Benzodiazepine use associated with brain injury, job loss and suicide

by CU Anschutz Medical Campus

Credit: CC0 Public Domain

Benzodiazepine use and discontinuation is associated with nervous system injury and negative life effects that continue after discontinuation, according to a new study from researchers at the University of Colorado Anschutz Medical Campus.

09 Jul 2023--"Despite the fact that benzodiazepines have been widely prescribed for decades, this survey presents significant new evidence that a subset of patients experience long-term neurological complications," said Alexis Ritvo, M.D, M.P.H., an assistant professor in psychiatry at the University of Colorado School of Medicine and medical director of the nonprofit Alliance for Benzodiazepine Best Practices. "This should change how we think about benzodiazepines and how they are prescribed."

"Patients have been reporting long-term effects from benzodiazepines for over 60 years. I am one of those patients. Even though I took my medication as prescribed, I still experience symptoms on a daily basis at four years off benzodiazepines. Our survey and the new term BIND give a voice to the patient experience and point to the need for further investigations," said Christy Huff, M.D, one of the paper's co-authors and a cardiologist and director of Benzodiazepine Information Coalition.

The survey was a collaborative effort among CU Anschutz, Vanderbilt University Medical Center, and several patient-led advocacy organizations that educate on benzodiazepine harms. Several members of the research team have lived experience with benzodiazepines, which informed the survey questions.

Symptoms were long-lasting, with 76.6% of all affirmative answers to symptom questions reporting the duration to be months or more than a year. The following ten symptoms persisted over a year in greater than half of respondents: low energy, difficulty focusing, memory loss, anxiety, insomnia, sensitivity to light and sounds, digestive problems, symptoms triggered by food and drink, muscle weakness and body pain.

Particularly alarming, these symptoms were often reported as new and distinct from the symptoms for which benzodiazepines were originally prescribed. In addition, a majority of respondents reported prolonged negative life impacts in all areas, such as significantly damaged relationships, job loss and increased medical costs. Notably, 54.4% of the respondents reported suicidal thoughts or attempted suicide.

BIND is thought to be a result of brain changes resulting from benzodiazepine exposure. A general review of the literature suggests that it occurs in roughly one in five long-term users. The risk factors for BIND are not known, and more research is needed to further define the condition, along with treatment options.

Previous studies had described this injury with various terminologies, perhaps the most well-known being protracted withdrawal. As part of the study, a scientific review board unified these names under the term benzodiazepine-induced neurological dysfunction (BIND) to more accurately describe the condition.

To better characterize BIND, Ritvo and colleagues analyzed data from a 2022 survey, published in Therapeutic Advances in Psychopharmacology, of current and former benzodiazepine users that asked about their symptoms and adverse life effects attributed to benzodiazepine use.

The survey of 1,207 benzodiazepine users from benzodiazepine support groups along with health and wellness sites is the largest of its kind. Respondents included those taking benzodiazepines (63.2%), in the process of tapering (24.4%) or fully discontinued (11.3%). Nearly all respondents had a prescription for benzodiazepines (98.6%) and 91% took them mostly as prescribed.

More information: PLOS ONE (2023), DOI: 10.1371/journal.pone.0285584

Alistair J. Reid Finlayson et al, Experiences with benzodiazepine use, tapering, and discontinuation: an Internet survey, Therapeutic Advances in Psychopharmacology (2022). DOI: 10.1177/20451253221082386

Common sedatives linked to increased risk of pneumonia in people with Alzheimer's disease

Commonly used sedatives called benzodiazepines are associated with an increased risk of pneumonia when used in people with Alzheimer disease, according to a study published in CMAJ (Canadian Medical Association Journal).

17 april 2017--"An increased risk of pneumonia is an important finding to consider in treatment of patients with Alzheimer disease," writes Dr. Heidi Taipale, Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland, with coauthors. "Benzodiazepines and Z-drugs are frequently prescribed for this population, and long-term use is typical. Pneumonia often leads to admission to hospital, and patients with dementia are at increased risk of death related to pneumonia."
Dementia, of which 60%-70% of cases are Alzheimer disease, is a risk factor for pneumonia, and many people with dementia are prescribed benzodiazepines and non- benzodiazepines (called Z-drugs), both of which have sedative effects.
To determine if there is a link between these drugs and pneumonia, Finnish researchers looked at data from national registries on 49 484 adults living in the community diagnosed with Alzheimer disease between 2005 and 2011 in Finland. The mean age of participants was 80 years and almost two-thirds (62.7%) were women. They matched 5232 patients taking benzodiazepines and 3269 patients taking Z-drugs with the remainder not taking either drug.
They found that benzodiazepines were linked to a 30% increased risk of pneumonia in patients with Alzheimer disease, and the risk was highest at the start of treatment (during the first 30 days).
Although the association with Z-drug use and pneumonia was not statistically significant, the authors did not conclude these drugs were safer as the study did not directly compare Z-drugs and benzodiazepines.
The authors suggest that the sedative nature of benzodiazepines may increase the risk of pneumonia by increasing the aspiration of saliva or food into the lungs.
The results are consistent with studies that have found an increased risk of pneumonia in patients of all ages taking benzodiazepines.
"Benefits and risks of the use of benzodiazepines should be carefully considered for patients with Alzheimer disease and include risk of pneumonia," the authors conclude.
In a related commentary, Dr. Paula Rochon from Women's College Hospital and the University of Toronto, with coauthors, writes this study "is a good reminder to clinicians to 'first do no harm' when prescribing these drugs for frail older women and men with dementia. Nonpharmacologic approaches should be the starting point when managing neuropsychiatric symptoms in this patient population, which should help to limit inappropriate use of these drugs."


Provided by Canadian Medical Association Journal

Despite risks, benzodiazepine use highest in older people

Prescription use of benzodiazepines—a widely used class of sedative and anti-anxiety medications—increases steadily with age, despite the known risks for older people, according to a comprehensive analysis of benzodiazepine prescribing in the United States. Given existing guidelines cautioning health providers about benzodiazepine use among older adults, findings from the National Institutes of Health-funded study raise questions about why so many prescriptions—many for long-term use—are being written for this age group.

21 dec 2014--The study found that among all adults 18 to 80 years old, about 1 in 20 received a benzodiazepine prescription in 2008, the period covered by the study. But this fraction rose substantially with age, from 2.6 percent among those 18 to 35, to 8.7 percent in those 65 to 80, the oldest group studied. Long-term use—a supply of the medication for more than 120 days—also increased markedly with age. Of people 65 to 80 who used benzodiazepines, 31.4 percent received prescriptions for long-term use, vs. 14.7 percent of users 18 to 35. In all age groups, women were about twice as likely as men to receive benzodiazepines. Among women 65 to 80 years old, 1 in 10 was prescribed one of these medications, with almost a third of those receiving long-term prescriptions.

"These new data reveal worrisome patterns in the prescribing of benzodiazepines for older adults, and women in particular," said Thomas Insel, M.D., director of the National Institute of Mental Health (NIMH), which supported the study. "This analysis suggests that prescriptions for benzodiazepines in older Americans exceed what research suggests is appropriate and safe."

Benzodiazepines—named for their chemical structure—are among the most commonly prescribed medications in developed countries. They include alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan).The most common uses of benzodiazepines are to treat anxiety and sleep problems. While effective for both conditions, the medications have risks, especially when used over long periods. Long-term use can lead to dependence and withdrawal symptoms when discontinued. In older people, research has shown that benzodiazepines can impair cognition, mobility, and driving skills, and they increase the risk of falls.

Despite the large number of prescriptions in the United States—85 million in 2007—relatively little was known prior to this study about the specifics of benzodiazepine prescribing in the United States relative to other countries. Mark Olfson, M.D., M.P.H., at the New York State Psychiatric Institute and Columbia University; Marissa King, Ph.D., at Yale University; and Michael Schoenbaum, Ph.D., at NIMH used data from a national prescription database (IMS LifeLink LRx Longitudinal Prescription database) and a national database on medical expenditures collected by the Agency for Healthcare Research and Quality to examine prescription patterns from 2008.

These medications can pose real risks, and there are often safer alternatives available," said Dr. Schoenbaum, who was senior author. "Our findings strongly suggest that we need strategies to reduce benzodiazepine use, particularly for older women."

Among the findings:

• Use of benzodiazepines increased steadily with age: 5.2 percent of adults 18 to 80 years old received one or more benzodiazepine prescriptions in 2008; 2.6 percent of those 18 to 35, 5.4 percent of those 36 to 50, 7.4 percent of those 51 to 64, and 8.4 percent of those 65 to 80.
• Overall, about one quarter of prescriptions involve long-acting formulations of benzodiazepines.
• Most prescriptions for benzodiazepines are written by non-psychiatrists. For adults 18 to 80 years old, about two thirds of prescriptions for long-term use are written by non-psychiatrists; for adults 65 to 80, the figure is 9 out of 10.

Benzodiazepines are effective in relieving anxiety and take effect more quickly than antidepressant medications often prescribed for anxiety. However, the prevalence of anxiety disorders declines with age. Practice guidelines recommend nonpharmacologic approaches and antidepressants over benzodiazepines as first-line treatment. Rates of insomnia increase with age, but practice guidelines recommend that health care providers consider behavioral interventions as first-line treatment over medication. Neither of these conditions explains the rates of prescribing benzodiazepines for older age groups.

Adding to concerns about the possible health consequences of benzodiazepine use, a recently reported study found an association between benzodiazepine use in older people and increased risk of Alzheimer's disease. The association was stronger with increasing length of use; the risk was nearly doubled for those using benzodiazepines for more than 180 days.

The study appears online December 18 in JAMA Psychiatry.

Provided by National Institutes of Health

Long-term use of pills for anxiety and sleep problems may be linked to Alzheimer's

Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

14 sept 2014--Taking benzodiazepines—widely prescribed drugs to treat anxiety and insomnia—is associated with an increased risk of developing Alzheimer's disease, particularly for long-term users, suggests a study published in BMJ today.

The researchers warn that unwarranted long-term use should be considered a public health concern.

Dementia currently affects about 36 million people worldwide and this number is expected to double every 20 years, reaching 115 million by 2015. Although a increased risk of dementia has been identified in benzodiazepine users, the nature of this association, whether causal or not, remains unclear.

So a team of researchers based in France and Canada set out to investigate the relationship between the risk of Alzheimer's disease and benzodiazepine exposure over a several years, as well as a potential dose-response relationship.

Using data from the Quebec health insurance program database (RAMQ), they tracked the development of Alzheimer's disease in a sample of elderly residents living in Quebec, Canada who had been prescribed benzodiazepines.

Over a period of at least six years, they identified 1,796 cases of Alzheimer's disease. They then compared each case with 7,184 healthy people matched for age, sex, and duration of follow-up.

Results show that past use of benzodiazepines for three months or more was associated with an increased risk (up to 51%) of Alzheimer's disease. The strength of association increased with longer exposure and with use of long-acting benzodiazepines rather than short-acting ones.

Further adjustment for symptoms that might indicate the start of dementia, such as anxiety, depression or sleep disorders, did not meaningfully alter the results.

In this large case-control study, benzodiazepine use was associated with an increased risk of Alzheimer's disease, say the authors. They emphasise that the nature of the link is still not definitive, but say the stronger association seen with long-term exposures "reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia."

Benzodiazepines are "indisputably valuable tools for managing anxiety disorders and transient insomnia" they write, but warn that treatments "should be of short duration and not exceed three months."

They conclude that their findings are of "major importance for public health, especially considering the prevalence and chronicity of benzodiazepine use in elderly populations and the high and increasing incidence of dementia in developed countries."

In view of the evidence, they conclude that "it is now crucial to encourage physicians to carefully balance the benefits and risks when initiating or renewing a treatment with benzodiazepines and related products in elderly patients."

In an accompanying editorial, Professor Kristine Yaffe of the University of California at San Francisco and Professor Malaz Boustani of the Indiana University Center for Aging Research, point out that in 2012 the American Geriatrics Society updated its list of inappropriate drugs for older adults to include benzodiazepines, precisely because of their unwanted cognitive side effects.

Yet almost 50% of older adults continue to use these drugs, they say. And without any formal monitoring system, the potential long term consequences on brain health are likely to be missed, adding to the growing prevalence of cognitive impairment among older people, they suggest.

Given the expanding numbers of older people likely to be treated with several drugs at a time, and/or who are at risk of Alzheimer's disease, this gap needs to be plugged, they say.

More information: www.bmj.com/cgi/doi/10.1136.bmj.g5205
www.bmj.com/cgi/doi/10.1136.bmj.g5312

Provided by British Medical Journal

Widely used sedatives/sleeping pills linked to increased fatal pneumonia risk

Commonly prescribed sleeping pills/sedatives may increase the risk of contracting pneumonia by as much as 50% and increase the risk of dying from it, suggests research published online in the journal Thorax.

06 dec 2012--Benzodiazepines have a wide range of uses and are commonly prescribed for anxiety, epilepsy, muscle spasm, and insomnia. They are also frequently used in palliative care, as a sedative, and to help those with an alcohol problem to "dry out."

Around 2% of the population in the UK and the US have taken benzodiazepines for 12 months or more, and among the elderly this prevalence rises to one in 10.

The use of these drugs has been linked to a heightened risk of infections and death from blood poisoning (sepsis) in critically ill patients, and the authors wanted to know if these drugs had a similar impact on the risk of developing fatal pneumonia.

The authors analysed the health records of patients whose details had been entered into the Health Improvement Network (THIN) database. This contains the records of over 9 million patients registered with various primary care organisations across the UK.

They focused on just under 5000 patients (cases) with a first recorded diagnosis of pneumonia between 2001 and 2002 and compared each of them with 6 patients, matched for age and sex, and drawn from the same practice, which added up to more than 29,500 in all (controls).

The cases were more likely to have had pneumonia before, to have had other serious illness, including a heart attack, depression, and psychotic illness; underlying illnesses; and to be current smokers than those in the comparison group.

The use of benzodiazepines in both groups was assessed, and classified as "current," "recent," or "past." The use of zopiclone, which is not a benzodiazepine, but which acts on the same chemical pathways in the body, was also assessed.

The results showed that benzodiazepines as a class of drug were associated with a significantly higher (54%) risk of contracting pneumonia, after taking account of previous bouts of the infection, smoking status, and other serious and underlying illness. An effect of similar magnitude was found for the use of zopiclone.

Individually, prescriptions for diazepam, lorazepam and temazepam, but not chlordiazepoxide, were all associated with an increased risk of contracting pneumonia.

A second analysis showed that the risk of dying within 30 days of being diagnosed with pneumonia was 22% higher among those taking benzodiazepines. And it was 32% higher within three years of diagnosis.

Diazepam, chlordiazeopoxide, lorezapam and temazapam were all individually associated with the long term risk of death in these patients.

The authors caution that their findings do not definitively prove cause and effect, but they suggest that there may be grounds for further investigation, especially as their findings echo those of clinical trials of sedative doses of benzodiazepines.

"Benzodiazepines and zopiclone are commonly prescribed medications that have significant immune effects," they write. "Given the widespread use of benzodiazepine drugs, further studies are required to evaluate their safety in the context of infection" they conclude.

More information: The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population cohort, Online First, doi 10.1136/thoraxjnl-2012-202374

Provided by British Medical Journal

Over 65s at increased risk of developing dementia with benzodiazepine

Patients over the age of 65 who begin taking benzodiazepine (a popular drug used to treat anxiety and insomnia) are at an approximately 50% increased risk of developing dementia within 15 years compared to never-users, a study published today on BMJ website suggests.

28 sept 2012--The authors say that "considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects indiscriminate widespread use should be cautioned against".

Benzodiazepine is a widely prescribed drug for the over 65s in many countries: 30% of this age group in France, 20% in Canada and Spain, 15% in Australia. Although less widespread in the UK and US it is still very widely used and many individuals take this drug for years despite guidelines suggesting it should be limited to a few weeks. Previous studies have found an increased risk of dementia, but others have been non-conclusive.

Researchers from France therefore carried out a study on 1063 men and women (average age 78) in France who were all free of dementia at the start. The study started in 1987 and follow-up was 20 years. The researchers used the first 5 years to identifying the factors leading to benzodiazepine initiation and evaluated then the association between new use of this drug and the development of dementia. They also assessed the association between further benzodiazepine initiation during the follow-up period and risk of subsequent dementia. Rates were adjusted for many factors potentially affecting dementia, such as age, gender, educational level, marital status, wine consumption, diabetes, high blood pressure, cognitive decline, and depressive symptoms.

95 out of the 1063 patients started taking benzodiazepine during the study. 253 (23.8%) cases of dementia were confirmed, 30 in benzodiazepine users and 223 in non-users. New initiation of the drug was associated with shorter dementia-free survival.

In absolute numbers, the chance of dementia occurring was 4.8 per 100 person years in the exposed group compared to 3.2 per 100 person years in the non-exposed group. A "person year" is a statistical measure representing one person at risk of development of a disease during a period of one year.

The authors say that although benzodiazepine remains useful for treating anxiety and insomnia, there is increasing evidence that its use may induce adverse outcomes in the elderly such as serious falls and fall-related fractures and this study may add dementia to the list. They say that their data add to the accumulating evidence that the use of benzodiazepines is associated with increased risk of dementia and, if true, that this "would constitute a substantial public health concern". Therefore, taken the evidence of potential adverse effects into account, physicians should assess expected benefits, limit prescriptions to a few weeks, and uncontrolled use should be cautioned against. They conclude that further research should "explore whether use of benzodiazepine in those under 65 is also associated with increased risk of dementia and that mechanisms need to be explored explaining the association"

Provided by British Medical Journal