Withdrawal occurs as the BZD concentration in blood and tissue declines, generally causing symptoms opposite to that of the drug’s therapeutic effects. Psychological symptoms include increased excitability, nightmares, anxiety, insomnia, panic attacks, depression, hallucinations, irritability, paranoid thoughts, social phobia, poor memory, poor concentration, delirium, and even psychosis. These symptoms may last for one to a few weeks after cessation, with duration and severity largely depending upon the amount of time spent chronically taking the BZD, the half-life of the specific BZD, and the daily dose consumed 26.
In 2018, Picton and colleagues summarized the cognitive effects of BZD in the elderly from published evidence. They found mixed findings of the association between BZD therapy and cognitive decline in elderly users (25). 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. To our knowledge, there are no systematic reviews with a meta-analysis that summarizes the current status of the cognitive effect of BZD use and abuse in the elderly population. This qualitative study was part of a larger project exploring patients’ experiences and perceptions of benzodiazepine use and addiction treatment that included 19 individual interviews completed in 2023 at a specialized outpatient addiction clinic in Stockholm 23. Non-Swedish speakers and individuals also in treatment for opioid use disorder were excluded.
5. Treatment for Benzodiazepine Withdrawal
The study found no significant cognitive impairment in adults with long-term use of BZD 20. A study of over 2000 older adults assessed the effects of chronic BZD use on cognition 21. Chronic use of BZD leads to a small but significant change in fluid intelligence, while long-term use of BZD correlates with worse cognitive decline when compared to the effects of using a high dosage 21.
Benzodiazepine Use and Cognitive Decline in the Elders
In Ireland, it has been reported that 92% of overdoses where methadone was implicated and 81% of deaths where heroin was implicated involved benzodiazepines predominantly 47. In France, because of social isolation or psychological troubles due to lockdown with the potential increase of marital conflicts and domestic violence, there was a prediction for increased consumption of benzodiazepines 50. Further data collection by the French addictovigilance centers, pharmacies, and addiction specialized centers revealed abuse or misuse with alcohol or other psychoactive substances.
1. The Effects of Benzodiazepine on Cognition
Alprazolam, lorazepam and clonazepam are high potently clinically used to treat panic disorders and serve as adjuncts for treating many other diseases 1. Due to their toxic effect on the central nervous system, appropriate care is necessary with BZD. BZDs lead to long-lasting impairment of episodic implicit memory while it only impairs implicit memory transiently 1. They also lead to disinhibition, impairing the user’s ability to appropriately assess the risky actions or behaviors. Other important indications for the use of BZDs include the treatment of catatonia, seizure disorders, benzodiazepine use, misuse, and abuse: a review and alcohol and BZD withdrawal. The drug class is the mainstay of treatment for catatonia, which is characterized by postural rigidity, immobility, purposeless activity, and disturbances in one’s consciousness 10.
Associated Data
- Available data from countries outside of the U.S. suggest that rates of misuse are similar to those reported in the U.S.
- Prevalence rates for past-year tranquilizer misuse were nearly identical to those reported for cocaine use.
- SAMHSA requires that any description of overall sample sizes based on the restricted-use data files be rounded to the nearest 100, which intends to minimize potential disclosure risk.
Benzodiazepine abuse rates among the elderly were as high as 58.6% in those over 61 (19). El Zahran et al (19) reported a slightly lower rate of 47.8% for abuse or inappropriate medication use among the elderly aged 66 and above. Similarly, Díaz-Gutiérrez et al (20) found that 40.6% of older adults consumed a daily dose that was higher than the defined or recommended, and Niznik et al (21) reported 47.2% chronic use of benzodiazepines in individuals aged 70 to 79. In the latter study, the rate of benzodiazepine abuse in the age groups of years, years, and 90+ years was 29.6%, 20.5%, and 2.6%, respectively. On the other hand, Schepis et al (22) documented a slightly lower use of sedatives for purposes other than treatment, namely 17.3%, in individuals aged over 65.
BZDs act by binding to the gamma-aminobutyric acid A (GABA-A) 17 receptors in the brain, inhibiting the brainstem arousal pathways. When BZDs interact with GABA-A receptors, ion channels open more frequently, increasing the inflow of chloride ions which increases membrane polarization and inhibits neuron firing resulting in central nervous system (CNS) depression 15. This mechanism results in anxiolytic, sedative, hypnotic, anticonvulsant and skeletal muscle-relaxing effects. Regular use of BZDs has been shown to cause serious, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal.
- A drug test can detect the presence of most benzodiazepines or their metabolites (substances produced when the drugs break down in your body).
- 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).
- This review therefore aims to present our current knowledge of benzodiazepine use and misuse, with an emphasis on alprazolam when data is available, and particularly in populations at higher risk for developing substance use disorders.
- Interestingly, a lower prevalence of withdrawal symptoms was noted in the experimental group without any change in pharmacologic treatment from control group 73.
Benzodiazepines also amplify the effects of opioids and, consequently, have been implicated in approximately 30 % of opioid overdose deaths. Despite their unfavorable profile, sharp increases in medical and non-medical use of benzodiazepines have been steadily reported worldwide. Alprazolam (Xanax®), a potent, short-acting benzodiazepine, is among the most prescribed and abused anxiolytics in the United States. This medication is commonly co-abused with opioids, increasing the likelihood for oversedation, overdose, and death.
The final eight articles were deemed suitable to be included for the conciseness of this review. Due to its short half-life, and rapid absorption, alprazolam is distinguished as one of the most rapid-acting BZD with fastest relief of symptomology, increasing its abuse liability 54. Alprazolam is widely used as monotherapy for panic disorder and anxiety and was found superior to other forms of monotherapy for these conditions including other BZD, non-SSRI antidepressants, and buspirone. This superior effect is thought to be due to its unique alpha-2 adrenergic activity, enhancing its potency for relieving panic and anxiety disorders. This same mechanism is also thought to be the cause behind alprazolam’s strong rebound hyperadrenergic effects with cessation 54,55.
This is more significant than the study by Weich et al. 47 which found a 2-fold increased hazard of death in 7 years. It was also reported that the risk of death in patients using less than 18 pills per year is increased by 3.6-fold 48. Many studies have examined the effects of benzodiazepines on cognition with varied results. Some of the variations in results may be attributed to cognitive criteria in which each study followed. In a prospective longitudinal study on the effects of psychotropic drugs in the cognition of the elderly, Allard et al. 19 found no significant long-term effect of BZD use on cognition. This is supported in a similar study of elderly adults on a BZD for six months with drug discontinuation one month later.