Benzodiazepine Use and Risk of Developing Alzheimer’s Disease or Vascular Dementia: A Case–Control Analysis

Imfeld, Patrick; Bodmer, Michael; Jick, Susan S.; Meier, Christoph

doi:10.1007/s40264-015-0319-3

Cited by 77 publications

(88 citation statements)

References 28 publications

(38 reference statements)

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“…Six studies were case-control design studies [17][18][19][20][21][22] and 4 were cohort studies [23][24][25][26] . The included studies were published between 1983 and 2013, thus spanning 31 years.…”

Section: Systematic Reviewmentioning

confidence: 99%

“…The included studies were published between 1983 and 2013, thus spanning 31 years. Five studies were conducted in Europe [18,19,[24][25][26] , 3 in Asia [17,21,22], and the remaining 2 in North America [20,23] . Eight studies reported that the age at the onset of dementia was over 65 years but 2 studies reported an age of onset below 60 years [24,25] .…”

Section: Systematic Reviewmentioning

confidence: 99%

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Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

et al. 2016

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Background: Benzodiazepines are a widely used medication in developed countries, particularly among elderly patients. However, benzodiazepines are known to affect memory and cognition and might thus enhance the risk of dementia. The objective of this review is to synthesize evidence from observational studies that evaluated the association between benzodiazepines use and dementia risk. Summary: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risk of benzodiazepines use on dementia outcome. All control observational studies that compared dementia outcome in patients with benzodiazepine use with a control group were included. We calculated pooled ORs using a random-effects model. Ten studies (of 3,696 studies identified) were included in the systematic review, of which 8 studies were included in random-effects meta-analysis and sensitivity analyses. Odds of dementia were 78% higher in those who used benzodiazepines compared with those who did not use benzodiazepines (OR 1.78; 95% CI 1.33-2.38). In subgroup analysis, the higher association was still found in the studies from Asia (OR 2.40; 95% CI 1.66-3.47) whereas a moderate association was observed in the studies from North America and Europe (OR 1.49; 95% CI 1.34-1.65 and OR 1.43; 95% CI 1.16-1.75). Also, diabetics, hypertension, cardiac disease, and statin drugs were associated with increased risk of dementia but negative association was observed in the case of body mass index. There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the sensitivity analyses. There was significant statistical and clinical heterogeneity among the studies for the main analysis and most of the sensitivity analyses. Key Messages: Our results suggest that benzodiazepine use is significantly associated with dementia risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

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Section: Systematic Reviewmentioning

confidence: 99%

Section: Systematic Reviewmentioning

confidence: 99%

Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

et al. 2016

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“…constipation, blurred vision, urinary retention, and delirium) associated with anticholinergic medications, it is prudent to minimize use of these medications and consider alternatives when possible as shown in a recent review [130], However, in this review paroxetine as a highly anticholinergic selective serotonin reuptake inhibitor antidepressant did not increase the risk for dementia when compared with other SSRIs [130]. In the clinical context benzodiazepine use has been associated with an increased risk of dementia, however a recent case control study in 26,459 patients aged ≥65 years with newly diagnosed Alzheimer's disease, long-term use of benzodiazepines was not associated with an increased risk of developing Alzheimer's disease [131]. In conclusion concerning the use of antidepressants in the treatment of dementia an acceptability analysis showed that SSRIs were generally well tolerated but results also suggest that there is insufficient evidence to reject the null hypothesis of no differences in efficacy between SSRIs and placebo in the treatment of depression in dementia [132].…”

Section: In the Treatment Of Dementia And Depression Think About Lithiummentioning

confidence: 99%

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

Lang¹,

Walter²

2017

Neurosignals

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The depressive state has been characterised as one of elevated inflammation, changed cardiovascular parameters and a deranged metabolic situation all of which holds promise for a better understanding and handling of treatment-resistance in affective disorders as well as for future developments in treatment algorithms. In this context several biomarkers are differentially regulated by antidepressant treatment and connected to metabolic, inflammatory, cardiovascular and apoptotic components of the pathophysiology, i.e. adiponectin, apolipoprotein-B, B-type natriuretic peptide, cortisol, CRP, cysteine, homocysteine, fibrinogen, adiponectin, BMI, glycated hemoglobin A1c, leptin, interferon-gamma, high-density lipoprotein, interleukin interleukin-1alpha, -1beta, -2, -4, -5, -6, -8, -10, -12, -13, -17, insulin-like growth factor-1, low-density lipoprotein, myeloperoxidase, osteoprotegerin, tumour necrosis factor alpha, troponins, triglycerides etc. In this context antidepressants exert different modulatory effects on the outcome, incidence and mortality concerning several severe disorders, i.e. cancer, diabetes, stroke, inflammation, stroke and cardiovascular risk. Vice versa different drugs used in the treatment of these disorders have a favourable effect in depressive states, e.g. statins, aspirine, NSAIDs, pioglitazone, celecoxib, peroxisome proliferator-activated receptor-gamma agonists and minocycline. In this review, actions of different antidepressant treatment strategies on cancer, stroke, diabetes and cardiovascular disorders are shown and the influence on the outcome of the disorders is differentially discussed. In conclusion a hypothetic model for the implication of actual findings in everyday clinical practice is proposed. In this context personalized treatment could be used to tailor treatment to specific individuals according to their clinical endophenotypes. Moreover a potential target for the development of novel intervention strategies might be used.

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confidence: 99%

“…2 Although there is uncertainty regarding increased risk of dementia associated with use of benzodiazepines (BZD) and BZD receptor agonists (see Imfeld et al), 3 Dr. James is correct in asserting that clinicians must consider this, as well as numerous other potential adverse consequences of hypnotic medication, particularly in the elderly.…”

mentioning

confidence: 99%

Adverse Effects of Hypnotic Medications

Buysse

Krystal

Neubauer

2017

Journal of Clinical Sleep Medicine

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We thank Dr. James for his comments 1 on our paper, Clinical Practice Guideline for Pharmacologic Treatment of Chronic Insomnia in Adults.2 Although there is uncertainty regarding increased risk of dementia associated with use of benzodiazepines (BZD) and BZD receptor agonists (see Imfeld et al.),3 Dr. James is correct in asserting that clinicians must consider this, as well as numerous other potential adverse consequences of hypnotic medication, particularly in the elderly.The adverse effects described in our systematic review were drawn only from the efficacy studies that met overall inclusion criteria. We note in our publication that "the data ( from studies included in this analysis) are scant and inconsistent, suggesting that caution should be applied in the assessment of relative risks associated with use of hypnotic medications." We also note that there are many additional observational studies that address these and other potential adverse effects; "Other reported adverse effects include-but are not limited to-dependency/withdrawal, cognitive impairment, falls/fractures, parasomnias, and driving impairment and motor vehicle accidents. Epidemiological studies have also suggested a possible link between hypnotic use and infection, depression and overall mortality risk. These complications are observed most frequently in older populations, who are among the most frequent users of these drugs." Per Dr. James' comment, dementia could be listed among the conditions related to BZD hypnotic use in epidemiological studies. Although these observational studies are beyond the scope of our investigation, they are by all means important considerations for clinicians who are prescribing these drugs. LETTERS TO THE EDITOR Adverse Effects of Hypnotic MedicationsResponse to James. Hypnotics and the risks of dementia.

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Benzodiazepine Use and Risk of Developing Alzheimer’s Disease or Vascular Dementia: A Case–Control Analysis

Abstract: After taking a prodromal phase into consideration, benzodiazepine use was not associated with an increased risk of developing AD or VaD.

Cited by 77 publications

References 28 publications

Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

Adverse Effects of Hypnotic Medications

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