Withdrawing Benzodiazepines in Patients With Anxiety Disorders.

The large class of CNS-depressant medications-the benzodiazepines-have been extensively used for over 50 years, anxiety disorders being one of the main indications. A substantial proportion (perhaps up to 20-30 %) of long-term users becomes physically dependent on them. Problems with their use became manifest, and dependence, withdrawal difficulties and abuse were documented by the 1980s. Many such users experience physical and psychological withdrawal symptoms on attempted cessation and may develop clinically troublesome syndromes even during slow tapering. Few studies have been conducted to establish the optimal withdrawal schedules. The usual management comprises slow withdrawal over weeks or months together with psychotherapy of various modalities. Pharmacological aids include antidepressants such as the SSRIs especially if depressive symptoms supervene. Other pharmacological agents such as the benzodiazepine antagonist, flumazenil, and the hormonal agent, melatonin, remain largely experimental. The purpose of this review is to analyse the evidence for the efficacy of the usual withdrawal regimes and the newer agents. It is concluded that little evidence exists outside the usual principles of drug withdrawal but there are some promising leads.

Benzodiazepine harm: how can it be reduced?

The benzodiazepines (BZDs) are anxiolytics, hypnotics, anticonvulsants, muscle-relaxants and induce anaesthesia. Adverse effects comprise sedation subjectively and cognitive and psychomotor impairment objectively. Complex skills such as driving can be compromised. Paradoxical excitement can have forensic implications. Long term use beyond the licensed durations is common but both efficacy and adverse effects associated with this have been poorly documented. Withdrawal and dependence have excited particular concern, and even polemic. Perhaps a third of long term (beyond 6 months) users experience symptoms and signs on attempting to withdraw - anxiety, insomnia, muscle spasms and tension and perceptual hypersensitivity. Uncommonly, fits or a psychosis may supervene. The patterns following withdrawal vary widely. The usual method of withdrawal is slow tapering but it may not obviate the problems completely. BZDs are also drugs of abuse either on their own or in conjunction with opioids and stimulants. Claims have been made that the use of BZDs is associated with increased mortality. This is a concern in view of the widespread usage of these drugs, particularly in the elderly. All of these factors impinge on the risk : benefit ratio and the severity of the indications. Harm reduction should focus on choice of alternative treatments both psychological and pharmacological. Guidelines emphasise that BZDs are not drugs of first choice and should only be used short term. Schedules are available to educate about methods of withdrawal in current users, emphasising the slow rate of taper. General principles of harm minimization in the addiction field are appropriate to BZD abuse.

Withdrawing benzodiazepines in primary care.

The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. The adverse effects of these drugs have been extensively documented and their effectiveness is being increasingly questioned. Discontinuation is usually beneficial as it is followed by improved psychomotor and cognitive functioning, particularly in the elderly. The potential for dependence and addiction have also become more apparent. The licensing of SSRIs for anxiety disorders has widened the prescribers' therapeutic choices (although this group of medications also have their own adverse effects). Melatonin agonists show promise in some forms of insomnia. Accordingly, it is now even more imperative that long-term benzodiazepine users be reviewed with respect to possible discontinuation. Strategies for discontinuation start with primary-care practitioners, who are still the main prescribers.This review sets out the stratagems that have been evaluated, concentrating on those of a pharmacological nature. Simple interventions include basic monitoring of repeat prescriptions and assessment by the doctor. Even a letter from the primary-care practitioner pointing out the continuing usage of benzodiazepines and questioning their need can result in reduction or cessation of use. Pharmacists also have a role to play in monitoring the use of benzodiazepines, although mobilizing their assistance is not yet routine. Such stratagems can avoid the use of specialist back-up services such as psychiatrists, home care, and addiction and alcohol misuse treatment facilities.Pharmacological interventions for benzodiazepine dependence have been reviewed in detail in a recent Cochrane review, but only eight studies proved adequate for analysis. Carbamazepine was the only drug that appeared to have any useful adjunctive properties for assisting in the discontinuation of benzodiazepines but the available data are insufficient for recommendations to be made regarding its use. Antidepressants can help if the patient is depressed before withdrawal or develops a depressive syndrome during withdrawal. The clearest strategy was to taper the medication; abrupt cessation can only be justified if a very serious adverse effect supervenes during treatment. No clear evidence suggests the optimum rate of tapering, and schedules vary from 4 weeks to several years. Our recommendation is to aim for withdrawal in <6 months, otherwise the withdrawal process can become the morbid focus of the patient's existence. Substitution of diazepam for another benzodiazepine can be helpful, at least logistically, as diazepam is available in a liquid formulation.Psychological interventions range from simple support through counselling to expert cognitive-behavioural therapy (CBT). Group therapy may be helpful as it at least provides support from other patients. The value of counselling is not established and it can be quite time consuming. CBT needs to be administered by fully trained and experienced personnel but seems effective, particularly in obviating relapse.The outcome of successful withdrawal is gratifying, both in terms of improved functioning and abstinence from the benzodiazepine usage. Economic benefits also ensue.Some of the principles of withdrawing benzodiazepines are listed. Antidepressants may be helpful, as may some symptomatic remedies. Care must be taken not to substitute one drug dependence problem for the original one.

Addiction and the pharmacology of cannabis: implications for medicine and the law.

The topic of drug addiction or misuse of drugs has numerous far-reaching ramifications into areas such as neuroscience, medicine and therapeutics, toxicology, epidemiology, national and international economics and politics, and the law. The general principles of drug addiction are first summarised. A recurring and intrinsic problem is lack of adequate characterisation of the independent variable, namely the drug taken. Secondly, it is not feasible to allocate subjects randomly to treatments. Thirdly, the heterogeneity of different forms of addiction precludes facile generalisations. "A problem drug user is anyone who experiences social, psychological, physical, or legal problems related to intoxication, and/or regular excessive consumption, and/or dependence as a consequence of their use of drugs" (UK Advisory Council on Misuse of Drugs, 1982). Cannabis is a genus of flowering plants whose products are used as recreational drugs. Claims have been made for a range of therapeutic properties. Its two main active principles are delta9 - tetrahydrocannabinol (THC) and cannabidiol (CBD). These compounds have contrasting pharmacological properties. THC is suspected of causing psychotic phenomena, but CBD seems more sedative and may even be antipsychotic. The past use of cannabis, particularly the concentrations of THC and CBD, can be monitored with hair analysis. Recent studies involving the administration of THC and CBD to human subjects are reviewed. Suggestions are made for further research into the pharmacology and toxicology of CBD. Such data may also point to a more rational evidence-based approach to the legal control of cannabis preparations.

Antiparkinsonian medication and pathological gambling.

Parkinson's disease is a common condition, usually treated by dopaminergic agents, both ergot and non-ergot. Many behavioural abnormalities are associated with such usage, including impulse control disorders (ICDs), dopamine dysregulation syndrome and 'punding'. Pathological gambling, a form of ICD, comprises persistent and maladaptive gambling of various types that disrupts personal, family or occupational activity. Pathological gambling may be associated with other abnormal actions such as pathological shopping, hoarding and hypersexuality. The incidence varies widely from study to study but may be up to 7% of users of dopaminergic agents. Recognition of this problem has led drug regulatory agencies to add precautions concerning pathological gambling to official drug information for the entire class of antiparkinsonian medications. The literature is not entirely consistent and opinions differ greatly, but pramipexole (a dopamine D2 and D3 agonist), and perhaps ropinirole (also a D2/D3 agonist), may be especially likely to be associated with pathological gambling, although the precise nature of the relationship is unclear. Treatment involves reducing the dose of the medication or switching to another medication; unfortunately, the Parkinson's disease may worsen. The mechanism of this adverse effect is believed to be excessive dopaminergic stimulation but probably not specifically involving D3 receptors. A parallel to addictive behaviour with stimulant drugs has been noted.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision.

In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

Pharmacotherapy of mood disorders and treatment discontinuation.

Depression is the most frequent and costly problem in primary care, where most of these patients are seen and treated. In many countries, the public regard antidepressant drugs as 'addictive', partly because of the withdrawal symptoms that can occur when they are discontinued. Indeed, discontinuation (withdrawal) symptoms can follow the stoppage of almost all classes of antidepressants, including selective serotonin receptor inhibitors (SSRIs). This is important because they are widely regarded as drugs of choice for both depression and the anxiety disorders. But is this true withdrawal or merely rebound? The antidepressant discontinuation syndrome is characterised by the time-locked emergence of new, clearly defined and quantifiable signs and symptoms that ensue on stopping or reducing the dose of an antidepressant. Thereby, it meets the criteria for a withdrawal syndrome. The symptoms are not usually severe or protracted. SSRIs vary in their propensity to be associated with a discontinuation syndrome: paroxetine appears to be the most likely. Patients should be warned of the possibility of developing such a reaction, but reassured that it is usually mild and self limiting. Tapering the dose, if practicable, is worthwhile. In severe cases, temporary reinstatement of the SSRI and slower tapering may be necessary. Escalation of antidepressant dosage, or 'street abuse', is rare with antidepressants. The use of antidepressants is generally beneficial, and efforts should be made to optimise our current use of these drugs as well as encouraging the development of newer, better and innovative compounds. To this end, physicians should educate themselves and the public about discontinuation and withdrawal, so that these clinical features can be put in a realistic context.

Limitations of current medical treatments for depression: disturbed circadian rhythms as a possible therapeutic target.

The proportion of diagnosed depressives prescribed antidepressants has increased markedly over the last 20 years, mainly following the introduction of the selective serotonin reuptake inhibitors. However, currently available antidepressants have notable limitations, relating to their only moderate efficacy relative to placebo, relatively slow onset of action, possible withdrawal symptoms, and problems of compliance. Sleep disturbances are often used to identify newly presenting depressive patients, and may be part of a more general alteration of bodily rhythms. There are links between pharmacological treatments and circadian rhythms in depression, which might represent another, new option for the development of a therapeutic approach to depression treatment. Many antidepressants affect sleep, some are sedative, and others have been used specifically in severely insomniac depressives. Disturbances in circadian rhythms may be an integral part of depressive mechanisms, and normalising them via an innovative mechanism of antidepressant action may be a fruitful avenue in the search for improved antidepressant agents.

Which antidepressants have demonstrated superior efficacy? A review of the evidence.

A review of published evidence of superior efficacy of a particular antidepressant in major depressive disorder may assist clinicians in making considered treatment choices. To identify such candidates, an international group of experts met to assess published evidence (identified through searches in Medline and Embase databases and discussions with experts in the field) from randomized, controlled trials and meta-analyses comparing two antidepressants under conditions of fair comparison. Criteria were defined to judge the strength of evidence. Two pivotal studies in moderate-to-severe major depressive disorder that demonstrate superiority on the primary efficacy measure, or alternatively one pivotal study supported by consistent results from meta-analyses, was considered to constitute evidence for definite superiority. Three antidepressants met these criteria: clomipramine, venlafaxine, and escitalopram. Three antidepressants were found to have probable superiority: milnacipran, duloxetine, and mirtazapine. Only escitalopram was found to have definite superiority in the treatment of severe depression; probable superiority was identified for venlafaxine and possible superiority for milnacipran and clomipramine. This review of published data found evidence that only a very few antidepressants are shown to be more effective than others.

Escitalopram versus paroxetine for social anxiety disorder: an analysis of efficacy for different symptom dimensions.

BACKGROUND: A previous factor analysis of pooled data demonstrated that the Liebowitz Social Anxiety Scale (LSAS) can be divided into six subscales. This paper examines data from a fixed-dose trial of escitalopram versus paroxetine, in order to determine the differential effects of these agents on symptom dimensions in social anxiety disorder (SAD). METHODS: Data from a 24-week randomised, placebo-controlled, comparative study of fixed doses of escitalopram (5 mg, 10 mg, 20 mg) versus paroxetine (20 mg) in SAD were examined. The six factors identified in a previous factor analysis of baseline data from escitalopram studies on the primary efficacy scale, the LSAS, were used to compute subscale scores. These were analysed using analysis of covariance (ANCOVA), and standardised effect sizes were calculated. RESULTS: The combined escitalopram data and the paroxetine data both demonstrated significant superiority to placebo on each of the 6 LSAS factors at week 24 (OC analysis). Escitalopram doses of 5 mg, 10 mg, and 20 mg were generally more effective than placebo for each of the factors. Escitalopram 20 mg was significantly more effective than paroxetine 20 mg on 5 of the 6 symptom dimensions. CONCLUSION: Factor analysis of the LSAS allows for useful secondary analyses that support and extend the primary efficacy analysis of this instrument. The analysis here indicates that different escitalopram doses are effective across the various symptom dimensions of SAD.

Atypical antipsychotics: from potassium channels to torsade de pointes and sudden death.

Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies.

A review of the management of antidepressant discontinuation symptoms.

Strong evidence supports the existence of a discontinuation syndrome following the withdrawal of antidepressant medication, particularly second-generation antidepressants. The syndrome is a common phenomenon and guidance as to best avoid the symptoms is essential for both practitioners and patients. The current study reviewed the available literature on the best methods of discontinuation for antidepressants in order to avoid or prevent the occurrence of any unpleasant side effects associated with antidepressant withdrawal. Accordingly, an electronic search of the PubMed/MedLine database and Google Scholar was conducted to find relevant literature published within the last 10 years. From this, 18 related articles were identified; five clinical studies, one case series, one consensus panel's recommendations and 11 literature reviews. Of the articles reviewed there is a general consensus as to tapering the drug slowly over a period of weeks or months. Also, in those patients who experience severe symptoms the drug should be reinstated and discontinued more gradually. The discontinuation syndrome does not occur as frequently or severely with longer-acting agents such as fluoxetine and therefore it is recommended that switching to this drug prior to withdrawal may be advisable. The articles reviewed also emphasize the need for patient education and reassurance throughout the discontinuation process. One in particular adds that cognitive behavioural therapy may be a useful tool in easing the patients' distress. However, this review highlights the lack of controlled data to support the available guidelines. Furthermore, the guidance which is available is somewhat conflicting. Research approaches should address this issue as well as develop appropriate methods of withdrawal for specific drugs.

Use of psychotropic medication in the general population of France, Germany, Italy, and the United Kingdom.

BACKGROUND: The use of psychotropic medications and its association with sleep and psychiatric and physical illnesses were studied in the general population. METHOD: A cross-sectional telephone survey was carried out using the Sleep-EVAL knowledge-base system. A representative sample of the noninstitutionalized general populations of France, Germany, Italy, and the United Kingdom, aged 15 years or over, was interviewed (N = 18,679; participation rate: 78.8%; target population: 204,605,391 inhabitants). Questions were asked about psychotropic medication intake (name of medication, indication, dosage, duration of intake, prescriber), sociodemographics, physical illnesses, and DSM-IV mental disorders. RESULTS: At the time of the interview, 6.4% of the subjects took a psychotropic medication. Anxiolytics were reported by 4.3% of the sample, hypnotics by 1.5%, antidepressants by 1.0%, and neuroleptics and other psychotropics by less than 1.0%. Hypnotics and anxiolytics were mostly used as a sleep disorder treatment. Antidepressants were taken appropriately for a depressive illness in only 44.1% of cases. Low doses of hypnotics and anxiolytics were found in about 10% of cases and low doses of antidepressants in 31.7% of cases. Subjects with a psychiatric disorder received a psychotropic treatment only infrequently (between 10% to 40.4%, depending on the disorder). All psychiatric disorders, including mood disorders, were treated mainly with an anxiolytic. A concomitant physical illness increased the likelihood of using a psychotropic treatment and was a strong predictor of adequate psychotropic dosage. CONCLUSION: Psychiatric pathology and sleep disorders remained mostly untreated or inadequately managed in the general population. Depression is underdiagnosed by the physicians and is treated with antidepressant in only 7% of cases. By contrast, anxiolytics are extensively prescribed, especially in France and Italy. The co-occurrence of organic and psychiatry disorders increases the frequency of medical consultations and the likelihood of being given a prescription for the mental disorder.

Treatment of generalised anxiety disorder with a short course of psychological therapy, combined with buspirone or placebo.

BACKGROUND: Very few studies have examined the combination of drug and psychological treatment in generalised anxiety disorder (GAD). Theoretically, buspirone should be a useful drug to combine with a learning-based therapy. METHODS: Sixty patients with GAD were randomly assigned to treatment with buspirone or placebo, combined with anxiety management training or non-directive therapy for a period of 8 weeks. RESULTS: Forty-four patients with a mean Hamilton Anxiety Scale score of 28 completed treatment. There were no significant differences between treatment groups. All groups showed significant improvement after 8 weeks compared to baseline. There were no baseline differences between those who completed the trial and those who did not but patients given buspirone were more likely to drop out. CONCLUSIONS: A short course of psychological therapy, whether or not accompanied by active medication, was an effective treatment for patients diagnosed as having quite severe symptoms of GAD. CLINICAL IMPLICATIONS AND LIMITATIONS: Dropouts led to a sample size which may have been too small to detect group differences. Cognitive therapy may have been more effective.

Tianeptine and paroxetine in major depressive disorder, with a special focus on the anxious component in depression: an international, 6-week double-blind study dagger.

Tianeptine (37.5 mg/day) and paroxetine (20 mg/day) were compared in a population of depressive patients without past or current history of co-morbid anxiety and/or important anxiolytic treatment. In a 6-week, double blind trial, the special focus was on anxious symptoms.Both drugs showed good efficacy on depressive symptomatology, assessed with MADRS and HDRS, but no difference was detected between tianeptine and paroxetine, for any assessment criterion. Despite the choice of selected depressive patients, without any co-morbid anxious disorder, anxiety scale scores at inclusion (HAMA and BAS) were appreciable but correlated poorly with depressive scores. Both tianeptine and paroxetine improved the apparent anxious component in depression. Tolerability of both drugs was good, although significantly better with tianeptine.Thus tianeptine and paroxetine are effective and safe treatments for major depression and may also act directly on the anxious component of the psychopathology. Copyright 2001 John Wiley & Sons, Ltd.

Benzodiazepines revisited--will we ever learn?

AIMS: To re-examine various aspects of the benzodiazepines (BZDs), widely prescribed for 50 years, mainly to treat anxiety and insomnia. It is a descriptive review based on the Okey Lecture delivered at the Institute of Psychiatry, King's College London, in November 2010. METHODS: A search of the literature was carried out in the Medline, Embase and Cochrane Collaboration databases, using the codeword 'benzodiazepine(s)', alone and in conjunction with various terms such as 'dependence', 'abuse', etc. Further hand-searches were made based on the reference lists of key papers. As 60,000 references were found, this review is not exhaustive. It concentrates on the adverse effects, dependence and abuse. RESULTS: Almost from their introduction the BZDs have been controversial, with polarized opinions, advocates pointing out their efficacy, tolerability and patient acceptability, opponents deprecating their adverse effects, dependence and abuse liability. More recently, the advent of alternative and usually safer medications has opened up the debate. The review noted a series of adverse effects that continued to cause concern, such as cognitive and psychomotor impairment. In addition, dependence and abuse remain as serious problems. Despite warnings and guidelines, usage of these drugs remains at a high level. The limitations in their use both as choice of therapy and with respect to conservative dosage and duration of use are highlighted. The distinction between low-dose 'iatrogenic' dependence and high-dose abuse/misuse is emphasized. CONCLUSIONS: The practical problems with the benzodiazepines have persisted for 50 years, but have been ignored by many practitioners and almost all official bodies. The risk-benefit ratio of the benzodiazepines remains positive in most patients in the short term (2-4 weeks) but is unestablished beyond that time, due mainly to the difficulty in preventing short-term use from extending indefinitely with the risk of dependence. Other research issues include the possibility of long-term brain changes and evaluating the role of the benzodiazepine antagonist, flumazenil, in aiding withdrawal.

Satisfaction with medication is correlated with outcome but not persistence in patients treated with placebo, escitalopram, or serotonin-norepinephrine reuptake inhibitors: a post hoc analysis.

OBJECTIVE: To test whether satisfaction with taking medication, assessed using item 15 of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), is associated with clinical outcome and persistence with treatment. METHOD: In this post hoc analysis, data were analyzed from 4 randomized placebo-controlled studies of patients with major depressive disorder treated with escitalopram (650 patients taking escitalopram and 534 taking placebo), together with data from 2 randomized trials of escitalopram versus venlafaxine or duloxetine (235 patients taking escitalopram and 233 taking a serotonin-norepinephrine reuptake inhibitor). The studies were published between 2002 and 2007. Instruments included the Q-LES-Q, which was assessed at baseline and week 8, and the Montgomery-Asberg Depression Rating Scale (MADRS), which was assessed at baseline and weeks 1, 2, 4, 6, and 8. RESULTS: At baseline, the mean ± SD MADRS total score was 30.0 ± 4.6, and the mean Q-LES-Q item 15 score was 2.9 ± 0.9. At week 8, the MADRS response rates of placebo-treated patients with a low, moderate, or high satisfaction with medication at baseline were 30%, 37%, and 46%, respectively (mixed model repeated measures [MMRM]). The corresponding MADRS response rates for escitalopram-treated patients with a low, moderate, or high satisfaction at baseline were 56%, 60%, and 67%, respectively (MMRM). Baseline satisfaction with medication was not significantly correlated with time to withdrawal (all reasons). The change in satisfaction with medication from baseline to endpoint was significantly correlated with symptomatic improvement on the MADRS (P < .001). CONCLUSIONS: Baseline satisfaction with medication after 1 week of placebo run-in is a moderator of treatment outcome but not of persistence of treatment in the acute treatment phase of depressed outpatients. Patient attitude toward medication should be taken into account before treatment is initiated.

Usage of benzodiazepines: A review.

Abstract Purpose. The use of benzodiazepines remains a source of controversy. Some prescribers believe that they are beneficial and espouse their use; others regard their risk:benefit ratio as too adverse for any but occasional use. This review considers these viewpoints based on the appropriate literature. Survey. The recent English-language literature relating to this topic was surveyed. The publications proved too heterogeneous for a formal meta-analysis, so a descriptive review is provided. Overview. Surveys of benzodiazepine use provide data mainly from the UK, Europe and North America. Prescribing patterns varied widely but long-term usage is common and sometimes the norm. Conclusions. Long-term prescription of benzodiazepines still takes place despite general warnings from the medical and other professions and drug regulatory bodies that long-term use is unjustified both from the lack of a systemic database establishing such efficacy and a large literature documenting the risks of long-term usage, such as dependence. The young and the old are particularly at risk. Continued monitoring is essential, but the regulatory authorities may need to take a more active role in curbing such undesirable practice.