The role of neurotransmitter receptors in antipsychotic medication efficacy for Alzheimer’s-related psychosis
Authors: Sharma Bhawana , Das Saumya , Mazumder Avijit , Rautela Deepraj Singh , Tyagi Pankaj Kumar , Khurana Navneet 
Published: June 2024

Background

Alzheimer's disease (AD) is marked by cognitive decline along with the presence of mental symptoms, most notably psychosis. Although antipsychotic drugs are commonly recommended to treat these symptoms, there is ongoing discussion on the safety and effectiveness of these drugs in AD patients. The therapeutic management of Alzheimer’s disease-related psychosis (ARP) is hampered by its limited therapy options, determining the precise brain regions in Alzheimer’s patients with understanding of the neurological substrates implicated in ARP. While new therapies including brexpiprazole and atypical antipsychotics present promising therapeutic choices, practical implementation and potential upcoming therapies approaches is discussed along with mechanism-based understanding of different neurotransmitters with pharmaceutical therapies. Our objective is to contribute to more efficient and individualized treatment approaches by offering a thorough resource for medical professionals and researchers working in the field of managing and researching psychosis associated with AD.

Results

The examination containing new data supporting newer therapeutic approaches that target receptors and providing better safety and effectiveness characteristics. This study point out gaps in our existing understanding and make recommendations for future research, emphasizing the necessity of clinical trials created especially for psychotic Alzheimer’s patients. Secondly, the neurochemical and neuropathological bases of ARP, with a focus on changes in the dopamine, serotonin, and glutamate systems of neurotransmitters are also described in detail. Different pharmacodynamics antipsychotic medications are covered in later sections of this paper, with an emphasis on how these medications' interactions with certain neurotransmitter receptors may affect their therapeutic efficacy and side-effects profile.

Conclusion

The review article summarizes the most recent findings regarding the contribution of neurotransmitter receptors to the effectiveness of antipsychotic drugs in the management of ADP. We provide a thorough overview of second-generation (atypical) antipsychotics, emphasizing how their unique affinity for neurotransmitter receptors influences their clinical application in psychosis associated with AD. The difficulties of treating Alzheimer’s with antipsychotics are also covered in this study, including the potential for cognitive impairment to worsen, the emergence of extrapyramidal symptoms, and other unfavorable effects. New approaches to studying and treating ARP including neuroinflammation-targeting medicines, transcranial magnetic stimulation (TMS), cerebrospinal fluid (CSF) biomarkers, and muscarinic acetylcholine receptor (mAChR) agonists like xanomeline. Reducing psychosis through treatment options could be improved by knowledge of N-methyl-D-aspartate glutamate receptors (NMDAR) hypofunction processes in gamma-aminobutyric acid (GABAergic) neurons.