Abrahamsson et al. investigated the relationship between hypnotic drug overdose versus non-overdose deaths in patients on opioid maintenance therapy. They showed that benzodiazepine increased the incidence of non-overdose death in these patients which may be attributed to its impairment of cognition, sensory, and motor skills and increased risk of fall leading to injuries 49. Despite the increase in risk, less than 13% of the non-overdose deaths were trauma related. A study investigating the prescription of opioids and BZD in veterans showed an increased risk of overdose death in veterans who have prescriptions for both BZD and opioids at the same time 50. The dose of BZD given also positively correlated with increased risk of an overdose death 50. Still, due to the severe potential for dependence and deadly withdrawal sequelae, guidelines for recommended use are no longer than a few weeks.

Risk Factors

Due to the discrepancy in the type of cognitive tasks used in the included studies, we could not obtain meta-analyzable data to examine the effects of BZD abuse on specific cognitive functions. Nevertheless, the results of the experiments in these studies were summarized in Table 2. Notably, for language ability, Mura et al. used the Isaacs Set Test to explore the effect of BZD abuse (41), and Ros-Cucurull used the Controlled Oral Word Association Test (47). In the domain of recognition, BZD abusers performed worse than controls in three different tasks in two studies (38, 47).

5. Functional Consequences Associated with Benzodiazepine Misuse.

For example, as previously reported, BZD users had significantly lower processing speeds when tested with the TMT. However, studies measuring processing speed with the coding task or block design task did not reveal any significant findings. The most common type of benzodiazepine misuse overall was use without a prescription, though this type of misuse use was less likely to be endorsed by respondents ≥50. Relative to younger adults, older respondents were more likely to report using their benzodiazepine more often than prescribed. Under “Adults overall”, a characteristic row presents the prevalence of as-prescribed or misuse within that stratum (e.g., 5.2% of adults reported misuse).

5. Issues with Clinical Use of Benzodiazepine

• Given the lack of consensus in the current literature, a meta-analysis study may help reveal the critical effects of BZD use in the elderly and identify areas that require further research.
• Future studies evaluating motives for benzodiazepine misuse among other vulnerable populations, including those with psychiatric disorders and benzodiazepine prescriptions, are needed to understand the relationship between motives and benzodiazepine misuse incidence and severity.
• Given their widespread use, abuse potential (23), and related risks, surprisingly little is known about benzodiazepine misuse.
• Benzodiazepine abuse is common in those on methadone maintenance treatment (MMT), so special consideration must be taken for those withdrawing from the drugs while on MMT 68.

Indeed, studies of people with AUD in treatment demonstrate even higher rates, with estimates of recent benzodiazepine misuse (self-reported past-month use or urine drug screen results) ranging from 19–40% (McHugh et al., 2018; Morel et al., 2016; Ogborne and Kapur, 1987; Ross, 1993). Although benzodiazepines are invaluable in the treatment of anxiety disorders, they have some potential for abuse and may cause dependence or addiction. It is important to distinguish between addiction to and normal physical dependence on benzodiazepines. Benzodiazepines are usually a secondary drug of abuse-used mainly to augment the high received from another drug or to offset the adverse effects of other drugs. Pharmacologic dependence, a predictable and natural adaptation of a body system long accustomed to the presence of a drug, may occur in patients taking therapeutic doses of benzodiazepines.

Source of benzodiazepines among adult misusers

Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States. Although prevalence estimates for misuse of specific benzodiazepine formulations appear to coincide with prescribing rates, certain benzodiazepines are more preferred than others, potentially reflecting higher abuse liability.

1. Overview of Findings and Implications

Most notably, benzodiazepine-related overdose deaths increased by more than 400% from 1996–2013 (Bachhuber et al., 2016) and emergency department visits for benzodiazepines increased by more than 300% from 2004 to 2011 (Jones and McAninch, 2015). These increases have occurred concurrently with rising rates of benzodiazepine prescribing. The number of benzodiazepine prescriptions not only increased 67% from the mid-1990s to 2013, but the quantity (i.e., dose equivalents) increased more than 3-fold over this time period (Bachhuber et al., 2016). The proportion of people with an opioid analgesic prescription who were also prescribed a benzodiazepine increased 41% from 2002 to 2014 (Hwang et al., 2016), despite evidence that concomitant opioid and benzodiazepine prescriptions increase risk of overdose (Sun et al., 2017).

• Most would agree that tolerance is a multifactorial process that occurs at different rates for different patients, and also depends on the profile of the benzodiazepine used.
• In the study by Yen et al (7), 28.8% of participants aged over 65 reported dependence, and 7.9% reported inappropriate use of benzodiazepine hypnotics.
• Two articles (34, 35) were from the same cohort study named The Canadian Study of Health and Aging (36).
• Prescribing benzodiazepines has been controversial due to the recognized deleterious effects of long-term treatment with these drugs.

However, with this ongoing, widespread use comes the dark reality of BZD dependence 6. The aim of this comprehensive review was to characterize the current state of the science on the epidemiology of benzodiazepine misuse. It is important to note that currently available quantitative measures of motives for benzodiazepine misuse focus on a limited range of motives and the factor structure for these measures is unclear (Messina et al., 2016; Vogel et al., 2013). Nonetheless, several qualitative studies provide a broader picture of the motives for benzodiazepine misuse.

TABLE 2: .

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Most developed countries have consistent data of benzodiazepine sales and consumption; however, data from developing countries is scarce, making health policies on the use of benzodiazepines a much tougher issue in these countries. This article aims to review the epidemiology of benzodiazepine use in Brazil, as well as to analyze how legislation, physician misinformation and economic factors might contribute to making benzodiazepine abuse a problem in the country. In conclusion, this meta-analysis indicated no significant global cognition deficit (MMSE scores) in BZD users, but did reveal deficits benzodiazepine use, misuse, and abuse: a review in elders with BZD abuse behaviors. BZD users performed significantly worse in the cognition domain of processing speed (digit symbol test scores) than the controls, but not in memory and learning (AVLT scores) or inhibitory control (SCWT scores).

Their relative safety compared to fellow depressants or barbiturates have increased the rate at which they are prescribed 25. The dependence on BZDs generally leads to withdrawal symptoms, which necessitates careful tapering of the medication when prescribed 26. Research has identified numerous risk factors, motives, consequences, and common patterns of benzodiazepine misuse. With the continued escalation of treatment admissions and overdose deaths related to benzodiazepine misuse, studies designed to better understand this growing public health problem should be a research priority for the field of substance use disorder research. Little is known about benzodiazepine misuse in older adults, despite high rates of prescribing in this group (Maust et al., 2018; Schepis et al., 2018b). Rates of tranquilizer and sedative misuse are lower in adults over the age of 50, as compared to younger age groups (Maust et al., 2018; Schepis et al., 2018b), and are lower than rates of prescription opioid misuse in this age group (Blazer and Wu, 2009).