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Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial
Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, De La Gandara JE, Agronin M et al.. JAMA, 2015-09-01
Topic: Brain proteins, microglia and lab models
Importance Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking. Objective To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation. Design, setting, and participants Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score ≥4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed. Interventions In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1:1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60). Main outcomes and measures The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]). Results A total of 194 patients (88.2%) completed the study. With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study. Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo (ordinary least squares z statistic, -3.95; P Conclusions and relevance In this preliminary 10-week phase 2 randomized clinical trial of patients with probable Alzheimer disease, combination dextromethorphan-quinidine demonstrated clinically relevant efficacy for agitation and was generally well tolerated. Trial registration clinicaltrials.gov Identifier: NCT01584440.
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APA 7th
Cummings, J. L., Lyketsos, C. G., Peskind, E. R., Porsteinsson, A. P., Mintzer, J. E., Scharre, D. W., et al. (2015). Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA. https://doi.org/10.1001/jama.2015.10214
Vancouver
Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, et al. Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA. 2015. doi:10.1001/jama.2015.10214. PMID: 26393847.
BibTeX
@article{cummings2015-26393847,
author = {Cummings, J. L. and Lyketsos, C. G. and Peskind, E. R. and Porsteinsson, A. P. and Mintzer, J. E. and Scharre, D. W. and De La Gandara, J. E. and Agronin, M. and others},
title = {{Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial}},
journal = {JAMA},
year = {2015},
doi = {10.1001/jama.2015.10214},
pmid = {26393847},
url = {https://doi.org/10.1001/jama.2015.10214}
}
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Key findings
- Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score ≥4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites.
- Results A total of 194 patients (88.2%) completed the study.
- Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo (ordinary least squares z statistic, -3.95; P < .001).
Why it matters
In this phase 2 trial, dextromethorphan-quinidine significantly reduced agitation scores compared with placebo in patients with Alzheimer disease. This suggests it may help treat agitation, though the study was designed as an early-phase trial.
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Study details
- Study designclinical trial
- Participants93
- Effect size88.2%
- Evidence strengthHigh
How this study scored 75/100
Published in a top-tier journal, and it is a randomized controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 93 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) |
| Randomized / blinded | 2 / 2 | Randomized and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 208 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.0 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 14.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 45 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Joao O. Siffert: h-index 25 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 14 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26393847) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 75 / 100 | — |
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