Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Source and Definition
2.2. Statistical Analysis
3. Results
3.1. Demographic Information
3.2. Etiologic Medications for Drug-Induced Cognitive Imparirment ADEs
3.3. Association between Medication Class and Serious Drug-Induced Cognitive Imparimrent
3.4. Clinical Predictors Increasing Risk of Hospitalization from Serious Drug-Induced Cognitive Impairment
3.5. Sensitivity Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
References
- Lam, R.W.; Kennedy, S.H.; McLntyre, R.S.; Khullar, A. Cognitive dysfunction in major depressive disorder: Effects on psychosocial functioning and implications for treatment. Can. J. Psychiatry 2014, 59, 649–654. [Google Scholar] [CrossRef] [PubMed]
- 2020 Alzheimer’s disease facts and figures. Alzheimers Dement. 2020; online ahead of print.
- Green, M.F. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J. Clin. Psychiatry 2006, 67, 3–8. [Google Scholar] [CrossRef] [PubMed]
- Tahami Monfared, A.A.; Byrnes, M.J.; White, L.A.; Zhang, Q. The humanistic and economic burden of Alzheimer’s disease. Neurol. Ther. 2022, 11, 525–551. [Google Scholar] [CrossRef] [PubMed]
- Nandi, A.; Counts, N.; Chen, S.; Seligman, B.; Tortorice, D.; Vigo, D.; Bloom, D.E. Global and regional projections of the economic burden of Alzheimer’s disease and related dementias from 2019 to 2050: A value of statistical life approach. EClinicalMedicine 2022, 51, 101580. [Google Scholar] [CrossRef] [PubMed]
- Petersen, R.C.; Lopez, O.; Armstrong, M.J.; Getchius, T.S.D.; Ganguli, M.; Gloss, D.; Gronseth, G.S.; Marson, D.; Pringsheim, T.; Day, G.S.; et al. Practice guideline update summary: Mild cognitive impairment: Report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology 2018, 90, 126–135. [Google Scholar] [CrossRef] [PubMed]
- Murman, D.L. The impact of age on cognition. Semin. Hear. 2015, 36, 111–121. [Google Scholar] [CrossRef] [PubMed]
- Bowen, J.D.; Larson, E.B. Drug-induced cognitive impairment. Drugs Aging 1993, 3, 349–357. [Google Scholar] [CrossRef] [PubMed]
- American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatric Society 2023 updated Beers Criteria® for potentially inappropriate medication use in older adults. J. Am. Geriatr. Soc. 2023, 71, 2052–2081. [Google Scholar] [CrossRef]
- Carriere, I.; Fourrier-Reglat, A.; Dartigues, J.F.; Rouaud, O.; Pasquier, F.; Ritchie, K.; Ancelin, M.L. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-city study. Arch. Intern. Med. 2009, 160, 1317–1324. [Google Scholar] [CrossRef] [PubMed]
- Barker, M.J.; Greenwood, K.M.; Jackson, M.; Crowe, S.F. Cognitive effects of long-term benzodiazepine use: A meta-analysis. CNS Drugs 2004, 18, 37–48. [Google Scholar] [CrossRef] [PubMed]
- Raei, K.; Rahimi, A.; Hosseini, S.R.; Moghadamnia, A.A.; Bijani, A. Anticholinergic drug use in elderly people: A population-based study in Ir. Casp. Intern. Med. 2021, 12, 593–599. [Google Scholar]
- Yoon, K.; Kim, J.T.; Kwack, W.G.; Kim, D.; Lee, K.T.; Yang, S.; Lee, S.; Choi, Y.J.; Chung, E.K. Potentially inappropriate medication use in patients with dementia. Int. J. Environ. Res. Public Health 2022, 19, 11426. [Google Scholar] [CrossRef] [PubMed]
- Ghaferi, A.A.; Schwartz, T.A.; Pawlik, T.M. STROBE reporting guidelines for observational studies. JAMA Surg. 2021, 156, 577–578. [Google Scholar] [CrossRef] [PubMed]
- Shin, Y.S.; Lee, Y.W.; Choi, Y.H.; Park, B.; Jee, Y.K.; Choi, S.K.; Kim, E.G.; Park, J.W.; Hong, C.S. Spontaneous reporting of adverse drug events by Korean regional pharmacovigilance centers. Pharmacoepidemiol. Drug Saf. 2009, 18, 910–915. [Google Scholar] [CrossRef] [PubMed]
- Jongsiriyanyong, S.; Limpawattana, P. Mild cognitive impairment in clinical practice: A review article. Am. J. Alzheimers Dis. Other Demen 2018, 33, 500–507. [Google Scholar] [CrossRef] [PubMed]
- Langa, K.M.; Levine, D.A. The diagnosis and management of mild cognitive impairment. A clinical review. JAMA 2014, 312, 2551–2561. [Google Scholar] [CrossRef] [PubMed]
- Aarsland, D.; Creese, B.; Politis, M.; Chaudhuri, K.R.; Ffytche, D.H.; Weintraub, D.; Ballard, C. Cognitive decline in Parkinson disease. Nat. Rev. Neruol 2017, 13, 217–231. [Google Scholar] [CrossRef] [PubMed]
- Nieoullon, A. Dopamine and the regulation of cognition and attention. Prog. Neurobiol. 2002, 67, 53–83. [Google Scholar] [CrossRef] [PubMed]
- Coupland, C.A.C.; Hill, T.; Dening, T.; Morriss, R.; Moore, M.; Hippisley-Cox, J. Anticholinergic drug exposure and the risk of dementia. A nested case-control study. JAMA Intern. Med. 2019, 179, 1084–1093. [Google Scholar] [CrossRef] [PubMed]
- Hanagasi, H.A.; Gurvit, H.; Unsalan, P.; Horozoglu, H.; Tuncer, N.; Feyzioglu, A.; Gunal, D.I.; Yener, G.G.; Cakmur, R.; Sahin, H.A.; et al. The effects of rasagiline on cognitive deficits in Parkinson’s disease patients without dementia: A randomized, double-blind, placebo-controlled, multicenter study. Mov. Disord. 2011, 26, 1851–1858. [Google Scholar] [CrossRef] [PubMed]
- Weintraub, D.; Hauser, R.A.; Elm, J.J.; Pagan, F.; Davis, M.D.; Choudhry, A. Rasagiline for mild cognitive impairment in Parkinson’s disease: A placebo-controlled trial. Mov. Disord. 2016, 31, 709–714. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.; Kim, C.W.; Shin, A.; Kang, H.; Jung, S.J. Effect of chemotherapy and radiotherapy on cognitive impairment in colorectal cancer: Evidence from Korean national health insurance database cohort. Epidemiol. Health 2021, 43, e2021093. [Google Scholar] [CrossRef] [PubMed]
- Pendergrass, J.C.; Targum, S.D.; Harrison, J.E. Cognitive impairment associated with cancer: A brief review. Innov. Clin. Neurosci. 2018, 15, 36–44. [Google Scholar] [PubMed]
- Parkman, H.P.; Mishra, A.; Jacobs, M.; Pathikonda, M.; Sachdeva, P.; Gaughan, J.; Krynetskiy, E. Clinical response and side effects of metoclopramide: Association with clinical, demographic, and pharmacogenetic parameters. J. Clin. Gastroenterl. 2012, 46, 494–503. [Google Scholar] [CrossRef] [PubMed]
- Okamoto, S.; Kobaysashi, E.; Murayama, H.; Liang, J.; Fukaya, T.; Shinkai, S. Decomposition of gender differences in cognitive functioning: National survey of the Japanese elderly. BMC Geriatr. 2021, 21, 38. [Google Scholar] [CrossRef] [PubMed]
- Cerri, S.; Mus, L.; Blandini, F. Parkinson’s disease in women and men: What’s the difference? J. Parkisons Dis. 2019, 9, 501–515. [Google Scholar] [CrossRef]
- Siegel, R.L.; Wagle, N.S.; Cercek, A.; Smith, R.A.; Jemal, A. Colorectal cancer statistics, 2023. CA Cancer J. Clin. 2023, 73, 233–254. [Google Scholar] [CrossRef] [PubMed]
- Drew, D.A.; Weiner, D.E.; Sarnak, M.J. Cognitive impairment in CKD. Pathophysiology, management, and prevention. Am. J. Kidney Dis. 2019, 74, 782–790. [Google Scholar] [CrossRef] [PubMed]
Sex a | |
---|---|
Men | 107 (42.1%) |
Women | 142 (55.9%) |
Age b (65.1, IQR 20.0) | |
<10 | 1 (0.4%) |
10 to 19 | 3 (1.2%) |
20 to 29 | 12 (4.7%) |
30 to 39 | 3 (1.2%) |
40 to 49 | 11 (4.3%) |
50 to 59 | 32 (12.6%) |
60 to 69 | 38 (15.0%) |
70 to 79 | 94 (37.0%) |
≥80 | 16 (1.6%) |
Causality | |
Certain | 19 (7.5%) |
Probable/Likely | 80 (31.5%) |
Possible | 155 (61.0%) |
Number of Concurrent Medications | |
1 | 235 (92.5%) |
2 | 17 (6.7%) |
3 | 1 (0.4%) |
4 | 1 (0.4%) |
Comorbidities c | |
Cancer | 37 (14.6%) |
Neuropsychiatric disorders | 35 (13.8%) |
Vascular disease | 29 (11.4%) |
Musculoskeletal disorders | 12 (4.7%) |
Diabetes | 11 (4.3%) |
Respiratory infection | 3 (1.2%) |
Others | 48 (18.9%) |
ADE types | |
Non-SAE | 220 (86.6%) |
SAE | 34 (13.4%) |
Report types d | |
Doctors | 96 (37.8%) |
Pharmacists | 77 (30.3%) |
Nurses | 64 (25.2%) |
Others | 11 (4.3%) |
Types of drug-induced cognitive impairments | |
Cognitive function declined or disorder | 147 (57.9%) |
Perception-related impairment | 67 (26.4%) |
Social function and emotion-related impairment | 15 (5.9%) |
Movement and problem-solving-related impairment | 14 (5.5%) |
Memory-related impairment | 6 (2.4%) |
Speech-related impairment | 5 (2.0%) |
Drug Class | No SAE (n = 220) | SAE (n = 34) | Total (n = 254) |
---|---|---|---|
Analgesics | 36 (16.4%) | 0 (0.0%) | 37 (14.6%) |
Acetaminophen | 5 (2.3%) | 0 (0.0%) | 5 (2.0%) |
Aspirin | 4 (1.8%) | 0 (0.0%) | 4 (1.6%) |
Celecoxib | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Codeine | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Dihydrocodeine | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Loxoprofen | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Meloxicam | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Morphine | 8 (3.6%) | 0 (0.0%) | 8 (0.8%) |
Naproxen sodium | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Oxycodone | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Tramadol | 8 (3.6%) | 0 (0.0%) | 8 (0.8%) |
Sedative-Hypnotics | 31 (14.1%) | 2 (5.9%) | 33 (13.0%) |
Zolpidem | 31 (14.1%) | 2 (5.9%) | 33 (13.0%) |
Antidepressants | 18 (%) | 0 (0.0%) | 18 (7.1%) |
Amitriptyline | 6 (2.7%) | 0 (0.0%) | 6 (2.4%) |
Duloxetine | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Escitalopram | 5 (2.3%) | 0 (0.0%) | 5 (2.0%) |
Fluoxetine | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Tianeptine | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Venlafaxine | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Anticonvulsants | 20 (9.09%) | 3 (8.8%) | 23 (9.06%) |
Divalproex | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Oxcarbazepine | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Pregabalin | 4 (1.8%) | 0 (0.0%) | 4 (0.4%) |
Gabapentin | 8 (3.6%) | 0 (0.0%) | 8 (0.8%) |
Sodium valproate | 3 (1.4%) | 0 (0.0%) | 3 (1.2%) |
Topiramate | 10 (4.5%) | 3 (8.8%) | 13 (5.1%) |
Anticancer drugs | 3 (1.4%) | 15 (44.12%) | 18 (7.09%) |
Fluorouracil | 0 (0.0%) | 10 (29.4%) | 10 (4.0%) |
Irinotecan | 0 (0.0%) | 5 (14.7%) | 5 (2.0%) |
Megestrol | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Methotrexate | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Paclitaxel | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Anti-cholesterol Drug | 13 (5.9%) | 0 (0.0%) | 13 (5.1%) |
Ezetimibe | 6 (2.7%) | 0 (0.0%) | 6 (2.4%) |
Rosuvastatin | 7 (3.2%) | 0 (0.0%) | 7 (2.8%) |
Anticholinergic | 12 (5.5%) | 1 (2.9%) | 13 (5.1%) |
Benztropine | 11 (5.0%) | 1 (2.9%) | 12 (4.7%) |
Glycopyrrolate | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Antihistamine | 10 (4.5%) | 0 (0.0%) | 10 (3.9%) |
Chlorpheniramine | 3 (1.4%) | 0 (0.0%) | 3 (1.2%) |
Bepotastine | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Dimenhydrinate | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Hydroxyzine | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Mequitazine | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Triprolidine | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Anti-Parkinson agents | 7 (3.2%) | 4 (11.8%) | 11 (4.3%) |
Carbidopa-levodopa | 6 (2.7%) | 0 (0.0%) | 6 (2.4%) |
Rasagiline | 0 (0.0%) | 4 (11.8%) | 4 (1.6%) |
Ropinirole | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Anxiolytic | 14 (3.6%) | 0 (0.0%) | 14 (5.5%) |
Alprazolam | 6 (2.7%) | 0 (0.0%) | 6 (2.4%) |
Buspirone | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Clonazepam | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Diazepam | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Lorazepam | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Midazolam | 2 (0.9%) | 0 (0.0%) | 2 (0.8%) |
Antipsychotic | 6 (2.7%) | 1 (2.94%) | 7 (2.8%) |
Clozapine | 0 (0.0%) | 1 (2.94%) | 1 (0.4%) |
Olanzapine | 1(0.5%) | 0 (0.0%) | 1 (0.4%) |
Quetiapine | 5 (2.3%) | 0 (0.0%) | 5 (2.0%) |
Dementia drugs | 2 (0.9%) | 0 (0%) | 2 (0.8%) |
Donepezil | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Memantine | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) |
Others | 48 (21.8%) | 8 (23.5%) | 56 (22.0%) |
Medications | Cases (n = 26) |
---|---|
Topiramate | 1 (3.8%) |
Clozapine | 1 (3.8%) |
Metoclopramide | 3 (11.5%) |
Rasagiline | 4 (15.4%) |
Calcium folinate | 5 (19.2%) |
Irinotecan | 5 (19.2%) |
Fluorouracil | 5 (19.2%) |
Methylprednisolone | 2 (7.7%) |
Clinical Predictors | OR (95% CI) | p-Value |
---|---|---|
Age | 0.998 (0.908–1.100) | 0.967 |
Men | 22.613 (3.717–137.570) | <0.001 |
Drug | 1.342 (0.939–1.920) | 0.106 |
Neuropsychiatric disorder | 0.495 (0.034–7.17) | 0.606 |
Vascular disorders | 2.911 (0.160–53.050) | 0.471 |
Cancer | 11.543 (2.560–52.110) | 0.001 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Sunwoo, Y.; Eom, S.H.; Yun, J.S.; Kim, Y.; Lee, J.; Lee, S.H.; Shin, S.; Choi, Y.J. Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System. Medicina 2024, 60, 1028. https://doi.org/10.3390/medicina60071028
Sunwoo Y, Eom SH, Yun JS, Kim Y, Lee J, Lee SH, Shin S, Choi YJ. Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System. Medicina. 2024; 60(7):1028. https://doi.org/10.3390/medicina60071028
Chicago/Turabian StyleSunwoo, Yongjun, Sae Hyun Eom, Ji Seong Yun, Yujin Kim, Jeongmin Lee, Soo Hyeon Lee, Sooyoung Shin, and Yeo Jin Choi. 2024. "Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System" Medicina 60, no. 7: 1028. https://doi.org/10.3390/medicina60071028