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Emerging Pharmacological Approaches for Psychosis and Agitation in Alzheimer's Disease
Camillo Imbimbo, Matteo Cotta Ramusino, Silvia Leone, Federico Mazzacane, Valentino De Franco, Alberto Gatti, Giulia Perini, Alfredo Costa. CNS drugs, 2024-12-02
Topic: Drug trials: efficacy and safety
Psychosis and agitation are among the most distressing neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD), linked to faster disease progression and earlier admission to nursing homes. While nonpharmacological treatments may alleviate mild behavioral symptoms, more severe syndromes often require pharmacological intervention. Brexpiprazole is the only medication approved for agitation in AD, although its limited clinical efficacy has raised criticism. No drugs have been approved for treating psychosis in AD, highlighting the critical need for new, effective, and safe treatments. Recent studies have elucidated part of the neurobiological basis of NPSs in the AD brain, offering insights for testing repurposed and novel drugs. We conducted a comprehensive nonsystematic literature review, aiming to provide a critical overview of both current treatments and emerging pharmacological interventions under clinical development for treating psychosis and agitation in AD. Additionally, we present strategies to optimize the clinical development of new drug candidates. We identify three promising compounds that are currently in phase 3 trials: xanomeline-trospium for AD psychosis, and dextromethorphan-bupropion and dexmedetomidine for agitation in AD. We propose that biomarkers linked to the neuropsychiatric traits of AD patients should be identified in dedicated studies and then included in phase 2 dose-range-finding studies with novel compounds to establish biological engagement. Furthermore, phase 3 placebo-controlled studies should be carried out in AD biomarker-confirmed subjects with narrower cognitive impairment ranges and precise NPS severity at screening. Alternative study designs, such as sequential phase approaches, may also be adopted.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Imbimbo, C., Ramusino, M. C., Leone, S., Mazzacane, F., De Franco, V., Gatti, A., et al. (2025). Emerging Pharmacological Approaches for Psychosis and Agitation in Alzheimer's Disease. CNS drugs. https://doi.org/10.1007/s40263-024-01133-9
Vancouver
Imbimbo C, Ramusino MC, Leone S, Mazzacane F, De Franco V, Gatti A, et al. Emerging Pharmacological Approaches for Psychosis and Agitation in Alzheimer's Disease. CNS drugs. 2025. doi:10.1007/s40263-024-01133-9. PMID: 39623197.
BibTeX
@article{imbimbo2025-39623197,
author = {Imbimbo, Camillo and Ramusino, Matteo Cotta and Leone, Silvia and Mazzacane, Federico and De Franco, Valentino and Gatti, Alberto and Perini, Giulia and Costa, Alfredo},
title = {{Emerging Pharmacological Approaches for Psychosis and Agitation in Alzheimer's Disease}},
journal = {CNS drugs},
year = {2025},
doi = {10.1007/s40263-024-01133-9},
pmid = {39623197},
url = {https://doi.org/10.1007/s40263-024-01133-9}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Additionally, we present strategies to optimize the clinical development of new drug candidates.
- We identify three promising compounds that are currently in phase 3 trials: xanomeline-trospium for AD psychosis, and dextromethorphan-bupropion and dexmedetomidine for agitation in AD.
- We propose that biomarkers linked to the neuropsychiatric traits of AD patients should be identified in dedicated studies and then included in phase 2 dose-range-finding studies with novel compounds to establish biological engagement.
- Furthermore, phase 3 placebo-controlled studies should be carried out in AD biomarker-confirmed subjects with narrower cognitive impairment ranges and precise NPS severity at screening.
- Alternative study designs, such as sequential phase approaches, may also be adopted.
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Study details
- Study designclinical trial
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (CNS drugs) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39623197) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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