Sedatives
Long-term use of pills for insomnia and anxiety linked to Alzheimer’s risk
New research bolsters the belief that long-term use of a prescription drug commonly used to alleviate anxiety, panic attacks and sleep problems is linked in aging patients to a higher risk of Alzheimer’s disease.
Researchers in France and Canada, using data from Quebec’s health insurance program, found that Alzheimer’s risk was up to 51 percent higher in elderly people who used benzodiazepines for three months or more. The researchers said the link appeared even stronger with longer duration of use or longer-acting benzodiazepines.
The team said it wasn’t clear whether the link between Alzheimer’s and benzodiazepines — which are marketed under brands such as Xanax, Ativan, Valium and Klonopin — was causal. The researchers also noted that it was possible that anxiety and sleep disorders could be associated with early symptoms of Alzheimer’s.
But the researchers also said the link between duration and use of the drugs suggests a possible direct connection worthy of further investigation. They urged physicians to use caution in prescribing the drugs to elderly patients.
The researchers — led by Sophie Billioti de Gage and Antoine Pariente at the University of Bordeaux — used data from Quebec’s public drug plan to track 1,796 Alzheimer’s cases over six years. The patients were at least 66 years old, living in the community and covered by the drug plan between 2000 and 2009. All had used benzodiazepines at least five years prior to the first diagnosis of Alzheimer’s — a criterion selected by the researchers to guard against finding possible reverse causation. The patients’ records were then compared with 7,184 control cases.
The study — which appeared Tuesday in the British Medical Journal — was in line with five previous studies that found an increased risk of Alzheimer’s and long-term use of benzodiazepines. An accompanying editorial in the medical journal — co-authored by Kristine Yaffe at the University of California at San Francisco and Malaz Boustani at Indiana University’s Center for Aging Research — noted that the 2012 American Geriatrics Society’s list of inappropriate drugs for older adults was updated to include benzodiazepines because of undesirable side effects on cognition.
Source : Washington Post (Sep 2014)
Valium (diazepam) Tablets
Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
ADVERSE REACTIONS
Postmarketing Experience
- Injury, Poisoning and Procedural Complications: There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.
Source : FDA (Oct 2013)
Sedatives May Raise Risk of Pneumonia
Taking benzodiazepines may raise the risk of pneumonia as well as the likelihood of dying from the disease, researchers found.
As a class, the sedatives were associated with more than a 50% increased chance of developing pneumonia (OR 1.54, 95% CI 1.42 to 1.67, P<0.001), Robert Sanders, PhD, of the Institute of Cognitive Neuroscience at University College London, and colleagues reported online in Thorax.
They also were tied to a 22% higher risk of 30-day and a 32% higher risk of long-term mortality, the researchers reported.
"Further research is required into the immune safety profile of benzodiazepines," they wrote.
Animal studies have shown that some benzodiazepines increase susceptibility to infection, and the class has been associated with infections and sepsis mortality in critically ill patients.
To further understand the relationship, Sanders and colleagues conducted a nested case-control study involving 4,964 cases of community-acquired pneumonia and 29,697 controls from the Health Improvement Network, a database of primary care patients in the U.K.
They found that all benzodiazepines, with the exception of chlordiazepoxide (Librium), were individually associated with an increased risk of the disease (P<0.001 for all):
- Diazepam (OR 1.49, 95% CI 1.34 to 1.65)
- Lorazepam (OR 2.20, 95% CI 1.68 to 2.89)
- Temazepam (OR 1.87, 95% CI 1.70 to 2.06)
They also found that zopiclone (Lunesta), which isn't a benzodiazepine but acts on GABA receptors, came with a significantly higher risk of developing pneumonia (OR 1.98, 95% CI 1.49 to 2.81, P<0.001).
With regard to mortality, benzodiazepines as a class were associated with a significantly higher risk of both 30-day and long-term death (HR 1.22, 95% CI 1.06 to 1.39 and HR 1.32, 95% CI 1.19 to 1.47, respectively).
All four benzodiazepines individually affected long-term mortality, the researchers reported, but only diazepam and lorazepam affected 30-day mortality on their own.
Sanders and colleagues noted that the study was limited because it couldn't exclude the possibility of unmeasured confounders, and also by the fact that prescription data were used as a proxy for exposure to the drugs.
Its design also poses the possibility of selection bias and precludes the ability to establish causality.
They concluded that future prospective cohort studies are needed to further investigate the relationship between benzodiazepines and infection, adding that other drugs targeting GABA receptors, such as topiramate, should be investigated as well.
Source : MedPage Today via Thorax Obiora E, et al "The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort" Thorax 2012; DOI: 10.1136/thoraxjnl-2012-202374.
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