Increased Odds of Cognitive Impairment in Adults with Depressive
                    Symptoms and Antidepressant Use

Shakila Meshkat; Michelle Wu; Vanessa K Tassone; Reinhard Janssen-Aguilar; Hilary Pang; Hyejung Jung; Wendy Lou; Venkat Bhat

doi:10.1055/a-2381-2061

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2025; 58(02): 71-79
DOI: 10.1055/a-2381-2061

Original Paper

Increased Odds of Cognitive Impairment in Adults with Depressive Symptoms and Antidepressant Use

Authors

Shakila Meshkat

¹Interventional Psychiatry Program, St. Michael’s Hospital, Toronto, Ontario, Canada
Michelle Wu

²Department of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Vanessa K Tassone

¹Interventional Psychiatry Program, St. Michael’s Hospital, Toronto, Ontario, Canada

³Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Reinhard Janssen-Aguilar

¹Interventional Psychiatry Program, St. Michael’s Hospital, Toronto, Ontario, Canada
Hilary Pang

⁴Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
Hyejung Jung

²Department of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Wendy Lou

²Department of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Venkat Bhat

¹Interventional Psychiatry Program, St. Michael’s Hospital, Toronto, Ontario, Canada

³Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

⁴Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

⁵Neuroscience Research Program, St. Michael’s Hospital, Toronto, Ontario, Canada

Abstract

Introduction The relationship between antidepressant use and class with cognition in depression is unclear. This study aimed to evaluate the association of cognition with depressive symptoms and antidepressant use (class, duration, number).

Methods Data from the National Health and Nutrition Examination Survey were examined for cognitive function through various tests and memory issues through the Medical Conditions questionnaire. Depressive symptoms were assessed using the Patient Health Questionnaire-9.

Results A total of 2867 participants were included. Participants with depressive symptoms had significantly higher odds of cognitive impairment (CI) on the animal fluency test (aOR=1.89, 95% CI=1.30, 2.73, P=0.002) and Digit Symbol Substitution test (aOR=2.58, 95% CI=1.34, 4.9, P=0.007), as well as subjective memory issues (aOR=7.25, 95% CI=4.26, 12.32, P<0.001) than those without depression. There were no statistically significant associations between any of the CI categories and depressive symptoms treated with an antidepressant and antidepressant use duration. Participants who were using more than one antidepressant had significantly higher odds of subjective memory issues than those who were using one antidepressant. Specifically, users of atypical antidepressants, selective serotonin reuptake inhibitors, or tricyclic antidepressants (TCAs) had significantly higher odds of subjective memory issues in comparison to no antidepressants, with TCAs showing the largest odds (aOR=4.21, 95% CI=1.19, 14.86, P=0.028).

Discussion This study highlights the relationship between depressive symptoms, antidepressant use, and CI. Future studies should further evaluate the mechanism underlying this phenomenon.

Keywords

depression - cognition - cognitive impairment - NHANES - antidepressants

Full Text

References

References
1 National Institute of Mental Health. Major depression. Available on: https://www.nimh.nih.gov/health/statistics/major-depression#part_2567
2 Murray CJ, Lopez AD. Evidence-based health policy—lessons from the Global Burden of Disease Study. Science 1996; 274: 740-743
3 Otte C, Gold SM, Penninx BW. et al. Major depressive disorder. Nat Rev Dis Primers 2016; 2: 1-20
4 Lam RW, Kennedy SH, McIntyre RS. et al. Cognitive dysfunction in major depressive disorder: Effects on psychosocial functioning and implications for treatment. Can J Psychiatry 2014; 59: 649-654
5 Snyder HR. Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: A meta-analysis and review. Psychol Bull 2013; 139: 81
6 Steffens DC, Otey E, Alexopoulos GS. et al. Perspectives on depression, mild cognitive impairment, and cognitive decline. Arch Gen Psychiatry 2006; 63: 130-138
7 Scult MA, Paulli AR, Mazure ES. et al. The association between cognitive function and subsequent depression: A systematic review and meta-analysis. Psychol Med 2017; 47: 1-7
8 McDermott LM, Ebmeier KP. A meta-analysis of depression severity and cognitive function. J Affect Disord 2009; 119: 1-8
9 Barnett JH, Salmond CH, Jones PB. et al. Cognitive reserve in neuropsychiatry. Psychol Med 2006; 36: 1053-1064
10 Richard E, Reitz C, Honig LH. et al. Late-life depression, mild cognitive impairment, and dementia. JAMA Neurol 2013; 70: 383-389
11 Hwang J, Kim S, Kim S. Gender differences in the impact of depression on cognitive decline among Korean older adults. Asia Pac J Public Health 2021; 33: 67-75
12 Carvalho AF, Miskowiak KK, Hyphantis TN. et al. Cognitive dysfunction in depression–pathophysiology and novel targets. CNS Neurol Disord-Drug Targets 2014; 13: 1819-1835
13 Keefe RS, McClintock SM, Roth RM. et al. Cognitive effects of pharmacotherapy for major depressive disorder: A systematic review. J Clin Psychiatry 2014; 75: 3169
14 Rosenblat JD, Kakar R, McIntyre RS. The cognitive effects of antidepressants in major depressive disorder: A systematic review and meta-analysis of randomized clinical trials. Int J Neuropsychopharmacol 2016; 19: pyv082
15 Prado CE, Watt S, Crowe SF. A meta-analysis of the effects of antidepressants on cognitive functioning in depressed and non-depressed samples. Neuropsychol Rev 2018; 28: 32-72
16 McIntyre RS, Cha DS, Soczynska JK. et al. Cognitive deficits and functional outcomes in major depressive disorder: Determinants, substrates, and treatment interventions. Depress Anxiety 2013; 30: 515-527
17 Wadsworth EJ, Moss SC, Simpson SA. et al. SSRIs and cognitive performance in a working sample. Human Psychopharmacol 2005; 20: 561-572
18 Podewils LJ, Lyketsos CG. Tricyclic antidepressants and cognitive decline. Psychosomatics 2002; 43: 31-35
19 Castellano S, Ventimiglia A, Salomone S. et al. Selective serotonin reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors improve cognitive function in partial responders depressed patients: Results from a prospective observational cohort study. CNS Neurol Disord-Drug Targets 2016; 15: 1290-1298
20 Kroenke K, Spitzer RL. The PHQ-9: A new depression diagnostic and severity measure. Psychiatr Ann 2002; 32: 509-515
21 Costantini L, Pasquarella C, Odone A. et al. Screening for depression in primary care with Patient Health Questionnaire-9 (PHQ-9): A systematic review. J Affect Disord 2021; 279: 473-483
22 Fillenbaum GG, van Belle G, Morris JC. et al. Consortium to Establish a Registry for Alzheimer’s Disease (CERAD): The first twenty years. Alzheimer’s Dement 2008; 4: 96-109
23 Gao S, Jin Y, Unverzagt FW. et al. Hypertension and cognitive decline in rural elderly Chinese. J Am Geriatr Soc 2009; 57: 1051-1057
24 Canning SJ, Leach L, Stuss D. et al. Diagnostic utility of abbreviated fluency measures in Alzheimer disease and vascular dementia. Neurology 2004; 62: 556-562
25 Jaeger J. Digit symbol substitution test: The case for sensitivity over specificity in neuropsychological testing. J Clin Psychopharmacol 2018; 38: 513-519
26 National Health and Nutrition Examination Survey 2013–2014 Data Documentation, Codebook, and Frequencies, Cognitive Functioning (CFQ_H) [(accessed on 30 January 2020)]. Available on: https://wwwn.cdc.gov/Nchs/Nhanes/2013–2014/CFQ_H.htm#CFDDS
27 Dong X, Li S, Sun J. et al. Association of coffee, decaffeinated coffee and caffeine intake from coffee with cognitive performance in older adults: National Health and Nutrition Examination Survey (NHANES) 2011–2014. Nutrients 2020; 12: 840
28 Beevers CG, Mullarkey MC, Dainer-Best J. et al. Association between negative cognitive bias and depression: A symptom-level approach. J Abnorm Psychol 2019; 128: 212
29 Dobielska M, Bartosik NK, Zyzik KA. et al. Mechanisms of cognitive impairment in depression. May probiotics help?. Front Psychiatry 2022; 13: 904426
30 Wiels W, Baeken C, Engelborghs S. Depressive symptoms in the elderly—An early symptom of dementia? A systematic review. Front Pharmacol 2020; 11: 34
31 Majd M, Saunders EF, Engeland CG. Inflammation and the dimensions of depression: A review. Front Neuroendocrinol 2020; 56: 100800
32 Gardner M, Lightman S, Kuh D. et al. Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages: Individual participant meta-analysis of five cohorts. Sci Rep 2019; 9: 4555
33 Arnone D, McIntosh AM, Ebmeier KP. et al. Magnetic resonance imaging studies in unipolar depression: Systematic review and meta-regression analyses. Eur Neuropsychopharmacol 2012; 22: 1-6
34 Li M, Lu S, Wang G. et al. The effects of gender differences in patients with depression on their emotional working memory and emotional experience. Behav Neurol 2015; 2015: 807343
35 Wang L, Xue Y, Cao S. et al. Sex differences in the cognitive function of first-diagnosed, drug-naïve depressed patients: An observational case-control study. J Affect Disord 2020; 276: 461-466
36 Moraros J, Nwankwo C, Patten SB. et al. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta-analysis. Depress Anxiety 2017; 34: 217-226
37 Sayyah M, Eslami K, AlaiShehni S. et al. Cognitive function before and during treatment with selective serotonin reuptake inhibitors in patients with depression or obsessive-compulsive disorder. Psychiatry J 2016; 2016: 5480391
38 Levkovitz Y, Caftori R, Avital A. et al. The SSRIs drug Fluoxetine, but not the noradrenergic tricyclic drug Desipramine, improves memory performance during acute major depression. Brain Res Bull 2002; 58: 345-350
39 Culang-Reinlieb ME, Sneed JR, Keilp JG. et al. Change in cognitive functioning in depressed older adults following treatment with sertraline or nortriptyline. Int J Geriatr Psychiatry 2012; 27: 777-784
40 Serretti A, Calati R, Goracci A. et al. Antidepressants in healthy subjects: What are the psychotropic/psychological effects?. Eur Neuropsychopharmacol 2010; 20: 433-453
41 Meneses A, Perez-Garcia G, Ponce-Lopez T. et al. Serotonin transporter and memory. Neuropharmacology 2011; 61: 355-363
42 Benmansour S, Cecchi M, Morilak DA. et al. Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level. J Neurosci 1999; 19: 10494-10501
43 Hirschfeld RM. Efficacy of SSRIs and newer antidepressants in severe depression: Comparison with TCAs. J Clin Psychiatry 1999; 60: 326-335
44 Podewils LJ, Lyketsos CG. Tricyclic antidepressants and cognitive decline. Psychosomatics 2002; 43: 31-35
45 McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol 2014; 17: 1557-1567
46 Raskin J, Wiltse CG, Siegal A. et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: An 8-week, double-blind, placebo-controlled trial. Am J Psychiatry 2007; 164: 900-909
47 Lövdén M, Fratiglioni L, Glymour MM. et al. Education and cognitive functioning across the life span. Psychol Sci Publ Int 2020; 21: 6-41
48 Mitchell AJ. A meta-analysis of the accuracy of the mini-mental state examination in the detection of dementia and mild cognitive impairment. J Psychiatr Res 2009; 43: 411-431
49 Brody DJ, Kramarow EA, Taylor CA. et al. Cognitive performance in adults aged 60 and over: National Health and Nutrition Examination Survey, 2011-2014. Natl Health Stat Report 2019; 1-23

Supplementary Material

Supplementary Material (PDF)