Benzodiazepine Dose Reduction Research Articles

Association Between Benzodiazepine or Z-Drug Prescriptions and Drug-Related Poisonings Among Patients Receiving Buprenorphine Maintenance: A Case-Crossover Analysis.

Persons with opioid use disorder who take benzodiazepines are at high risk for overdose. The objective of this study was to evaluate the association of benzodiazepine and Z-drug use with drug-related poisonings among patients receiving buprenorphine maintenance treatment. A case-crossover study design was used to analyze prescription claims among persons ages 12-64 with opioid use disorder who had buprenorphine prescriptions and had claims data in the IBM MarketScan databases (2006-2016), encompassing 14,213,075 person-days of observation time for 23,036 individuals who experienced drug-related poisoning. The exposures were buprenorphine prescriptions and benzodiazepine or Z-drug prescriptions, standardized as daily diazepam-equivalent milligram doses and separated by pharmacologic properties (short-acting or long-acting benzodiazepines, Z-drugs). The outcome of interest was nonfatal drug-related poisoning. Conditional logistic regression was used to evaluate variation in benzodiazepine or Z-drug and buprenorphine use between poisoning and nonpoisoning days. Buprenorphine treatment days were associated with a nearly 40% reduction in the risk of poisoning events (odds ratio=0.63, 95% CI=0.60, 0.66) compared with nontreatment days, whereas benzodiazepine or Z-drug treatment days were associated with an 88% increase in the risk of such events (95% CI=1.78, 1.98). In stratified analyses by dose, we observed a 78% (95% CI=1.67, 1.88) and 122% (95% CI=2.03, 2.43) increase in poisonings associated with low-dose and high-dose benzodiazepine or Z-drug treatment days, respectively. High-dose, but not low-dose, benzodiazepine or Z-drug treatment was associated with increased poisonings in combination with buprenorphine cotreatment (odds ratio=1.64, 95% CI=1.39, 1.93), but this was lower than the odds risk associated with benzodiazepine or Z-drug treatment in the absence of buprenorphine (low-dose: odds ratio=1.69, 95% CI=1.60, 1.79; high-dose: odds ratio=2.23, 95% CI=2.04, 2.45). Increased risk of nonfatal drug-related poisoning is associated with benzodiazepine or Z-drug treatment in patients with opioid use disorder, but this risk is partially mitigated by buprenorphine treatment. Dose reduction of benzodiazepines or Z-drugs while maintaining buprenorphine treatment may provide the advantage of lowering drug-related poisoning risk.

Clinical impact of antipsychotic and benzodiazepine reduction: findings from a multicomponent psychotropic reduction program within long-term aged care.

To explore the relationships between dose changes to antipsychotic and/or benzodiazepine medications and resident outcomes, including variations in neuropsychiatric symptoms, quality of life (QoL), and social withdrawal, within a multicomponent, interdisciplinary antipsychotic and benzodiazepine dose reduction program. Prospective, observational, longitudinal study. The Reducing Use of Sedatives (RedUSe) project involved 150 Australian Long-Term Care Facilities (LTCFs) incorporating auditing and benchmarking of prescribing, education, and multidisciplinary sedative reviews. A convenience sample of LTCFs (n = 28) involved in RedUSe between January 2015 and March 2016. Permanent residents (n = 206) of LTCFs involved in RedUSe taking an antipsychotic and/or benzodiazepine daily. Residents were excluded if they had a severe psychiatric condition where antipsychotic therapy should generally be maintained long-term (e.g., bipolar disorder, schizophrenia) or were considered end-stage palliative. Neuropsychiatric symptoms (Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory (CMAI)), QoL (Assessment of Quality of Life-4D), and social withdrawal (Multidimensional Observation Scale for Elderly Subjects-withdrawal subscale) were measured at baseline and 4 months where nursing staff completed psychometric tests as proxy raters. There was no evidence that psychometric measures were worsened following dose reductions. In fact, dose reduction was associated with small, albeit non-statistically significant, improvements in behavior, particularly less physically non-aggressive behavior with both drug groups (-0.36 points per 10% reduction in antipsychotic dose, -0.17 per 10% reduction in benzodiazepine dose) and verbally agitated behavior with benzodiazepine reduction (-0.16 per 10% dose reduction), as measured with the CMAI. Furthermore, antipsychotic reduction was associated with non-statistically significant improvements in QoL and social withdrawal. Antipsychotic and benzodiazepine dose reduction in LTCFs was not associated with deterioration in neuropsychiatric symptoms, QoL, or social withdrawal. Trends toward improved agitation with antipsychotic and benzodiazepine dose reduction require further evaluation in larger, prospective, controlled studies.

Deprescribing benzodiazepines among hospitalised older adults: quality improvement initiative

Benzodiazepines are recognised as being potentially inappropriate medications for seniors due to their considerable side-effect profile, yet they are commonly prescribed and infrequently discontinued (deprescribed). The study’s primary objective was...

Prescribing and facilitating withdrawal from benzodiazepines in primary health care

The chronic use of benzodiazepine anxiolytics and hypnotics is a controversial issue and it is envisaged by most family physicians as a health problem. Although benzodiazepines act rapidly and are well tolerated, its prevalent use is raising clinical concerns. A narrative review was conducted to summarize benzodiazepine indications, adverse effects and risks associated with overuse. Available strategies to discontinue these drugs at primary care setting are also explored. Benzodiazepines main indications are anxiety and insomnia, when the disorder is severe, disabling or subjecting the individual to extreme distress. However, treatment should be as short as possible, not exceeding eight to twelve weeks for anxiety or four weeks for insomnia. The evidence shows that systematic approaches with brief interventions and recommendation for gradual dose reduction of benzodiazepines seem to have good results among benzodiazepines users. This review is the first step of the development, implementation and effectiveness evaluation of a novel benzodiazepine withdrawal program, to be conducted by family doctors.

Benzodiazepine dose reduction in prisoner patients: 15years' teamwork between psychiatrists and pharmacists.

Benzodiazepines are widely consumed in prisons, despite the iatrogenic risks associated with this therapeutic class. A multidisciplinary pharmacotherapy programme was therefore initiated by pharmacists in 2001. The aim of this study was to demonstrate the efficacy of teamwork between psychiatrists and pharmacists in benzodiazepine dose adjustment, with 15years of hindsight. In this retrospective study, daily prescribed benzodiazepine doses were compared between a reference group of patients in prisons in Lyon, France, in 2000, and four groups after psychiatrist-pharmacist teamwork in 2004, 2008, 2012 and 2016. A number of 1249 patients were included. Prescribed doses of benzodiazepine decreased in the intervention groups, to a mean of 29-35mg diazepam equivalent per day, compared to the control group (42mg/day) (P<.001). The first 4-year period (2000-2004) demonstrated that monthly meetings and systematic pharmaceutical medication review had an impact on prescribed benzodiazepines, limiting consumed doses. The others (2004-2008, 2008-2012 and 2012-2016) confirmed that physicians' adherence to prescription guidelines and the efficacy of pharmacotherapy programme was maintained, particularly in those inmates taking high doses. A continuous quality programme conducted by psychiatrists and pharmacists showed positive impact in reducing doses of benzodiazepine prescribed to prisoner patients and contributing to reduce risk of benzodiazepine-related problems.

Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial.

BackgroundPatients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short-term usage. Melatonin, a naturally occurring nocturnal hormone, has the potential to stabilize disrupted circadian rhythmicity. Our aim was to investigate how prolonged-release melatonin affects rest-activity patterns in medicated patients with severe mental illness and if benzodiazepine dose reduction is associated with changes in circadian rhythm parameters.MethodData were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg) or matching placebo, and usual benzodiazepine dosage was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6 h, from baseline to follow-up, in the whole sample was analyzed using paired samples t-test.ResultsA subsample of 48 patients participated in the actigraphic assessment: 20 in the melatonin group and 28 in the placebo group. Rest-activity cycles varied from regular to highly disrupted. Melatonin significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre tapering, but differences did not reach statistical significance.ConclusionOur data suggest melatonin as an aid during benzodiazepine withdrawal for patients distressed by disrupted circadian rest-activity cycles. Benzodiazepine tapering might result in diminished sedentary behavior but further research is needed.Trial registrationClinicalTrials NCT01431092, clinicaltrials.gov. Registered 31 August 2011.

Neurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo.

Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment. It is unclear whether benzodiazepine-induced cognitive impairment is reversible. Amelioration of cognitive dysfunction may be facilitated during benzodiazepine tapering by add-on melatonin due to its anti-inflammatory and neuroprotective properties. We examined how melatonin and benzodiazepine withdrawal affect cognition, subjective well-being, and psychosocial functioning. Eighty patients with schizophrenia or bipolar disorder were randomized to add-on treatment once daily with either prolonged-release melatonin or placebo in a 24-week, double-blind clinical trial. All participants gradually tapered usual benzodiazepine dosage in a closely monitored treatment setting. We used the Brief Assessment of Cognition in Schizophrenia (BACS) to assess neurocognitive performance with additional assessments of subjective well-being and psychosocial functioning. BACS composite and subscale scores (except motor speed) significantly improved in parallel with benzodiazepine dose reduction, but there was no additional effect of melatonin. Cognitive performance was still markedly impaired post-tapering compared with normative data. Neither benzodiazepine withdrawal nor treatment group affected subjective well-being or psychosocial functioning. In conclusion, add-on melatonin does not seem to affect cognition, well-being, or psychosocial functioning in patients with severe mental illness. The observed improvement in cognitive performance could not be distinguished from retest effects, which may in turn have been facilitated by the benzodiazepine tapering.

Objective and subjective sleep quality: Melatonin versus placebo add-on treatment in patients with schizophrenia or bipolar disorder withdrawing from long-term benzodiazepine use

Benzodiazepines are frequently long-term prescribed for the treatment of patients with severe mental illness. This prescribing practice is problematic because of well-described side effects including risk of dependence. We examined the efficacy of prolonged-release melatonin on objective and subjective sleep quality during benzodiazepine discontinuation and whether sleep variables were associated with benzodiazepine withdrawal. Eligible patients included adults with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder and long-term use of benzodiazepines in combination with antipsychotics. All participants gradually tapered the use of benzodiazepines after randomization to add-on treatment with melatonin versus placebo. Here we report a subsample of 23 patients undergoing sleep recordings (one-night polysomnography) and 55 patients participating in subjective sleep quality ratings. Melatonin had no effect on objective sleep efficiency, but significantly improved self-reported sleep quality. Reduced benzodiazepine dosage at the 24-week follow-up was associated with a significantly decreased proportion of stage 2 sleep. These results indicate that prolonged-release melatonin has some efficacy for self-reported sleep quality after gradual benzodiazepine dose reduction, and that benzodiazepine discontinuation is not associated with rebound insomnia in medicated patients with severe mental illness. However, these findings were limited by a small sample size and a low retention rate.

Medication monitoring for people with dementia in care homes: the feasibility and clinical impact of nurse-led monitoring.

Objectives. People with dementia are susceptible to adverse effects of medicines. However, they are not always closely monitored. We explored (1) feasibility and (2) clinical impact of nurse-led medication monitoring. Design. Feasibility “before-and-after” intervention study. Setting. Three care homes in Wales. Participants. Eleven service users diagnosed with dementia, taking at least one antipsychotic, antidepressant, or antiepileptic medicine. Intervention. West Wales Adverse Drug Reaction (ADR) Profile for Mental Health Medicines. Outcome Measures. (1) Feasibility: recruitment, retention, and implementation. (2) Clinical impact: previously undocumented problems identified and ameliorated, as recorded in participants' records before and after introduction of the profile, and one month later. Results. Nurses recruited and retained 11 of 29 eligible service users. The profile took 20–25 minutes to implement, caused no harm, and supplemented usual care. Initially, the profile identified previously undocumented problems for all participants (mean 12.7 (SD 4.7)). One month later, some problems had been ameliorated (mean 4.9 (3.6)). Clinical gains included new prescriptions to manage pain (2 participants), psoriasis (1), Parkinsonian symptoms (1), rash (1), dose reduction of benzodiazepines (1), new care plans for oral hygiene, skin problems, and constipation. Conclusions. Participants benefited from structured nurse-led medication monitoring. Clinical trials of our ADR Profile are feasible and necessary.

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol.

BackgroundTreatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life.Methods/DesignRandomized, blinded, two-armed, parallel superiority trial. We plan to include 80 consenting outpatients diagnosed with schizophrenia or schizoaffective disorder, 18-55 years of age, treated with antipsychotic drug(s) and at least one benzodiazepine derivative for the last three months before inclusion. Exclusion criteria: currently under treatment for alcohol or drug abuse, aggressive or violent behavior, known mental retardation, pervasive developmental disorder, dementia, epilepsy, terminal illness, severe co morbidity, inability to understand Danish, allergy to melatonin, lactose, starch, gelatin, or talc, hepatic impairment, pregnancy or nursing, or lack of informed consent. After being randomized to prolonged-release melatonin (Circadin®) 2 mg daily or matching placebo, participants are required to slowly taper off their benzodiazepine dose. The primary outcome measure is benzodiazepine dose at 6 months follow-up. Secondary outcome measures include sleep, psychophysiological, and neurocognitive measures. Data are collected at baseline and at 6 months follow-up regarding medical treatment, cognition, psychophysiology, sleep, laboratory tests, adverse events, psychopathology, social function, and quality of life. Data on medical treatment, cognition, psychophysiology, adverse events, social function, and quality of life are also collected at 2 and 4 months follow-up.DiscussionThe results from this trial will examine whether melatonin has a role in withdrawing long-term benzodiazepine administration in schizophrenia patients. This group of patients is difficult to treat and therefore often subject to polypharmacy which may play a role in the reduced life expectancy of patients compared to the background population. The results will also provide new information on the association of chronic benzodiazepine treatment with sleep, psychophysiology, cognition, social function, and quality of life. Knowledge of these important clinical aspects is lacking in this group of patients.Trial RegistrationClinicalTrials NCT01431092

Patient-controlled benzodiazepine dose reduction in a community mental health service.

A prescribing audit identified suboptimal benzodiazepine use which stimulated a discontinuation programme [prescribing policy, psychoeducation, anxiety management] to encourage benzodiazepine cessation. Benzodiazepine status was re-assessed at 12 and 24 month follow-ups. 158 patients were receiving benzodiazepines at study onset. At 12 month follow-up, 68 of these were still receiving benodiazepines. This was due to discontinuation (n = 32), dose reduction (n = 26) and service dropout (n = 71). Benzodiazepine status at follow-up was predicted by attendance at anxiety management sessions (p = 0.01) and shorter duration of benzodiazepine use (p = 0.005). Patients attending anxiety management sessions were 2.5 times more likely to reduce use. Discontinuation followed four patterns: (a) rapid and complete discontinuation (n = 19); (b) total discontinuation in a gradual manner (n = 13); (c) partial dose reduction without total discontinuation (n = 18) and (d) almost total discontinuation with continued low-dose use (n = 8). The patients that achieved total discontinuation were younger (p = 0.01) and in receipt of benzodiazepine agents for a shorter duration (p = 0.009). At 24 month follow-up only three patients had relapsed into benzodiazepine use and a further 13 had achieved total discontinuation. Many chronic benzodiazepine users can achieve lasting discontinuation with patient-controlled dose tapering. Patient refusal and service dropout are common during discontinuation programmes. Anxiety management is a valuable adjunct to discontinuation.