Evidence map›Paper›PMID 40949788›Full record

ArticleMetabolism open2025

Selective serotonin reuptake inhibitors and glucose metabolism in Alzheimer's disease and related dementias: A systematic review and meta-analysis of brain metabolic and adverse event data.

Faisal Alzenaidi, Osama Aldoweesh, Salman Alghofaili, Abdulaziz Fadel, Razan Ali Awad Lasloom, Dhay Alharbi, Faris Almalki, Atheer Ahmad Alkhairi, Maram Alharbi, Norah Ahmed Alhamdan and 1 more

Abstract read
In one paragraph

Article in Metabolism open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Faisal AlzenaidiCollege of Medicine, Qassim University, Buraydah, Saudi Arabia.
Osama AldoweeshCollege of Medicine, Qassim University, Buraydah, Saudi Arabia.
Salman AlghofailiCollege of Medicine, Qassim University, Buraydah, Saudi Arabia.
Abdulaziz FadelCollege of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Razan Ali Awad LasloomCollege of Medicine, Najran University, Najran, Saudi Arabia.
Dhay AlharbiCollege of Pharmacy, Buraydah Colleges, Buraydah, Saudi Arabia.
Faris AlmalkiHospital Pharmacist, United Doctors Hospital, Jeddah, Saudi Arabia.
Atheer Ahmad AlkhairiCollege of Medicine, Umm Al-Qura University, Al-Qunfudah, Saudi Arabia.
Maram AlharbiCollege of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
Norah Ahmed AlhamdanConsultant of Neurology, Department of Medicine, Qassim University, Buraydah, Saudi Arabia.
Ahmed Y AzzamDirector of Clinical Research and Clinical Artificial Intelligence, ASIDE Healthcare, Lewes, DE, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression in Alzheimer's disease (AD), however their effects on glucose metabolism remain poorly understood. We conducted a systematic review and meta-analysis to evaluate SSRI effects on brain glucose metabolism and metabolic adverse events in AD patients. Methods: Following PRISMA 2020 guidelines, we searched multiple databases up to July 11, 2025 for studies investigating SSRI effects on glucose-related outcomes in AD patients. Despite significant heterogeneity in study designs and populations, we performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. We performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. Advanced Bayesian hierarchical modeling and Markov simulations projected long-term metabolic outcomes. Results: Twelve studies with total included 7143 participants met our inclusion criteria, including nine randomized controlled trials and three observational studies. Brain FDG-PET revealed SSRI use restored dorsal raphe nucleus hypometabolism (standardized mean difference 0.87, 95 % CI: 0.52-1.22, P-value = 0.001). Meta-analysis demonstrated increased gastrointestinal adverse events (risk ratio 2.15, 95 % CI: 1.68-2.76, P-value<0.001, with moderate between-study heterogeneity), with sertraline showing highest rates. Citalopram 30 mg provided significant weight loss protection (risk ratio 0.13, 95 % CI: 0.02-0.98, P-value = 0.02), though this exceeds the recommended 20 mg maximum dose for elderly patients due to cardiac safety considerations. Long-term diabetes incidence showed no increased risk (hazard ratio 0.75, 95 % CI: 0.50-1.12, P-value = 0.15). Bayesian modeling revealed 85 % probability of beneficial brain metabolic effects and 89 % probability of citalopram superiority for weight protection. Conclusions: SSRIs restore brain glucose metabolism in AD patients while causing manageable peripheral metabolic effects. Citalopram appears the best for weight-sensitive patients, while sertraline requires gastrointestinal monitoring. These findings support SSRI safety for metabolic outcomes in AD treatment, however longer-term studies with controlled metabolic outcomes are needed to confirm our findings. The observed citalopram weight protection benefit was documented at 30 mg daily, which exceeds recommended dosing limits for elderly patients due to cardiac safety concerns.

Indexed as

Alzheimer's diseaseDementiaGlucose metabolismMetabolismSelective serotonin reuptake inhibitors

Identifiers

PMID40949788
PMCPMC12423674

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.