Discontinuation of long-term benzodiazepine use: 10-year follow-up.

BACKGROUND: Several interventions aiming at discontinuation of long-term benzodiazepine use have been proven effective in the short term. However, data on the persistence of discontinuation are lacking. OBJECTIVES: To assess 10-year follow-up status in patients who succeeded in stopping benzodiazepine use after a discontinuation letter from the patient's own GP. To identify determinants of successful discontinuation on the long term. METHODS: Follow-up data of patients who participated in a large prospective, controlled stepped care intervention programme among long-term benzodiazepine users in primary care. RESULTS: At 10-year follow-up, the percentage of benzodiazepine abstinence was 58.8%. Non-abstinent patients used lower doses of benzodiazepine. Being abstinent at 21 months after the intervention predicted abstinence at 10-year follow-up. CONCLUSIONS: Ten years after a minimal intervention to decrease long-term benzodiazepine use, the majority of patients who were able to discontinue benzodiazepine use initially, does not use benzodiazepines at 10-year follow-up. Patients who did not succeed in maintaining abstinence from benzodiazepines appear to use lower or average dosages.

Consequences of a benzodiazepine discontinuation programme in family practice on psychotropic medication prescription to the participants.

BACKGROUND: Whether long-term benzodiazepine users who participate in a family practice-based benzodiazepine discontinuation programme substitute benzodiazepines by other psychotropics is not clear. OBJECTIVE: To evaluate the impact of a benzodiazepine discontinuation programme on non-benzodiazepine psychotropic prescription in family practice. METHODS: In family practices in the Netherlands, 2425 long-term benzodiazepine users participated in a two-step benzodiazepine discontinuation programme. The programme started with a discontinuation letter (Step 1). Subjects unable to stop (N = 1707) were offered participation in Step 2, a three-group randomized trial with a taper procedure with group psychotherapy, a taper without psychotherapy and usual care. Only 156 subjects agreed to participate. The comparison group consisted of 1821 long-term users from family practices not participating in the programme. The main outcome was the change in prescription of non-benzodiazepine psychotropic medication from baseline (3 months before the start of the programme) till 21 months after the start of the programme. Four logistic regression models were performed concerning antidepressant prescription in the follow-up. RESULTS: Only antidepressants were prescribed in relevant numbers. The prescription of antidepressants was not related to the programme. (P-value of experimental versus control group varied between 0.18 and 0.85 in the four models). The most important predictor of antidepressant prescription in follow-up was baseline antidepressant prescription [odds ratio (OR): 67.2; 95% confidence interval (95% CI): 49.8-90.7]. Subjects, of whom the prescription of benzodiazepines had been discontinued completely, had been prescribed less antidepressants (OR: 0.8; 95% CI: 0.6-1.0). CONCLUSION: An effective benzodiazepine reduction programme was not accompanied by a substitute use of other psychotropics.

Long-term outcome of two forms of randomised benzodiazepine discontinuation.

About two-thirds of long-term users of benzodiazepines in the population are able to discontinue this drug with the aid of supervised programmes for tapering off. Little is known about the long-term outcome of such programmes, and they have never been compared with usual care. After a 15-month follow-up of a randomised controlled trial comparing such a programme with and without psychotherapy with usual care, we found significantly higher longitudinal abstinence rates in long-term benzodiazepine users who received a benzodiazepine tapering-off programme without psychotherapy (25 out of 69, 36%) compared with those who received usual care (5 out of 33,15%; P=0.03).

Predictors of discontinuation of benzodiazepine prescription after sending a letter to long-term benzodiazepine users in family practice.

BACKGROUND: Predictors of benzodiazepine discontinuation after sending a discontinuation letter by the family practitioner have not been established sufficiently. OBJECTIVE: To identify predictors of short- and long-term discontinuation of benzodiazepine use and relapse in use after a minimal intervention with a discontinuation letter followed by an offer for an evaluation consultation. METHODS: Predictors of benzodiazepine discontinuation and relapse in use were studied by logistic regression analysis and survival analysis within a family practice population of long-term benzodiazepine users (n = 1707) addressed by a discontinuation letter and followed for 21 months. RESULTS: A lower baseline prescription, a shorter duration of use, male gender and use of an agent with a half-life time <24 hours were predictive of complete discontinuation in the short (6 months) and long term (21 months). Multiple agent use at baseline, use of antidepressants at 6 months and benzodiazepine type (anxiolytic/hypnotic) at baseline predicted relapse. Attendance at an evaluation consultation 3 months after the letter was sent was not predictive of discontinuation or relapse. CONCLUSIONS: Amount of baseline use and duration of use are the main determinative characteristics of successful discontinuation. The discontinuation letter intervention is suitable for use with a broad group of long-term benzodiazepine users in family practice and can be used as a first step within a stepped care approach to decrease long-term benzodiazepine use.

The absence of benzodiazepine craving in a general practice benzodiazepine discontinuation trial.

This study aimed to assess benzodiazepine craving longitudinally and to describe its time course by means of the Benzodiazepine Craving Questionnaire (BCQ). Subjects were long-term benzodiazepine users participating in a two-part treatment intervention aimed to reduce long-term benzodiazepine use in general practice in The Netherlands. Four repeated measurements of benzodiazepine craving were taken over a 21-month follow-up period. Results indicated that (1) benzodiazepine craving severity decreased over time, (2) patients still using benzodiazepines experienced significantly more severe craving than patients who had quit their use after one of the two interventions, and (3) the way in which patients had attempted to quit did not influence the experienced craving severity over time, however, (4) patients who had received additional tapering off, on average, reported significantly more severe craving than patients who had only received a letter as an incentive to quit. Although benzodiazepine craving is prevalent among (former) long-term benzodiazepine users during and after discontinuation, craving severity decreases over time to negligible proportions. Self-reported craving can be longitudinally monitored and quantified by means of the BCQ.

Development and psychometric evaluation of the Benzodiazepine Craving Questionnaire.

AIM: To assess the scalability, reliability and validity of a newly constructed self-report questionnaire on craving for benzodiazepines (BZs), the Benzodiazepine Craving Questionnaire (BCQ). SETTING AND PARTICIPANTS: The BCQ was administered once to a sample of 113 long-term and 80 former long-term general practice BZ users participating in a large BZ reduction trial in general practice. MEASUREMENTS: (1) Unidimensionality of the BCQ was tested by means of the Rasch model. (2) The Rasch-homogeneous BCQ items were assessed for subject and item discriminability. (3) Discriminative and construct validity were assessed. FINDINGS: The BCQ met the requirements for Rasch homogeneity, i.e. BZ craving as assessed by the scale can be regarded as a unidimensional construct. Subject and item discriminability were good. Construct validity was modest. Highest significant associations were found with POMS depression (Kendall's tau-c = 0.15) and Dutch Shortened MMPI negativism (Kendall's tau-c = 0.14). Discriminative validity was satisfactory. Highest discriminative power was found for a subset of eight items (Mann-Whitney U Z = - 3.6, P = 0.000). The first signs of craving are represented by the acknowledgement of expectations of positive outcome, whereas high craving is characterized by direct intention to use. CONCLUSIONS: The BCQ proved to be a reliable and psychometrically sound self-report instrument to assess BZ craving in a general practice sample of long-term BZ users.

Tapering off long-term benzodiazepine use with or without group cognitive-behavioural therapy: three-condition, randomised controlled trial.

BACKGROUND: Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition. AIMS: To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice, and to evaluate the value of additional group cognitive-behavioural therapy (CBT). METHOD: A 3-month randomised, 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT, tapering off alone or usual care. RESULTS: Tapering off led to a significantly higher proportion of successful discontinuations than usual care (62% nu. 21%). Adding group CBT did not increase the success rate (58% v. 62%). Neither successful discontinuation nor intervention type affected psychological functioning. Both tapering strategies showed good feasibilityin general practice. CONCLUSIONS: Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice. The addition of group CBT is of limited value.

[Long-term use of benzodiazepines]. / Het langdurig gebruik van benzodiazepinen.

Benzodiazepines are the most prescribed drugs in the Netherlands. There is scarcely an indication for long-term benzodiazepine use. Long-term use may lead to dependency and is associated with an increased risk of accidents/falls and cognitive function impairment. Therefore national and international guidelines advocate a conservative prescription policy, especially with respect to long-term prescription. It appears that these guidelines are not followed in practice. A standard sized general practice in the Netherlands contains, on average, 75 long-term benzodiazepine users. There appear to be both patient and GP related factors which influence the maintenance of this long-term use of benzodiazepines.

[Treatment methods for discontinuation of long-term benzodiazepine use]. / Behandelmethoden om langdurig benzodiazepinegebruik te staken.

Treatment strategies for discontinuing long-term benzodiazepine usage can be divided into minimal interventions and gradual discontinuation programs. Minimal interventions invite patients to quit their long-term benzodiazepine usage on their own by making them aware of the adverse effects. This type of intervention is successful in about one fifth of patients. Gradual discontinuation programs are more extensive interventions in order to help those patients who are unable to discontinue benzodiazepine use on their own. These programs are successful in two-thirds of the patients and can be combined with additional pharmacological or psychological treatment. Once the withdrawal symptoms have diminished, most patients have an improved psychological functioning compared to when they were using benzodiazepines. Furthermore, no increase in medical consumption has been found.

Present and future management of asthma and COPD: proceedings from WONCA 1998.

On 15 June 1998, a workshop on asthma and chronic obstructive pulmonary disease (COPD) was held at the WONCA conference in Dublin. Based on the current guidelines for diagnosis and treatment of asthma and COPD, new developments and present and future research projects were discussed. Based on these guidelines and the research findings, new developments were positioned. The final conclusion of this workshop was that there is a need to continue exchanging ideas at an international level. So an initiative to start a Scientific Group of Primary Care Research within the European Respiratory Society has been taken.

Are anti-oxidant and anti-inflammatory treatments effective in different subgroups of COPD? A hypothesis.

The treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids or anti-oxidants is still under debate and the identification of sub-groups of COPD patients who may benefit from either anti-inflammatory or anti-oxidant treatment is needed. We re-analysed data from an earlier study of inhaled beclomethasone therapy in COPD (n = 28) and asthma (n = 28) patients in order to determine patient characteristics that predict a favourable inhaled steroid treatment effect. A higher bronchodilatory response, a faster decline of FEV1 prior to the treatment period and a lower Tiffeneau index were significantly related to more beneficial treatment effects. Increased smoking tended to be related to less steroid treatment benefits, though it was not statistically significant. In this paper these findings are presented in light of the available literature on anti-inflammatory and anti-oxidant COPD treatment. On this basis the hypothesis is presented that anti-oxidant treatment might be relatively more effective among those COPD patients who respond less well to inhaled steroids (low reversibility and heavy smoking).

Urinary sex hormone excretions in premenopausal women and coronary heart disease risk: a nested case-referent study in the DOM-cohort.

The low incidence of coronary heart disease (CHD) in premenopausal women is partly ascribed to protection by endogenous estrogen production. As a consequence, we hypothesized that premenopausal women with low endogenous estrogen production or high androgen production might be at increased risk for CHD. We studied the relationship between urinary sex hormone excretions and CHD risk by means of a nested case-referent study within a cohort of premenopausal (ages 40-49 yrs) women (n = 11,284). This cohort was formed at a breast cancer screening project in 1982-1986 (The Diagnostisch Onderzoek Mammacarcinoom [DOM] Project). Baseline data included self-administered questionnaires and anthropometric measurements. At the time of screening the women were instructed to collect an overnight urine sample on day 22 of three separate cycles. These urine samples were stored at -20 degrees C. Up to June 1991, 45 subjects were admitted to local hospitals on diagnosis of CHD (29 with myocardial infarction, and 16 with angiographically confirmed coronary disease). Referents were sampled from the cohort, matched for age and year of screening in a 1:3 ratio. In a follow-up study, menopausal state of the subjects was assessed yearly by mailed questionnaires. Urinary excretions of estrone-glucuronide, pregnanediol-glucuronide, and testosterone-glucuronide adjusted by creatinine were similar for cases and referents. Cases had no earlier menopause than referents, although cases had more anovulatory cycles. The occurrence of CHD in middle-aged women is not preceded by a low premenopausal endogenous estrogen production or high androgen production. Anovulatory cycles appear more frequently in women who develop CHD many years later.

Urinary excretions of high molecular weight beta-thromboglobulin and albumin are independently associated with coronary heart disease in women, a nested case-control study of middle-aged women in the Diagnostisch Onderzoek Mammacarcinoom (DOM) Cohort, Utrecht, Netherlands.

Increased plasma levels of beta-thromboglobulin, a platelet activation marker, are observed in coronary artery disease. Urinary albumin excretion, a marker of endothelial cell perturbation, is related to cardiovascular disease in diabetes. To test the value of these markers in predicting forthcoming coronary disease, the relations between urinary excretions of high molecular weight beta-thromboglobulin (HMW-beta TGf) and albumin and subsequent coronary disease in a cohort of 15,484 middle-aged women were investigated in a nested case-control study. Baseline questionnaire data and urine samples were available from a breast cancer screening program in Utrecht during 1982-1985. Cases were Utrecht hospital admissions for myocardial infarction (n = 50) or angiographically confirmed coronary disease (n = 28) from 1982-1985 to 1990-1991. Classifying events occurred a median of 5.1 years after baseline. Controls were a random sample from the cohort, individually case matched for baseline examination date and age, at a 1:2 ratio. HMW-beta TG/creatinine ratios (ng/mmol, mean +/- standard error) were 5.3 +/- 0.3 in cases and 4.7 +/- 0.3 in controls; albumin/creatinine ratios (mg/mmol, median) were, respectively, 0.37 and 0.22. Crude odds ratios for classification in the highest compared with the lowest tertiles of HMW-beta TG/creatinine and albumin/creatinine distributions were elevated for cases compared with controls: HMW-beta TG/creatinine odds ratio = 2.4, 95% confidence interval 1.1-5.0; albumin/creatinine odds ratio = 2.1, 95% confidence interval 1.0-4.1. These relations persisted after adjustment for smoking, hypertension, Quetelet index, and menopausal status. Both urinary HMW-beta TG and albumin excretion are markers of coronary disease risk in middle-aged women, indicating that increased platelet activation and endothelial cell perturbation precede coronary heart disease events in women.

Passive smoking and sister-chromatid exchanges in lymphocytes.

The object of this study was to determine whether exposure to environmental tobacco smoke is associated with DNA damage reflected by the frequency of sister-chromatid exchange (SCE) in lymphocytes. Within a cross-sectional design, 106 male non-smoking adults, employees of two administrative companies, were divided on the basis of self-reported exposure into high and low passive smoking groups. The high exposed subjects (passive smokers, n = 50) lived with smokers, worked with smokers and were exposed to tobacco smoke for an average of 70 h/week. The low exposed non-smokers (n = 56) were exposed for an average of 5 h/week. Plasma cotinine levels for the passive smokers ranged between 0.4 and 9.0 ng/ml (median 1.4 ng/ml), and for the low exposed group between 0.0 and 1.9 ng/ml (median 0.4 ng/ml) (p less than 0.0001; Mann-Whitney test). No difference was observed between the two groups in the frequency of SCEs in lymphocytes: 4.66 +/- 0.05 for passive smokers and 4.68 +/- 0.04 for low exposed non-smokers (mean +/- SEM) (p = 0.80; t-test). Reclassification of subjects on the basis of plasma cotinine levels did not change the results substantially. These results are in accordance with observations that the increase in cancer risk due to passive smoking is small in comparison with the increase due to active smoking. The SCE test may be too insensitive to be useful for the evaluation of possible cytogenetic effects related to passive smoking.