Benzodiazepines and anxiolytics increase risk for dementia, mortality

Benzodiazepines (Xanax®, Halcion®, Ativan®, Restoril®, lorazepam, Valium®, Klonopin®, Librium®, etc.) are known to increase the risk for dementia as documented in a study published in BMJ (British Medical Journal). The authors examined data for 1063 men and women free of dementia and did not start taking benzodiazepines until at least the third year of follow-up observations and found a significant association:

"During a 15 year follow-up, 253 incident cases of dementia were confirmed. New use of benzodiazepines was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60). Sensitivity analysis considering the existence of depressive symptoms showed a similar association (hazard ratio 1.62). A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia. The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46. Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia compared with never users."

It's important to note that other serious symptoms, bad enough on their own, can arise before progressing to full-blown dementia. They note:

"Insomnia, depression, and anxiety...can be prodromal symptoms of dementia...As treatment options remain limited, identifying factors contributing to dementia is critical."

The authors conclude:

"The findings of this large prospective population based study show that new use of benzodiazepines is associated with an approximately 50% increase in the risk of dementia. The results remained robust after control for potential confounders, in pooled analysis across the follow-up time, and in a nested case-control study. Considering the extent to which benzodiazepines are now prescribed, physicians and regulatory agencies should consider the increasing evidence of the potential adverse effects of this drug class for the general population."

Just as considering only lung cancer when accounting for adverse effects of smoking, the incidence of dementia brings in its train a host of other ill effects for the brain.Now another study hot off the presses from BMJ offers evidence that benzodiazepines along with anxiolytics and the Z drugs commonly used for insomnia—zaleplon (Sonata®), zolpidem (Ambien®), and zopiclone—significantly increase the risk of mortality in general. The authors state their intent:

"Evidence of adverse effects including increased risk of dementia and other psychomotor impairments (daytime fatigue, ataxia, falls, and road traffic incidents), cancer, pneumonia, and other infections has increased concerns of an association with premature mortality...A recent study found that the mortality risk extended to those with low levels of use, was greater in younger people, and that heavy use of hypnotics increased the risk of developing cancer...We tested the hypothesis that people taking anxiolytic or hypnotic drugs, or both, are at significantly increased risk of death compared with non-users and to estimate the size of this association after adjusting for a wide range of potential confounders using prescribing data from UK primary care."

To do so they examined data for 34,727 patients aged 16 years and older who were prescribed anxiolytic or hypnotic drugs, or both and 69,418 patients with no such prescriptions as controls, followed over an average period of 7.6 years for death from all causes. Their data both a significantly increased risk for mortality and an increase in other ills:

"Physical and psychiatric comorbidities and prescribing of non-study drugs were significantly more prevalent among those prescribed study drugs than among controls. The age adjusted hazard ratio for mortality during the whole follow-up period for use of any study drug in the first year after recruitment was 3.46 and 3.32 after adjusting for other potential confounders. Dose-response associations were found for all three classes of study drugs (benzodiazepines, Z drugs (zaleplon, zolpidem, and zopiclone), and other drugs). After excluding deaths in the first year, there were approximately four excess deaths linked to drug use per 100 people followed for an average of 7.6 years after their first prescription."

Commenting on these findings they state:

We found evidence of an association between prescription of anxiolytic and hypnotic drugs and mortality over an average follow-up period of 7.6 years among more than 100,000 age and general practice matched adults. In patients who were prescribed these drugs, there was an estimated overall statistically significant doubling of the hazard of death (hazard ratio 2.08), after adjusting for a wide range of potential confounders, including physical and psychiatric comorbidities, sleep disorders, and other drugs. This association remained significant and followed a dose-response pattern after restricting analyses to those with at least 12 months of follow-up and to those who were only prescribed the study drugs in the first year after recruitment."

Moreover, a host of other ills (comorbidities) can be experienced along the way to a doubling of mortality risk which can be rendered more difficult to treat due to adverse brain effects of these medications. The authors summarize in their conclusion:

"These findings are consistent with previous evidence of a statistically and clinically significant association between anxiolytic and hypnotic drugs and mortality. Using prescribing data from a large primary care database and after adjusting for a wide range of potential confounders, prescriptions for these drugs were associated with significantly increased risks of mortality over an average follow-up period of 7.6 years. This association followed a dose-response pattern for all three classes of study drug and extended beyond the time of use."