CoChat
Sign Up
Cited by 12Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsTreatment of Major Depression

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Global cognitive effects of second-generation antidepressants in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials

Open access
Qin, Mengting, Wu, Jing, Zhou, Qidong, Liang, Zhihou, Su, Ying·2022·Journal of Psychiatric Research
DOI 10.1016/j.jpsychires.2022.09.039
Open this paper in CoChat — free account

Abstract

The second-generation antidepressants (SGAs) are used widely in patients with Alzheimer's disease (AD) for the treatment of mood disorder, sleep disturbance and psychiatric symptoms. Several evidences from AD mice confirmed that antidepressants could delaying cognitive decline. However, the conclusions varied in randomized controlled trials (RCTs) based on patients. This meta-analysis summarizes the cognitive impact of SGAs on AD patients with different neuropsychiatric symptoms (NPS). Results show there is no effect on cognition and depression between SGAs treatment and controls, and this remains in subgroups analyses of duration of medication (<12 weeks or ≥12 weeks), drug classes (SSRIs or non-SSRIs), combination with anti-dementia medication, various NPS, and degree of AD. The available evidence provides no support for the efficacy of SGAs for cognition and depression of AD patients. The implications of the findings and their mechanism relevance are also discussed in this paper.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.jpsychires.2022.09.039

Cites

10 of 10 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Previous studies of antidepressant use and cognitive decline in people with dementia have shown mixed findings.

    “Previous studies of antidepressant use and cognitive decline in people with dementia have shown mixed findings.”

    From Antidepressant use and cognitive decline in patients with dementia: a national cohort study (2025) · cites this paper as [47]

  • In the majority of cases reported, antidepressants had the same effect on cognition as placebo.

    “In the majority of the cases reported, antidepressants had the same effect on cognition as placebo [44–47]”

    From Antidepressant use and cognitive decline in patients with dementia: a national cohort study (2025) · cites this paper as [47]

  • A meta-analysis that included 15 RCTs involving 1616 patients with AD found that second-generation antidepressants had no effect on global cognition measured by MMSE.

    “A meta-analysis that included 15 RCTs involving a total of 1616 patients with AD found that second-generation antidepressants had no effect on global cognition measured by MMSE, and this remained in subgroup analyses of duration of medication, drug classes, combination with anti-dementia medication, various NPS, and degree of AD [47].”

    From Antidepressant use and cognitive decline in patients with dementia: a national cohort study (2025) · cites this paper as [47]

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 45

  1. Amidfar, 2017, Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study, J. Clin. Pharm. Therapeut., 42, 44, 10.1111/jcpt.12469 · DOI
  2. An, 2017, The effect of escitalopram on mood and cognition in depressive alzheimer's disease subjects, J Alzheimers Dis, 55, 727, 10.3233/JAD-160225 · DOI
  3. Arbus, 2010, Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort, Int. Psychogeriatr., 22, 120, 10.1017/S1041610209990780 · DOI
  4. Arvanitakis, 2019, Diagnosis and management of dementia: review, JAMA, 322, 1589, 10.1001/jama.2019.4782 · DOI
  5. Banerjee, 2021, Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial, Lancet (London, England), 398, 1487, 10.1016/S0140-6736(21)01210-1 · DOI
  6. Camargos, 2014, Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study, Am. J. Geriatr. Psychiatr. : official journal of the American Association for Geriatric Psychiatry, 22, 1565, 10.1016/j.jagp.2013.12.174 · DOI · Paper page
  7. Chi, 2014, Depression in Alzheimer's disease: epidemiology, mechanisms, and management, J Alzheimers Dis, 42, 739, 10.3233/JAD-140324 · DOI
  8. Choe, 2016, Multicenter, randomized, placebo-controlled, double-blind clinical trial of escitalopram on the progression-delaying effects in Alzheimer's disease, Int. J. Geriatr. Psychiatr., 31, 731, 10.1002/gps.4384 · DOI · Paper page
  9. Cirrito, 2020, Effect of escitalopram on Abeta levels and plaque load in an Alzheimer mouse model, Neurology, 95, e2666, 10.1212/WNL.0000000000010733 · DOI
  10. Clerici, 2012, Memantine effects on behaviour in moderately severe to severe Alzheimer's disease: a post-marketing surveillance study, Neurol. Sci., 33, 23, 10.1007/s10072-011-0618-0 · DOI
  11. Dudas, 2018, Antidepressants for treating depression in dementia, Cochrane Database Syst. Rev., 8
  12. Dutcher, 2014, Effect of medications on physical function and cognition in nursing home residents with dementia, J. Am. Geriatr. Soc., 62, 1046, 10.1111/jgs.12838 · DOI
  13. Feighner, 1999, Mechanism of action of antidepressant medications, J. Clin. Psychiatr., 60, 4
  14. Finkel, 2004, A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil, Int. J. Geriatr. Psychiatr., 19, 9, 10.1002/gps.998 · DOI
  15. Galts, 2019, Depression in neurodegenerative diseases: common mechanisms and current treatment options, Neurosci. Biobehav. Rev., 102, 56, 10.1016/j.neubiorev.2019.04.002 · DOI
  16. Gaynes, 2009, What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression, Psychiatr. Serv., 60, 1439, 10.1176/ps.2009.60.11.1439 · DOI · Paper page
  17. Graipaspong, 2016, Cholinesterase inhibitors and behavioral & psychological symptoms of alzheimer's disease, J. Med. Assoc. Thai., 99, 433
  18. Henry, 2011, Efficacy and tolerability of antidepressants in the treatment of behavioral and psychological symptoms of dementia, a literature review of evidence, Am J Alzheimers Dis Other Demen, 26, 169, 10.1177/1533317511402051 · DOI
  19. Higgins, 2003, Measuring inconsistency in meta-analyses, BMJ, 327, 557, 10.1136/bmj.327.7414.557 · DOI · Paper page
  20. Howard, 2011, Determining the minimum clinically important differences for outcomes in the DOMINO trial, Int. J. Geriatr. Psychiatr., 26, 812, 10.1002/gps.2607 · DOI · Paper page
  21. Hsu, 2021, Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: a systematic review and meta-analysis, Ageing Res. Rev., 69, 10.1016/j.arr.2021.101362 · DOI
  22. Jamieson, 2019, Depression related cerebral pathology and its relationship with cognitive functioning: a systematic review, J. Affect. Disord., 250, 410, 10.1016/j.jad.2019.03.042 · DOI
  23. Lavretsky, 2020, A randomized double-blind placebo-controlled trial of combined escitalopram and memantine for older adults with major depression and subjective memory complaints, Am. J. Geriatr. Psychiatr., 28, 178, 10.1016/j.jagp.2019.08.011 · DOI · Paper page
  24. Lozupone, 2018, Pharmacotherapy for the treatment of depression in patients with alzheimer's disease: a treatment-resistant depressive disorder, Expet Opin. Pharmacother., 19, 823, 10.1080/14656566.2018.1471136 · DOI
  25. Ma, 2017, Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice, Oncotarget, 8, 27676, 10.18632/oncotarget.15398 · DOI
  26. Maier, 2020, Bupropion for the treatment of apathy in alzheimer disease: a randomized clinical trial, JAMA Netw. Open, 3, 10.1001/jamanetworkopen.2020.6027 · DOI · Paper page
  27. Moretti, 2002, Depression and Alzheimer's disease: symptom or comorbidity?, Am. J. Alzheimer's Dis. Other Dementias, 17, 338, 10.1177/153331750201700607 · DOI
  28. Mowla, 2007, Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer's dementia? A double-blind, placebo-controlled clinical trial, J. Clin. Psychopharmacol., 27, 484, 10.1097/jcp.0b013e31814b98c1 · DOI · Paper page
  29. Mowla, 2007, Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment?: a double-blind, placebo-controlled, clinical trial, J. Clin. Psychopharmacol., 27, 67, 10.1097/JCP.0b013e31802e0002 · DOI
  30. Padala, 2012, Reversal of SSRI-associated apathy syndrome by discontinuation of therapy, Ann. Pharmacother., 46, 10.1345/aph.1Q656 · DOI
  31. Palmer, 1987, Monoaminergic innervation of the frontal and temporal lobes in Alzheimer's disease, Brain Res., 401, 231, 10.1016/0006-8993(87)91408-9 · DOI
  32. Petracca, 2001, A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease, Int. Psychogeriatr., 13, 233, 10.1017/S104161020100761X · DOI
  33. Quinn, 2005, Comparing rat's to human's age: how old is my rat in people years?, Nutrition, 21, 775, 10.1016/j.nut.2005.04.002 · DOI
  34. Rashidi-Ranjbar, 2020, Frontal-executive and corticolimbic structural brain circuitry in older people with remitted depression, mild cognitive impairment, Alzheimer's dementia, and normal cognition, Neuropsychopharmacology, 45, 1567, 10.1038/s41386-020-0715-y · DOI
  35. Reddy, 2021, Selective serotonin reuptake inhibitor citalopram ameliorates cognitive decline and protects against amyloid beta-induced mitochondrial dynamics, biogenesis, autophagy, mitophagy and synaptic toxicities in a mouse model of Alzheimer's disease, Hum. Mol. Genet., 30, 789, 10.1093/hmg/ddab091 · DOI
  36. Rodriguez, 2012, The serotonergic system in ageing and Alzheimer's disease, Prog. Neurobiol., 99, 15, 10.1016/j.pneurobio.2012.06.010 · DOI
  37. Rosenberg, 2012, The association of psychotropic medication use with the cognitive, functional, and neuropsychiatric trajectory of Alzheimer's disease, Int. J. Geriatr. Psychiatr., 27, 1248, 10.1002/gps.3769 · DOI · Paper page
  38. Scoralick, 2017, Mirtazapine does not improve sleep disorders in Alzheimer's disease: results from a double-blind, placebo-controlled pilot study, Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society, 17, 89, 10.1111/psyg.12191 · DOI · Paper page
  39. Taylor, 2021, Preliminary evidence that cortical amyloid burden predicts poor response to antidepressant medication treatment in cognitively intact individuals with late-life depression, Am. J. Geriatr. Psychiatr., 29, 448, 10.1016/j.jagp.2020.09.019 · DOI
  40. Teri, 2000, Treatment of agitation in AD: a randomized, placebo-controlled clinical trial, Neurology, 55, 1271, 10.1212/WNL.55.9.1271 · DOI · Paper page
  41. Torrisi, 2019, Fluoxetine and vortioxetine reverse depressive-like phenotype and memory deficits induced by abeta1-42 oligomers in mice: a key role of transforming growth factor-beta1, Front. Pharmacol., 10, 693, 10.3389/fphar.2019.00693 · DOI
  42. Tsai, 2010, Effects of BDNF polymorphisms on antidepressant action, Psychiatry Investig, 7, 236, 10.4306/pi.2010.7.4.236 · DOI
  43. Weintraub, 2010, Sertraline for the treatment of depression in Alzheimer disease: week-24 outcomes, Am. J. Geriatr. Psychiatr. : official journal of the American Association for Geriatric Psychiatry, 18, 332, 10.1097/JGP.0b013e3181cc0333 · DOI
  44. Zhou, 2019, Fluoxetine delays the cognitive function decline and synaptic changes in a transgenic mouse model of early Alzheimer's disease, J. Comp. Neurol., 527, 1378, 10.1002/cne.24616 · DOI
  45. Zhou, 2019, Effect of memantine combined with citalopram on cognition of BPSD and moderate Alzheimer's disease: a clinical trial, Exp. Ther. Med., 17, 1625

Cited by

Sorted by citations

Metadata

Authors
Qin, M., Wu, J., Zhou, Q., Liang, Z., & Su, Y.
Affiliations
  • Wuhan Union Hospital (CN)
  • Huazhong University of Science and Technology (CN)
Corresponding author
Su, Ying
ORCID
Venue
Journal of Psychiatric Research
Publisher
Elsevier BV
Published
2022-11
Volume
155
Pages
371-379
ISSN
0022-3956 (ISSN-L)
DOI
10.1016/j.jpsychires.2022.09.039
OpenAlex
W4297200823
Cited by
12
References
10
Citations by year
2026: 2 · 2025: 6 · 2024: 2 · 2023: 2
FWCI
0.34
Type
journal article
Language
en
Update notices
erratum (2022-12-01)
Open access
Licence
Locations
  • Journal of Psychiatric Research (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Ministry of Science and Technology of the People&apos;s Republic of China
  • Hubei Province Natural Science Foundation
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
second-generation antidepressants, Alzheimer's disease, cognitive decline, neuropsychiatric symptoms, depression, sleep disorders, selective serotonin reuptake inhibitors, anti-dementia drugs, treatment duration, drug class comparison
MeSH terms
Alzheimer Disease, Animals, Antidepressive Agents, Cognition, Randomized Controlled Trials as Topic, Antidepressive Agents, Second-Generation, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review