Posted by Squiggles on February 5, 2007, at 20:27:59
In reply to Re: Just a question, posted by bassman on February 5, 2007, at 19:58:15
> Please go find those research articles that say that tolerance and addiction are common with benzos; I'm sure we'd all like to see them.:>}
Sigh....
1: Can J Psychiatry. 2006 Jun;51(7):445-52. Links
Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program.* Voshaar RC,
* Gorgels WJ,
* Mol AJ,
* van Balkom AJ,
* Mulder J,
* van de Lisdonk EH,
* Breteler MH,
* Zitman FG.Department of Psychiatry, Radboud University Nijmegen Medical Centre, The Netherlands. r.oudevoshaar@psy.umcn.nl
OBJECTIVE: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. METHOD: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in general practice. RESULTS: Of 180 patients, we completed follow-up for 170 (94%). Of these, 50 (29%) achieved long-term success, defined as no use of benzodiazepines during follow-up. Independent predictors of success were as follows: offering a taper-off program with group therapy (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.5 to 3.9) or without group therapy (HR 2.9; 95% CI, 1.8 to 4.8); a lower daily benzodiazepine dosage at the start of tapering off (HR 1.5; 95% CI, 1.2 to 1.9); a substantial dosage reduction by patients themselves just before the start of tapering off (HR 2.1; 95% CI, 1.4 to 3.3); less severe benzodiazepine dependence, as measured by the Benzodiazepine Dependence Self-Report Questionnaire Lack of Compliance subscale (HR 2.4; 95%CI, 1.1 to 5.2); and no use of alcohol (HR 1.7; 95% CI, 1.2 to 2.5). Patients who used over 10 mg of diazepam equivalent, who had a score of 3 or more on the Lack of Compliance subscale, or who drank more than 2 units of alcohol daily failed to achieve long-term abstinence. CONCLUSIONS: Benzodiazepine dependence severity affects long-term taper outcome independent of treatment modality, benzodiazepine dosage, psychopathology, and personality characteristics. An identifiable subgroup needs referral to specialized care.
PMID: 16838826 [PubMed - indexed for MEDLINE]
1: Drugs. 1983 May;25(5):514-28. Links
Rational use of anxiolytic/sedative drugs.* Lader M,
* Petursson H.The benzodiazepines are the most effective, safest, and most widely used antianxiety drugs. As a class of drugs, there are few major differences between the various benzodiazepine derivatives. The main distinguishing features are different plasma half-lives and the presence or absence of pharmacologically active metabolites. Plasma half-lives vary considerably, from 2 to 3 hours to more than 100 hours. All benzodiazepines are equally effective in the short term management of anxiety and insomnia, and their classification into 'anxiolytics' and 'hypnotics' is not justified. There are numerous other indications for benzodiazepine use, such as muscle spasm in osteoarthritic conditions, and acute alcohol withdrawal, but the benzodiazepines have no antidepressive or analgesic effects. While there is no good evidence for their long term efficacy in the treatment of anxiety and insomnia, the benzodiazepines are more effective and safer than their main predecessors, the barbiturates. Some of the benzodiazepines, particularly those with long plasma half-lives which are commonly used as hypnotics, have a prolonged duration of action and cause marked 'hang-over' effects. Alcohol enhances the effects of these drugs, and thus can also increase their side effects. Adversely effects such as oversedation, tremor, ataxia and confusion are much more common in elderly patients. Ever since the benzodiazepines were first marketed 20 years ago their use has increased rapidly, and it is now estimated that between 12 and 16% of the adult population in developed countries use tranquillisers at some time each year. However, their overall use has probably diminished somewhat in the last few years. Although their indications are very common, it is possible that some of this extensive usage may be the result of dependence. Until recently, published reports of such dependence were comparatively few. However, withdrawal symptoms have now been demonstrated in a substantial proportion of patients on long term, normal dose benzodiazepine treatment. The abstinence syndrome usually lasts for 8 to 10 days, and is characterised by insomnia, anxiety, loss of appetite and bodyweight, tremor, perspiration, and a host of perceptual disturbances. More serious developments such as epileptic fits and psychosis are probably infrequent during withdrawal from therapeutic doses. The overall incidence of benzodiazepine dependence remains unknown.
PMID: 6134609 [PubMed - indexed for MEDLINE]
1: Curr Opin Pharmacol. 2005 Feb;5(1):47-52.Click here to read Links
GABAA receptor subtypes: any clues to the mechanism of benzodiazepine dependence?* Wafford KA.
Department of Molecular and Cellular Neuroscience, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, Essex CM20 2QR, UK. keith_wafford@merck.com
Chronic use of benzodiazepines for the treatment of anxiety has revealed that these drugs can lead to dependence as indicated by withdrawal symptoms following cessation and tolerance to the drugs effects. Together with their reinforcing properties, this has led to them being labelled as scheduled drugs. Our new knowledge regarding the molecular structure of the benzodiazepine binding site and the growing ability to differentiate GABA(A) receptor subtypes, either by genetic manipulation or subtype selective compounds, have begun to facilitate our understanding of what underlies the mechanism of benzodiazepine dependence. In addition, the involvement of GABA(A) receptors in this phenomenon is leading to a greater understanding of other drugs such as alcohol and opiates.
PMID: 15661625 [PubMed - indexed for MEDLINE]
1: Gen Hosp Psychiatry. 2006 Sep-Oct;28(5):374-8.Click here to read Links
Outcome of new benzodiazepine prescriptions to older adults in primary care.* Simon GE,
* Ludman EJ.Group Health Cooperative, Center for Health Studies, Seattle, WA 98101, USA. simon.g@ghc.org <simon.g@ghc.org>
OBJECTIVE: The objective of this study was to examine the indications for benzodiazepine use, and the baseline characteristics, duration of use and clinical outcomes of older primary care patients prescribed benzodiazepines. METHODS: Computerized records were used to identify outpatients (n=129) aged >or=60 years who received new benzodiazepine prescriptions from primary care physicians of a group model managed care organization. A baseline telephone survey assessed indications for prescription, sleep quality (Pittsburgh Sleep Quality Index), depression (Symptom Checklist depression scale and Structured Clinical Interview for DSM-IV), alcohol use (CAGE) and functional status (SF-36). A 2-month follow-up survey assessed benzodiazepine use, sleep quality and depression. RESULTS: The most common indications for prescription were insomnia (42%) and anxiety (36%). At baseline, participants reported moderate sleep disturbance (mean Pittsburgh Sleep Quality Index=9.3, S.D.=4.0), only 15% met criteria for current depressive episode and only 3% reported at-risk alcohol use. After 2 months, 30% of participants used benzodiazepines at least daily. Both those continuing daily use and those not continuing daily use reported significant improvements in sleep quality and depression, with no difference between groups in rates of improvement. CONCLUSIONS: Initial benzodiazepine prescriptions to older adults are typically intended for the treatment of anxiety or insomnia, with little evidence for occult depression or alcohol abuse. A significant minority develops a pattern of long-term use, raising concerns about tolerance and dependence.
PMID: 16950371 [PubMed - indexed for MEDLINE]
1: Pharmacol Ther. 2003 May;98(2):171-95.Click here to read Links
Neuroadaptive processes in GABAergic and glutamatergic systems in benzodiazepine dependence.* Allison C,
* Pratt JA.Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Taylor Street, G4 ONR, Glasgow, UK.
Knowledge of the neural mechanisms underlying the development of benzodiazepine (BZ) dependence remains incomplete. The gamma-aminobutyric acid (GABA(A)) receptor, being the main locus of BZ action, has been the main focus to date in studies performed to elucidate the neuroadaptive processes underlying BZ tolerance and withdrawal in preclinical studies. Despite this intensive effort, however, no clear consensus has been reached on the exact contribution of neuroadaptive processes at the level of the GABA(A) receptor to the development of BZ tolerance and withdrawal. It is likely that changes at the level of this receptor are inadequate in themselves as an explanation of these neuroadaptive processes and that neuroadaptations in other receptor systems are important in the development of BZ dependence. In particular, it has been hypothesised that as part of compensatory mechanisms to diazepam-induced chronic enhancement of GABAergic inhibition, excitatory mechanisms (including the glutamatergic system) become more sensitive [Behav. Pharmacol. 6 (1995) 425], conceivably contributing to BZ tolerance development and/or expression of withdrawal symptoms on cessation of treatment, including increased anxiety and seizure activity. Glutamate is a key candidate for changes in excitatory transmission mechanisms and BZ dependence, (1) since there are defined neuroanatomical relationships between glutamatergic and GABAergic neurons in the CNS and (2) because of the pivotal role of glutamatergic neurotransmission in mediating many forms of synaptic plasticity in the CNS, such as long-term potentiation and kindling events. Thus, it is highly possible that glutamatergic processes are also involved in the neuroadaptive processes in drug dependence, which can conceivably be considered as a form of synaptic plasticity. This review provides an overview of studies investigating changes in the GABAergic and glutamatergic systems in the brain associated with BZ dependence, with particular attention to the possible differential involvement of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in these processes.
PMID: 12725868 [PubMed - indexed for MEDLINE]
1: J Subst Abuse Treat. 1991;8(1-2):19-28. Links
Protracted withdrawal syndromes from benzodiazepines.* Ashton H.
Department of Pharmacological Sciences, The University, Newcastle upon Tyne, England.
The benzodiazepine withdrawal syndrome is a complex phenomenon which presents serious difficulties in definition and measurement. It is particularly difficult to set out precise limits on its duration. Many withdrawal symptoms are a result of pharmacodynamic tolerance to benzodiazepines, some mechanisms for which are discussed. Such tolerance develops unevenly in different brain systems and may be slow to reverse. Withdrawal symptoms occurring in the first week after cessation of drug use tend to merge with more persistent symptoms that may last for many months. These prolonged symptoms do not necessarily constitute "true" pharmacological withdrawal symptoms, but are nevertheless related to long-term benzodiazepine use. Such symptoms can include anxiety, which may partly result from a learning deficit imposed by the drugs, and a variety of sensory and motor neurological symptoms. The protracted nature of some of these symptoms raises the possibility that benzodiazepines can give rise not only to slowly reversible functional changes in the central nervous system, but may also occasionally cause structural neuronal damage.
PMID: 1675688 [PubMed - indexed for MEDLINE]
1: J Clin Psychiatry. 1987 Dec;48 Suppl:12-6. Links
Long-term anxiolytic therapy: the issue of drug withdrawal.* Lader M.
Department of Clinical Psychopharmacology, University of London, England.
Although widespread use has confirmed their efficacy as anxiolytic agents, the benzodiazepine drugs are indicated only for short-term or intermittent therapy at as low a therapeutic dose as possible because of their liability for causing dependence or abuse. When first introduced, benzodiazepine drugs appeared to be therapeutically equal or superior to barbiturate agents, while causing fewer side effects, being safer in overdose, and producing fewer dependence and abuse problems. Although benzodiazepine drugs have become the most commonly prescribed anxiolytic agents, evidence has emerged that their use in long-term therapy can cause severe withdrawal problems, even when relatively low doses are used or when the drug is discontinued gradually. Based on results from both animal models and clinical investigations, buspirone appears to be as effective in treating anxiety as the benzodiazepine drugs while causing fewer withdrawal problems. Data suggest no appreciable propensity to cause physical dependence or abuse associated with buspirone therapy. The drug demonstrates no cross-tolerance with either the barbiturate agents or the benzodiazepine drugs and seems to be a dysphoriant at high doses rather than a euphoriant. Although buspirone seems to be an appropriate drug for patients requiring longer-term anxiolytic therapy, careful monitoring for withdrawal problems and other adverse side effects is essential as buspirone is introduced to successive markets.
PMID: 2891684 [PubMed - indexed for MEDLINE]
1: Fundam Clin Pharmacol. 2006 Jun;20(3):235-8.Click here to read Links
Benzodiazepines prescription in Dakar: a study about prescribing habits and knowledge in general practitioners, neurologists and psychiatrists.* Dieye AM,
* Sylla M,
* Ndiaye A,
* Ndiaye M,
* Sy GY,
* Faye B.Laboratoire de Pharmacologie et de Physiologie, Faculte de Medecine, de Pharmacie et d'Odonto-stomatologie, Universite Cheikh Anta DIOP, BP5005, Dakar, Senegal. ctdieye@yahoo.fr
Benzodiazepines are relatively well-tolerated medicines but can induce serious problems of addiction and that is why their use is regulated. However, in developing countries like Senegal, these products are used without clear indications on their prescription, their dispensation or their use. This work focuses on the prescription of these medicines with a view to make recommendations for their rational use. Benzodiazepine prescription was studied with psychiatrists or neurologists and generalists in 2003. Specialist doctors work in two Dakar university hospitals and generalists in the 11 health centres in Dakar. We did a survey by direct interview with 29 of 35 specialists and 23 of 25 generalists. All doctors were interviewed in their office. The questionnaire focused on benzodiazepine indications, their pharmacological properties, benzodiazepines prescribed in first intention against a given disease and the level of training in benzodiazepines by doctors. Comparisons between specialists and generalists were made by chi-square test. Benzodiazepines were essentially used for anxiety, insomnia and epilepsy. With these diseases, the most benzodiazepines prescribed are prazepam against anxiety and insomnia and diazepam against epilepsy. About 10% of doctors do not know that there is a limitation for the period of benzodiazepine use. The principal reasons of drugs choice are knowledge of the drugs, habit and low side effects of drugs. All generalists (100%) said that their training on benzodiazepines is poor vs. 62.1% of specialists, and doctors suggest seminars, journals adhesions and conferences to complete their training in this field. There are not many differences between specialists and generalists except the fact that specialists prefer prazepam in first intention in the insomnia treatment where generalists choose bromazepam. In addition, our survey showed that specialists' training in benzodiazepines is better than that of generalists. Overall, benzodiazepine prescription poses problems particularly in training, and national authorities must take urgent measures for rational use of these drugs.
PMID: 16671957 [PubMed - indexed for MEDLINE]
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OK - don't make me go there again - each one of these articles has a link to similar ones when you look at the right hand column in the PubMed window;
Squiggles
poster:Squiggles
thread:729587
URL: http://www.dr-bob.org/babble/20070201/msgs/730163.html