Auvelity (bupropion/dextromethorphan) / Axsome Therap - LARVOL DELTA

Auvelity (Dextromethorphan-Bupropion) for Agitation and Aggression in Alzheimer's Disease Dementia: Mechanism, Efficacy, Safety, and Clinical Considerations. (PubMed, Psychopharmacol Bull) - "Clinicians must, however, monitor for blood pressure changes and potential CYP2D6 drug-drug interactions. 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."

Journal • Review • Alzheimer's Disease • Anesthesia • CNS Disorders • Cognitive Disorders • Dementia

A Study to Evaluate the Efficacy and Safety of AXS-05 for Smoking Cessation in Adults (clinicaltrials.gov) - P3 | N=705 | Recruiting | Sponsor: Axsome Therapeutics, Inc.

New P3 trial • Tobacco Cessation

Commercial Highlights (The Manila Times) - "New-to-brand prescriptions, representing new AUVELITY patient starts, increased 126% among patients ≥65 years of age during the first eight weeks following the Alzheimer’s disease agitation launch compared to the same period in the prior quarter...Overall new-to-brand prescriptions in the second quarter of 2026 increased 26% compared to the first quarter of 2026, reflecting the early impact of the sales force expansion which was completed in the second quarter. Approximately 266,000 total prescriptions were written for AUVELITY in the second quarter of 2026, representing year-over-year and quarter-over-quarter increases of 34% and 12%, respectively...Payer coverage for AUVELITY across all channels is currently at approximately 89% of all lives covered."

Commercial • Alzheimer's Disease • Major Depressive Disorder

Second Quarter 2026 Financial Highlights (The Manila Times) - "AUVELITY net product sales were $180.3 million for the second quarter of 2026, representing 51% year-over-year growth. AUVELITY net product sales for the comparable period in 2025 were $119.6 million....SYMBRAVO net product sales were $2.3 million for the second quarter of 2026, representing 461% year-over-year growth. SYMBRAVO was launched in June 2025 and had net product sales of $0.4 million for the second quarter of 2025."

Sales • Alzheimer's Disease • Migraine

Initiating dextromethorphan-bupropion extended release in patients with major depressive disorder: Delphi panel expert consensus recommendations. (PubMed, Curr Med Res Opin) - "To establish consensus recommendations for initiating dextromethorphan-bupropion extended release (45 mg/105 mg) (AUVELITY) for the treatment of major depressive disorder (MDD) in adults. Key consensus recommendations (abbreviated here) included: (1) dextromethorphan-bupropion is recommended as a first-line treatment for MDD, including with co-occurring symptoms of anxiety; (2) HCPs should individualize treatment decisions that prioritize safety considerations noted in the Prescribing Information; (3) dextromethorphan-bupropion is recommended for patients with inadequate response, residual symptoms, and/or intolerable side effects associated with prior MDD treatment(s); (4) when switching from (or adding to current) medication, the potential for a drug interaction should be considered, consistent with the dextromethorphan-bupropion label; and (5) switching from ketamine or esketamine should be done with caution, and with an awareness of the short-to-intermediate..."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Dextromethorphan-bupropion-associated pharmacovigilance signals based on the FAERS database: An observational study. (PubMed, Medicine (Baltimore)) - "In clinical applications, practitioners should closely monitor occurrences of psychiatric disorders, nervous system disorders, general disorders, administration site conditions, and other events. Meanwhile, professional clinicians should be alerted to the AEs signals not mentioned in the label to secure clinical use."

Adverse events • Journal • Observational data • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry

Dextromethorphan/bupropion (Auvelity) for agitation in Alzheimer's dementia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Targeting Neuroinflammation in Depression: The Integrative Role of Sigma-1 Receptor Modulation. (PubMed, J Neurochem) - "We also evaluate advances in representative Sig-1R agonists and review available clinical trial data, including results on the novel multi-target agent AXS-05...In summary, the Sigma-1 receptor serves as a key regulator of cellular homeostasis and adaptation. Its agonists represent a promising therapeutic strategy that moves beyond symptomatic monoaminergic modulation to mechanistically target the core inflammatory and proteostatic disturbances in depression, offering the potential for improved treatment efficacy."

Journal • Review • CNS Disorders • Depression • Immunology • Inflammation • Mood Disorders • Psychiatry • Solid Tumor • NLRP3

Combination therapies: A new approach to disease modification in Parkinson’s? (WPC 2026) - " By considering the recent approval of Auvelity, a combination of dextromethorphan and bupropion for the treatment of major depressive disorder, it was clear that understanding the mechanism by which combinations of agents are producing a synergistic effect is paramount. Combination therapies represent an, as yet, unexplored avenue for disease modification in PD. Through understanding the different biological pathways involved in the condition and learning how to successfully develop a combination therapy from other disease indications, it is hoped that combination therapies could accelerate the quest to find a cure for Parkinson’s."

Combination therapy • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Movement Disorders • Parkinson's Disease

Case Report: Oral glutamatergic augmentation for trauma-related disorders with fluoxetine-/bupropion-potentiated dextromethorphan ± piracetam: a four-patient case series. (PubMed, Front Psychiatry) - "Traditional monoaminergic medications often offer limited relief for the physical and cognitive symptoms of post-traumatic stress disorder (PTSD) and complex PTSD. These findings are strictly hypothesis-generating and broaden the ketamine/Auvelity framework to trauma-spectrum presentations. They suggest that further controlled investigation into oral NMDA-AMPA modulators may be warranted for trauma-related conditions."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Bipolar Disorder • Cardiovascular • CNS Disorders • Depression • Hypertension • Mood Disorders • Pain • Post-traumatic Stress Disorder • Psychiatry

First Quarter 2026 Financial Highlights (The Manila Times) - "AUVELITY net product revenue was $153.2 million for the first quarter of 2026, representing 59% year-over-year growth. AUVELITY net product sales for the comparable period in 2025 were $96.2 million...SYMBRAVO net product revenue was $4.1 million for the first quarter of 2026."

Sales • Alzheimer's Disease • Major Depressive Disorder • Migraine

Commercial Highlights (The Manila Times) - "Approximately 223,000 prescriptions were written for AUVELITY in the first quarter of 2026...The commercial launch of AUVELITY in Alzheimer’s disease agitation is on track for June 2026...Approximately 17,000 prescriptions were written for SYMBRAVO in the first quarter of 2026...Payer coverage for SYMBRAVO in the commercial channel expanded by 17 million new covered lives, effective May 2026. Overall payer coverage for SYMBRAVO across all channels is now at approximately 57% of all lives, with the proportion of covered lives in the commercial and government channels at approximately 56% and 57%, respectively."

Commercial • Launch US • Alzheimer's Disease • Dementia • Migraine

The U.S. Food and Drug Administration today approved an expanded use for Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride) extended-release tablets to treat agitation associated with dementia due to Alzheimer’s disease in adults. (FDA) - "The first randomized study (NCT03226522) was a five-week trial in which participants received either Auvelity or a placebo."

FDA approval • Alzheimer's Disease • Dementia

Pharmacotherapeutic landscape for the management of agitation associated with Alzheimer's disease. (PubMed, Expert Opin Pharmacother) - "Brexpiprazole establishes regulatory feasibility, while dextromethorphan-based combinations, particularly AXS-05, appear promising, including signals for durability. Progress will depend on harmonized outcomes, longer-term safety data, and pragmatic trials that prioritize function, caregiver impact, and crisis prevention."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry

Dextromethorphan-Bupropion on Striatal Activity in Adults With Major Depressive Disorder (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Roger McIntyre

New P2 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

DXM, CYP2D6-inhibiting antidepressants, piracetam, and glutamine: proposing a ketamine-class antidepressant regimen with existing drugs. (PubMed, Front Psychiatry) - "Intravenous ketamine achieves this flip but is hampered by dissociation and logistics, while dextromethorphan + bupropion (Auvelity®) primarily supplies the initial NMDA blockade and yields slower, less durable benefit. We hypothesize that a fully oral, low-cost, four-component regimen may be able to approximate ketamine's full plasticity cascade (1) dextromethorphan (DXM) for NMDA antagonism; (2) a potent CYP2D6 inhibitor (fluoxetine, paroxetine, or high-dose duloxetine) to prolong DXM exposure; (3) piracetam as an AMPA positive allosteric modulator; and (4) micronized L-glutamine to restore presynaptic glutamate pools and buffer against excitotoxicity. Preclinical evidence supports mechanistic synergy along the same axis, but the full combination remains untested in humans. This hypothesis warrants formal preclinical and clinical evaluation."

Journal • CNS Disorders • Depression • Psychiatry

Drugs for dementia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Movement Disorders • Parkinson's Disease

sNDA for AXS-05 for the treatment of Alzheimer’s disease agitation granted Priority Review with PDUFA target action date of April 30, 2026 (The Manila Times)

PDUFA • Alzheimer's Disease

Open-Label Safety Study of AXS-05 in Subjects With TRD (EVOLVE) (clinicaltrials.gov) - P2 | N=181 | Terminated | Sponsor: Axsome Therapeutics, Inc. | Completed ➔ Terminated; This study was terminated once overall program objectives were met.

Trial termination • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Axsome Therapeutics…announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s supplemental New Drug Application (NDA) for AXS-05 (dextromethorphan HBr and bupropion HCl) for the treatment of Alzheimer’s disease agitation, and has granted the application Priority Review designation (GlobeNewswire) - "The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2026....The supplemental NDA is the culmination of a comprehensive clinical development program of AXS-05 in Alzheimer’s disease agitation, including four randomized, double-blind, controlled Phase 3 clinical trials and a long-term safety trial."

FDA filing • PDUFA • Priority review • Alzheimer's Disease • Psychomotor Agitation

AXS-05 (GlobeNewswire) - "Alzheimer’s Disease Agitation: Axsome has submitted a supplemental NDA (sNDA) to the FDA for AXS-05 in Alzheimer’s disease agitation. The Company plans to announce the FDA’s decision on acceptance of the filing."

FDA filing • Alzheimer's Disease

Axsome Therapeutics Reports Third Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "AUVELITY net product sales were $136.1 million for the third quarter of 2025, representing 69% year-over-year growth, and 14% sequential growth compared to the second quarter of 2025. AUVELITY net product sales for the third quarter of 2024 were $80.4 million...SUNOSI net product revenue was $32.8 million for the third quarter of 2025, representing 35% year-over-year growth, and 9% sequential growth compared to the second quarter of 2025....SYMBRAVO net product sales were $2.1 million for the third quarter of 2025, the first full quarter of commercialization following its launch in June 2025."

Sales • Major Depressive Disorder • Migraine • Narcolepsy • Obstructive Sleep Apnea

Dextromethorphan as augmentation therapy in major depressive disorder: A randomized controlled trial (ECNP 2025) - P4 | "Research on sub-anaesthetic doses of ketamine has revealed rapid, sustained antidepressant effects, emphasizing NMDA receptors as a key target...The US FDA approved a fixed-dose combination of Dextromethorphan Hydrobromide and Bupropion Hydrochloride (Auvelity) for adult MDD...Patients aged 18-65 years, with a clinical diagnosis of mild to moderate MDD (DSM5), who were on sertraline 50mg or any other SSRI in an equivalent dose for ≤4 weeks, were recruited for the study...The occurrence of adverse events was comparable in both study groups. Conclusion Early augmentation of SSRIs with dextromethorphan(30mg/day) for the treatment of mild to moderate MDD may improve clinical outcomes significantly in terms of improvement in symptoms, response rate and remission rate."

Clinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • BDNF

Axsome Therapeutics Highlights Data Across Its Leading Neuroscience Pipeline at Psych Congress 2025 (GlobeNewswire) - "Six poster presentations showcase clinical and real-world data in major depressive disorder, Alzheimer’s disease agitation, narcolepsy, and obstructive sleep apnea."

Clinical data • Alzheimer's Disease • Major Depressive Disorder • Narcolepsy • Obstructive Sleep Apnea

New and emerging pharmacologic treatments for MDD. (PubMed, Front Psychiatry) - "Furthermore, the combination of dextromethorphan and bupropion has shown promise. Brexanolone, administered via infusion, and zuranolone, available as an oral formulation, both have demonstrated efficacy in clinical settings. Novel treatments targeting opioid pathways, such as esmethadone, and selective kappa receptor antagonists offer new hope for addressing the symptoms of MDD through mechanisms not traditionally associated with antidepressant action."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry