Benzodiazepines May Increase Dementia Risk

Dementia is becoming more common as the population ages. While the currently available treatments for this disorder offer little benefit, they present significant side effects. To help stem a growing problem that could overwhelm our health care system in the future, it is crucial to avoid factors that may increase the risk of dementia.

One suspected risk factor for dementia is the use of benzodiazepines. Past research studying benzodiazepine use and the development of dementia has yielded conflicting results, partly due to the poor quality of many of these studies.

A recent study published in the British Medical Journal (BMJ) provides the strongest evidence to date linking benzodiazepine use to an increased dementia risk. This large, carefully conducted study used a prospective design and avoided some of the key weaknesses of earlier studies. The authors found that benzodiazepine use by elderly patients increased the risk of developing dementia by approximately 40 to 60 percent.

What are benzodiazepines?

Benzodiazepines are commonly used as tranquilizers (“minor tranquilizers,” or anti-anxiety pills) and sleeping pills (see table below). They are also used to treat severe agitation, seizures, and alcohol withdrawal and to medicate patients prior to a variety of medical and dental procedures. These drugs have many side effects, including the potential, with long-term use, to cause drug-induced dependence and addiction.

Older adults have a much more difficult time eliminating benzodiazepines from their bloodstreams. As a result, these drugs can accumulate in their bodies more than in younger people, making older adults more sensitive to serious adverse effects including unsteady gait, dizziness, falls, increased risk of an auto accident, drug-induced or drug-worsened impairment of thinking, memory loss, and addiction.

Despite these significantly increased risks, sleeping pills and minor tranquilizers are prescribed much more often for older adults than for younger ones, for much longer periods of time and usually not at a reduced dose that could decrease their negative effects.

Benzodiazepines Available in the U.S. For Generalized Anxiety or Insomnia

* Do Not Use Except for Panic Disorders
** Do Not Use
*** Limited Use (offers limited benefit or benefits certain people or conditions)

BMJ study overview

In 1987, researchers in France began a large prospective study, known as the PAQUID study, to assess normal and pathological brain aging. Between 1987 and 1989, the researchers randomly selected a representative sample of 3,777 people aged 65 years or older from the general population in two areas of southwest France. The subjects then were followed every two to three years for up to 20 years.

Of the 3,777 participants in the PAQUID study, 1,063 qualified for enrollment in a sub-study designed to look at the association between benzodiazepine use and the subsequent development of dementia. These sub-study subjects were followed for up to 15 years following an initial, five-year baseline observation period confirming that they were:

• free from any use of benzodiazepines for at least the first three years of the five-year observation period; and
• free from any signs of dementia during the five-year period.

These inclusion criteria allowed the researchers to adjust for potentially confounding factors, including cognitive decline before starting benzodiazepines. By doing so, the researchers significantly limited the possibility that any association seen between benzodiazepine use and dementia would be due to reverse causation, a potential flaw of some of the earlier studies. (Reverse causation might occur because patients with early dementia often develop insomnia, anxiety and depression — major indications for prescribing benzodiazepines. As a result, the development of dementia could lead to treatment with benzodiazepines, rather than the reverse.)

Data on drug use were collected using standardized questionnaires at each follow-up visit, and subjects or their caregivers were asked about prescription and over-the-counter drugs used regularly during the two weeks prior to the follow-up. The interviewer also visually inspected each subject’s drug bottles.

At baseline and each follow-up visit, the subjects were evaluated by trained neuropsychologists. During face-to-face interviews, information was collected on personal characteristics, demographics, life habits, health conditions, drug use, functional status, depression symptoms and cognition.

To further avoid bias, the neuropsychologists conducting the interviews were blinded to the purpose of the study. Subjects were screened for signs of dementia, and any subject with suspected dementia was then examined by a neurologist to confirm the diagnosis. Confirmed dementia was the primary outcome measure of the sub-study, the results of which were published in the Sept. 27, 2012, issue of BMJ.

Results of the BMJ study

Following the initial five-year baseline observation period, a total of 253 (24 percent) of the 1,063 subjects developed dementia over the subsequent 15-year follow-up period. This included 30 (32 percent) of the 95 subjects who started benzodiazepines during the last two years of the five-year baseline observation period and 223 (23 percent) of the 968 subjects who did not use benzodiazepines during the same period.

After controlling for multiple confounding factors, subjects who started on benzodiazepines during the last two years of the five-year baseline observation period had a 60 percent higher probability of developing dementia compared to subjects who did not use benzodiazepines during the baseline observation period. These results were unchanged when adjusting for subjects who had significant symptoms of depression at the baseline evaluation.

In a separate analysis, the researchers also measured the incidence of dementia in subjects who became new users of benzodiazepines over five successive follow-up periods compared to subjects who never used the drugs through these same time periods. They then pooled the results across the groups of subjects for these five time periods of exposure and found that new users of benzodiazepines had, on average, a 40 percent higher risk of developing dementia compared to nonusers of these drugs.

Implications of the BMJ study

In discussing their results, the authors of the BMJ study concluded:

[I]ncreasing evidence shows that [benzodiazepine] use may induce adverse outcomes, mainly in elderly people, such as serious falls and fall related fractures. Our data add to the accumulating evidence that use of benzodiazepines is associated with increased risk of dementia, which, given the high and often chronic consumption of these drugs in many countries, would constitute a significant public health concern. Therefore, physicians should carefully assess the expected benefits of the use of benzodiazepines in the light of these adverse effects and, whenever possible, limit prescription to a few weeks as recommended by the good practice guidelines. In particular, uncontrolled chronic use of benzodiazepines in elderly people should be cautioned against.

Worst Pills, Best Pills News has always listed nine of the 11 benzodiazepines approved for anxiety or insomnia in this country as “Do Not Use” drugs. The only exceptions are alprazolam, which is listed as “Do Not Use” except for panic attacks, and oxazepam, which is listed as “Limited Use” and is the only sleeping pill or tranquilizer that we recommend for older adults.

The data presented by the PAQUID study researchers affirm our long-standing general recommendation against using benzodiazepines, especially on a long-term basis. Given the lack of effective and safe treatment for dementia, it is imperative that people of all ages, but particularly older adults, avoid exposure to any factors that may predispose them to its development.

What You Can Do

Too often, doctors immediately prescribe benzodiazepines whenever patients complain of insomnia or anxiety. If you have either of these symptoms, you should initially seek nondrug interventions.

Many patients with anxiety will improve with brief counseling provided by a general practitioner or a psychologist. Talking to nonmedical people — a friend, a spouse, a relative, a clergy member — may help to identify causes of anxiety and potential solutions. Gathering the courage to talk about difficult concerns will generally be a better solution than taking pills. Getting regular exercise also can help relieve anxiety. For some people, a specialized form of psychotherapy can treat anxiety.

If medication is needed, it is best to see a psychiatrist. Benzodiazepine use should be limited to short periods of time (a week to 10 days) at the lowest dose needed to manage your symptoms.

Likewise, for insomnia, you should pursue the many nondrug interventions that have been extensively covered in past issues of Worst Pills, Best Pills News.

You should not discontinue the use of any medication without first consulting your prescribing doctor. This is especially true for these drugs because they are addictive.