Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal.

Benzodiazepines (BZD) are two-ring heterocyclic compounds consisting of a benzene ring fused with a diazepine ring. Since its discovery in the 1950s, BZD’s sedative, hypnotic, anti-anxiety, and anti-convulsive effects have been increasingly accepted, making BZD use highly prevalent among adults (1) and especially in the elders (2). For example, BZD and related drugs are the third most abused prescription drug in America, with roughly 1-3% of the world population being subject to abuse (4). However, inappropriate BZD prescriptions can promote BZD misuse, facilitate the development of BZD addiction, and significantly affect the users’ overall quality of life (5, 6). Therefore, it is critical for pharmacists, clinicians, and patients to be informed on the latest research regarding the adverse effects of BZD use and abuse.

Data availability

• Benzodiazepine (BZD) abuse has reached epidemic levels and results in poor outcomes, particularly when combined with concomitant central nervous system depressants.
• They found mixed findings of the association between BZD therapy and cognitive decline in elderly users (25).
• 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.
• Additionally, given the continual rise of anxiety and sleep-disordered problems over the decades, BZDs remain a regular fixture in the United States today 7.
• Although limited, data indicate that over 20% of adolescents and adults with a benzodiazepine prescription have diverted their medications (Boyd et al., 2007; McCabe et al., 2011b; McLarnon et al., 2011).

Descriptions of studies performed on specific treatments of benzodiazepine dependence and withdrawal symptoms. In 2018, between 8.3% and 12.8% of BZD users in Switzerland have prescriptions from multiple physicians which resulted in the inability to track the number of prescriptions a patient is given yearly 40. In a survey of British general practitioners, many reported pressures in prescribing BZD to patients and a lack of adequate knowledge on alternative psychological treatment for insomnia 41. Some people who are prescribed benzodiazepines become dependent on them and end up misusing them. Doctors recommend waiting until all benzodiazepines pass out of your system before you drink alcohol. That could take up to 20 hours for shorter-acting drugs like alprazolam (Xanax) and lorazepam (Ativan, Loreev).

1. Overview of Findings and Implications

The mentioned studies revealed that the majority of participants were taking one type of benzodiazepine or benzodiazepine-related medication, while some were taking two or even three. There are also encouraging case reports and case series with the use of other antiseizure medications to help alleviate symptoms of benzodiazepine withdrawal. There are 3 case reports suggesting that valproate may be benzodiazepine use, misuse, and abuse: a review effective for the treatment of sedative-hypnotic withdrawal, but a double-blind, placebo-controlled study failed to replicate the results (Rickels et al., 1999). The included studies utilized a variety of psychometric measurements, rendering it challenging to produce generalizable and informative conclusions. In this paper, we organize cognitive domains based on a commonly used framework (29, 30).

Systematic Review Protocol

They found that the hazard of death was doubled in patients prescribed BZD compared to control patients 47. There was an association between the prescription of anxiolytic drugs and mortality, resulting in 4 excess deaths in the anxiolytic drug group within an average of 7.6 years 47. They found a 35% increased chance of developing a new non-melanoma cancer in users of hypnotics 48. In agreeing with some of the studies above, there was also a 4.6-fold increase in the hazard of death in patients on hypnotics over 2.5 years 48.

Main Findings of BZD Abuse

Interestingly, those who used alcohol while taking BZD experienced no difference in discontinuation rate from those who did not use alcohol 64. People with psychiatric symptoms and disorders also appear to be more vulnerable to benzodiazepine misuse. This is consistent with findings that regulating negative affective and somatic states is the most common motive for benzodiazepine misuse. Yet, it is unclear if psychiatric distress is an antecedent or consequence of benzodiazepine misuse (or both), and findings from the reviewed studies provide partial support for both explanations.

Main Findings of BZD Use

• The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations.
• Interestingly, studies with young adults showed opposing results (51, 52), suggesting BZD use significantly impairs participants’ global cognitive functioning.
• Effort on this manuscript was supported by NIDA grant K23 DA and the Sarles Young Investigator Award (Dr. McHugh).
• Overview of tasks used to assess cognitive functioning in benzodiazepine users across different cognitive domains.

Interestingly, despite ICU care and administration of beta-blockers and alpha-blockers, the pseudo-pheochromocytoma was only successfully treated by alprazolam re-instatement (Orzack et al., 1988). Alprazolam is a high-potency triazolobenzodiazepine that is US Food and Drug Administration (FDA)-approved for the treatment of anxiety and panic disorders. Alprazolam is biotransformed by hepatic microsomal oxidation, yielding 4 and α-hydroxyalprazolam as its principal metabolites, and is metabolized by cytochrome P450 (CYP) 3A4 (Greenblatt and Wright, 1993). Another important finding in this study is that the results of cognitive performance are highly dependent on the type of cognitive measurements in the study.

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.

Prevalence of benzodiazepine use, misuse, and use disorders among U.S. adults

Under “benzodiazepine users overall”, a row presents the proportion of benzodiazepine use within that stratum that is as-prescribed or misuse (e.g., among adults 18-25, 51.0% benzodiazepine use reported is misuse). Respondents could report benzodiazepine use through survey queries regarding tranquilizer or sedative use. NSDUH classifies tranquilizers as medications specifically for relief of anxiety or muscle spasms and sedatives as those for insomnia. This analysis is limited to the 10,290 respondents who specifically reported benzodiazepine use in response to the tranquilizer and sedative items (see online Appendix for additional detail). Against the backdrop of the gradual adoption of new guidelines for prescribing benzodiazepines, it is important to emphasize that long-term users are particularly at risk—both of having received insufficient information in the past and of developing addiction due to prolonged use. Although addiction guidelines offer recommendations for tapering 38, this process requires prescribers to first assess and diagnose patients, and secondly, to have the necessary resources to support patients throughout tapering.

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).