Benzodiazepines and Polypharmacy - The Issues are Many and Potentially Deadly
By Don Drake, Connelly Law Offices, Ltd.
"In our last blog, we discussed how benzodiazepines affect families and how they came into use," stated professional fiduciary and certified elder law Attorney RJ Connelly III. "Let’s do a quick review on benzodiazepines, how use continues to be high among older adults, and why women are prescribed more of these drugs than men. We will then delve into this week's topic, the other effects of benzodiazepines on our seniors."
"A recent Athena Health report shows that those over sixty-five are prescribed benzodiazepines more than any other age group," points out Attorney RJ Connelly. "And ten percent of women over sixty-five are prescribed one of these drugs compared to just six percent of men, nearly twice the rate, and there is a reason why this disparity exists."
According to Dr. Robert Roca, the American Psychiatric Association's Council of Geriatric Psychiatry chair, “women are more likely to express distress,” while at the same time, men tend to hold their feelings, leading to increased prescriptions for benzodiazepines for women. As we discussed, the problem is that men tend to use alcohol to deal with anxiety, which is an issue for future discussion.
So now, let’s look at the dangers of combining these drugs with other medications. When it comes to overdose risk, the combination of benzodiazepines and opioids is indeed the most dangerous, a concern that prompted a Black Box warning by the Food and Drug Administration regarding using these two classes of medications together.
"A 2017 study shows that combining opioids with benzodiazepines is especially risky in the first 90 days of concurrent use," said Attorney RJ Connelly. "These include the following benzodiazepines - alprazolam (Xanax), diazepam (Valium), and clonazepam (Klonopin), which are most frequently prescribed to seniors to alleviate anxiety."
The study Attorney Connelly alluded to examined data from over 71,000 Medicare Part D beneficiaries to determine how simultaneous use of opioids and benzos influences overdose risk over time. Patients were divided based on whether they had only taken opioids before overdose or had a supply of opioids and a benzo drug. For those in the group with a supply of both, the researchers subdivided by the cumulative number of days the patients had taken an opioid with a benzodiazepine.
The analysis showed that overdose risk was five times higher for patients taking both drugs during the first 90 days than those only taking just an opioid. The risk was doubled for those taking both drugs during the next 90 days. After 180 days, the risk of overdose was roughly the same as taking only opioids. There are a number of reasons for this, including the patient's understanding of the side effects and when to report them as well as how the patient takes them. In any case, it is essential to know that based on this study, if an overdose is to occur, it will be in the first three to six months, something caretakers should be aware of.
"Although we focus on the combination of opioids and benzodiazepines, there are multiple classifications of medications that interact with benzos that can cause serious complications," stated Attorney Connelly. "Let's look at four classes of medication that need to be monitored."
Insomnia Drugs - Known as “Z-drugs” and prescribed to help battle insomnia, many medical providers are unaware that they have a similar mechanism of action as benzodiazepines. These drugs include Ambien, Lunesta, and Sonata. When these medications are combined with benzodiazepines, they can cause blackout spells. Another 2017 study of emergency room visits for adverse events involving benzodiazepines or “Z-drugs” found a 4-fold increased risk of severe events when the two medications were combined.
Stomach medications - Known as proton pump inhibitors (PPIs) used to treat acid reflux, medications such as Prilosec, Nexium, Prevacid, and Protonix have been shown to increase the blood levels of benzodiazepines by interfering with the way the liver clears them from the body. As a result, the side effects of benzodiazepines are magnified, causing increased confusion, sedation, dizziness, falls, and driving mishaps. The most common PPIs associated with these side effects are Prilosec and Nexium.
Fluoroquinolone Antibiotics - Fluoroquinolones are antibiotics commonly used to treat various illnesses, such as respiratory and urinary tract infections. These medications include Cipro, Levaquin, and Avelox. Since they compete for the same binding site as benzos, the antibiotics block the benzos, leading to acute withdrawal symptoms in those taking them long-term. Benzo withdrawal can be life-threatening, resulting in seizures, high fevers, and psychosis.
Muscle Relaxers - Xanax (alprazolam) and Flexeril, Amrix (cyclobenzaprine) produce sedating effects. When drugs that have similar effects are mixed, the result is an enhancement of the effects of both drugs. When alprazolam and cyclobenzaprine are used together, the result is typically an increase in the side effects associated with these drugs and increased levels of sedation.
Effects on the Body
"There are also significant effects on the body of the individual using benzodiazepines regularly," said Attorney RJ Connelly. "Many of these can mimic the onset of dementia."
Memory Impairment - In most studies, benzodiazepines have been shown to block a person's ability to learn new information. Research indicates that this results from the brain's inability to transfer short-term memory to long-term memory. Elderly patients are more sensitive than younger ones to the effects of benzodiazepines and memory problems. As a result, family and friends may be willing to chalk this up to aging issues or even the onset of dementia rather than looking at benzodiazepines as the cause.
Cognitive and Psychomotor Effects - Both short-term and long-term use of benzodiazepines have been shown to affect cognitive and psychomotor functioning. These include sedation, drowsiness, coordination issues, vertigo, and dizziness.
Accidents - Benzodiazepine use has been shown to affect driving skills, especially in seniors. Even some less potent benzodiazepines have been associated with increased falls resulting in hip fractures.
Anxiety and Depression - In many users, anxiety did not decrease with benzodiazepines, while depression seemed to appear during medication use.
Other Concerns
In articles published in late 2017 and earlier this year, benzodiazepines and related drug use were associated with a 40 percent increase in mortality among persons with Alzheimer's, according to a study released by the University of Eastern Finland. The findings were published in the International Journal of Geriatric Psychiatry.
The study found that the risk of death was increased right from the initiation of benzodiazepines and related drug use. The increased risk of death may result from the adverse events of these drugs, including fall-related injuries, such as hip fractures, pneumonia, and stroke.
One theory put forward by the researchers, based at several institutions across Finland, is that the sedative effects of benzodiazepines may increase the risk of pneumonia by boosting the likelihood of aspiration of saliva or food into the lungs.
This theory correlates with the study’s finding that pneumonia risk is highest at the start of benzodiazepine use, as the sedative effect is more pronounced initially before tolerance is built up, according to researchers.
Regarding stroke risk, the researchers found benzodiazepines were associated with a 20 percent increased risk of stroke among persons with Alzheimer's disease. The findings encourage careful consideration of the use of benzodiazepines and benzodiazepine-like drugs among persons with Alzheimer's disease, as stroke is one of the leading causes of death in this group.
As mentioned earlier, benzodiazepine use while using alcohol can be a deadly combination. A recent study shows that seniors who go to hospital emergency rooms because of drug interaction usually the result of combining these two potent sedatives, which results in a synergistic effect, meaning that each drug amplifies the effect of the other, causing exaggerated side effects. Again, this results in falls, car accidents, and respiratory issues.
Commonly Prescriber Benzodiazepines
So how do you know if someone you love is taking these drugs? Check the bottles. Below is a list of some of the most commonly prescribed benzodiazepines:
alprazolam (Xanax)
diazepam (Valium)
lorazepam (Ativan)
chlordiazepoxide (Librium)
clonazepam (Klonopin)
clorazepate (Tranxene)
estazolam (ProSom)
flurazepam (Dalmane)
oxazepam (Serax)
temazepam (Restoril)
triazolam (Halcion)
quazepam (Doral)
Be especially concerned if this person exhibits some of the symptoms we mentioned earlier. And more than anything else, if visiting a medical professional about odd behaviors or symptoms that may indicate the presence of dementia, provide them with the list of medications they are taking.
"Keep in mind that these drugs are designed for short-term use," said Attorney RJ Connelly. "If someone has been using them regularly for over a few weeks, know that withdrawal symptoms can be powerful and potentially deadly. More importantly, never suggest stopping any medication without consulting the prescribing physician. It could be that the benefits of benzodiazepines may very well outweigh the possible side effects."
As you can see, many parallels exist between the so-called opioid epidemic and the continued over-prescribing of benzodiazepines for long-term use among seniors. Unfortunately, despite the documented dangers, little has been done to educate the public on their dangers. And medical professionals, who have access to the literature regarding the dangers of benzodiazepines, continue to prescribe these drugs at alarmingly high rates.
"Be aware of what medications an elderly loved one is taking," stated Attorney RJ Connelly. "Stay involved in their treatment and care, and don't chalk up new behaviors as conditions of aging. Finally, don't be afraid to ask questions."
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