Short-term Benzodiazepine Research Articles

Suspected benzodiazepine withdrawal-associated seizures in 3 young dogs undergoing mechanical ventilation.

To describe new onset of generalized seizures in 3 young dogs following cessation of a benzodiazepine-containing sedation protocol to facilitate mechanical ventilation (MV) for hypoxemia. Three dogs under 5 months of age underwent MV due to severe hypoxemia. All 3 dogs were sedated with a constant rate infusion of benzodiazepines as part of their sedation protocol to facilitate MV. All 3 dogs had an acute onset of generalized seizures within 36hours of sedation cessation and weaning from MV. All 3 dogs' seizures were successfully managed with a slow, tapering course of benzodiazepines. One dog was additionally treated with levetiracetam at the time of initial seizure activity, which was discontinued 1year following discharge and absence of ongoing seizure activity. All 3 dogs were discharged successfully with no reports of ongoing seizures or neurologic deficits after discharge. Young dogs managed with benzodiazepines to facilitate MV may have acute onset of generalized seizures following cessation, which can be successfully managed with short-term benzodiazepine therapy. The 3 cases in this series demonstrated a positive outcome and were successfully managed following acute onset of generalized seizure activity post-MV.

Short-term, but not long-term, beneficial effects of concomitant benzodiazepine use on clinical course in patients with schizophrenia.

This study aims to examine possible differences in the effect on the course characteristics of the disease in cases of no use, short-term use and long-term use of benzodiazepines in patients with schizophrenia. In this retrospective observational study, the sample comprised patients with schizophrenia who were admitted to our psychiatric clinics from January 2015 to January 2019. Patients were also retrospectively tracked from the date of the first admission during the specified time until the end of the observation period (24 months) for clinical course characteristics. Data for 1710 patients with schizophrenia were included in the analyses. Patients with short-term benzodiazepines use had fewer psychiatric hospitalizations and shorter lengths of stay at psychiatric services than patients with no use or long-term use. Rates of antipsychotic drug discontinuation and suicidal behavior were also significantly lower among short-term benzodiazepines users than among those with no use or long-term use. In conclusion, our study indicates that short-term benzodiazepines use is associated with a better clinical course in patients with schizophrenia. Future studies should evaluate the effects of different benzodiazepines use patterns on disease prognosis with longer-term follow-up and prospective methodology and should concomitantly examine psychopathological variables.

Is the Long-Term Use of Benzodiazepines Associated With Worse Cognition Performance in Highly Educated Older Adults?

Background: Benzodiazepines (BZD) are common medications for sedative, hypnotic, and anxiolytic that are especially prevalent in older adults. Previous studies have shown that BZD use could impair users' cognition, significantly affecting their quality of life. Past research has shown that higher education might play a protective role in the process of cognitive decline. Very few studies had examined the cognitive effects of BZD on highly educated older adults. The study aimed to explore how cognitive functions would be affected by benzodiazepines among highly educated older adults.Method: 140 older adults with an average education period of 14.8 years were included in this study. The subjects were divided into three separate groups, the long-term BZD users (≥180 days), short-term BZD users (<180 days), and non-users. Demographics and cognitive assessments for the three groups were analyzed using the analysis of variance (ANOVA), the chi-squared test, and the analysis of covariance (ANCOVA). To examine the association between BZD use and cognition a multiple linear aggression approach was used.Result: All three groups were significantly different from each other when looking at executive functioning in the Trail Making Test B (TMT-B). Compared to the control group, short-term BZD users showed significant defects in TMT-B time (p = 0.002) and TMT-B errors (p < 0.001); long-term BZD users showed significant defect on TMT-B time (p = 0.041). Compared to short-term BZD users, long-term BZD users showed significant merit on TMT-B errors (p = 0.001). No significant differences were found in other cognitive tasks that reflected general cognition, verbal memory, language fluency, and visual memory. After adjusting for demographic, increased BZD use over time was positively associated with scores for the revised Brief Visuospatial Memory Test (r = 0.377, p = 0.012).Conclusion: BZD use may be significantly associated with worse executive functioning in highly educated older adults. However, there is no association between the duration of BZD use and increased cognitive deficits in highly educated older adults. This study identified future experimental directions including potential longitudinal studies, within-subject studies comparing mood disorder patients' cognitive performance before and after onset of BZD use, and between-subject studies that directly compare BZD's effect on subjects with the same baseline of cognitive functioning.

A clinical method of evaluating simple reaction time and reaction accuracy is sensitive to a single dose of lorazepam.

Benzodiazepines are useful and commonly prescribed. Unfortunately, they are associated with subtle but functionally significant neurocognitive side effects that increase the risk of motor vehicle accidents and falls. The objective of this study was to determine whether clinically feasible measures of simple reaction time and reaction accuracy are sensitive to a single dose of lorazepam. Using a randomized, double-blind, crossover design, 26 healthy adults (13 women; age = 26.9 ± 8.2 yr) were given 1.0 mg lorazepam or placebo 90 minutes prior to two data collection sessions. Participants completed simple and reaction accuracy tasks using a standardized "ruler drop" testing paradigm during each session. Outcomes were mean and variability of simple reaction time and reaction accuracy, which evaluates a participant's ability to catch the device solely on the random 50% of trials that lights affixed to it illuminate on release. Reaction accuracy requires a go/no-go decision within 420 ms before the falling device strikes the floor. As compared with placebo, lorazepam increased simple reaction time variability (range = 43 ± 18 vs. 60 ± 23 ms, respectively; p = 0.004 and standard deviation = 14.6 ± 5.7 vs. 19.7 ± 7.3 ms, respectively; = 0.006) and decreased reaction accuracy (90 ± 7% vs. 84 ± 11%, respectively; p = 0.010). Given prior work demonstrating associations between simple reaction time and reaction accuracy and functional outcomes such as self-protection, response to perturbations, and fall risk, these clinically available measures may have a role in identifying subtle, functionally significant cognitive changes related to short-term benzodiazepine use.

The long-term but not short-term use of benzodiazepine impairs motoric function and upregulates amyloid β in part through the suppression of translocator protein

Many elderly American women use CNS depressant benzodiazepine (BZD) to ameliorate anxiety or insomnia. However, the chronic use of BZD (cBZD) is prevalent, causing adverse effects of BZD that include movement deficit. We previously reported that cBZD upregulates neurotoxic amyloid β42 (Aβ42) and downregulates neuroprotective translocator protein (TSPO) in the cerebellum, the brain area of movement and balance. The aim of the current study is two-fold: 1) to determine a direct effect of TSPO (inhibition) on cBZD-induced Aβ42 and Aβ-associated molecules; Aβ-producing-protein presenilin-1 (PS1) and Aβ-degrading-enzyme neprilysin and 2) to determine whether Aβ42 upregulation and motoric deficit occur upon a long-term (cBZD) rather than a short-term BZD (sBZD) treatment. Old female mice received BZD (lorazepam) for 20 days (cBZD) or 3 days (sBZD) with or without prototype TSPO ligand PK11195 and were tested for motoric performance for 3 days using Rotarod. ELISA was conducted to measure Aβ42 level and neprilysin activity in cerebellum. RT-PCR and immunoblot were conducted to measure the mRNA and protein levels of TSPO, PS1, and neprilysin. cBZD treatment decreased TSPO and neprilysin but increased Aβ42 accompanied by motoric deficit. Chronic PK11195 treatment acted as a TSPO inhibitor by suppressing TSPO expression and mimicked or exacerbated the effects of cBZD on all parameters measured except for PS1. None of the molecular and behavioral changes induced by cBZD were reproduced by sBZD treatment. These data suggest that cBZD upregulates Aβ42 and downregulates neprilysin in part through TSPO inhibition, the mechanisms distinct from sBZD, collectively contributing to motoric deficit.

Risks of Benzodiazepines in Chronic Obstructive Pulmonary Disease with Comorbid Posttraumatic Stress Disorder.

Benzodiazepines are associated with mortality and poor outcomes among patients with chronic obstructive pulmonary disease (COPD), but use of benzodiazepines for dyspnea among patients with end-stage disease may confound this relationship. Assess the mortality risks of long-term benzodiazepine exposure among patients with COPD and comorbid post-traumatic stress disorder (PTSD), patients with chronic nonrespiratory indications for benzodiazepines. We identified all patients with COPD and PTSD within the Veteran's Health Administration between 2010 and 2012. We calculated propensity scores for benzodiazepine use and compared overall and cause-specific mortality of patients with long-term (≥90 d) benzodiazepine use relative to matched patients without use. Secondary analyses assessed propensity-adjusted survival by characteristics of benzodiazepine exposure. Among 44,555 eligible patients with COPD and PTSD, 23.6% received benzodiazepines long term. In the matched sample of 19,552 patients, we observed no mortality difference (hazard ratio [HR] for long-term use, 1.06; 95% confidence interval [CI], 0.95-1.18) but greater risk of death by suicide among those with long-term use (HR, 2.33; 95% CI, 1.14-4.79). Among matched and unmatched patients, short-term benzodiazepine use, but not long-term use, was associated with increased mortality (short-term: HR, 1.16; 95% CI, 1.05-1.28; long-term: HR, 1.03; 95% CI, 0.94-1.13). Risks for respiratory compromise related to long-term benzodiazepine use in COPD may be less than previously estimated, but short-term use of benzodiazepines could still pose a mortality risk. Suicide associated with benzodiazepine use in this population warrants further investigation.

(Zlo)upotreba i adiktivni potencijal benzodiazepina - analiza potrošnje u Srbiji u periodu 2014-2016

Benzodiazepines, as substances of abuse or recreational drugs, have largely suppressed the use of barbiturates, methaqualone and glutethimide. The advantage of benzodiazepines, used for medical use or abuse, compared with older drugs is certainly a safer profile and lower risk of serious toxic effects after overdose. Benzodiazepines are much safer drugs in the case of overdose compared with barbiturates, however they also have a number of side effects, including the development of tolerance and dependence. Short-term benzodiazepines, such as lorazepam, bromazepam and alprazolam, have the greatest addictive potential and they are the most commonly used anxiolytics in our population. The benzodiazepine consumption analysis in our country points to possible irrational prescribing and abuse. Benzodiazepines research and analysis of the consequences of their long-term use are aimed on changing patients' attitude, education, and raising awareness of better control of prescribing these medicines by healthcare professionals. In recent years an intensive research has been carried out to discover selective anxiolytic agents that will provide the same or similar efficacy and tolerability with less side effects.

Memory and hippocampal architecture following short-term midazolam in western diet-treated rats

The impact of short-term benzodiazepine exposure on cognition in middle-aged or older patients is a highly debated topic among anesthesiologists, critical care physicians and public media. “Western diet” (WD) consumption is linked to impaired cognition as well. The combination of benzodiazepines with substantial exposure to WD might set the stage for increased hippocampal vulnerability for benzodiazepines leading to exaggerated cognitive impairment in the postoperative period. In this study, Fischer 344 rats were fed either WD or standard rodent diet from 5 to 10.5 months of age. Rats were exposed to midazolam or placebo two days prior to an MRI scan using Diffusional Kurtosis Imaging (DKI) to assess brain microstructural integrity, followed by behavioral testing using a water radial arm maze. Hippocampal tissue was collected to assess alterations in protein biochemistry in brain regions associated with learning and memory. Our results showed that rats exposed to the combination of midazolam and WD had significantly delayed time of learning and exhibited spatial memory impairment. Further, we observed an overall increase of kurtosis metrics in the hippocampus and increased expression of the mitochondrial protein VDAC2 in midazolam-treated rats. Our data suggest that both the short-acting benzodiazepine midazolam and WD contribute to negatively affect the brain in middle-aged rats. This study is the first application of DKI on the effects of midazolam and WD exposure, and the findings demonstrate that diffusion metrics are sensitive indicators of changes in the complexity of neurite architecture.

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

Benzodiazepine Use Among Patients With Schizophrenia in Taiwan: A Nationwide Population-Based Survey

Benzodiazepine Use Among Patients With Schizophrenia in Taiwan: A Nationwide Population-Based Survey

S21-04 Community Psychiatry Services in a Developing Country like Sri Lanka

Catatonia is a syndrome characterized by concurrent motor, emotional, and behavioral symptoms. Short-term benzodiazepine administration and electroconvulsive therapy have proven to be safe and useful for treatment of this syndrome.This study aimed to explore the evidence of effectiveness of lorazepam as a first line treatment for catatonia in a tertiary psychiatry centre in India given the lack of facilities for ECT in primary care centers of developing countries. We examined the response rate of lorazepam in Catatonia.Clinical charts of 107 inpatients, admitted over a duration of two years, with a primary diagnosis of catatonia were examined for response with lorazepam trial. Trial was considered as having received 3–6 mg per day of lorazepam for at least 3 days.Among the patients who were given lorazepam treatment, 32 out of 99(32.3%) showed response (with complete resolution of catatonic symptoms). Improvement in catatonic symptoms was seen in 68 out of 99 (68.7%) patients.Lorazepam is cost effective and could rapidly relieve catatonic signs, even without the use of ECT in a significant proportion of catatonic patients. Its early use can prevent disease progression and complications.

Response rate of lorazepam in catatonia: A developing country's perspective

Background Catatonia is a syndrome characterized by concurrent motor, emotional, and behavioral symptoms. Short-term benzodiazepine administration and electroconvulsive therapy have proven to be safe and useful for treatment of this syndrome. Aims This study aimed to explore the evidence of effectiveness of lorazepam as a first line treatment for catatonia in a tertiary psychiatry centre in India given the lack of facilities for ECT in primary care centers of developing countries. We examined the response rate of lorazepam in Catatonia. Methodology Clinical charts of 107 inpatients, admitted over a duration of two years, with a primary diagnosis of catatonia were examined for response with lorazepam trial. Trial was considered as having received 3–6 mg per day of lorazepam for at least 3 days. Results Among the patients who were given lorazepam treatment, 32 out of 99(32.3%) showed response (with complete resolution of catatonic symptoms). Improvement in catatonic symptoms was seen in 68 out of 99 (68.7%) patients. Conclusions Lorazepam is cost effective and could rapidly relieve catatonic signs, even without the use of ECT in a significant proportion of catatonic patients. Its early use can prevent disease progression and complications.

Acute cross tolerance to midazolam, and not pentobarbital and pregnanolone, after a single dose of chlordiazepoxide in monkeys discriminating midazolam

Although cross tolerance can develop among positive gamma-aminobutyric acidA (GABAA) modulators acting at the same modulatory site, cross tolerance does not always develop to drugs acting at sites that are different from the site of action of the drug administered chronically. To examine the relationship between cross tolerance and site of action, four rhesus monkeys discriminated midazolam and, on separate occasions, received 32 mg/kg of chlordiazepoxide 24 h before dose-effect determinations for drugs acting at different sites. Midazolam, pentobarbital, and pregnanolone produced >80% midazolam-lever responding. Although monkeys responded on the midazolam lever 2-4 h after 32 mg/kg of chlordiazepoxide, they responded on the saline lever 24 h later. Twenty-four hours after an acute injection of 32 mg/kg of chlordiazepoxide, midazolam dose-effect curves were shifted 4.6-fold to the right, whereas pregnanolone dose-effect curves were shifted three-fold to the left. Sensitivity to pentobarbital increased in one monkey and decreased in others 24 h after chlordiazepoxide administration. Decreased sensitivity to midazolam shows that acute cross tolerance develops after chlordiazepoxide administration, although it does not develop to drugs acting at other sites on GABAA receptors. These differences among positive GABAA modulators suggest that even short-term benzodiazepine administration changes GABAA receptors, and those changes impact modulatory sites differently.

Fatal Consequence of Short-Term Benzodiazepine Administration Followed by Proton-Pump-Inhibitor Therapy

Fatal Consequence of Short-Term Benzodiazepine Administration Followed by Proton-Pump-Inhibitor Therapy

Fatal consequence of short-term benzodiazepine administration followed by proton-pump-inhibitor therapy.

Fatal consequence of short-term benzodiazepine administration followed by proton-pump-inhibitor therapy.

Postoperative Confusion Increases in Elderly Long-Term Benzodiazepine Users

We investigated the relationship between postoperative confusion and duration of benzodiazepine exposure, preoperative anxiety, depressive state, and cognitive function in elderly patients regularly taking benzodiazepines. We studied 328 patients ranging in age from 65 to 80 yr who underwent orthopedic surgery. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of the patient's medicine chest. Postoperative confusion was assessed by using a confusion-assessment method. The patients were divided into two groups: those who regularly took benzodiazepines and those who did not. Fifty-seven (17%) of 328 patients were treated with benzodiazepines. There were no significant differences in preoperative Mini-Mental State (MMS) scores, anxiety scores, or depression scores between benzodiazepine users and nonusers. Postoperative confusion occurred in 15 (26%) of 57 benzodiazepine users and in 34 (13%) of 271 nonusers (P < 0.01). The patients who had a score <23 on the MMS were 5 (9%) of 57 benzodiazepine users and 8 (3%) of 271 nonusers (P < 0.05). Postoperative confusion occurred in 13 (35%) of 37 long-term benzodiazepine users (daily use for >1 yr) and in 2 (10%) of 20 short-term users (daily use for <1 yr). The incidence of postoperative confusion was significantly more frequent in long-term than in short-term benzodiazepine users or nonusers of benzodiazepines. The patients who developed a score <23 on the MMS were 5 (14%) of 37 long-term benzodiazepine users and 0 (0%) of 20 short-term benzodiazepine users. In conclusion, the incidence of postoperative confusion was significantly more frequent in long-term benzodiazepine users.

A Comparison of Patterns of Tranquiliser Intake, Anxiety and Health Locus ofControl between Short- and Long-TermBenzodiazepine Users

This study investigates the impact of physical illness, health locus of control and anxiety level on long- and short-term benzodiazepine (BZD) use in patients of an internal medicine department. There was no significant difference observed between the continuing and discontinuing group after hospital admission in terms of average daily dose of BZD. However, the continuing patients rated the condition of their somatic illness significantly higher than the discontinuing group, although this difference was not confirmed by the objective assessment of the treating physician. The non-continuing group displayed significantly higher control over health- and sickness-related events. The somatic and physical anxiety factor was significantly higher in the continuing group at initial investigation as well as at follow-up. On the basis of these results, we conclude that an increased focus on the psychosomatic element might reduce the risk of long-term tranquiliser use in patients with physical illness.

Benzodiazepines in the treatment of catatonic syndrome

During a 5-month period, 18 (8%) of 212 patients admitted to a psychiatric unit affiliated to a teaching hospital were found to have a catatonic syndrome associated with various nonorganic mental disorders. Signs and symptoms of motor retardation predominated the clinical presentations. In the course of a prospective, open study, all 18 patients were challenged by a small dose of oral lorazepam or intramuscular diazepam. Catatonic signs and symptoms in 2 patients showed an immediate, complete, and sustained response to the medication. The remaining 16 patients were maintained on 1 of the 2 benzodiazepines for the next 48 h when their motor status was re-evaluated. Significant clinical improvement was detected in all but 2 patients. However, 9 patients needed electroconvulsive treatment to achieve further improvement. Short-term benzodiazepine administration proved to be a safe and effective treatment of the catatonic syndrome.

Short term benzodiazepine therapy may not be ruled out in those who have had diazepam dependency

Short term benzodiazepine therapy may not be ruled out in those who have had diazepam dependency