brexpiprazole and Alzheimer-Disease

The purpose is to review the results and clinical implications of recent studies of neuropathology in relation to neuropsychiatric symptoms (NPS) in Alzheimer's disease and related dementias, and discuss new therapeutic approaches based on evidence from clinical trials.. In a large autopsy series from a national consortium, multiple neuropathologies of dementia subtypes were common and increased severity of specific NPS during life was associated with greater severity of neuropathology across diagnoses. Based on three clinical trials, brexpiprazole, which is an antipsychotic with dopamine and serotonin receptor partial agonism properties, was recently approved for the treatment of agitation in Alzheimer's dementia by the U.S. Food and Drug Administration (FDA). Its therapeutic profile indicates modest efficacy with high safety. Brexpiprazole has not been compared to other antipsychotics that are commonly prescribed to treat agitation in dementia, though none of them have been approved for this indication. Other drugs that showed positive results in Phase 2 trials are being tested in Phase 3 trials. These include cannabinoids and drug combinations that inhibit dextromethorphan metabolism peripherally, thereby increasing its bioavailability in the brain. Apathy is common in several types of dementia, and there is initial evidence that treatment with methylphenidate, a psychostimulant, may be efficacious with good tolerability.. Greater understanding of the associations between NPS and dementia subtypes can improve clinical management of these disorders. In addition to the approval of brexpiprazole to treat agitation in Alzheimer's dementia, there is optimism about other medications based on ongoing clinical trials. Along with short-term improvement, altering the adverse impact on NPS on long-term prognosis remains an important challenge for the field.

Topics: Alzheimer Disease; Antipsychotic Agents; Apathy; Humans; Quinolones; Thiophenes; United States

Behavioral and psychological symptoms of dementia are symptoms of disturbed perception, mood, behavior, and thought content that occurred frequently. These symptoms, which include apathy, depression, anxiety, psychosis, agitation, and aggression, can serve as predictors of and early clinical diagnostic markers for Alzheimer's disease (AD) and are common precipitants of institutional care. Agitation and psychosis are associated with accelerated disease progression and increased tau phosphorylation in patients with AD. Current guidelines recommend the use of second-generation antipsychotics for the treatment of agitation and psychosis in AD, but only after first-line non-pharmacological interventions and for no longer than 12 weeks because long-term use of these drugs is associated with an increased risk of mortality and an increased frequency of cerebrovascular events. Therefore, new antipsychotic drugs with improved efficacy and safety are needed as an alternative to current antipsychotic drugs. In this report, we discuss some of the most relevant advances in the field of agitation and psychosis in AD and focus on the recent positive clinical evidence observed with two new antipsychotics drugs: brexpiprazole and pimavanserin. Brexpiprazole is a receptor partial agonist (D2, D3, 5-HT1A), receptor antagonist (5-HT2A/B, α1B/α2C) according to the neuroscience-based nomenclature. Two recent phase III clinical trials have shown that brexpiprazole 2 mg/day is effective for the treatment of agitation in patients with AD and has an improved tolerability and safety profile compared with currently available second-generation antipsychotics. Pimavanserin is a receptor antagonist (5-HT2A, 5-HT2C) that has been given market authorization for psychosis occurring in Parkinson's disease. Recent phase II studies suggest that this drug is effective in AD patients with more severe psychosis, although further long-term studies are needed to better define the efficacy and long-term safety profile of pimavanserin for the treatment of psychosis in AD.

Topics: Alzheimer Disease; Antipsychotic Agents; Anxiety; Humans; Piperidines; Psychotic Disorders; Quinolones; Thiophenes; Urea

Topics: Alzheimer Disease; Antipsychotic Agents; Humans; Psychomotor Agitation; Quinolones; Thiophenes

Topics: Alzheimer Disease; Dementia; Double-Blind Method; Humans; Quinolones; Thiophenes

Schizophrenia is a disabling psychiatric disorder marked by progressive loss of functionality in activities of daily living with each relapse. Antipsychotics, the mainstay of therapy for schizophrenia, treat hallucinations and delusions but may have intolerable side effects, including metabolic disturbances and extrapyramidal symptoms. Brexpiprazole, a second-generation antipsychotic with dopamine partial agonist properties, was approved by the US FDA in 2015 for the treatment of schizophrenia and adjunctive treatment of major depressive disorder and by the EU in 2018 for adults with schizophrenia. Additionally, brexpiprazole has recently been studied for the treatment of agitation in Alzheimer's dementia, an area of largely unmet need. Overall, well-tolerated brexpiprazole expands the armamentarium of treatment options available for these conditions.

Topics: Alzheimer Disease; Antipsychotic Agents; Humans; Quinolones; Schizophrenia; Thiophenes