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Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease
Tariot PN, Schneider LS, Cummings J, Thomas RG, Raman R, Jakimovich LJ, Loy R, Bartocci B et al.. Archives of general psychiatry, 2011-08-01
Topic: Amyloid, tau and blood-test diagnosis
Context Agitation and psychosis are common in Alzheimer disease and cause considerable morbidity. We attempted to delay or to prevent agitation and psychosis with the use of divalproex sodium (valproate). Objective To determine whether treatment with valproate could delay or prevent emergence of agitation or psychosis. Design, setting, and patients A multicenter, randomized, double-blind, placebo-controlled trial of flexible-dose valproate in 313 (of 513 screened) individuals with moderate Alzheimer disease who had not yet experienced agitation or psychosis. The study was conducted from November 1, 2005, through March 31, 2009, at 46 sites in the United States. Intervention Participants were randomly assigned to valproate treatment at a target dose of 10 to 12 mg per kilogram of body weight per day or identical-appearing placebo for 24 months followed by a 2-month period of single-blind placebo treatment. Main outcome measure Time to emergence of clinically significant agitation or psychosis. Results A total of 122 participants (59 receiving valproate and 63 receiving placebo) completed 24 months of treatment while taking study medication; 42 (27 receiving valproate and 15 receiving placebo) reached 24 months having discontinued study medication; 150 reached month 26. There was no difference between groups in time to emergence of agitation or psychosis (Cox proportional hazard ratio, 0.96; P = .88). There was no difference between groups in change on any secondary outcome. The valproate group had higher rates of somnolence, gait disturbance, tremor, diarrhea, and weakness. Eighty-eight participants underwent magnetic resonance imaging scans at baseline and 12 months; the valproate group showed greater loss in hippocampal and whole-brain volume, accompanied by greater ventricular expansion (P Conclusion Valproate treatment did not delay emergence of agitation or psychosis or slow cognitive or functional decline in patients with moderate Alzheimer disease and was associated with significant toxic effects.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tariot, P. N., Schneider, L. S., Cummings, J., Thomas, R. G., Raman, R., Jakimovich, L. J., et al. (2011). Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Archives of general psychiatry. https://doi.org/10.1001/archgenpsychiatry.2011.72
Vancouver
Tariot PN, Schneider LS, Cummings J, Thomas RG, Raman R, Jakimovich LJ, et al. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Archives of general psychiatry. 2011. doi:10.1001/archgenpsychiatry.2011.72. PMID: 21810649.
BibTeX
@article{tariot2011-21810649,
author = {Tariot, P. N. and Schneider, L. S. and Cummings, J. and Thomas, R. G. and Raman, R. and Jakimovich, L. J. and Loy, R. and Bartocci, B. and others},
title = {{Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease}},
journal = {Archives of general psychiatry},
year = {2011},
doi = {10.1001/archgenpsychiatry.2011.72},
pmid = {21810649},
url = {https://doi.org/10.1001/archgenpsychiatry.2011.72}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Main outcome measure Time to emergence of clinically significant agitation or psychosis.
- Results A total of 122 participants (59 receiving valproate and 63 receiving placebo) completed 24 months of treatment while taking study medication; 42 (27 receiving valproate and 15 receiving placebo) reached 24 months having discontinued study medication; 150 reached month 26.
- Eighty-eight participants underwent magnetic resonance imaging scans at baseline and 12 months; the valproate group showed greater loss in hippocampal and whole-brain volume, accompanied by greater ventricular expansion (P < .001).
Why it matters
In this trial, valproate did not delay or prevent the emergence of agitation or psychosis in people with moderate Alzheimer disease. This means valproate was not effective for preventing these symptoms.
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Study details
- Participants122
- Evidence strengthHigh
How this study scored 71/100
Published in a peer-reviewed journal, and it is a randomized controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of general psychiatry) |
| Journal's citation record | 4 / 4 | Archives of General Psychiatry: journal h-index 543 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomized controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 122 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 2 / 2 | Randomized and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 224 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.2 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 12.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Pierre N. Tariot: h-index 102 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Arizona: institution h-index 1,336 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21810649) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 71 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/archgenpsychiatry.2011.72
- PubMed: 21810649
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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