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Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design
Soto M, Andrieu S, Nourhashemi F, Ousset PJ, Ballard C, Robert P, Vellas B, Lyketsos CG et al.. International psychogeriatrics, 2015-02-01
Topic: Amyloid, tau and blood-test diagnosis
Background The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer's disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD. Methods We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013. Results We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of "clinically significant A/A." There was considerable heterogeneity in study design. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials. Conclusions This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.
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APA 7th
Soto, M., Andrieu, S., Nourhashemi, F., Ousset, P. J., Ballard, C., Robert, P., et al. (2015). Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design. International psychogeriatrics. https://doi.org/10.1017/s1041610214001720
Vancouver
Soto M, Andrieu S, Nourhashemi F, Ousset PJ, Ballard C, Robert P, et al. Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design. International psychogeriatrics. 2015. doi:10.1017/s1041610214001720. PMID: 25226218.
BibTeX
@article{soto2015-25226218,
author = {Soto, M. and Andrieu, S. and Nourhashemi, F. and Ousset, P. J. and Ballard, C. and Robert, P. and Vellas, B. and Lyketsos, C. G. and others},
title = {{Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design}},
journal = {International psychogeriatrics},
year = {2015},
doi = {10.1017/s1041610214001720},
pmid = {25226218},
url = {https://doi.org/10.1017/s1041610214001720}
}
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Key findings
- Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing.
- This may result from the absence of biological efficacy for medications tested in treating A/A.
- Results We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing.
- Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo.
- Each of the completed RCTs used a different definition of "clinically significant A/A." There was considerable heterogeneity in study design.
Why it matters
This review of 18 trials found that 7 of 10 completed trials of drugs for agitation and aggression in Alzheimer's disease showed no greater benefit than placebo. It highlights problems with trial design and outcome measurement rather than offering a treatment, cure, or prevention.
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Study details
- Participants18
- Evidence strengthHigh
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International psychogeriatrics) |
| Journal's citation record | 2 / 4 | International Psychogeriatrics: journal h-index 161 (OpenAlex, 2026-10-29) |
| 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 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 18 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) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 3 / 7 | Cited 39 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 3 / 6 | Cited 4.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Paul B. Rosenberg: h-index 56 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25226218) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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