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Background: The prevalence of benzodiazepine consumption in European countries remains at 2-3% of the general population despite the well-documented disadvantages of long-term use., Aims: To review systematically the success rates of different benzodiazepine discontinuation strategies., Method: Meta-analysis of comparable intervention studies., Results: Twenty-nine articles met inclusion criteria. Two groups of interventions were identified; minimal intervention (e.g. giving simple advice in the form of a letter or meeting to a large group of people; n=3), and systematic discontinuation (defined as treatment programmes led by a physician or psychologist; n=26). Both were found to be significantly more effective than treatment as usual: minimal interventions (pooled OR=2.8, 95% CI 1.6-5.1); systematic discontinuation alone (one study, OR=6.1, 95% CI 2.0-18.6). Augmentation of systematic discontinuation with imipramine (two studies, OR=3.1, 95% CI 1.1-9.4) or group cognitive-behavioural therapy for patients with insomnia (two studies, OR=5.5, 95% CI 2.3-14.2) was superior to systematic discontinuation alone., Conclusions: Evidence was found for the efficacy of stepped care (minimal intervention followed by systematic discontinuation alone) in discontinuing long-term benzodiazepine use.

Aims: Despite claims that comorbid anxiety disorders tend to lead to a poor outcome in the treatment of alcohol dependence, the few studies on this topic show conflicting results., Objective: To test whether the outcome of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder is worse than that of similar patients without a comorbid phobic disorder., Methods: The probabilities of starting to drink again and of relapsing into regular heavy drinking in (i) a group of 81 alcohol-dependent patients with comorbid social phobia or agoraphobia were compared with those in (ii) a group of 88 alcohol-dependent patients without anxiety disorders in a naturalistic follow-up using Cox regression analysis., Results: Adjusted for initial group differences, the hazard ratio for the association of phobic disorders with resumption of drinking was 1.05 (95% CI, 0.85-1.30, P = 0.66) and the adjusted hazard ratio for the association of phobic disorders with a relapse into regular heavy drinking was 1.02 (95% CI, 0.78-1.33, P = 0.89)., Conclusion: The findings of this study do not confirm the idea that alcohol-dependent patients who have undergone alcohol-dependence treatment are at greater risk of a relapse if they have a comorbid anxiety disorder. No differences were found in abstinence duration or time to relapse into regular heavy drinking between patients with and without comorbid phobic disorders.

Background: Discontinuation of benzodiazepine usage has never been evaluated in economic terms. This study aimed to compare the relative costs and outcomes of tapering off long-term benzodiazepine use combined with group cognitive behavioural therapy (TO+CBT), tapering off alone (TOA) and usual care., Method: A randomised controlled trial was conducted, incorporating a cost-effectiveness analysis from a societal as well as a pharmaceutical perspective. The cost of intervention treatment, prescribed drugs, healthcare services, productivity loss, and patients' costs were measured using drug prescription data and cost diaries. Costs were indexed at 2001 prices. The principal outcome was the proportion of patients able to discontinue benzodiazepine use during the 18-month follow-up. A secondary outcome measure was quality of life (Health Utility Index Mark III [HUI-3] and the Medical Outcomes Study 36-item Short-Form Health Survey [SF-36])., Results: A total of 180 patients were randomised to one of TO+CBT (n = 73), TOA (n = 73) or usual care (n = 34). Intervention treatment costs were an average of 172.99Euro per patient for TO+CBT and 69.50Euro per patient for TOA. Both treatment conditions significantly reduced benzodiazepine costs during follow-up compared with usual care. The incremental cost-effectiveness ratios (ICERs) showed that, for each incremental 1% successful benzodiazepine discontinuation, TO+CBT cost 10.30-62.53Euro versus usual care, depending on the study perspective. However, TO+CBT was extendedly dominated or was dominated by TOA. This resulted in ICERs of 0.57Euro, 10.21Euro and 48.92Euro for TOA versus usual care from the limited pharmaceutical, comprehensive pharmaceutical and societal perspective, respectively., Conclusions: TO+CBT and TOA both led to a reduction in benzodiazepine costs. However, it remains uncertain which healthcare utilisation has a causal relationship with long-term benzodiazepine consumption or its treatment. Although the ICERs indicated better cost effectiveness for TOA than for TO+CBT, the differences were relatively small. The addition of group CBT to tapering off had no clinical or economic advantages. Extrapolation of our data showed that the investment in TOA was paid back after 19 months when corrected for treatment gain with usual care.

Context: Attentional bias to disease-relevant emotional cues is considered to be pathogenetically relevant in anxiety disorders., Objective: To investigate functional neural correlates and disease specificity of attentional bias across different anxiety disorders., Design: A cognitive and emotional Stroop task, consisting of congruent and incongruent color words, obsessive-compulsive disorder (OCD)-related and panic-related negative words, and neutral words, was used in 3 patient groups and a control group during functional magnetic resonance imaging., Setting: Academic outpatient department for anxiety disorders., Patients and Participants: Medication-free patients with OCD (n = 16), panic disorder (PD) (n = 15), and hypochondriasis (n = 13) and 19 controls., Main Outcome Measure: Voxel-wise analyses of cerebral blood flow changes for contrasts of interest (incongruent vs congruent color words, OCD-related vs neutral words, and panic-related vs neutral words) within and between groups., Results: During incongruent vs congruent color naming, all patient groups recruited additional posterior brain regions relative to controls, but performance was impaired only in OCD. In OCD, color naming OCD-related, but not PD-related, words correlated with increased activation of frontal-striatal and temporal regions, although performance was unimpaired. In contrast, in PD, increased frontal-striatal involvement was found during color naming both OCD-related and panic-related words. In PD, color naming panic-related words was slowed and correlated with increased activation of the right amygdala and hippocampus. Patients with hypochondriasis showed a similar activation pattern to patients with PD., Conclusions: Our results support the hypothesis of increased distractibility for irrelevant information in patients with OCD, PD, and hypochondriasis associated with frontal-striatal and limbic involvement compared with controls. Although patients with OCD did not display an attentional bias in behavior relative to controls, there was a clear, specific neural response during color naming OCD-related words, involving mainly ventral brain regions. In contrast, generalized emotional interference effects were found in PD and hypochondriasis, involving ventral and widespread dorsal brain regions, reflecting not only unconscious emotional stimulus processing but also increased cognitive elaboration.

Objective: Evidence has emerged which indicates that the post-treatment relapse rate for alcohol-dependent patients with a comorbid anxiety disorder is higher than for alcohol-dependent patients without a comorbid anxiety disorder. The question raised by this evidence is whether the relapse rate in these dually diagnosed patients could be reduced if they were given additional treatment for the comorbid anxiety disorder. We attempted to answer this question by conducting a trial among patients with a double diagnosis of alcohol dependence and agoraphobia or social phobia., Method: We conducted a 32-week randomized controlled trial among 96 abstinent patients with a primary diagnosis of alcohol dependence and a comorbid anxiety disorder involving agoraphobia or social phobia. The patients were randomly assigned to an intensive psychosocial relapse-prevention program on its own (n = 49) or in combination with an anxiety treatment program comprising cognitive behavioral therapy (CBT) and optional pharmacotherapy consisting of an SSRI (n = 47). The primary outcome measure was the percentage of patients who suffered an alcohol relapse during a 32-week period. The secondary outcome measures were total abstinence, a reduction in the days of heavy drinking, and less severe anxiety symptoms., Results: Although the additional therapy clearly reduced the anxiety symptoms, it had no significant effect on the alcohol relapse rates., Conclusion: Anxiety treatment for alcohol-dependent patients with a comorbid anxiety disorder can alleviate anxiety symptoms, but it has no significant effect on the outcome of alcohol treatment programs.

Minimal intervention strategies to decrease long-term benzodiazepine use have not yet been evaluated in large primary care based studies with a blinded control condition and a long follow-up period. The purpose of this study was to assess the effects of a letter with a discontinuation advice sent to long-term benzodiazepine users in family practice followed by an evaluation consultation offer. The experimental group consisted of 2425 long-term benzodiazepine users, 1707 of whom were addressed by a discontinuation letter and an evaluation consultation offer. The control group consisted of 1821 long-term users. Primary endpoints were the number of prescribed daily dosages (PDD) and the percentage of subjects without prescription (quitters). At 21 months a reduction in benzodiazepine prescription of 26% was observed in the experimental group, versus 9% in the control group (PDD difference=12.5; 95%-ci: 8.2-16.8). In the experimental group 13% and in the control group 5% of the study completers were benzodiazepine prescription free through the full follow-up period (RR=2.6; 95%-ci: 2.0-3.4). The percentage of quitters at short-term (6 months) was 24% in the experimental group versus 12% in the control group (RR=2.1; 95%-ci: 1.8-2.4). It is concluded that this intervention strategy steadily reduces long-term benzodiazepine use in family practice.

Objective: The purpose of this study was to review effectiveness studies of self-help manuals for anxiety disorders in primary care., Methods: A systematic review of six identified randomized controlled trials was carried out. In addition to outcome, the articles were coded on quality variables., Results: The studies included differed with respect to the methodological quality, measurements used and size of the study population. Despite these differences, global results suggest that a self-help manual is an effective treatment possibility for primary care patients with anxiety disorders. The more time that was spent on guidance on the use of the self-help manual the greater was its effectiveness., Conclusion: Treatment with a self-help manual for anxiety disorders may be effective in primary care. Data are lacking on the feasibility and cost-effectiveness of these manuals.

Background: Dysfunction of frontal-striatal, particularly orbitofrontal-striatal, circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD), characterized by obsessions, ritualistic behavior, anxiety, and specific cognitive impairments. In addition, neuropsychological studies in OCD have reported impairments in visuospatial tasks and executive functions, such as planning., Objective: To determine whether dorsal prefrontal-striatal dysfunction mediates planning impairment in patients with OCD., Design: A parametric self-paced pseudorandomized event-related functional magnetic resonance imaging version of the Tower of London task was used in 22 medication-free patients with OCD and 22 healthy control subjects. This paradigm, allowing flexible responding and post hoc classification of correct responses, was developed to compare groups likely to differ in performance., Results: Behavioral results showed significant planning impairments in OCD patients compared with control subjects. During planning, decreased frontal-striatal responsiveness was found in OCD patients, mainly in dorsolateral prefrontal cortex and caudate nucleus. In addition, OCD patients showed increased, presumably compensatory, involvement of brain areas known to play a role in performance monitoring and short-term memory processing, such as anterior cingulate, ventrolateral prefrontal, and parahippocampal cortices., Conclusions: These findings support the hypothesis that decreased dorsal prefrontal-striatal responsiveness is associated with impaired planning capacity in OCD patients. Because the described frontal-striatal dysfunction in OCD is independent of state anxiety and disease symptom severity, we conclude that executive impairment is a core feature in OCD.

Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder (OCD). Functional imaging studies, however, have yielded inconsistent results, presumably due to methodological differences (patient inclusion criteria, stimulus paradigm, imaging technique, and absence of control groups). In the present study, randomized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls. A total of 21 subjects (11 OCD patients and 10 healthy controls) were scanned using H(2)(15)O positron emission tomography (PET). Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences. State anxiety and obsessionality were rated after each scan using visual analogue scales. Main effects of stimulus type (contamination vs. neutral) were found in bilateral occipital cortex in both groups. A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients. Sensitization effects were observed in the right amygdala in the OCD group; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity. The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures, specifically the amygdala, resulting in an inadequate fear response in OCD patients with contamination fear.

This randomised controlled trial was conducted to compare zolpidem to an equivalent dose of temazepam with respect to subjective rebound insomnia after cessation of 4 weeks of treatment in chronic insomnia (zolpidem 10 mg, n=79; temazepam 20 mg, n=84). Both agents improved total sleep time (TST) as well as sleep onset latency (SOL) significantly during the 4 treatment weeks. Prevalence rates for rebound insomnia, defined as a worsening of TST or SOL of more than 40% compared to baseline, were 27% for TST and 53% for SOL in the Zolpidem condition and 26% and 58%, respectively, in the temazepam condition. No significant differences were found between both agents with respect to rebound insomnia, nor with respect to their efficacy or safety. We conclude that in clinical practice zolpidem has no advantages over temazepam with respect to rebound insomnia.

Background: Patients with a double diagnosis of alcohol dependence and phobic disorders are a common phenomenon in both alcohol and anxiety disorder clinics. If we are to provide optimum treatment we need to know more about the clinical characteristics of this group of comorbid patients., Objective: To answer the following questions. (1). What are the clinical characteristics of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder? (2). Are alcohol dependence and other clinical characteristics of comorbid patients different from those of 'pure' alcohol-dependent patients? (3). Are the anxiety symptoms and other clinical characteristics of comorbid patients different from those of 'pure' phobic patients?, Method: Three groups of treatment-seeking patients were compared on demographic and clinical characteristics: alcohol dependent patients with a comorbid phobic disorder (n = 110), alcohol-dependent patients (n = 148) and patients with social phobia or agoraphobia (n = 106). In order to diagnose the comorbid disorders validly, the assessment took place at least 6 weeks after detoxification., Results: Comorbid patients have high scores on depressive symptoms and general psychopathology: 25% of patients have a current and 52% a lifetime depressive disorder. The majority have no partner and are unemployed, they have a high incidence of other substance use (benzodiazepine, cocaine, cannabis) and a substantial proportion of comorbid patients have been emotionally, physically and sexually abused. They do not have a more severe, or different type of alcohol dependence or anxiety disorder than 'pure' alcohol-dependent patients and phobic patients respectively., Conclusion: Comorbid patients constitute a complex part of the treatment-seeking population in alcohol clinics and psychiatric hospitals. These findings should be taken into account when diagnosing and treating alcohol-dependent patients with a comorbid phobic disorder.

Aims: It has been repeatedly stated that comorbid anxiety disorders predict poor outcome of alcoholism treatment. This statement is based on the high comorbidity of alcohol use disorders and anxiety disorders, and the negative influence of other comorbid psychiatric disorders on the outcome of treatment of alcohol dependence. This review focuses on outcome results of alcohol-dependent patients with a comorbid anxiety disorder. We try to answer the question whether anxiety disorders should be treated in alcohol-dependent patients to improve outcome results in alcoholism treatment., Methods: In a search through Pubmed, Psychinfo and Cochrane, we found only 12 articles on this subject. We distinguished three perspectives: (1) studies on the predictive value of comorbid anxiety disorders on the outcome of alcoholism treatment; (2) studies on the improvement of abstinence rates and anxiety symptoms by offering pharmacological treatment for comorbid anxiety disorders; (3) studies on psychotherapeutic treatment., Results: Most studies showed methodological limitations. Only one high quality study showed that comorbid anxiety disorders predict poor outcome of the treatment of alcohol dependence., Conclusions: We cannot conclude that comorbid anxiety disorders in alcohol-dependent patients need a specific treatment to prevent relapse. However, medication and perhaps cognitive behavioural therapy can be useful in alcohol-dependent patients with a comorbid anxiety disorder to reduce anxiety symptoms. Methodological implications for further research are discussed.

Background: In this paper the effects of cognitive therapy on the belief in causal catastrophic misinterpretations (CCMs) of bodily sensations in panic disorder patients were studied., Methods: CCMs were formulated at the start of treatment and assessed at every treatment session for credibility during panic attacks and during that session. The relation between the belief in CCMs and other measures of panic was also studied. Sixty-six patients rated their belief in 1-3 CCMs during treatment with cognitive therapy. They also filled in questionnaires (ACQ and BSQ) at the start and end of treatment and kept a panic diary., Results: The belief in CCMs diminished significantly in the course of treatment. A significant correlation between panic frequency and belief in CCMs during panic attacks, but not during treatment sessions, was found. Relations between improvement in panic frequency, ACQ- and BSQ-scores on the one hand and belief in CCMs on the other, also revealed significant correlations with belief ratings during panic attacks only., Conclusions: Especially ratings of belief during panic attacks are important in assessing the outcome of cognitive therapy in panic disorder. This measure can be considered as a severity measure. Belief in CCMs during treatment sessions seems to have little clinical significance., (Copyright 2002 S. Karger AG, Basel)

Background: In this study the effects of treatment with cognitive therapy, antidepressants or pill-placebo on the locus of control orientation in panic disorder patients were analysed, as well as the relation of this panic locus of control with panic frequency and cognitive measures of panic., Methods: A Multidimensional Anxiety Locus of Control scale (MALC) was developed and completed with other measures (ACQ and BSQ) before and after treatment. Patients also kept a panic diary., Results: Four subscales were derived from the MALC: one Internal, and three external (a Chance, a Medication, and a Therapist) locus of anxiety control orientation scales. Cognitive therapy was superior over pill-placebo on most outcome measures whereas antidepressants were only superior in reducing the number of panic attacks. Treatment with cognitive therapy resulted in an increase of 'internal' anxiety control orientation and a decrease of 'chance' and 'medication' orientation, in comparison with antidepressant therapy. The residualized gain scores on the MALC subscales correlated with clinical improvement in subjects treated with cognitive therapy only., Conclusions: Results suggest that the locus of control orientation is important in evaluating the differential effects of treatments in panic disorder. A differential effect on panic locus of control in favor of cognitive therapy in comparison to medication was found., (Copyright 2002 S. Karger AG, Basel)