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Extended-release physostigmine in Alzheimer disease: a multicenter, double-blind, 12-week study with dose enrichment. Physostigmine Study Group
van Dyck CH, Newhouse P, Falk WE, Mattes JA.. Archives of general psychiatry, 2000-02-01
Topic: Amyloid, tau and blood-test diagnosis
Background The efficacy of extended-release physostigmine salicylate, an acetylcholinesterase inhibitor, was evaluated in 850 subjects with mild-to-moderate Alzheimer disease (AD) in a multicenter trial. Methods Subjects initially entered a dose-enrichment phase in which they received 1 week each of physostigmine salicylate, 24 mg/d and 30 mg/d, and daily placebo. Among the subjects who completed this phase, 35.9% responded to physostigmine treatment, whereas 62.4% were considered nonresponders, and 1.6% could not be evaluated because of missing data. After a 4-week placebo-washout phase, 176 responder subjects were randomized to receive their best dose of physostigmine or placebo in a 12-week double-blind phase. Primary efficacy measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC+), and the Clinical Global Impression of Change (CGIC). Results In the intent-to-treat analysis of the double-blind phase, physostigmine-treated subjects scored -2.02 points better than placebo-treated subjects on the ADAS-Cog (F1,167 = 6.42 [P = .01]) and 0.33 points higher on the CIBIC+ (F1,150 = 5.68 [P = .02]). No significant improvement was observed on the CGIC or the secondary outcome measures. Nausea and vomiting were experienced by 47.0% of all physostigmine-treated subjects during the double-blind phase. Conclusions Physostigmine demonstrated a statistically significant benefit compared with placebo on a clinical global rating of change and an objective test of cognitive function. Given the frequency of gastrointestinal side effects, the role of this agent in clinical use remains to be determined.
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APA 7th
van Dyck, C. H., Newhouse, P., Falk, W. E., & Mattes, J. A. (2000). Extended-release physostigmine in Alzheimer disease: a multicenter, double-blind, 12-week study with dose enrichment. Physostigmine Study Group. Archives of general psychiatry. https://doi.org/10.1001/archpsyc.57.2.157
Vancouver
van Dyck CH, Newhouse P, Falk WE, Mattes JA. Extended-release physostigmine in Alzheimer disease: a multicenter, double-blind, 12-week study with dose enrichment. Physostigmine Study Group. Archives of general psychiatry. 2000. doi:10.1001/archpsyc.57.2.157. PMID: 10665618.
BibTeX
@article{vandyck2000-10665618,
author = {van Dyck, C. H. and Newhouse, P. and Falk, W. E. and Mattes, J. A.},
title = {{Extended-release physostigmine in Alzheimer disease: a multicenter, double-blind, 12-week study with dose enrichment. Physostigmine Study Group}},
journal = {Archives of general psychiatry},
year = {2000},
doi = {10.1001/archpsyc.57.2.157},
pmid = {10665618},
url = {https://doi.org/10.1001/archpsyc.57.2.157}
}
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Key findings
- Results In the intent-to-treat analysis of the double-blind phase, physostigmine-treated subjects scored -2.02 points better than placebo-treated subjects on the ADAS-Cog (F1,167 = 6.42 [P = .01]) and 0.33 points higher on the CIBIC+ (F1,150 = 5.68 [P = .02]).
- No significant improvement was observed on the CGIC or the secondary outcome measures.
- Conclusions Physostigmine demonstrated a statistically significant benefit compared with placebo on a clinical global rating of change and an objective test of cognitive function.
Why it matters
Extended-release physostigmine scored better than placebo on two cognitive and global measures in people with mild-to-moderate Alzheimer disease, but showed no significant improvement on another global measure or secondary outcomes. Nausea and vomiting were common side effects.
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Study details
- Participants850
- Effect size35.9%; 62.4%; 1.6%
- Evidence strengthHigh
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design because the record does not state it. We have no data on journal's citation record and senior author's track record, so those were left out: it earned 46 of the 92 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of general psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 2000 — older than 20 years, still counted |
| Sample size | 2 / 4 | 850 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 3 / 7 | Cited 30 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.1 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 2 / 6 | Cited 2.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10665618) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 46 / 92 | Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 46 of the 92 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
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