New York-based Axsome Therapeutics (Nasdaq: AXSM) announced that the US FDA has approved Auvelity (dextromethorphan HBr/bupropion HCl) for the treatment of agitation associated with dementia due to Alzheimer’s disease, marking the drug’s second approved indication. The approval represents a first-in-class designation for this indication, with Auvelity acting on NMDA and sigma-1 receptors — a mechanism distinct from existing pharmacological approaches to Alzheimer’s disease-related agitation.
Auvelity was initially approved by the US FDA in 2022 for major depressive disorder in adults. The new indication extends its use to agitation associated with Alzheimer’s disease dementia, a neuropsychiatric condition the company describes as affecting up to 76% of patients with Alzheimer’s disease. The approved dosing regimen for this indication begins with 30 mg dextromethorphan/105 mg bupropion once daily in the morning for seven days, escalating to twice-daily dosing from day eight, with a further increase to the maximum recommended dose of 45 mg/105 mg twice daily from day fifteen, based on tolerability. The prescribing information specifies that Auvelity should not be used on an as-needed basis for this indication.
The drug’s activity as an oral NMDA receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor underpins its proposed role in modulating glutamate and monoamine signaling pathways implicated in Alzheimer’s disease agitation. The most common adverse effects reported in the agitation indication were dizziness and indigestion, a profile distinct from those observed in the MDD indication, where dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and excessive sweating were more frequently reported.