Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study

Heath, Laura; Gray, Shelly L.; Boudreau, Denise M.; Thummel, Ken; Edwards, Karen L.; Fullerton, Stephanie M.; Crane, Paul K.; Larson, Eric B.

doi:10.1111/jgs.15508

Cited by 34 publications

(22 citation statements)

References 43 publications

(112 reference statements)

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“…The chronic use of anticholinergic antidepressants might contribute to this pathogenic transformation [318]. It is also well-known that over 60% of patients chronically treated with antipsychotics develop extrapyramidal symptoms which may induce severe motor disability [319]. Over 80% of nursing home residents are daily consumers of psychotropic drugs [320,321] which are prescribed in excessive doses, for excessive duration, and without adequate monitoring and/or indications for their use [322].…”

Section: Further Considerationsmentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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Section: Further Considerationsmentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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“…In a cohort study excluding antidepressant exposure in the years preceding dementia diagnosis, cumulative use of most antidepressants was not associated with later dementia, except for paroxetine, which increased its risk. 20 Taking a lag time into account, we found no association. The stratification according to treatment duration did not allow us to identify any association, whatever the treatment duration, that is 3 months or less or more than 3 months compared with no dispensing.…”

Section: Discussionmentioning

confidence: 64%

The risk of dementia in patients using psychotropic drugs: Antidepressants, mood stabilizers or antipsychotics

Tournier

Pambrun

Maumus-Robert

et al. 2021

Acta Psychiatr Scand

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Objective:The risk of dementia associated with the use of psychotropic drugs is not fully understood. A nested case-control study was carried out to assess the risk of dementia broadly defined or Alzheimer's disease associated with antidepressants, mood stabilizers or antipsychotics. Methods:A cohort was formed from healthcare claim databases including all patients aged 50 and over with a first dispensing of the psychotropic drugs concerned between 2006 and 2017. Patients who developed dementia over the study period were considered as cases. The association between drug exposure prior to a five-year lag time and diagnosis of dementia was assessed by conditional logistic regression models. Results:No association was found between dementia, either broadly defined or Alzheimer disease, and antidepressant or mood stabilizers. Findings were conflicting with regard to antipsychotics. First-and second-generation antipsychotics (FGA and SGA) were not associated with Alzheimer disease. SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (Odds ratio [OR] 2.00; 95%CI 1.06-3.79; p = 0.03). In a sensitivity analysis using a lag time of 3 years, ever use of SGA and SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (OR 1.71; 1.10-2.67; p = 0.02 and OR 1.84; 1.03-3.32; p = 0.04, respectively). Conclusion:The association between antipsychotics and dementia should be further investigated to establish patients, specific drugs, and patterns of treatment at risk. Prescribers should remain cautious when prescribing them.

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“…Studies that did not assess for history or severity of depression prior to inclusion yielded contradictory results [58]. One study found paroxetine is associated with a higher risk of developing AD compared to other SSRIs or no use [65]. Paroxetine's anticholinergic action could increase the risk of cognitive effects in vulnerable populations.…”

Section: Limitations Of the Existing Evidence In Admentioning

confidence: 99%

Opportunities for Drug Repurposing of Serotonin Reuptake Inhibitors: Potential Uses in Inflammation, Infection, Cancer, Neuroprotection, and Alzheimer’s Disease Prevention

et al. 2021

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Serotonin reuptake inhibitors (SRIs) are safe and widely used for a variety of indications including depressive disorders, anxiety, and chronic pain. Besides inhibiting the serotonin transporter, these medications have broad-spectrum properties in many systems. Their roles have been studied in cancer, Alzheimer’s disease, and infectious processes. The COVID-19 pandemic highlighted the importance of drug repurposing of medications already in use. We conducted a narrative review of current evidence and ongoing research on drug repurposing of SRIs, with a focus on immunomodulatory, antiproliferative, and neuroprotective activity. SRIs may have clinical use as repurposed agents for a wide variety of conditions including but not limited to COVID-19, Alzheimer’s disease, and neoplastic processes. Further research, particularly randomized controlled trials, will be necessary to confirm the utility of SRIs for new indications.

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Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study

Cited by 34 publications

References 43 publications

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

The risk of dementia in patients using psychotropic drugs: Antidepressants, mood stabilizers or antipsychotics

Opportunities for Drug Repurposing of Serotonin Reuptake Inhibitors: Potential Uses in Inflammation, Infection, Cancer, Neuroprotection, and Alzheimer’s Disease Prevention

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