Americans love benzodiazepines (aka benzos). These anti-anxiety agents are used as all-purpose psych drugs. Millions of people take benzos to calm jittery nerves, ease anxiety and overcome insomnia. They include alprazolam, chlordiazepoxide, clonazepam, diazepam and lorazepam. The generic names have become almost as familiar as the brands: Xanax, Librium, Klonopin, Valium and Ativan. But despite their widespread popularity, these medications have side effects. And they’re hard to stop. Could taking a benzo, especially over the long run, raise your risk for Alzheimer disease?
Good News and Bad Benzo News:
A study published in the journal BMC Medicine (July 2, 2024) offers some fascinating insights into benzodiazepine use and its relationship to memory problems. The data came from the Rotterdam Study and involved 5,433 “cognitively healthy” older adults. The mean follow-up was 11.2 years.
All had normal cognitive function at the beginning of the study in 1990 and all took regular tests every four years to assess their brains. Researchers used pharmacy records to tell who was taking a benzodiazepine, at what dose and for how long. During the study 13.3% of all participants developed dementia.
The good news:
“In this prospective population-based study, benzodiazepine use was not associated with increased dementia risk.”
The bad news:
“In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala.”
Put another way, the use of benzos was associated with accelerated brain shrinkage in areas of the brain that are important for memory and judgment.
Mother’s Little Helper:
During the 1960s and 1970s, benzodiazepines were incredibly popular. Drugs like Librium and Valium topped the hit parade of most prescribed drugs. The Rolling Stones alerted the public to the dangers of sedatives in its iconic song “Mothers Little Helper” in the 1966 album Aftermath.
Many people were convinced the yellow pills in the song were 5 mg Valiums. Another possibility was Miltown (meprobamate), which preceded benzos. One other possibility was Nembutal. This barbiturate (pentobarbital) was very popular in its day. By now, you get the picture. Americans have had a love affair with sedatives, sleeping pills, anti-anxiety agents and tranquilizers for many decades. The Stones captured the culture with these lyrics:
- “Mother needs something today to calm her down
- And though she’s not really ill, there’s a little yellow pill
- She goes running for the shelter of a mother’s little helper
- And it helps her on her way, gets her through her busy day…”
Benzos and a Connection with Alzheimer Disease:
The Dutch study cited above may give many physicians and patients reassurance that benzodiazepines are not associated with clear signs of Alzheimer disease. But an earlier study from Finland raised some worrisome questions (Acta Psychiatrica Scandinavica, Aug, 2018).
The scientists reviewed the prescription drug use of people diagnosed with this condition between 2005 and 2011, a total of 70,719 men and women. They compared this to the medications used by healthy neighbors of a similar age and sex. There were 282,862 of these matched controls.
What they found was that people who used benzodiazepines for anxiety or sleep and even those who used Z-drugs such as zolpidem or zaleplon for sleep were 6 percent more likely to be diagnosed with Alzheimer disease. Although this increase was statistically significant, it is very modest. So many older people take these medicines, however, that the increase in risk is a concern.
Short-Acting Benzos and Z-Drugs:
Spanish researchers analyzed data from Catalonia between 2002 and 2015 (International Journal of Neuropsychopharmacology, April 19, 2022). Records for the Catalan Health Service had 83,138 people over 45 who took a benzodiazepine or a Z-drug during that time. As controls, 84,652 people of a similar age in the same database did not take any such drug. According to the analysis, people who took a short-acting benzo were 11 percent more likely to develop Alzheimer disease. Those using Z-drugs had a 20 percent greater risk. Long-term use appeared especially problematic.
Benzos and a Link to Alzheimer Disease | Old News!
These are not the first studies to reveal a connection between benzodiazepine use and dementia. A study published in the BMJ back in 2014 found that benzos could increase the risk of Alzheimer disease by nearly 50 percent, especially among long-term users.
The authors concluded:
“Benzodiazepine use is associated with an increased risk of Alzheimer’s disease…Unwarranted long term use of these drugs should be considered as a public health concern.”
They go on to say:
“Our findings are of major importance for public health, especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries.”
Other researchers have performed data analysis and concluded that benzodiazepine use is not linked to Alzheimer disease (BMJ, Feb. 2, 2016). But a recent review of previous research concluded that there is an association between benzodiazepine use and the development of dementia (Pharmacotherapy, Aug. 11, 2018).
Conclusions from the New Dutch Study:
The researchers reporting on the Rotterdam Study state:
“The absence of an association between benzodiazepine use and dementia risk contradicts findings from recent meta-analyses of previous research, which showed an association between benzodiazepine use and increased risk of dementia with pooled odds ratios of 1.33 to 1.78. The discrepancy might be attributed to variation in study design.”
In other words, previous research has reported an increased risk of dementia between 33 and 78 percent.
The Dutch study did not find such an association but did report:
“When including benzodiazepine exposure in a time-varying manner up to dementia diagnosis as a sensitivity analysis, we indeed observed a positive association.”
The authors conclude:
“Given the availability of effective alternative pharmacological and non-pharmacological treatments for anxiety and sleep problems, it is important to carefully consider the necessity of prolonged benzodiazepine use in light of potential detrimental effects on brain health.”
In other words, brain shrinkage in the hippocampus and amygdala is probably not a good thing and people might want to avoid long-term use of benzos when they can.
Final Words About Benzos and Alzheimer Disease:
Benzodiazepines and Z-drugs have their place. After a crisis or the loss of a loved one, some people need an anti-anxiety agent to help them cope or get some sleep. Such drugs can be helpful for short-term use. When weeks stretch into months and months stretch into years and years stretch into decades, such drugs pose problems. For one thing, they are very hard to stop.
People taking short-acting benzos like alprazolam or lorazepam often complain of withdrawal symptoms if they stop too suddenly. Even diazepam or clonazepam can trigger a “discontinuation syndrome.”
Older people may be especially susceptible to dizziness and falls while taking benzos. If there is an increased risk for Alzheimer disease, that is a double whammy. Learn more about this problem in our Guide to Drugs and Older People.
Researchers are learning that many things contribute to dementia. Our genes are one factor. If mom and dad had Alzheimer disease, our chances of experiencing cognitive decline are increased. Head injuries are another important factor.
There is also a growing awareness that certain infections may pose problems. If the virus that causes chickenpox (varicella-zoster) can remain dormant for decades and then trigger an outbreak of shingles, could it also contribute to dementia? Our nationally syndicated radio show (Aug. 6, 2024) is devoted to this very topic.
# 1394 is titled Viruses, Vaccines and Alzheimer Disease
Then there is exposure to anticholinergic drugs. You can learn more about Commonly Prescribed Anticholinergic Drugs Linked to Dementia at this link. Here is a link to a list of of anticholinergic drugs. Most healthcare professionals are surprised to discover that it contains medications as diverse as certain drugs for asthma and COPD, depression, hypertension, overactive bladder, incontinence, motion sickness and dizziness.
Other chemicals and medications may also play a role in mental decline. Whether benzodiazepines plays an important role in that process still remains to be determined.
Share your own experience with benzodiazepines below in the comment section. Was stopping challenging? If so, how did you deal with the “discontinuation syndrome”?
