What side effects are associated with this type of intervention?

Common treatments for agitation in dementia, such as antipsychotics and NMDA receptor antagonists, have a range of side effects. First-generation antipsychotics can cause significant extrapyramidal symptoms (EPS) and tardive dyskinesia, while second-generation antipsychotics are associated with metabolic effects and a lower risk of EPS. NMDA receptor antagonists, like memantine, may cause dizziness, headache, confusion, and constipation. It is important to monitor these side effects closely and discuss them with a healthcare provider to ensure the best treatment plan for the patient.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of neuropsychiatric symptoms in dementia, including antipsychotics like olanzapine, risperidone, and quetiapine, which have been studied for their efficacy in managing agitation. However, specific approvals for NMDA receptor antagonists and Sigma-1 receptor agonists, similar to AXS-05, are not detailed in the provided context. Broadly, treatments for agitation in dementia often involve antipsychotics and other medications aimed at managing behavioral symptoms.

What other types of research exist?

ANAVEX2-73, a mixed muscarinic and sigma-1 receptor agonist, is a promising alternative. It has shown efficacy in blocking tau hyperphosphorylation and reducing amyloid load in Alzheimer's disease models, which may help alleviate agitation in dementia patients.

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NMDA receptor antagonist

AXS-05 for Alzheimer's Disease Agitation (ADVANCE-2 Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for agitation in dementia include NMDA receptor antagonists, Sigma-1 receptor agonists, antipsychotics, and acetylcholinesterase inhibitors. NMDA receptor antagonists, such as memantine, work by modulating glutamatergic neurotransmission, which can help reduce excitotoxicity and neuronal damage, potentially alleviating agitation. Sigma-1 receptor agonists, like those in AXS-05, may enhance neuroprotection and modulate neurotransmitter systems, contributing to improved mood and reduced agitation. Antipsychotics, such as risperidone, target dopamine and serotonin receptors to manage psychotic symptoms and agitation. Acetylcholinesterase inhibitors, like donepezil, increase acetylcholine levels, which can improve cognitive function and reduce behavioral symptoms. These mechanisms are crucial as they address the neurochemical imbalances and neuronal dysfunctions that contribute to agitation in dementia patients.

Verified Trial

Phase 3

Recruiting

Research Sponsored by Axsome Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 weeks

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new medication called AXS-05 to see if it can help reduce agitation in people with Alzheimer's disease. The goal is to find out if AXS-05 can balance brain chemicals to calm agitation and improve behavior. AXS-05, a combination of dextromethorphan and bupropion, is being investigated for its potential to treat agitation in Alzheimer's disease and has shown promise in early clinical trials.

Who is the study for?

This trial is for people with Alzheimer's disease who are experiencing significant agitation. Participants must be diagnosed based on specific criteria and able to follow the study procedures. Those with non-Alzheimer's dementia or deemed medically unfit by the investigator cannot join.

What is being tested?

The trial is testing AXS-05 against a placebo to see if it can safely reduce agitation in Alzheimer's patients. It involves multiple centers, where participants are randomly assigned to receive either the real drug or a placebo without knowing which one they're getting.

What are the potential side effects?

While not specified here, common side effects of drugs like AXS-05 may include nausea, headache, dizziness, and sleep disturbances. The exact side effects will be monitored throughout the trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohen-Mansfield Agitation Inventory (CMAI)

Side effects data

From 2019 Phase 3 trial • 327 Patients • NCT04019704

29%

All Others, occurring in <5% of Subjects

16%

Dizziness

13%

Nausea

Headache

Diarrhea

Somnolence

Dry mouth

Pancreatitis

100%

80%

60%

40%

20%

Study treatment Arm

AXS-05

Placebo

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: AXS-05Experimental Treatment1 Intervention

Up to 5 weeks

Group II: PlaceboPlacebo Group1 Intervention

Up to 5 weeks

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AXS-05

2018

Completed Phase 3

~1390

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for agitation in dementia include NMDA receptor antagonists, Sigma-1 receptor agonists, antipsychotics, and acetylcholinesterase inhibitors. NMDA receptor antagonists, such as memantine, work by modulating glutamatergic neurotransmission, which can help reduce excitotoxicity and neuronal damage, potentially alleviating agitation. Sigma-1 receptor agonists, like those in AXS-05, may enhance neuroprotection and modulate neurotransmitter systems, contributing to improved mood and reduced agitation. Antipsychotics, such as risperidone, target dopamine and serotonin receptors to manage psychotic symptoms and agitation. Acetylcholinesterase inhibitors, like donepezil, increase acetylcholine levels, which can improve cognitive function and reduce behavioral symptoms. These mechanisms are crucial as they address the neurochemical imbalances and neuronal dysfunctions that contribute to agitation in dementia patients.

Recent advances in the management of neuropsychiatric symptoms in dementia.Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies.