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Neuropsychiatric Adverse-Event Reporting With Brexpiprazole Across Approved Indications: A Disproportionality Analysis Using the FDA Adverse Event Reporting System (FAERS)
Za'areer MA, Jafari AA.. Research Square, 2026-09-08
Topic: Drug trials: efficacy and safety
Background Brexpiprazole is an atypical antipsychotic approved for major depressive disorder, schizophrenia, and, most recently (May 2023), agitation associated with Alzheimer’s disease. Three primary comparisons were performed (A vs B, A vs C, A vs B + C combined) alongside five pre-planned sensitivity analyses: primary suspect reports only, restriction to patients aged ≥ 65 years, collapsed MedDRA terms, a quetiapine active comparator analysis, and serious versus non-serious adverse event proportions. Results After deduplication, 9,113 brexpiprazole reports were identified: 682 Alzheimer’s disease, 6,858 MDD, and 1,573 schizophrenia cases. Compared to MDD patients, Alzheimer’s patients had higher reporting of delirium (ROR 32.91, 95% CI 12.26–88.33), falls (ROR 8.06, 95% CI 5.43–11.94), hallucination (ROR 10.01, 95% CI 6.73–14.90), neuroleptic malignant syndrome (ROR 11.47, 95% CI 3.62–36.36), and agitation (ROR 5.09, 95% CI 3.44–7.52; noting potential indication-outcome overlap). Akathisia and tardive dyskinesia were reported significantly less frequently. The overall pattern of findings was supported by multiple sensitivity analyses, including restriction to patients aged ≥ 65 years, where the hallucination signal strengthened further (ROR 30.59, 95% CI 12.34–75.87). Falls were not significantly disproportionate versus quetiapine users with Alzheimer’s disease (ROR 1.02), supporting the possibility of an antipsychotic class effect. Serious adverse events were documented in 50.3% of Alzheimer’s cases compared to 12.1% in MDD (p < 0.001) and 32.1% in schizophrenia (p < 0.001). Conclusion Brexpiprazole was associated with a distinct neuropsychiatric adverse-event reporting pattern in Alzheimer’s disease compared with psychiatric indications, with the most consistent signals observed for delirium, falls, and agitation. Hallucination and neuroleptic malignant syndrome were disproportionately reported compared with MDD but not schizophrenia. These findings provide clinically relevant hypothesis-generating evidence to inform prescriber vigilance and future pharmacovigilance priorities for the first FDA-approved pharmacological treatment for Alzheimer’s-associated agitation.
Key findings
- Background Brexpiprazole is an atypical antipsychotic approved for major depressive disorder, schizophrenia, and, most recently (May 2023), agitation associated with Alzheimer’s disease.
- Three primary comparisons were performed (A vs B, A vs C, A vs B + C combined) alongside five pre-planned sensitivity analyses: primary suspect reports only, restriction to patients aged ≥ 65 years, collapsed MedDRA terms, a quetiapine active comparator analysis, and serious versus non-serious adverse event proportions.
- Results After deduplication, 9,113 brexpiprazole reports were identified: 682 Alzheimer’s disease, 6,858 MDD, and 1,573 schizophrenia cases.
- Compared to MDD patients, Alzheimer’s patients had higher reporting of delirium (ROR 32.91, 95% CI 12.26–88.33), falls (ROR 8.06, 95% CI 5.43–11.94), hallucination (ROR 10.01, 95% CI 6.73–14.90), neuroleptic malignant syndrome (ROR 11.47, 95% CI 3.62–36.36), and agitation (ROR 5.09, 95% CI 3.44–7.52; noting potential indication-outcome overlap).
- Akathisia and tardive dyskinesia were reported significantly less frequently.
Study details
- Effect sizeOR 32.91; OR 8.06; OR 10.01
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 26 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. We have no data on 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 and multi-centre collaboration, so those were left out: it earned 16 of the 62 points we could judge it on, which is 26 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 16 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 16 of the 62 points we could judge it on is 26 out of 100. |
| Total | 26 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Za'areer, M. A., & Jafari, A. A. (2026). Neuropsychiatric Adverse-Event Reporting With Brexpiprazole Across Approved Indications: A Disproportionality Analysis Using the FDA Adverse Event Reporting System (FAERS). Research Square. https://doi.org/10.21203/rs.3.rs-10907540/v1
Vancouver
Za'areer MA, Jafari AA. Neuropsychiatric Adverse-Event Reporting With Brexpiprazole Across Approved Indications: A Disproportionality Analysis Using the FDA Adverse Event Reporting System (FAERS). Research Square. 2026. doi:10.21203/rs.3.rs-10907540/v1.
BibTeX
@article{zaareer2026-bd508402,
author = {Za'areer, M. A. and Jafari, A. A.},
title = {{Neuropsychiatric Adverse-Event Reporting With Brexpiprazole Across Approved Indications: A Disproportionality Analysis Using the FDA Adverse Event Reporting System (FAERS)}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10907540/v1},
url = {https://doi.org/10.21203/rs.3.rs-10907540/v1}
}
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