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Addiction (Abingdon, England) Jan 2023A total of 2.4 million adults in England were dispensed a benzodiazepine or Z-drug (BZRA) in 2017/18, and more than 250 000 patients in the UK take BZRAs beyond the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
A total of 2.4 million adults in England were dispensed a benzodiazepine or Z-drug (BZRA) in 2017/18, and more than 250 000 patients in the UK take BZRAs beyond the recommended duration. Deprescribing is a clinician-guided process of withdrawing inappropriate drugs. This review aimed to evaluate the evidence base supporting the feasibility and clinical effectiveness of all forms of deprescribing initiatives used to discontinue long-term (≥ 4 weeks) BZRAs.
METHOD
Systematic review of randomized controlled trials evaluating BZRAs deprescribing among adults in community, primary or outpatient settings. MEDLINE, Embase and PsycINFO were searched from inception to February 2021. Primary outcomes were successful discontinuation in the short (< 4 weeks) or long term (≥ 4 weeks) and the occurrence of withdrawal symptoms, behavioural or psychological symptoms. Studies were categorized as pharmacological or non-pharmacological supported interventions. Study quality was assessed using the Cochrane risk-of-bias tool. Where appropriate, risk ratios (RRs), mean differences and 95% confidence intervals (CIs) were calculated, and Mantel-Haenszel methods using the random-effect meta-analysis was undertaken to calculate summary effect estimates.
RESULTS
Ten studies were included (n = 1431 participants). Heterogeneity in study design and effect was observed. Benzodiazepines were successfully deprescribed when gradually tapered with non-pharmacological support compared with gradual tapering alone in the short term (n = 124; RR = 2.02; 95% CI = 1.41, 2.89) and long term (n = 123; RR = 2.45; 95% CI = 1.56, 3.85). Benzodiazepine deprescribing was more successful when supported by non-pharmacological methods versus routine care (n = 189; RR = 3.26; 95% CI = 2.36, 4.51). Quality of evidence reporting effectiveness was very low to low.
CONCLUSIONS
It may be feasible to deprescribe benzodiazepines depending on the process and support mechanisms employed.
Topics: Adult; Humans; Benzodiazepines; Deprescriptions; Feasibility Studies; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 35815384
DOI: 10.1111/add.15997 -
Drug and Alcohol Dependence Feb 2023Individuals with a substance use disorder (SUD) have high rates of hospital service utilization including emergency department (ED) presentations and hospital... (Review)
Review
BACKGROUND AND AIMS
Individuals with a substance use disorder (SUD) have high rates of hospital service utilization including emergency department (ED) presentations and hospital admissions. Acute care settings offer a critical opportunity to engage individuals in addiction care and improve health outcomes especially given that the period of transition from hospital to community is challenging. This review summarizes literature on interventions for optimizing transitions in care from hospital to community for individuals with a SUD.
METHODS
The literature search focused on key terms associated with transitions in care and SUD. The search was conducted on three databases: MEDLINE, CINAHL, and PsychInfo. Eligible studies evaluated interventions acting prior to or during transitions in care from hospital to community and reported post-discharge engagement in specialized addiction care and/or return to hospital and were published since 2010.
RESULTS
Title and abstract screening were conducted for 2337 records. Overall, 31 studies met inclusion criteria, including 7 randomized controlled trials and 24 quasi-experimental designs which focused on opioid use (n = 8), alcohol use (n = 5), or polysubstance use (n = 18). Interventions included pharmacotherapy initiation (n = 7), addiction consult services (n = 9), protocol implementation (n = 3), screening, brief intervention, and referral to treatment (n = 2), patient navigation (n = 4), case management (n = 1), and recovery coaching (n = 3).
CONCLUSIONS
Both pharmacologic and psychosocial interventions implemented around transitions from acute to community care settings can improve engagement in care and reduce hospital readmission and ED presentations. Future research should focus on long-term health and social outcomes to improve quality of care for individuals with a SUD.
Topics: Humans; Aftercare; Emergency Service, Hospital; Hospitalization; Hospitals; Patient Discharge; Substance-Related Disorders; Transitional Care
PubMed: 36634575
DOI: 10.1016/j.drugalcdep.2023.109763 -
Translational Psychiatry May 2016Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders... (Meta-Analysis)
Meta-Analysis Review
Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm, as well as on its neuropharmacological working mechanisms are limited. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.
Topics: Animals; Cerebellum; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Ibogaine; Illicit Drugs; Male; Motor Activity; Neurons; Self Administration; Substance-Related Disorders
PubMed: 27244235
DOI: 10.1038/tp.2016.71 -
Addiction (Abingdon, England) Feb 2023To evaluate qualitative research on substance use and substance use disorders (SUDs) among refugees in terms of practitioners' and substance users' attitudes, beliefs... (Review)
Review
AIMS
To evaluate qualitative research on substance use and substance use disorders (SUDs) among refugees in terms of practitioners' and substance users' attitudes, beliefs and experiences.
METHODS
Six medical, allied health and social sciences databases (EBSCO, PubMed, ScienceDirect, Web of Science, Scholar and the Cochrane Library) were systematically searched in a time frame between January and April 2021 to identify original peer-reviewed articles describing qualitative findings related to substance use among refugees (alcohol, illicit drugs, tobacco and prescription drugs). Study selection, critical appraisal and detailed extraction were performed via the Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Systematic Reviews (PRISMA) (2018). Three independent reviewers selected the relevant abstracts and articles. Synthesis of the evidence identified prominent themes relating to the context and consequences of substance use.
RESULTS
Twenty-six studies were included in this review. Twenty-three studies applied qualitative methods and three applied mixed methods. Synthesis of the evidence from the included studies resulted in four main findings: there is a considerable susceptibility of refugees to substance use and SUDs; the harmful consequences of substance use are complicated by the social insecurities of refugees; there are rather high barriers to treatment and health facilities for refugees in many host countries; and there is a strong need to improve effective access to treatment, interventions and prevention approaches.
CONCLUSIONS
Refugees are at high risk for substance use and substance use disorders and often face high barriers to treatment and interventions in host countries.
Topics: Humans; Refugees; Substance-Related Disorders; Qualitative Research; Illicit Drugs; Drug Users
PubMed: 35929580
DOI: 10.1111/add.16021 -
The Cochrane Database of Systematic... Aug 2023Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem.
OBJECTIVES
To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes.
SEARCH METHODS
We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, two other databases, and three trials registers from their inception to 9 August 2022. We also checked the reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), irrespective of publication status and language, comparing a pharmacological intervention to placebo, no treatment, or another pharmacological intervention for asymptomatic carotid stenosis.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. Two review authors independently extracted the data and assessed the risk of bias of the trials. A third author resolved disagreements when necessary. We assessed the evidence certainty for key outcomes using GRADE.
MAIN RESULTS
We included 34 RCTs with 11,571 participants. Data for meta-analysis were available from only 22 studies with 6887 participants. The mean follow-up period was 2.5 years. None of the 34 included studies assessed neurological impairment and quality of life. Antiplatelet agent (acetylsalicylic acid) versus placebo Acetylsalicylic acid (1 study, 372 participants) may result in little to no difference in ipsilateral major or disabling stroke (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.47 to 2.47), stroke-related mortality (RR 1.40, 95% CI 0.54 to 3.59), progression of carotid stenosis (RR 1.16, 95% CI 0.79 to 1.71), and adverse events (RR 0.81, 95% CI 0.41 to 1.59), compared to placebo (all low-certainty evidence). The effect of acetylsalicylic acid on major bleeding is very uncertain (RR 0.98, 95% CI 0.06 to 15.53; very low-certainty evidence). The study did not measure neurological impairment or quality of life. Antihypertensive agents (metoprolol and chlorthalidone) versus placebo The antihypertensive agent, metoprolol, may result in no difference in ipsilateral major or disabling stroke (RR 0.14, 95% CI 0.02 to1.16; 1 study, 793 participants) and stroke-related mortality (RR 0.57, 95% CI 0.17 to 1.94; 1 study, 793 participants) compared to placebo (both low-certainty evidence). However, chlorthalidone may slow the progression of carotid stenosis (RR 0.45, 95% CI 0.23 to 0.91; 1 study, 129 participants; low-certainty evidence) compared to placebo. Neither study measured neurological impairment, major bleeding, adverse events, or quality of life. Anticoagulant agent (warfarin) versus placebo The evidence is very uncertain about the effects of warfarin (1 study, 919 participants) on major bleeding (RR 1.19, 95% CI 0.97 to 1.46; very low-certainty evidence), but it may reduce adverse events (RR 0.89, 95% CI 0.81 to 0.99; low-certainty evidence) compared to placebo. The study did not measure neurological impairment, ipsilateral major or disabling stroke, stroke-related mortality, progression of carotid stenosis, or quality of life. Lipid-lowering agents (atorvastatin, fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin) versus placebo or no treatment Lipid-lowering agents may result in little to no difference in ipsilateral major or disabling stroke (atorvastatin, lovastatin, pravastatin, and rosuvastatin; RR 0.36, 95% CI 0.09 to 1.53; 5 studies, 2235 participants) stroke-related mortality (lovastatin and pravastatin; RR 0.25, 95% CI 0.03 to 2.29; 2 studies, 1366 participants), and adverse events (fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin; RR 0.76, 95% CI 0.53 to1.10; 7 studies, 3726 participants) compared to placebo or no treatment (all low-certainty evidence). The studies did not measure neurological impairment, major bleeding, progression of carotid stenosis, or quality of life.
AUTHORS' CONCLUSIONS
Although there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.
Topics: Humans; Warfarin; Carotid Stenosis; Metoprolol; Atorvastatin; Chlorthalidone; Fluvastatin; Pravastatin; Probucol; Rosuvastatin Calcium; Stroke; Hemorrhage; Aspirin; Ischemic Stroke; Atherosclerosis
PubMed: 37565307
DOI: 10.1002/14651858.CD013573.pub2 -
CNS Drugs Apr 2022Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder and during euthymia. However, the treatment potential of hypnotic agents that might be used to manage sleep disturbance in BD is not well understood. Similarly, melatonin and medications with a melatonin-receptor agonist mechanism of action may have chronotherapeutic potential for treating people with the disorder, but the impact of these substances on sleep and circadian rhythms and core symptoms in BD is unclear.
OBJECTIVE
Our aim was to conduct a systematic review and meta-analysis evaluating the current evidence for hypnotic and melatonin/melatonin-receptor agonist pharmacotherapy for symptoms of sleep disturbance, mania, and depression in patients with BD.
METHODS
AMED, Embase, MEDLINE and PsychINFO databases were searched for studies published in English from the date of inception to 31 October 2021. Studies included in this review were randomised controlled trials (RCTs) and non-controlled/non-randomised studies for BD that examined hypnotic medications selected based on a common pattern of usage for treating insomnia (i.e. chloral, clomethiazole, diphenhydramine, doxepin, doxylamine, promethazine, suvorexant, zaleplon, zolpidem, zopiclone, and eszopiclone) and melatonin and the melatonin-receptor agonist drugs ramelteon and agomelatine. Risk of bias was assessed using the RoB2 and AXIS tools. Pooled effect sizes for RCT outcomes were estimated using random-effects models.
RESULTS
A total of eleven studies (six RCTs and five experimental feasibility studies) involving 1279 participants were included. Each study examined melatonin or melatonin-receptor agonists. No studies of hypnotics were found that fulfilled the review inclusion criteria. Pilot feasibility studies suggested beneficial treatment effects for symptoms of sleep disturbance, depression, and mania. However, the pooled effect of the two available RCT studies assessing sleep quality via Pittsburgh Sleep Quality Index scores was not statistically significant (g = - 0.04 [95% CI - 0.81 to 0.73]) and neither was the pooled effect for depressive symptoms (four studies; g = - 0.10 [95% CI - 0.27 to 0.08]). Some RCT evidence suggests ramelteon might prevent relapse into depression in BD. The largest efficacy signal detected was for manic symptoms (four studies; g = - 0.44 [95% CI - 1.03 to 0.14]) but there was substantial heterogeneity between studies and patient characteristics. In the two RCTs assessing manic symptoms during acute mania, adjunctive melatonin demonstrated superior treatment effects versus placebo.
CONCLUSIONS
There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD. Few studies assessed sleep-related symptoms, and none quantitatively examined endogenous melatonin patterns or other circadian rhythms. Melatonin may be a promising candidate for the adjunctive treatment of bipolar mania. However, dose-finding studies and studies with larger sample sizes are needed to confirm its efficacy. We recommend parallel monitoring of sleep and circadian rhythms in future trials. Chronobiology-informed trial designs are needed to improve the quality of future studies.
PROTOCOL REGISTRATION
PROSPERO (CRD42020167528).
Topics: Bipolar Disorder; Humans; Hypnotics and Sedatives; Mania; Melatonin; Sleep; Sleep Wake Disorders
PubMed: 35305257
DOI: 10.1007/s40263-022-00911-7 -
Journal of Attention Disorders Jul 2020Comorbid ADHD and substance use disorder (SUD) presents frequently in adolescence, a developmental period that may promote the emergence of substance misuse among...
Comorbid ADHD and substance use disorder (SUD) presents frequently in adolescence, a developmental period that may promote the emergence of substance misuse among individuals with ADHD. Comorbid ADHD and SUD in adolescence results in significant and unique treatment challenges, necessitating examination into effective interventions. This systematic review examined existing research into the treatment of comorbid adolescent ADHD and SUD. Findings from a small number of pharmacological intervention studies suggest potential efficacy of extended-release stimulant and nonstimulant medications. Efficacy of psychotherapeutic interventions has not been systematically examined. Current research on treatments for comorbid ADHD and SUD in adolescence is limited. Future placebo-controlled clinical trials using large samples are needed to examine the efficacy of psychotherapeutic interventions, the heightened risk of prescription stimulant misuse, and the long-term maintenance of treatment gains in this population. Clinical guidelines for the treatment of comorbid ADHD and SUD are discussed.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Substance-Related Disorders
PubMed: 25655767
DOI: 10.1177/1087054715569280 -
The American Journal on Addictions Oct 2017Recent neurobiological evidences along with clinical observations justify the use of N-acetylcysteine (NAC) as a medication for craving. The objective of our study was... (Review)
Review
BACKGROUND AND OBJECTIVES
Recent neurobiological evidences along with clinical observations justify the use of N-acetylcysteine (NAC) as a medication for craving. The objective of our study was to assess the evidence of efficacy of NAC for craving in substance use disorders in randomized clinical trials (RCTs).
METHODS
Systematic review of the RCTs literature (PROSPERO number 56698) until February, 2017, using MEDLINE, Cochrane Library and clinicaltrials.gov. We included seven RCTs (n = 245); most with small-to-moderate sample sizes. The main outcome was the Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I and the χ test. Publication bias was evaluated using the Begg's funnel plot and the Egger's test. Meta-regression was performed using the random-effects model.
RESULTS
Comparing NAC versus placebo, NAC was significantly superior for craving symptoms (Hedges' g = 0.94; 95%CI 0.55-1.33). The funnel plot showed the risk of publication bias was low and between-study heterogeneity was not significant (I = 44.4%, p = 0.07 for the χ test). A subgroup analysis performed using meta-regression showed no particular influence.
DISCUSSION AND CONCLUSIONS
NAC was superior to placebo for craving reduction in SUDs. The relatively small number of trials and their heterogeneous methodology were possible limitations; however, these positive thrilling results stimulate further studies for clarifying the potential impact of NAC for craving symptoms in SUDs.
SCIENTIFIC SIGNIFICANCE
The safety profile of NAC and favorable tolerability, in addition to being an over-the-counter medication, presents with an interesting potential clinical use for craving in SUDs.
SCIENTIFIC SIGNIFICANCE
The safety profile of NAC and its favorable tolerability, in addition to being anover-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. (Am J Addict 2017;26:660-666).
Topics: Acetylcysteine; Craving; Humans; Neurotransmitter Agents; Substance-Related Disorders; Treatment Outcome
PubMed: 28898494
DOI: 10.1111/ajad.12620 -
Frontiers in Psychiatry 2022Substance use disorders (SUDs) are a common yet poorly studied comorbidity in individuals with psychotic disorders. The co-occurrence of the two complicates recovery and...
BACKGROUND
Substance use disorders (SUDs) are a common yet poorly studied comorbidity in individuals with psychotic disorders. The co-occurrence of the two complicates recovery and interferes with pharmacological and behavioral treatment response and adherence. Recently, researchers have been exploring both invasive and non-invasive neuromodulation techniques as potential treatment methods for SUDs. We review the evidence that neuromodulation may reduce substance craving and consumption in individuals with schizophrenia.
METHODS
A comprehensive literature search of PubMed, MEDLINE, and PsycINFO databases was conducted ( = 1,432). Of these, we identified seven studies examining the effects of repetitive transcranial magnetic stimulation (rTMS) and two studies using transcranial direct current stimulation (tDCS) on drug consumption and craving in schizophrenia or schizoaffective disorders.
RESULTS
Despite the limited number of studies in this area, the evidence suggests that rTMS to the dorsolateral prefrontal cortex (DLPFC) may reduce cannabis and tobacco use in patients with schizophrenia and schizoaffective disorder. Findings with tDCS, however, were inconclusive.
DISCUSSION
Our systematic review suggests that rTMS applied to DLPFC is a safe and promising therapeutic technique for the management of comorbid schizophrenia and SUDs, with the majority of the evidence in tobacco use disorder. However, there was substantial heterogeneity in study methods, underscoring the need to optimize stimulation parameters (e.g., frequency, duration, and target regions). Larger clinical trials are needed to establish the efficacy of rTMS in reducing drug consumption and craving in psychotic patients, ideally in comparison to existing pharmacological and behavioral interventions.
PubMed: 35237187
DOI: 10.3389/fpsyt.2022.793938 -
The Australian and New Zealand Journal... Nov 2016The aim of this study was to systematically review the evidence-base for the effectiveness of culturally unadapted, culturally adapted and culture-based interventions... (Review)
Review
OBJECTIVE
The aim of this study was to systematically review the evidence-base for the effectiveness of culturally unadapted, culturally adapted and culture-based interventions for Indigenous adults with mental or substance use disorders.
METHODS
We conducted a systematic search of scientific databases, government websites and web-based Indigenous research repositories. We sought studies using designs comparing an intervention group to a control/comparator group or pre- and post-test designs, published between 2000 and 2015 examining interventions to improve individual-level outcomes (e.g. remission, symptoms, quality of life, functioning) or service-level outcomes (e.g. number of interventions delivered) for Indigenous adults with mental or substance use disorders in Australia, Canada, New Zealand or the United States.
RESULTS
A total of 16 studies met inclusion criteria. Virtually all North American studies (6 US and 1 Canadian) evaluated culturally unadapted interventions, all of which were interventions for substance use. Two-thirds of Australian and New Zealand studies evaluated culturally adapted interventions and included samples with mental disorders. Of eight culturally unadapted psychological/psychosocial, pharmacological and educational intervention studies, seven reported significant improvements on at least one measure of psychological well-being, mental health problem severity, or significantly reduced alcohol or illicit drug use. Of seven culturally adapted psychological/psychosocial intervention studies, all reported significant improvement on at least one measure of symptoms of mental illness, functioning, and alcohol use. One culture-based psychological/psychosocial intervention study significantly reduced problem severity in medical and psychiatric domains.
CONCLUSION
There remains inconclusive evidence regarding interventions due to a small and methodologically weak evidence-base. The literature would be enhanced by intervention replication and outcome standardisation, validating the outcome instruments used in Indigenous populations, including sample size calculations and using stronger research designs (e.g. interrupted time-series designs). Robust implementation and outcomes research is needed to further progress evidence-based practice in Indigenous mental health.
Topics: Adult; Australia; Canada; Culturally Competent Care; Humans; Mental Disorders; New Zealand; Population Groups; Substance-Related Disorders; United States
PubMed: 27514405
DOI: 10.1177/0004867416662150