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Addiction to benzodiazepines is a consumer behavior providing pleasure and relief, characterized by the repeated failure of its control and its persistence in spite of its damage. Our work is related to the study of socio-demographic features, clinical diagnosis and treatment of a sample of patients addicted to benzodiazepines monitored intermediate care center for drug addicts (CIST) of Annaba (Eastern Algeria) during the period from 1 January December 31, 2009. Our preliminary results cover a population of young adults, predominantly male, regularly consume two types of benzodiazepines in over half the cases and for a period exceeding 5 years. Results to follow.
Panic disorder is a chronic condition for many patients and can be socially, emotionally and occupationally disabling. Until recently, clomipramine and alprazolam were the only drugs approved for its treatment. While widely used in the US and Europe, both belong to drug classes (tricyclics and benzodiazepines) with well-recognised side effects that can be problematic and thus limit their use. Recently, paroxetine became the first selective serotonin reuptake inhibitor to receive approval and licensing for panic disorder.
The short- and long-term efficacy and tolerability of paroxetine in panic disorder has been established in clinical trials of almost 1,000 patients meeting Diagnostic and Statistical Manual (DSM)-IIIR criteria for panic disorder, with or without agoraphobia. In a 12-week double-blind study of 120 panic patients receiving standardised cognitive therapy, paroxetine was significantly more effective than placebo in reducing panic attack frequency. In a 12-week placebo-controlled comparison in 367 panic patients, paroxetine was at least as effective as clomipramine and better tolerated. There was also some evidence that paroxetine had an earlier onset of action than clomipramine.
A 9-month extension of the placebo-controlled comparison with clomipramine showed that the efficacy of paroxetine and clomipramine is maintained when treatment is continued into the longer term. In a relapse prevention study, 105 responders to 3 months' treatment with paroxetine or placebo were re-randomised, either to continue existing treatment or to receive placebo for 3 months. Only 5% of patients who continued to take paroxetine experienced a relapse compared with 30% of those who switched to placebo (P = 0.002). Paroxetine was generally well tolerated. In the short-term trials, the frequency of withdrawals due to adverse events (7.3%) was lower than that for placebo (11.4%) or clomipramine (14.9%). In the longer term, the dropout rate due to adverse events increased in the clomipramine group (19.0%) but was unchanged in the paroxetine group (7.4%). Since most patients with panic disorder will require prolonged treatment, the long-term tolerability of paroxetine and its lack of potential for dependence are important advantages that will encourage good compliance with treatment and improve the quality of life of patients.
Panic disorder is widespread in Australia, often in combination with other psychiatric conditions such as agoraphobia or major depression. Pharmacotherapy for panic disorder in Australia commenced with benzodiazepines, and later progressed to tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). More recently, treatment has moved towards use of the selective serotonin reuptake inhibitors (SSRIs), which are effective and better tolerated. Paroxetine is the first drug of this class to receive approval for treatment of panic disorder in Australia.
Long-term (minimum six months) safety and efficacy studies with an anti-anxiety agent are aimed at identifying the emergence of any clinical effects not observed during shorter periods of treatment including the identification of late occurring adverse events, loss of therapeutic benefit, or post-treatment withdrawal effects. There is the need to establish diagnostic criteria for persistent anxiety for patients who truly benefit from long-term therapy. Risk factors predisposing to drug dependence should be assessed prior to continuous use. Ideally, long-term continuous studies should be blinded, comparative and placebo-controlled, with an adequate duration of the withdrawal phase. The treatment response of the elderly in comparison to the overall patient sample should be emphasised.
This objectives of this study were three-fold: retrospectively evaluate anxiolytic/hypnotic consumption by psychiatric inpatients, identify the risk factors of prolonged intakes, and prospectively measure the impact of hospitalisation on the use of those drugs. Three hundred and seventy-six patients hospitalised in 11 psychiatric departments in the Paris region were studied using a structured interview for the anxiolytic/hypnotic treatments, DSM-III-R criteria, GHQ-12, HAD, Spiegel's questionnaire, COVI's anxiety scale and the CGI. Eighty-five per cent of the patients had taken one anxiolytic/hypnotic or more in the 3 months preceding hospitalisation. Hospitalisation induced little change in anxiolytic/hypnotic use: dosage frequency increased from 77% to 84% between the week preceding hospitalisation and that preceding discharge; 26% of consumers were taking at least two anxiolytics or two hypnotics in the first period vs. 23% in the second. The absence of withdrawal during hospitalisation was related to the high age and a diagnosis of depression rather than schizophrenia, to the existence of continuous intake over the 3 months preceding hospitalisation and to higher drug doses during the 7 days preceding hospitalisation. Prescription of treatment at the end of hospitalisation in previously non-user subjects was related to a higher HAD anxiety score at discharge.
Cognitive impairment in long-term high-dose diazepam abusers (dose > 30 mg diazepam/day; duration of abuse > 12 months) was examined by administering four memory-related tests and comparing the outcomes with those of matched controls. Deficits were found in spatial and visual learning, spatial and visual short-term memory (STM) as well as for spatial and visual long-term memory (LTM). As for verbal aspects of memory, solely the acquisition of novel verbal material (verbal learning) was impaired, Furthermore, deficits in a concentration task were observed. In chronic abuse the established memory deficits are similar to cognitive impairment after single doses. Relaxing or anxiety-reducing effects of diazepam were no longer present. The results of this experimental study demonstrate the risks of diazepam use beyond therapeutic range.
The effect of zopiclone (7.5 mg) on attention, vigilance and memory components was evaluated during a nocturnal period in comparison to a placebo, to zolpidem (10 mg) and to flunitrazepam (1 mg) in a double blind, randomized study, after administration of a single dose in 16 young healthy volunteers. It appears that there is a clear effect on attention and vigilance; this effect is apparent during the kinetic phase of the absorption of the medication. The effect on memory is transient and is absent four hours after the ingestion of the drug. The objective results are not strictly consistent with the chronology of the subjective parameters (Leeds scale — Visual Analogue Scale). The three hypnotics under comparison do not fundamentally differ except in their kinetic/pharmacodynamic effect relationship. One important fact, taking the parameters as a whole, is that there is no objective “residual” effect.
Little consensus exists on the risk of benzodiazepine (BZD) dependence. We investigated how often BZD dependence and related concepts have been defined in the literature on BZD effects in humans. In addition, the definitions of BZD dependence were compared in order to assess the similarity of contents. From a total of 250 papers (published between 1988 and 1991) 51 provided 126 dependence-related definitions. Six studies referred to the DSM definitions and one to the WHO definition. The obsolete concept of addiction was frequently defined (n=13), with little consensus about its meaning. Psychological and physical dependence were defined fairly often (n=29), also with low levels of consensus. We conclude that the discussion on the risk of BZD dependence would be well-served by attempting to improve consensus first. This may lead to more meaningful data on the incidence, prevalence and relevant co-factors of BZD dependence. An outline for criteria for benzodiazepine dependence is presented.
Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression.
To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment.
This was a naturalistic study using data from 54 female and 28 male patients (mean age of 54 years) that consecutively visited our psychiatric unit. They received active tDCS (five consecutive days, 2 mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20 minutes). The outcome variable (mood) was evaluated using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Predictor variables were age, gender, disorder and pharmacological treatment (seven dummy variables). We performed univariate and multivariate analyses as to identify predictors associated to the outcome.
After 5 days of treatment, BDI and HDRS scores decreased significantly (29% ± 36%, 18% ± 9%, respectively, P < 0.01 for both). Benzodiazepine use was independently associated with a worse outcome in both univariate (β = 4.92, P < 0.01) and multivariate (β = 5.8, P < 0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (β = –4.7, P = 0.02). A similar trend was observed for tricyclics (β = –4, P = 0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs.
tDCS over the DLPFC acutely improved depressive symptoms. Besides the inherent limitations of our naturalistic design, our results suggest that tDCS effects might vary according to prior pharmacological treatment, notably benzodiazepines and some antidepressant classes. This issue should be further explored in controlled studies.
A non-pharmacological method to reduce anxiety is “progressive relaxation” (PR). The aim of the method is to reduce mental stress and associated mental processes by means of progressive suppression of muscle tension. The study was addressed to evaluate changes in brain glucose metabolism induced by PR in patients under a stressing state generated by a diagnostic medical intervention. The effect of PR was compared to a dose of sublingual diazepam, with the prediction that both interventions would be associated with a reduction in brain metabolism. Eighty-four oncological patients were assessed with 18F-fluorodeoxyglucose-positron emission tomography. Maps of brain glucose distribution from 28 patients receiving PR were compared with maps from 28 patients receiving sublingual diazepam and with 28 patients with no treatment intervention. Compared to reference control subjects, the PR and diazepam groups showed a statistically significant, bilateral and generalized cortical hypometabolism. Regions showing the most prominent changes were the prefrontal cortex and anterior cingulate cortex. No significant differences were identified in the direct comparison between relaxation technique and sublingual diazepam. Our findings suggest that relaxation induced by a physical/psychological procedure can be as effective as a reference anxiolytic in reducing brain activity during a stressful state.
Data on psychotropic medications of older patients with schizophrenia spectrum disorder are scarce. Specifically, information about the use of benzodiazepines among older patients with schizophrenia spectrum disorder is very limited. Because benzodiazepine use in older patients has been associated with many disabling side effects, its use in actual practice must be described and questioned. This study aimed at exploring the prevalence of benzodiazepine use and the clinical factors associated with such use among older patients with schizophrenia spectrum disorder.
Data from the Cohort of individuals with Schizophrenia Aged 55 years or more (CSA) were used to examine the prevalence of benzodiazepine use among older patients with schizophrenia spectrum disorder. Demographic and clinical characteristics associated with benzodiazepine prescription were also explored.
The prevalence of benzodiazepine use was 29.8% of older patients with schizophrenia spectrum disorder. These patients were significantly more likely to have medical comorbidities, cognitive and social functioning impairments, to report a lifetime history of suicide attempt, to be institutionalized, and to have been hospitalized in a psychiatric service in the past year compared to those without a benzodiazepine prescription (all p<0.05). There were no between-group differences in schizophrenia severity and psychiatric comorbidity.
Although it can be hypothesized that benzodiazepine prescription is part of a short-term therapeutic strategy toward patients with more severe trouble or comorbid disorders, our results suggest a strong link between benzodiazepine prescription and a particularly vulnerable subpopulation of older patients with schizophrenia spectrum disorder.
In addition to suicide prediction, neuroscience can be expected to contribute in a unique and substantial way to the treatment of suicide risk. For psychotropic drugs such as lithium and clozapine a specific antisuicidal effect has been demonstrated, independent of effects on associated psychiatric disorders. The results from studies with ketamine are promising as they indicate a rapid and sustained relief of suicidal thoughts. Neurostimulation and neuromodulation provide new approaches to treatment, with a substantial impact on suicide risk. Novel pharmacological compounds targeting the vulnerability to suicidal behavior include drugs that affect the stress-response system and neuroprotective factors.
To determine the association between the use of opioids and benzodiazepines and the risk of falls with hip fracture in populations older than 65 years in Colombia.
A case-control study with patients older than 65 years with diagnosis of hip fracture. Two controls were obtained per case. The drugs dispensed in the previous 30 days were identified. Sociodemographic, diagnostic, pharmacological (opioids and benzodiazepines), and polypharmacy variables were analyzed. A logistic regression model was used to analyze the risk of fall with hip fracture while using these drugs.
We included 287 patients with hip fractures and 574 controls. There was a female predominance (72.1%) and a mean age of 82.4 ± 8.0 years. Of the patients, 12.7% had been prescribed with opioids and 4.2% with benzodiazepines in the previous month. The adjusted multivariate analysis found that using opioids (OR:4.49; 95%CI:2.72–7.42) and benzodiazepines (OR:3.73; 95%CI:1.60–8.70) in the month prior to the event was significantly associated with a greater probability of suffering a fall with hip fracture.
People who are taking opioids and benzodiazepines have increased risk for hip fracture in Colombia. Strategies to educate physicians regarding the pharmacology of older adults should be strengthened.
Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.
The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.
The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.
Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.
Behavioral and psychological symptoms of dementia (BPSD) are a common problem in long-term care facilities (LTC). Clinical guidelines dictate that first-line treatments for BPSD are psychosocial and behavioral interventions; if these are unsuccessful, psychotropic medications may be trialed at low doses and their effects can be monitored.
There have previously been no studies with nationally representative samples to investigate psychotropic administration in LTCs in Australia. This study determines the prevalence of psychotropic administration in a representative stratified random sample of 446 residents living with dementia from 53 Australian LTCs. Questionnaire and medical chart data in this study is drawn from a larger cross-sectional, mixed methods study on quality of life in Australian LTCs.
It was found that 257 (58%) residents were prescribed psychotropic medications including: antipsychotics (n = 160, 36%), benzodiazepines (n = 136, 31%), antidepressants (n = 117, 26%), and anti-dementia medications (n = 9, 2%). BPSD were found to be very common in the sample, with 82% (n = 364) of participants experiencing at least one BPSD. The most prevalent BPSD were depression (n = 286, 70%) and agitation (n = 299, 67%).
Although detailed background information was not collected on individual cases, the prevalence found is indicative of systematic industry-wide, over-prescription of psychotropic medications as a first-line treatment for BPSD. This study highlights a clear need for further research and interventions in this area.
The aim of the present study is to investigate the impact of benzodiazepine use on cognitive performance in primary care patients with first cognitive complaints. The association between the exposition to benzodiazepines (short and long half-life) and cognitive performance, evaluated through the Mini Mental State Examination (MMSE), was tested through analysis of the covariance and logistic regression models. Within the 4,249 participants (mean age 77.0 ± 8.2, 66.4% women), 732 (17%) were on benzodiazepines. When compared with non-users, short- and long-acting benzodiazepine users presented overlapping adjusted MMSE mean scores (respectively, mean MMSE score: 25.3, 95%CI 25.2–25.5; 25.4, 95%CI 25.1–25.7, and 25.9, 95%CI 25.3–26.4; p = 0.156). When tested according to the logistical regression model, after adjusting for potential confounders, no association was found between short and long acting benzodiazepine use and a MMSE < 24 (respectively, OR 0.9, 95%CI 0.7–1.2; OR 0.8, 95%CI 0.7–1.3) as compared with non-users. In conclusion, according to the results of our study, benzodiazepine use seems not to impact on cognitive performance- as assessed with the MMSE- of primary care patients referring to GPs for first cognitive complaints.
To investigate whether the use of long-acting benzodiazepines, in individuals aged 65 and over is mediated by physical or psychological factors.
Long-acting benzodiazepine consumption among older people has implications for mortality, morbidity and cost-effective prescribing. Two models explain benzodiazepine use in this age group, one linked to physical illness and disability and one to psychological factors.
Secondary analysis of baseline data from a study of 1059 community-dwelling non-disabled people aged 65 years and over recruited from three general practices in London. For this analysis, use of long-acting benzodiazepines was defined as any self-reported use of diazepam or nitrazepam in the last four weeks. Associations between demographic factors, health service use, and physical and psychological characteristics and benzodiazepine use were investigated.
The prevalence of benzodiazepine use in this sample was 3.3% (35/1059). In univariate analyses, benzodiazepine use was associated with female gender, low income, high consultation rates, physical factors (medication for arthritis or joint pain, polypharmacy, difficulties in instrumental activities of daily living, recent pain) and psychological factors (poor self-perceived health, social isolation, and symptoms of anxiety or agitation). In a multivariate logistic regression analysis only two factors retained statistically significant independent associations with benzodiazepine use: receiving only the state pension (OR=4.0, 95% CI: 1.70, 9.80) and pain in the past four weeks (OR=3.79, 95% CI: 1.36, 10.54).
Restless legs syndrome (RLS) is a common neurological movement disorder, characterized by restless and unpleasant sensations in the deep inside of legs. The symptoms of RLS are less noticeable during daytime, but more prevalent at night. Therefore, the disorder can induce low quality of life, insomnia, and impairment of daytime activity. RLS in end-stage renal disease (ESRD) patients is especially problematic due to premature discontinuation of dialysis and increased mortality. The prevalence of RLS among dialysis patients is much higher compared to the prevalence of the same disorder in patients with normal renal functions. Even though there are recommended treatment guidelines for the general population established by Medical Advisory Board of the RLS foundation, which include the use of dopamine agonists, levodopa, gabapentin, benzodiazepines, and opioids, limited information is available on the effects of these therapies in ESRD patients. Since the existing clinical data were extrapolated from small sample sizes in short-term clinical trials, further clinical studies are still needed to better assess the efficacy, safety, and tolerability of these medications in patients with ESRD.
One of the main changes in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was the separation of Stress Related Disorders from the Anxiety chapter. This separation paves the way to examine the unique characteristics of posttraumatic stress disorder (PTSD) (ie, identifiable onset, memory processes, etc) and related neural mechanisms. The time that elapses between the traumatic event and the manifestation of the disorder may also be addressed as the “golden hours,” or the window of opportunity in which critical processes take place and relevant interventions may be administrated.
In July 2015, the Canadian Agency for Drugs and Technologies in Health (CADTH) released a Rapid Response report summary, with a critical appraisal, on discontinuation strategies for patients with long-term benzodiazepines (BDZ) use. The CADTH document is a review of the literature. It includes studies whose intervention is BDZ discontinuation. Also, clinical guidelines, systematic reviews and meta-analyses are included. What emerges from the CADTH guidelines is that the best strategy remains gradual tapering of BDZ with little evidence for the use of adjunctive medications. The results show that simple interventions such as discontinuation letters from clinicians, self-help information and support in general, added to gradual tapering may be associated with a two- to three-fold higher chance of successful withdrawal, compared with treatment as usual. We suggest possible implications for day-to-day clinical practice.