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Viggo R. K. Jørgensen - One of the best experts on this subject based on the ideXlab platform.
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An Approach to Reduce Benzodiazepine and Cyclopyrrolone Use in General Practice A Study Based on a Danish Population
CNS Drugs, 2012Co-Authors: Viggo R. K. JørgensenAbstract:Background: The global use of benzodiazepines and Cyclopyrrolones is generally high. The hypnotic and anxiolytic effects of these agents typically diminish after a period of weeks or months of continuous use. Patients may thus be caught in a trap where the usefulness of these substances is reduced and doses are consequentially escalated, and where a subsequent phased reduction in dose can be difficult. Although considerable resources have been expended on reducing the use of these agents, no unambiguous and effective method has been identified.
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Benzodiazepine Withdrawal - Does This Lead to an Increase in the Use of Antipsychotics?
The Open Drug Safety Journal, 2012Co-Authors: Viggo R. K. JørgensenAbstract:Introduction: In 2004, two Danish GPs in the town of Thyboron introduced a more restrictive approach to the prescription of benzodiazepines (BD) and Cyclopyrrolones (CP). A prescription could only be renewed following personal consultation, and medication could only be prescribed for one month at a time. Every month, the practitioner and the pa- tient had to consider whether current levels of consumption were appropriate or whether a reduction was to be imple- mented. This approach reduced the consumption of anxiolytics and hypnotics by 87% and 92%, respectively, over a 3- year period. There is a general paucity of knowledge as to whether an intervention such as the one described above actu- ally reduces drug consumption, or merely transfers consumption to other drugs, where especially antipsychotics (AP) are in the spotlight. Materials and Methods: The current article describes the consumption of AP before and after the intervention. Consump- tion was followed via the Danish Medicines Agency's website Ordiprax, where one can determine the amount of prescrip- tion medications sold in pharmacies by individual medical practices. Results: In both practices, a non-significant increase in the overall consumption of AP was observed during the course of the intervention against BD and CP. Although the consumption of some AP subgroups experienced a significant increase, no specific pattern could be observed. Conclusion: The intervention against BD and CP did not result in a significant increase in total prescription volumes of AP. It cannot be excluded that the intervention influenced individual prescriptions.
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Benzodiazepine reduction in general practice. Are the elderly neglected
Journal of Affective Disorders, 2011Co-Authors: Viggo R. K. JørgensenAbstract:In two Danish general practices a few simple rules applicable to all age groups were introduced in order to reduce consumption of benzodiazepines (BZ) and Cyclopyrrolones (CP). These rules, termed the "Thyboron-Model", included the termination of telephone prescriptions, the issuance of prescriptions only following personal consultation and the restriction of prescriptions to a maximum of a single month's consumption. The purpose of the present demographic analysis is to investigate whether the intervention was successful for the elderly, who are considered to be a special target group. The findings presented here reveal that the number of BZ and CP users increased with increasing age. Furthermore, the results indicate that the intervention was effective in reducing the consumption of BZ and CP for middle-aged and elderly patients, and that there is a significantly better effect of this model for middle-aged than for elderly patients. These findings constitute the first demographic evaluation of the effects of the "Thyboron-Model" with focus on the special target group of elderly patients, and indicate that it is advisable to introduce these simple rules for all age groups, especially since they also are effective on elderly patients.
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Benzodiazepine and cyclopyrrolone reduction in general practice — Does this lead to concomitant change in the use of antipsychotics?: A study based on a Danish population
Journal of Affective Disorders, 2010Co-Authors: Viggo R. K. JørgensenAbstract:Abstract Introduction In the period 2004–2006, 15 doctors in the Danish municipality of Lemvig introduced a more restrictive approach to the prescription of benzodiazepines and Cyclopyrrolones. A prescription could be renewed only following personal consultation, and prescriptions were issued for only a single month's usage. The intervention reduced the prescription of benzodiazepine anxiolytics by 50%, Cyclopyrrolones by 57% and benzodiazepine hypnotics by 55% over a 1½ year period. There is a paucity of knowledge about whether such an intervention reduces drug consumption in general or merely shifts consumption to other drugs. Here especially antipsychotics (AP) are in the spotlight. Materials and methods The current article describes the prescription of antipsychotics before and after the intervention. Consumption was followed via the Danish Medicines Agency's website Ordiprax, where the quantity of pharmacy-sold prescription drugs by individual medical practices can be monitored. Results The overall increase in the prescription of antipsychotics during the intervention described here was not more than 3.1% of the reduction in prescriptions of benzodiazepine and cyclopyrrolone measured in defined daily doses (DDD). Conclusion The intervention against benzodiazepine and cyclopyrrolone did not result in an uncontrollable increase in the prescription of antipsychotic drugs. It cannot be excluded that the intervention impacted individual prescriptions. For future interventions of a similar nature, it is recommended that GPs are trained in the use of antipsychotics.
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Benzodiazepine and cyclopyrrolone reduction in general practice--does this lead to change in the use of antidepressants? A study based on a Danish population.
Journal of Affective Disorders, 2010Co-Authors: Viggo R. K. JørgensenAbstract:Abstract Background The consumption of benzodiazepines and Cyclopyrrolones has in recent years attracted considerable interest due to serious side effects. In twelve health care practices in Denmark a few simple rules to reduce the consumption were established. Telephone recipes were abolished, and prescriptions were issued for only a single month's usage and only following personal consultation. These rules are generally in accordance with recommendations applicable in, for example, England, Norway and Denmark. After 15 months, consumption was roughly halved. There is a general lack of knowledge about whether an intervention as described above leads to a substitution with other medicines. Here, especially antidepressants are in the spotlight. Methods In the twelve health care practices, the consumption of antidepressants before, during and after the intervention was followed. Results The total consumption of antidepressants rose by 5.2% per year during the 18 month observation period. This should be compared to the fact that the county had an increase of 8.6% per year during the same period. This increase occurred mainly in the group of selective serotonin reuptake inhibitors. Limitations The study does not provide information about prescription changes for individual users, or for changes in the number of users. The study is limited to the total prescribed volume of antidepressants. Conclusion The average prescription volume for the twelve health care practices corresponds to a relative decline. Fears that an intervention of the type mentioned above would lead to an uncontrollable increase in the consumption of antidepressants are unfounded.
Daniel Monti - One of the best experts on this subject based on the ideXlab platform.
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Histamine H_1 Receptor Antagonists in the Treatment of Insomnia
CNS Drugs, 2000Co-Authors: Jaime M. Monti, Daniel MontiAbstract:Neuroanatomical, neurochemical and neuropharmacological studies support a role for histamine in the control of the waking state. In this respect, the histamine H_1 receptor plays a predominant role. Acute administration of first-generation H_1 receptor antagonists [chlorphenamine (chlorpheniramine), diphenhydramine, mepyramine (pyrilamine) and triprolidine] produces somnolence, an increased likelihood of falling asleep and reduced concentration. These effects led to the use of these drugs as over-the-counter medications to promote sleep. The widespread use of sedative antihistamines as sleep aids stems from inappropriate attempts by undiagnosed and untreated patients with insomnia to resolve their sleep disturbance. The limited number of studies directed at disclosing the effects of first-generation antihistamines on sleep in patients with insomnia tend to suggest that these compounds are effective for the treatment of chronic insomnia; however, methodological flaws limit the validity of their conclusions. In addition, the development of acute tolerance to the sedative effects of first-generation H_1 receptor antagonists further calls into question their effectiveness as sleep aids in transient, short or long term insomnia. Despite their widespread use, current evidence suggests that sedative antihistamines compare unfavourably with the benzodiazepine, cyclopyrrolone (zopiclone), imidazopyridine (zolpidem) and pyrazolopyrimidine (zaleplon) hypnotics, which consistently improve the difficulty falling asleep or maintaining sleep that is experienced by individuals with chronic insomnia.
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Pharmacological Treatment of Chronic Insomnia
CNS Drugs, 1995Co-Authors: Jaime M. Monti, Daniel MontiAbstract:Insomnia is defined as the inability to get the amount or quality of sleep necessary for optimal functioning and well being. Long term or chronic insomnia has been conventionally considered to be that lasting for at least 21 to 30 nights; however, it usually persists for months or years. It is more frequent in women than in men, and becomes more pronounced with age. Chronic insomnia is associated with mental disorders, psychophysiological conditions, inadequate sleep hygiene, neurological disorders and drug dependency. The most prevalent diagnosis is chronic insomnia associated with psychiatric disorders, followed in precedence by psychophysiological conditions. In chronic psychophysiological insomnia, idiopathic insomnia and insomnia associated with generalised anxiety, nonpharmacological strategies and sleeppromoting medication (e.g. hypnotics) are indicated. In patients with chronic insomnia associated with major depressive disorders, antidepressants that induce acute sedation (e.g. amitriptyline, doxepin, trazodone) represent the primary drug treatments of choice. When necessary, hypnotics can be added. Currently used hypnotics include benzodiazepine derivatives, the cyclopyrrolone zopiclone and the imidazopyridine zolpidem. Hypnotics with a short halflife show the best profile of efficacy versus adverse effects with regard to morning awakening and daytime functioning. In patients with chronic insomnia, hypnotics reduce sleep-onset latency, decrease the number of nocturnal awakenings and reduce the time spent awake. The increase in total sleep time is related to greater amounts of non-rapid eye movement (NREM) sleep. Few differences exist between benzodiazepines, zopiclone and zolpidem in terms of effectiveness in inducing and maintaining sleep. However, in contrast to the benzodiazepines and zopiclone, zolpidem does not suppress slow-wave sleep. Sleep laboratory and clinical studies tend to indicate that benzodiazepines are only effective when administered for relatively short periods of time in patients with chronic insomnia. Furthermore, a rebound insomnia has been described for short- and intermediate-acting benzodiazepines and zopiclone, and a withdrawal syndrome, denoting the presence of psychological and physical dependence, follows the abrupt cessation ofbenzodiazepine administration. In contrast, no evidence of tolerance or rebound insomnia has been observed in relation to zolpidem administration.
Jaime M. Monti - One of the best experts on this subject based on the ideXlab platform.
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Histamine H_1 Receptor Antagonists in the Treatment of Insomnia
CNS Drugs, 2000Co-Authors: Jaime M. Monti, Daniel MontiAbstract:Neuroanatomical, neurochemical and neuropharmacological studies support a role for histamine in the control of the waking state. In this respect, the histamine H_1 receptor plays a predominant role. Acute administration of first-generation H_1 receptor antagonists [chlorphenamine (chlorpheniramine), diphenhydramine, mepyramine (pyrilamine) and triprolidine] produces somnolence, an increased likelihood of falling asleep and reduced concentration. These effects led to the use of these drugs as over-the-counter medications to promote sleep. The widespread use of sedative antihistamines as sleep aids stems from inappropriate attempts by undiagnosed and untreated patients with insomnia to resolve their sleep disturbance. The limited number of studies directed at disclosing the effects of first-generation antihistamines on sleep in patients with insomnia tend to suggest that these compounds are effective for the treatment of chronic insomnia; however, methodological flaws limit the validity of their conclusions. In addition, the development of acute tolerance to the sedative effects of first-generation H_1 receptor antagonists further calls into question their effectiveness as sleep aids in transient, short or long term insomnia. Despite their widespread use, current evidence suggests that sedative antihistamines compare unfavourably with the benzodiazepine, cyclopyrrolone (zopiclone), imidazopyridine (zolpidem) and pyrazolopyrimidine (zaleplon) hypnotics, which consistently improve the difficulty falling asleep or maintaining sleep that is experienced by individuals with chronic insomnia.
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Pharmacological Treatment of Chronic Insomnia
CNS Drugs, 1995Co-Authors: Jaime M. Monti, Daniel MontiAbstract:Insomnia is defined as the inability to get the amount or quality of sleep necessary for optimal functioning and well being. Long term or chronic insomnia has been conventionally considered to be that lasting for at least 21 to 30 nights; however, it usually persists for months or years. It is more frequent in women than in men, and becomes more pronounced with age. Chronic insomnia is associated with mental disorders, psychophysiological conditions, inadequate sleep hygiene, neurological disorders and drug dependency. The most prevalent diagnosis is chronic insomnia associated with psychiatric disorders, followed in precedence by psychophysiological conditions. In chronic psychophysiological insomnia, idiopathic insomnia and insomnia associated with generalised anxiety, nonpharmacological strategies and sleeppromoting medication (e.g. hypnotics) are indicated. In patients with chronic insomnia associated with major depressive disorders, antidepressants that induce acute sedation (e.g. amitriptyline, doxepin, trazodone) represent the primary drug treatments of choice. When necessary, hypnotics can be added. Currently used hypnotics include benzodiazepine derivatives, the cyclopyrrolone zopiclone and the imidazopyridine zolpidem. Hypnotics with a short halflife show the best profile of efficacy versus adverse effects with regard to morning awakening and daytime functioning. In patients with chronic insomnia, hypnotics reduce sleep-onset latency, decrease the number of nocturnal awakenings and reduce the time spent awake. The increase in total sleep time is related to greater amounts of non-rapid eye movement (NREM) sleep. Few differences exist between benzodiazepines, zopiclone and zolpidem in terms of effectiveness in inducing and maintaining sleep. However, in contrast to the benzodiazepines and zopiclone, zolpidem does not suppress slow-wave sleep. Sleep laboratory and clinical studies tend to indicate that benzodiazepines are only effective when administered for relatively short periods of time in patients with chronic insomnia. Furthermore, a rebound insomnia has been described for short- and intermediate-acting benzodiazepines and zopiclone, and a withdrawal syndrome, denoting the presence of psychological and physical dependence, follows the abrupt cessation ofbenzodiazepine administration. In contrast, no evidence of tolerance or rebound insomnia has been observed in relation to zolpidem administration.
G. Biggio - One of the best experts on this subject based on the ideXlab platform.
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The effect of Cyclopyrrolones on GABA_A receptor function is different from that of benzodiazepines
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: A. Concas, M. Serra, G. Santoro, E. Maciocco, T. Cuccheddu, G. BiggioAbstract:The effects of the Cyclopyrrolones zopiclone and suriclone on the function of the central γ-aminobutyric acid type A (GABA_AA) receptor complex in mouse brain were evaluated both in vitro and in vivo. Added in vitro to mouse cerebral cortical membranes, these compounds potently inhibited [^3H]flumazenil binding with IC_50 (50% inhibitory concentration) values of 35.8 nM (zopiclone) and 1.1 nM (suriclone). Similar results were obtained with cerebellar membranes, indicating that these drugs do not discriminate between putative type I and type II benzodiazepine receptors. The interaction of Cyclopyrrolones with recognition sites present at the level of the GABA receptor complex appears to be competitive, because zopiclone decreased the affinity of the receptors for [^3H]flumazenil without affecting the maximal number of binding sites. Moreover, zopiclone and suriclone did not affect the rate of dissociation of [^3H]flumazenil from benzodiazepine receptors. The in vitro efficacy of zopiclone appeared different from that of suriclone and the benzodiazepines diazepam and flunitrazepam. Thus, zopiclone failed to affect muscimol-stimulated ^36Cl^− uptake and only slightly inhibited t -[^35S]butylbicyclophosphorothionate ([^35S]TBPS) binding. In contrast, like diazepam and flunitrazepam, suriclone increased muscimol-stimulated ^36Cl^− uptake and markedly inhibited [^35S]TBPS binding. On the other hand, suriclone, like zopiclone, did not modify [^3H]muscimol binding to mouse cerebral cortical membranes. Moreover, zopiclone antagonized the reduction in [^35S]TBPS binding elicited by the benzodiazepine receptor full agonist diazepam. Consistent with its low efficacy in vitro, oral administration of zopiclone (2.5 to 100 mg/kg, p.o.) in mice failed to modify [^35S]TBPS binding subsequently measured in cerebral cortical membranes “ex vivo”. In contrast, suriclone (10 to 20 mg/kg, p.o.), like diazepam, decreased [^35S]TBPS binding measured ex vivo. Moreover, both zopiclone (50 to 100 mg/kg, p.o.) and suriclone (1 to 10 mg/kg, p.o.) abolished the increase in [^35S]TBPS binding induced by isoniazid (200 mg/kg, s.c.). These results suggest that suriclone may enhance GABAergic transmission with an efficacy similar to that of diazepam. In contrast, the low efficacy of zopiclone both in vitro and in vivo suggests that this drug may act as a partial agonist at benzodiazepine receptors.
Birgit Signora Toft - One of the best experts on this subject based on the ideXlab platform.
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Intervention Against the Excessive Use of Anxiolytica and Hypnotica in Two General Practices
The Open Drug Safety Journal, 2010Co-Authors: Viggo R. K. Jørgensen, Birgit Signora ToftAbstract:This publication describes the successful reduction in the use of benzodiazepines as anxiolytics by 87%, as well as the reduction in the use of benzodiazepines and Cyclopyrrolones as hypnotics by 92%, for two general practitioners over a period of three years. The measures implemented were few and simple: Cessation of telephone prescriptions. Issue of prescriptions only following consultation. Prescriptions limited to a single months requirements. At each monthly consultation, the patient as well as the practitioner was required to re-evaluate the need and extent of the subsequent prescriptions. During the first three months, only four to five additional consultancies per week per 1000 patients were required. Subse- quently, this number was stabilized at approximately one additional consultancy per week. The routine implementation of the aforementioned simple procedure is to be recommended for the ordination of BD and CP drugs, as the effect is both significant and persistent.
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reduction in the use of benzodiazepines and Cyclopyrrolones in general practice
Pharmacy Practice (internet), 2008Co-Authors: Viggo R. K. Jørgensen, Birgit Signora ToftAbstract:In 2003, the Danish Minister for the Interior and Health instructed general practitioners to reduce prescriptions of benzodiazepines (BZD) and Cyclopyrrolones (CP) by 50%. However, no effective methods were specified. In Denmark, it is estimated that there are approximately 100,000 BZD-dependent patients, constituting approximately 2% of the population.Objective: This article describes the implementation of a successful, simple and voluntary intervention to reduce the use of dependence-inducing drugs, while at the same time challenging practitioners' ingrained habits and prejudices in this field.Methods: The rules implemented were essentially in accordance with the official Danish rules, such that a prescription for BZD and CP could only be issued for one month at a time, and only following consultation. Use was monitored using the Danish registration system, Ordiprax, which monitors sales of prescription medicine. Two Danish general practices, comprising a patient base of approximately 2300 were studied. With the exception of the severely physically or mentally ill, all users of BZD and CP were included.Results: After 2½ years, the use of BZD and CP was reduced by 75% and 90%, respectively. The reorganization of prescription patterns was seen to be significantly easier than physicians had expected. During the first three months, only four to five additional visits per week per 1000 patients were required. Subsequently, this number was stabilized at one to two additional visits. The usual collaborative partners, such as psychiatrists, homecare services, hospitals and substance abuse units were essentially not deployed. No serious withdrawal effects arose.Conclusion: The implementation of the aforementioned simple procedures is to be recommended for the prescription of BZD and CP drugs, as the effect is immediate and easily attainable, with a reasonable work input required on the part of general practitioners.
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Reducing the use of benzodiazepines and Cyclopyrrolones in clinical practice.
Pharmacy Practice (internet), 2006Co-Authors: Viggo R. K. Jørgensen, Birgit Signora Toft, Max Van Soest FoghAbstract:Objective: Recently, the use of benzodiazepines (BZD) and Cyclopyrrolones (CP) has drawn a great deal of attention. About 100,000 patients - approximately 2% of the Danish population - are believed to be addicted to BZD. This article describes a simple and effective method of reducing the use of dependency-producing drugs in clinical practice.Methods: Design: Local rules were implemented according to Danish directive CIR nr 12 13/01/2003 regarding addictive drugs. Prescriptions for BZD and CP were only issued on a monthly basis, and only following personal consultation. This monthly requirement forced the physician as well as the patient to evaluate whether the existing prescription pattern was indicated, or whether a drug-reducing regime should be introduced. The prescription pattern was monitored using the Ordiprax System (Institute for Rational Pharmacotherapy, IRF), which records pharmacy's sales of prescription drugs as prescribed by clinical practices. Two individual clinics in Thyboron - Harboore Community, covering some 2300 patients, were surveyed. All patients using BZD or CP were included in this study, with the exception of patients suffering from serious psychiatric or physical disorders.Results: After 15 months, the use of BZD and CP was reduced by 50% and 75%, respectively. The process of changing prescription habits was far easier than expected. A whole group of patients, initially invisible to the physician, was exposed. During the first three months, as few as 4-5 additional consultations for every 1000 patients was required. There was essentially no need for assistance from our usual partners, including psychiatrists, hospitals, specialist units for addictive treatment.Conclusion: We strongly recommend that these simple procedures be incorporated into daily routine when prescribing either a BD or a CP.
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Reducing the use of addictive drugs in clinical practice
Ugeskrift for Læger, 2006Co-Authors: Viggo R. K. Jørgensen, Birgit Signora Toft, Max Van Soest FoghAbstract:INTRODUCTION: The use of benzodiazepines (BDs) and Cyclopyrrolones (CPs) has drawn a great deal of political attention over the past years. There are estimated to be approximately 100,000 BD addicts in Denmark. This article describes a simple but effective method of reducing the use of addictive drugs in clinical practice. MATERIALS AND METHODS: Two solo clinics in Thyboron-Harboore Community decided to work strictly according to directive CIR no. 12 of 13 January 2003. All BDs and CPs were prescribed for one month at a time and could be renewed only by the doctor after a personal consultation. This monthly requirement forced the doctor as well as the patient to evaluate whether the existing prescription pattern or a drug-reducing regime was indicated. The prescription pattern was monitored using Ordiprax, which showed the amount of prescription medicines sold by pharmacies. RESULTS: After 15 months, the patients" use of BD was reduced by 50% and their use of CP by 75%. The process of changing prescription habits was far easier than expected. An entire group of patients, previously invisible to the doctors, was exposed. During the first three months, only four to five additional consultations for every 1,000 assigned patients were required each week. There was practically no need of any assistance from our usual partners, such as psychiatrists, hospitals, special wards for addictive treatment or primary health care. CONCLUSION: We strongly recommend that this simple procedure be made a daily routine when prescribing either a BD or a CP.
