Axsome Therapeutics' AXS-05, a novel oral NMDA receptor antagonist, is showing promise as a targeted treatment for agitation in Alzheimer's disease (AD). The combination drug, containing dextromethorphan and bupropion, aims to address agitation through a unique mechanism of action, potentially offering a safer alternative to traditional antipsychotics.
Addressing Agitation in Alzheimer's Disease
Agitation affects up to 70% of individuals with Alzheimer's disease, posing significant challenges for patients, caregivers, and healthcare professionals. Current pharmacologic treatments often rely on off-label use of typical antipsychotics, which carry substantial risks, including somnolence, cerebrovascular events, extrapyramidal symptoms, increased hospitalization rates, and mortality.
AXS-05: A Novel Approach
AXS-05 combines dextromethorphan, the primary therapeutic component, with bupropion, which extends dextromethorphan's half-life. Dextromethorphan modulates the excitatory neurotransmitter glutamate by blocking glutamate, potentially mitigating agitation symptoms. According to George Grossberg, MD, Samuel W. Fordyce professor and director of Geriatric Psychiatry at Saint Louis University School of Medicine, bupropion is used in low doses to slow the metabolism of dextromethorphan, reducing the need for frequent administration.
Advantages Over Traditional Treatments
One key advantage of AXS-05 is that it is not an antipsychotic, thus avoiding the boxed warning about increased mortality associated with that drug class. Furthermore, AXS-05 appears to have a reasonable side effect profile, without causing excessive sedation or motor impairment. Clinical trials suggest that it takes about two weeks to see separation from placebo, indicating that it is not an acute medication for immediate calming but rather a maintenance therapy.
Clinical Trial Data and Future Prospects
Pivotal trial data for AXS-05 is anticipated, with ongoing studies expected to provide further evidence of its efficacy. If these trials yield positive results, AXS-05 could become an FDA-approved treatment for agitation in Alzheimer's dementia, filling a critical unmet need in managing this challenging symptom.
