned her PharmD from Midwestern University – Glendale and is board certified in geriatric pharmacy.