Effects Of Benzodiazepine Use Research Articles

The Effect of Preoperative Benzodiazepine Usage on Postoperative Opioid Consumption After Hand Surgery: A Multicenter Analysis.

Background Prescription rates of opioids and benzodiazepines have steadily increased in the last decadewith the percentage of prescription opioid overdose deaths involving benzodiazepines more than doubling during that time. Orthopaedic surgery is one of the highest-volume opioid prescribing medical specialties, but the effects of benzodiazepine use on orthopaedic surgery patient outcomes are not well understood. The purpose of the study was to utilize the state Prescription Drug Monitoring Program (PDMP) database to investigate if perioperative benzodiazepine use predisposes patients to prolonged opioid use following hand and upper extremity orthopaedic surgery. Methods This study was retrospective and conducted at three urban academic institutions. All patients who underwent carpal tunnel release, thumb basal joint arthroplasty, and distal radius fracture open reduction internal fixation performed by 14 board-certified, fellowship-trained orthopaedic hand and upper extremity surgeons between April 2018 and August 2019, were collected via a database query. All opioid and benzodiazepine prescriptions were collected from three months preoperatively to six months postoperatively. Results In this study, 634 patients met the inclusion criteria presented to one of the three institutions during the 18-month study period. Patients consisted of 276 carpal tunnel releases, 217 distal radius fracture open reduction internal fixations, and 141 thumb basal joint arthroplasties. Benzodiazepine users were 14.6% more likely to fill an additional opioid prescription (p<0.005) and were 10.8% more likely to experience prolonged three to six-month postoperative opioid use (p<0.005). Conclusion This study found that patients who use benzodiazepines are at a higher risk of filling additional opioid prescriptions and prolonged opioid use following hand and upper extremity surgery. Prescribers should take this into account when prescribing opioids after upper extremity orthopaedic surgery.

0392 The Effect of Benzodiazepine Use on Non-REM Sleep Instability in Community-Dwelling Older Men

Abstract Introduction Previous studies on the implications of benzodiazepine (BZD), a widely prescribed pharmacotherapeutic treatment method for sleep insomnia, on sleep architecture demonstrated significantly reduced EEG activity in low-frequency bands. In this study, we explore the effect of BZD on NREM sleep instability also known as cyclic alternating pattern (CAP) in community-dwelling older men. Methods CAP was scored in overnight EEG recordings from 30 older men on long-acting BZD (LBZD), 35 older men on short-acting BZD (SBZD), and 50 age-matched men who did not use BZD (NBZD), participating in the Osteoporotic Fractures in Men Sleep Study (MrOS sleep). A high performance automated detection system determined the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). The relationship between CAP parameters and BZD use was determined using the Kruskal-Wallis test by ranks with Bonferroni correction for post-hoc analysis. Results CAP rate was significantly decreased in older men using long-acting BZD (NBZD: 59.6±18.0%, LBZD: 46.9±13.1%, SBZD: 53.0±20.1%) as compared to non-BZD user (p &amp;lt; 0.01). All BZD users demonstrated significantly lower frequencies of A1-phases (NBZD: 19.9±23.0 no./h, LBZD: 6.9±13.3 no./h, SBZD: 4.5±9.9 no./h) as compared to non-BZD users (LBZD: p &amp;lt; 0.01, SBZD: p &amp;lt; 0.001). The A2+A3 index did not show any variations between the three groups. Conclusion Older men using long-acting BZD demonstrate a significantly reduced CAP rate during sleep, particularly less frequent A1-phases, compared to the control group. Moreover, short-acting BZD user show significantly less frequent A1-phases but no difference in CAP rate and A2+A3-phases than older men using no BZD. Hence, BZD usage has a major adverse effect on the occurrence of EEG slow waves. Support The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

Effects of benzodiazepine use in chronic insomnia on cognitive function and EEG

Effects of benzodiazepine use in chronic insomnia on cognitive function and EEG

Authors’ Reply

We thank Weinhandl1 for his comments regarding our analyses using the US Renal Data System of the association between gabapentin and pregabalin use and adverse outcomes among patients on hemodialysis.2 We acknowledge that we were limited in our ability to reliably capture benzodiazepine exposure with our available data, because benzodiazepines were not covered by Medicare Part D until 2013.3–5 Using more recent data from 2013, among a comparable cohort of 162,965 adult Medicare-covered patients on chronic hemodialysis with continuous Part D coverage during 2013, we found that the prevalence rates of gabapentin, pregabalin, and benzodiazepine use were 21% (n=33,900), 4% (n=7102), and 23% (n=37,112), respectively. The prevalence of benzodiazepine use is within the range that has been reported in prior studies involving patients on hemodialysis.6 Overall, the prevalence of concomitant use (defined as at least one instance of overlapping prescriptions in 2013) of gabapentin and benzodiazepine was 5.5% (n=8907), with a median overlap duration of 62 days (25th interquartile range, 28–152 days). Twenty-six percent of gabapentin users had concomitant benzodiazepine use, and 22% of gabapentin nonusers had concomitant benzodiazepine use. The prevalence of concomitant use of pregabalin and benzodiazepine was 1.3% (n=2054), with a median overlap duration of 57 days (interquartile range, 26–137 days). Twenty-nine percent of pregabalin users had concomitant benzodiazepine use, and 22% of pregabalin nonusers had concomitant benzodiazepine use. Gabapentin and pregabalin use had virtually no association with benzodiazepine use on the basis of the point-biserial correlation (Table 1). The point-biserial correlation is mathematically equivalent to the Pearson correlation and can be interpreted on the same scale (0–0.5 is weak, 0.5–0.8 is moderate, and 0.8–1 is strong). Although Pearson correlations are not usually used for binary variables, such as medication exposure, they are, in fact, what a regression program uses to adjust one predictor for another one with a correlation of zero, indicating no adjustment. Table 1. - Association between gabapentin and pregabalin use with benzodiazepine use Benzodiazepine Users (n=37,112), n (%) Benzodiazepine Nonusers (n=125,853), n (%) Correlation a Gabapentin users, n=33,900 8907 (26) 24,993 (74) 0.04 Gabapentin nonusers, n=129,065 28,205 (22) 100,860 (78) Pregabalin users, n=7102 2054 (29) 5048 (71) 0.03 Pregabalin nonusers, n=155,863 35,058 (22) 120,805 (78) aPoint-biserial correlation. Correspondingly, the effect of benzodiazepine use on event rates would need to be massive to explain away the gabapentin or pregabalin associations. Thus, confounding by concomitant benzodiazepine use was unlikely to have had a large effect on our results. The letter of Weinhandl1 also mentions the possibility of unmeasured confounding by opioid use, and we would like to note that we adjusted for concomitant use of opioids in our analyses. We appreciate the interest in our research, and thank you for the opportunity to elaborate on our methodology. Disclosures None.

Obstetrical and neonatal outcomes after benzodiazepine exposure during pregnancy: Results from a prospective registry of women with psychiatric disorders.

The goal of this analysis was to examine the effect of benzodiazepine use during pregnancy on maternal and neonatal outcomes in a cohort of women with psychiatric disorders. 794 evaluable women from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications were followed across pregnancy (N = 144 exposed to benzodiazepines and N = 650 unexposed). Data obtained through maternal report and medical records included maternal outcomes (cesarean section, preeclampsia) and neonatal outcomes (birth weight, breathing difficulty, feeding difficulty, head circumference, 5-minute Apgar score, muscular and/or extrapyramidal symptoms, NICU admission, prematurity). In adjusted analyses, infants exposed to benzodiazepines in utero were more likely to be admitted to the NICU (OR: 2.02, 95% CI: 1.11, 3.66) and to have small head circumferences (OR: 3.89, 95% CI: 1.25, 12.03) compared to unexposed infants. Other neonatal adverse effects such as respiratory distress or muscular symptoms including hypotonia were not observed. There were no significant differences in adverse obstetrical outcomes. Infants exposed to benzodiazepines during pregnancy had an increased risk of NICU admissions and small head circumferences. Confounding from psychiatric symptoms and other variables cannot be ruled out as contributors to these findings.

Benzodiazepine use and cognitive decline in the elderly.

Published evidence on the relationship between benzodiazepine exposure and altered cognition in the geriatric population is reviewed. Benzodiazepines constitute one of the most commonly prescribed medication classes and are used primarily for management of anxiety and insomnia. Despite strong recommendations based on high-quality evidence warning of the potential cognitive adverse effects of benzodiazepine use, particularly in patients 65 years of age or older, published literature suggests that a substantial proportion of the U.S. geriatric population use these medications in a chronic fashion. The body of evidence suggesting that benzodiazepine use may be a modifiable risk factor for dementia continues to grow. Evidence exists to suggest that benzodiazepine use in the elderly population is associated with cognitive decline, dementia, and Alzheimer's disease, although evidence regarding the correlation between benzodiazepine use and dementia is conflicting; the more recent studies in this area have focused on eliminating causation bias. Pharmacists in a variety of settings can educate patients and assist providers in selecting an appropriate medication regimen for anxiety or insomnia that is tailored to each elderly patient's needs and takes into account the immediate and long-term safety of the patient. Investigations of the association between benzodiazepine therapy and cognitive decline in elderly patients have yielded mixed findings. Stronger links have emerged from studies examining longer- rather than shorter-acting benzodiazepines, longer rather than shorter durations of use, or earlier rather than later exposure. Questions remain about causality and the impact of confounders on study interpretation.

The Residual Medium and Long-term Cognitive Effects of Benzodiazepine Use: An Updated Meta-analysis.

This study presents an updated meta-analysis of the effects of benzodiazepines on cognitive functioning in long-term, current users of these agents, those who have recently withdrawn and on those who have successfully abstained following withdrawal. The study represents an update of the previous meta-analyses published by our group. A comprehensive search of the computerized databases Medline and PsycINFO was undertaken to identify studies that assessed the cognitive effects of benzodiazepines published up to 28 November 2016 (the date of the last update). Nineteen studies (eight studies published since the previous meta-analyses and 11 studies included in the previous studies) were included. The results of the analysis for current users revealed statistically significant, negative effects for the cognitive domains of working memory, processing speed, divided attention, visuoconstruction, recent memory, and expressive language. For those who had withdrawn and successfully abstained following withdrawal, deficits were observed for the domains of recent memory, processing speed, visuoconstruction, divided attention, working memory, and sustained attention. The results of the study are important in that they corroborate the mounting evidence that a range of neuropsychological functions are impaired as a result of long-term benzodiazepine use, and that these are likely to persist even following withdrawal. The findings highlight the residual neurocognitive compromise associated with long-term benzodiazepine therapy as well as the important clinical implications of these results.

Benzodiazepines and risk for hepatic encephalopathy in patients with cirrhosis and ascites.

There is limited evidence to support the belief that benzodiazepines increase cirrhosis patients' risk of hepatic encephalopathy (HE). We aimed to examine the association between benzodiazepine use and HE development in cirrhosis patients. We used data on 865 cirrhosis patients with ascites from three trials to study the effect of benzodiazepine use on development of first-time HE. For each patient, we classified periods of benzodiazepine use by the number of days since initiation. We used Cox regression to compare the risk of HE in current benzodiazepine users vs. non-users adjusting for confounders. Cirrhosis patients were not at increased risk of HE for the first two days of benzodiazepine use, but then faced a five-fold increased risk of HE during days 3 to 10 of benzodiazepine use. The risk of HE was not increased for those who had been using benzodiazepines for more than 28 days. Cirrhosis patients who had begun using benzodiazepines between 3 and 10 days previously had a markedly increased risk of developing first-time HE. Cirrhosis patients who had been using benzodiazepines for just one or two days or continued use for more than 28 days did not have such an excess risk.

The Impact of Benzodiazepine Use on Mortality Among Polysubstance Users in Vancouver, Canada.

Illicit drug use is a well-established risk factor for increased morbidity and mortality. However, little is known about the impact of benzodiazepine use on mortality among populations of polysubstance users. This study aimed to identify the effect of benzodiazepine use on mortality among a prospective cohort of people in Canada who inject drugs (PWID). A cohort of PWID in Vancouver, Canada, was prospectively followed from May 1996 through November 2013. Data on participants were linked to the provincial vital statistics registry to ascertain mortality rates and causes of death. Multivariable extended Cox regression with time-dependent variables was used to investigate the relationship between benzodiazepine use and time to all-cause mortality. During the study period, 2,802 participants were followed for a median of 67 months (interquartile range: 25-107). In total, 527 (18.8%) participants died, for an incidence density of mortality of 2.9 (95% confidence interval [CI] 2.7, 3.2) deaths per 100 person-years. After adjusting for HIV infection and other potential confounders, benzodiazepine use was independently associated with increased all-cause mortality (adjusted hazard ratio = 1.86, 95% CI 1.38, 2.51) and had a higher risk for mortality than all other traditional substances of abuse among this population. Results were consistent when non-overdose mortality was considered. In this setting, benzodiazepine use was more strongly associated with mortality than any other substance of abuse. Greater recognition of the safety concerns related to benzodiazepines and strategies to prevent diversion to illicit use are needed.

Commentary on Raitasalo et al. (2015): the great potential in nation-wide registers to study prescription drug use and abuse.

In their paper, Raitasalo et al. 1 identify mothers who are at greater risk for benzodiazepine use; namely, those with substance use problems and psychiatric problems. A second important finding is that the use of benzodiazepines was lowest during pregnancy for all groups, followed by a sharp increase during the years after the children were born. While, from our perspective, the study is important in several ways, this commentary can address only a few of these. One point is that information about the use of addictive prescription drugs among women of childbearing age is scarce; there is a lack of information on both the effect of benzodiazepine use during pregnancy and the effect that maternal use may have on the children. Observational studies using data from prescription registries are therefore an appropriate approach to map the prevalence of benzodiazepine use, as well as the use of other prescription drugs such as z-hypnotics and opioids. By studying any benzodiazepine use, Raitasalo et al.’s study captures the full spectrum of use. Some studies have shown that the misuse of benzodiazepines is associated with several negative risk factors and behaviours 2, 3. While less is known about the consequences of the therapeutic use of benzodiazepines, a recent study refuted any strong association between prenatal therapeutic use of benzodiazepines and lower language competence in offspring at age 3 years 4. This study adds the important knowledge that many female benzodiazepine users of childbearing age belong to groups with other risk factors, such as substance abuse, psychiatric disease or poverty. Thus, Raitasalo et al. show that benzodiazepine use is another factor that might be important in identifying ‘at-risk’ families. In order to identify families that should be offered additional follow-up as a preventive measure, it is therefore important to also include questions about addictive prescription drug use. When clinicians receive a positive response to questions on the use of such prescription drugs there is reason to ask follow-up questions, as they would for a positive response to questions on drinking or depression. Benzodiazepine users are often co-medicated with other prescription drugs, such as other hypnotics and opioids 4-8. As co-occurring use is common, this might suggest that mothers who use hypnotics or opioids should receive the same attention from clinicians trying to identify at-risk families as do mothers using benzodiazepines. Further studies on the effects of various patterns of benzodiazepine use in different life periods are warranted. Raitasalo et al. point out that previous research is inconsistent with regard to whether or not in-utero exposure to benzodiazepines increases the risk of negative birth outcomes 1, 9-11. Clearly, this should be given further attention. While randomized controlled trials are the gold standard with which to study outcomes from prescription drug use, pregnant women are often excluded from clinical trials. The large, prospective observational data available in nation-wide registers may therefore be the most effective way to investigate possible teratogenic effects from prescription drugs 12. The sharp increase in benzodiazepine use during the years after childbirth is cause for concern, as parental prescription drug use is associated with prescription drug use in their children as adults 13. For instance, repeated use of both benzodiazepines and opioids among mothers is associated with the increased risk that their children also become repeated users of benzodiazepines and opioids, respectively 14. The study by Raitasalo et al. 1 underscores some of the opportunities offered by nation-wide registers. One advantage is the inclusion of whole populations; a second advantage is that registry data allow for large samples, well suited to study rare outcomes: for instance, short- and long-term outcomes in children exposed to benzodiazepines in utero. A third advantage is that when personal identification numbers are assigned to all residents, such as in Nordic countries, this enables the matching of person-level data from several registers. This allows for controlling for important confounding variables such as education, employment and marital status, children, mental and physical health, and allows for data matching for parents and children. Another advantage is that as the registers are established and in use and data are available, they represent a relatively cost- and time-effective way of conducting large-scale prospective studies. Registry studies such as the one by Raitasalo and colleagues are important, because they provide both a complete description of drug use that might be problematic and needing further research attention, and as a background from which to enable clinicians to identify families at risk of different factors and behaviours. None.

Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or quetiapine-treated outpatients with bipolar I or II disorder: Results from the Bipolar CHOICE trial

BackgroundLittle is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders. MethodsThe study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-based treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up. Selected outcomes were also compared between patients who did and did not initiate benzodiazepines during follow-up using stabilized inverse probability weighted analyses. ResultsSignificant improvement in all outcome measures occurred within each benzodiazepine exposure group. Benzodiazepine users (at baseline or during follow-up) experienced significantly less improvement in BISS total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users. There were no significant differences in these measures between patients who did and did not initiate benzodiazepines during follow-up in the weighted analyses. There was no significant effect of benzodiazepine use on any outcome measure in patients with comorbid anxiety or substance use disorders. LimitationsThis is a secondary analysis of data from a randomized effectiveness trial that was not designed to address differential treatment response according to benzodiazepine use. ConclusionsAdjunctive benzodiazepines may not significantly affect clinical outcome in lithium- or quetiapine-treated patients with bipolar I or II disorder over 6 months, after controlling for potential confounding factors.

Commentary on “Benzodiazepine use possibly increases cancer risk: A population-based retrospective cohort study in Taiwan.” Kao CH, Sun LM, Su KP, Chang SN, Sung FC, Muo CH, Liang JA, Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.: J Clin Psychiatry 2012;73(4):e555–e60

To evaluate the possible association between benzodiazepine use and subsequent cancer risk in Taiwan. In this population-based retrospective cohort study, we used data from 1996 to 2000 obtained from the Taiwanese National Health Insurance system to investigate the possible association between benzodiazepine use and cancer risk. The exposure cohort (mean age = 47.9 years, standard deviation = 17.3 years) consisted of 59,647 patients using benzodiazepine. Each patient from the exposure cohort was randomly frequency matched by age and sex to a person from the cohort with no benzodiazepine exposure (the comparison group; mean age = 46.4 years, standard deviation = 17.8 years). Each study subject was followed until a diagnosis of cancer was made (according to the International Classification of Diseases Ninth Revision Clinical Modification) or until the time the subject was censored for loss to follow-up, death, or termination of insurance, or to the end of 2009. A Cox proportional hazard regression analysis was conducted to estimate the effects of benzodiazepine use on cancer risk. In the group with benzodiazepine use, the overall risk of developing cancer was 19% higher than in the group without benzodiazepine exposure, and the difference between the groups was statistically significant (hazard ratio [HR] = 1.19; 99.6% confidence interval [CI], 1.08-1.32). With regard to individual types of cancer, the risks of developing liver cancer (HR = 1.45; 99.6% CI, 1.10-1.90), prostate cancer (HR = 1.72; 99.6% CI, 1.10-2.70), and bladder and kidney cancer (HR = 1.76; 99.6% CI, 1.16-2.67) were significantly higher for the benzodiazepine cohort. This population-based study has shed light on a possible relationship between benzodiazepine use and increased cancer risk. Further large, thorough investigations are needed to confirm these findings.

Benzodiazepine Use Possibly Increases Cancer Risk

To evaluate the possible association between benzodiazepine use and subsequent cancer risk in Taiwan. In this population-based retrospective cohort study, we used data from 1996 to 2000 from the Taiwanese National Health Insurance system to investigate the possible association between benzodiazepine use and cancer risk. The exposure cohort (mean age = 47.9 years, standard deviation [SD] = 17.3 years) consisted of 59,647 patients with benzodiazepine use. Each patient from the exposure cohort was randomly frequency-matched by age and sex to a person from the cohort with no benzodiazepine exposure (the comparison group; mean age = 46.4 years, SD = 17.8 years). Each study subject was followed until a diagnosis of cancer was made (according to ICD-9-CM) or until the time the subject was censored for loss to follow-up, death, or termination of insurance-or to the end of 2009. A Cox proportional hazard regression analysis was conducted to estimate the effects of benzodiazepine use on cancer risk. In the group with benzodiazepine use, the overall risk of developing cancer was 19% higher than in the group without benzodiazepine exposure, and the difference between the groups was statistically significant (hazard ratio [HR] = 1.19; 99.6% CI, 1.08-1.32). With regard to individual types of cancer, the risk of developing liver cancer (HR = 1.45; 99.6% CI, 1.10-1.90), prostate cancer (HR = 1.72; 99.6% CI, 1.10-2.70), and bladder and kidney cancer (HR = 1.76; 99.6% CI, 1.16-2.67) was significantly higher for the benzodiazepine cohort. This population-based study has shed light on a possible relationship between benzodiazepine use and increased cancer risk. Further large, thorough investigations are needed to confirm these findings.

Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS)

BackgroundBenzodiazepine use is widespread in older people, although its benefit is uncertain.AimTo investigate the long-term effect of benzodiazepine use upon dementia risk.MethodsA prospective cohort of men seen on five occasions...

Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors

Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors

The effect of chronic benzodiazepine use on cognitive functioning in older persons: good, bad or indifferent?

This study investigates the effects of benzodiazepine (BZ) use on cognitive performance in elderly persons in a longitudinal design. Data were obtained from the Longitudinal Aging Study Amsterdam (LASA), in the Netherlands. 2,105 respondents (>/=62 years of age) were included and had repeated measurements over a period of 9 years. For all BZs the type, dosage, frequency and duration of use was measured. The equivalent of a dose of diazepam was determined with regard to type and dosage and a cumulative dosage was calculated. General cognitive functioning was measured with the Mini-Mental State Examination, information processing speed was measured with the coding task, fluid intelligence with Raven's Coloured Progressive Matrices and episodic memory with the Auditory Verbal Learning Test. Multilevel analyses were used to investigate the relationship between BZ use and cognitive decline. A negative effect of BZ use on cognitive performance was found. However, the effect sizes were very small. This study suggests that both duration and cumulative exposure to BZ has a small negative effect on the long-term cognitive functioning of elderly people in the community.

Quality of life and benzodiazepine drug use by community-dwelling elderly: a stress and coping perspective

Framed in Lazarus and Folkman theory of stress and coping, a model of onset of long-term benzodiazepine use among community-dwelling older adults is presented within a perspective of quality of life enhancement. We focus on heightened emotional reactivity, and subsequent effect on cognitive appraisal of life circumstances (loss of control over the event and negative appraisal of personal resources). We examine ensuing coping strategy, namely an increased reliance on both emotion-reduction and problem-solving coping strategies. The effects of benzodiazepine use on quality of life are brought forth. Alternatives to benzodiazepine use are suggested.

Benzodiazepine prescription practices and substance abuse in persons with severe mental illness.

Benzodiazepines have many benefits for persons with severe mental disorders, but they may also lead to or exacerbate substance abuse. An American Psychiatric Association taskforce established practice guidelines in 1990 to assist physicians in managing these and other potential side effects of benzodiazepine use. The objectives of this study were to determine the prevalence of benzodiazepine use among persons with psychiatric disorders and to evaluate compliance with published prescribing guidelines. We studied benzodiazepine use among New Hampshire Medicaid beneficiaries aged 18 to 64 years with ICD-9 diagnoses that were grouped under the headings "schizophrenia," "bipolar disorder," "major depression," and "other psychiatric disorders" from Jan. 1995 through Dec. 1999. Rates and length of use, frequency of high-potency/fast-acting prescriptions, and diazepam-equivalent dosages were compared for those with and without retrospectively determined evidence of substance abuse, substance dependence, or a procedure code indicating treatment for a substance use disorder (SUD). Five-year prevalence of benzodiazepine use for persons with and without SUD was 63% versus 54% for schizophrenia, 75% versus 58% for bipolar disorder, 66% versus 49% for major depression, and 48% versus 40% for other psychiatric disorders. Differences were statistically significant over 5 years and in 1999 (p <.0001). Among persons with major depression or other psychiatric disorders, those with comorbid SUD were more likely to use fast-acting/high-potency benzodiazepines; there were no such differences for those with schizophrenia or bipolar disorder. Persons with bipolar disorder or other psychiatric disorders and SUD received significantly higher diazepam-equivalent dosages than did those without SUD. Contrary to published guidelines, rates of benzodiazepine use are higher among Medicaid beneficiaries with severe mental illness and co-occurring SUD than among persons with severe mental illness alone. Additional research and possibly a reassessment of prescribing guidelines are recommended.

Sleep EEG power spectra, insomnia, and chronic use of benzodiazepines.

The present study examined the sleep microstructure in relation to insomnia and chronic use of benzodiazepines in older adults. The participants were 46 older adults, aged 55 or older (mean age = 62.9), who were divided into three groups: insomnia sufferers using BZ chronically (n = 15), drug-free insomnia sufferers (n = 15), and self-defined good sleepers (n = 16). Participants completed 3 consecutive nights of polysomnography in the laboratory. Spectral analyses were carried on the second night of sleep recordings. Stages 2, 3, and 4 of the first 4 cycles of the second night were retained for the analysis. Results showed no significant differences between drug-free insomnia sufferers and good sleepers. However, benzodiazepine users exhibited significantly less delta and theta activity over the night than did good sleepers. When compared to drug-free insomnia sufferers, benzodiazepine users had less delta and theta activity within cycle 2 only. Regarding high-frequency bands, benzodiazepine users had more beta 1 activity within cycle 3 than did good sleepers and more than both drug-free insomnia sufferers and good sleepers within cycle 4. The findings show that spectral analysis is an efficient tool to detect and quantify the effects of benzodiazepine use on sleep structure, particularly with older adults, a group for whom macrostructure sleep alterations due to physiologic aging are hard to distinguish from sleep changes induced by insomnia and the use of hypnotic drugs. In addition, these results raise important questions about the effects and indications of prolonged use of benzodiazepine medications in older adults with insomnia complaints.

Is the use of benzodiazepines associated with incident disability?

This study examined the association between benzodiazepine use and incident disability with an emphasis on elucidating whether the underlying health conditions that result in benzodiazepine use (confounding factors) or intrinsic adverse effects of benzodiazepine use were responsible for functional decline. Cohort study with follow-up of 4 to 5 years. A health maintenance organization (HMO) in western Washington. Individuals aged 65 and older from a random sample of HMO enrollees who participated in a health promotion intervention trial (n = 1,519). Benzodiazepine use was ascertained from computerized pharmacy records. Self-reported functional status was assessed using a six-item physical function scale ranging from vigorous activity to self-care activities of daily living (ADLs). Two outcomes were examined: decline in overall physical function and limitations in self-care ADLs. Multivariate models were examined that included demographic characteristics, health status, and health behaviors that were likely to be confounders. Several analyses were conducted to examine whether benzodiazepine use or confounding factors were responsible for functional decline. Benzodiazepine use was significantly associated with incident loss of physical function (hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.02-2.24) in the fully adjusted model. Although use of benzodiazepines was associated with limitations in ADLs, it was not significant when adjusting for other factors (HR = 1.71, 95% CI = 0.87-3.34). Several of our findings suggest that the health conditions leading to benzodiazepine use may partly or fully explain these associations: (1) use of anxiolytic benzodiazepines (HR = 1.95, 95% CI = 1.24-3.07), but not hypnotic agents (HR = 1.21, 95% CI = 0.73-2.00), was associated with functional decline; (2) adjustment for health status variables minimized these associations; and (3) there was little evidence of dose response. A modestly increased risk for decline in physical function was associated with benzodiazepine use, especially of anxiolytic agents. The health conditions that result in benzodiazepine use may be more important in the pathogenesis of disability than benzodiazepine use itself. Although there are many reasons for avoiding benzodiazepines in older adults, it is still unclear whether use contributes independently to functional decline.