{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:47:06Z","timestamp":1791380826266,"version":"4.3.3"},"reference-count":0,"publisher":"MedWorks Media","issue":"4S1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Psychopharmacol Bull"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Agitation and aggression in Alzheimer\u2019s disease (AD) are highly distressing behavioral symptoms traditionally managed with off-label atypical antipsychotics, despite boxed warnings for increased mortality in elderly patients. The emergence of Auvelity (dextromethorphan-bupropion) provides a critical, non-antipsychotic therapeutic alternative.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Mechanism<\/jats:title>\n                    <jats:p>This combination utilizes bupropion as a CYP2D6 inhibitor to achieve therapeutic central nervous system concentrations of dextromethorphan. Dextromethorphan acts as an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, bypassing dopaminergic blockade to promote synaptic plasticity via glutamatergic and monoaminergic modulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Efficacy<\/jats:title>\n                    <jats:p>Key clinical trials (ADVANCE-1 and ACCORD) demonstrate that dextromethorphan-bupropion produces rapid, statistically significant reductions in Cohen-Mansfield Agitation Inventory (CMAI) scores. Furthermore, it offers robust long-term maintenance, demonstrating a 3.6-fold lower risk of agitation relapse compared to placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Safety<\/jats:title>\n                    <jats:p>The combination therapy was generally well-tolerated in trials, successfully avoiding the sedation, cognitive blunting, and heightened fall risks characteristic of antipsychotics. Clinicians must, however, monitor for blood pressure changes and potential CYP2D6 drug-drug interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dextromethorphan-bupropion represents a highly efficacious, safer paradigm shift in the pharmacological management of AD-associated agitation, offering targeted symptom relief while minimizing the severe risks associated with standard antipsychotic use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.64719\/pb.20773","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:49:08Z","timestamp":1789807748000},"page":"82-87","source":"Crossref","is-referenced-by-count":0,"title":["Auvelity (Dextromethorphan-Bupropion) for Agitation and Aggression in Alzheimer\u2019s Disease Dementia: Mechanism, Efficacy, Safety, and Clinical Considerations"],"prefix":"10.64719","volume":"56","author":[{"given":"Mridul","family":"Sarangal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmi","family":"Sarangal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Vora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karishma","family":"Soni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54175","published-online":{"date-parts":[[2026,9,17]]},"container-title":["Psychopharmacology Bulletin"],"original-title":[],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:49:09Z","timestamp":1789807749000},"score":1,"resource":{"primary":{"URL":"https:\/\/medworksmedia.com\/pb-article\/auvelity-dextromethorphan-bupropion-for-agitation-and-aggression-in-alzheimers-disease-dementia-mechanism-efficacy-safety-and-clinical-considerations\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":0,"journal-issue":{"issue":"4S1","published-online":{"date-parts":[[2026,9,17]]}},"URL":"https:\/\/doi.org\/10.64719\/pb.20773","relation":{},"ISSN":["2472-2448"],"issn-type":[{"value":"2472-2448","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}