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Physostigmine for Alzheimer's disease
Coelho F, Birks J.. The Cochrane database of systematic reviews, 2001-01-01
Topic: Amyloid, tau and blood-test diagnosis
Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Main results Fifteen studies were included using four different methods of administration of physostigmine. There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo. The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59, 13.54) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. The best dose physostigmine (mean 27mg/day) was associated with a 2.0 point improvement on ADAS-Cog score (mean difference -2.02, 95% confidence interval -3.59, -0.45 on an intention to treat basis) compared with placebo at 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% confidence limits 1.15, 8.07) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% confidence limits 3.17, 7.33), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%confidence limits 4.29, 9.95) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming compared
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Coelho, F., & Birks, J. (2001). Physostigmine for Alzheimer's disease. The Cochrane database of systematic reviews. https://doi.org/10.1002/14651858.cd001499
Vancouver
Coelho F, Birks J. Physostigmine for Alzheimer's disease. The Cochrane database of systematic reviews. 2001. doi:10.1002/14651858.cd001499. PMID: 11405996.
BibTeX
@article{coelho2001-11405996,
author = {Coelho, F. and Birks, J.},
title = {{Physostigmine for Alzheimer's disease}},
journal = {The Cochrane database of systematic reviews},
year = {2001},
doi = {10.1002/14651858.cd001499},
pmid = {11405996},
url = {https://doi.org/10.1002/14651858.cd001499}
}
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Key findings
- Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia.
- Main results Fifteen studies were included using four different methods of administration of physostigmine.
- There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo.
- The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period.
- The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks.
Why it matters
This review found that conventional oral physostigmine showed no benefit compared with placebo, while controlled-release physostigmine produced small improvements on two symptom measures in a group of identified responders. Physostigmine was also linked to significantly more patients withdrawing from trials and more side effects such as nausea and vomiting.
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Study details
- Participants29
- Effect sizeOR 5.92; OR 3.05; OR 4.82
- Evidence strengthHigh
How this study scored 63/100
Published in a leading specialty journal, and it is a systematic review of all the studies on the question.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (The Cochrane database of systematic reviews) |
| Journal's citation record | 3 / 4 | Cochrane Database of Systematic Reviews: journal h-index 468 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question (from PubMed type “Systematic Review”) |
| 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 | 2001 — older than 20 years, still counted |
| Sample size | 1 / 4 | 29 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 75 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.8 citations a year over 27 year(s) since 2001 |
| Impact for its field and year | 2 / 6 | Cited 1.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jacqueline Birks: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 11405996) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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Read the original
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