Development of self-efficacy and expectancy measures for benzodiazepines

This study aimed to develop and assess the reliability and validity of a pair of self-report questionnaires to measure self-efficacy and expectancy associated with benzodiazepine use, the Benzodiazepine Refusal Self- Efficacy Questionnaire (BRSEQ) and the Benzodiazepine Expectancy Questionnaire (BEQ). Internal structure of the questionnaireswas established by principal component analysis (PCA) in a sample of 155 respondents, and verified by confirmatory factor analyses (CFA) in a second independent sample (n=139) using structural equation modeling. The PCA of the BRSEQ resulted in a 16-item, 4-factor scale, and the BEQ formed an 18-item, 2-factor scale. Both scales were internally reliable. CFA confirmed these internal structures and reduced the questionnaires to a 14-item self-efficacy scale and a 12-item expectancy scale. Lower self-efficacy and higher expectancy were moderately associated with higher scores on the SDS-B. The scales provide reliable measures for assessing benzodiazepine self-efficacy and expectancies. Future research will examine the utility of the scales in prospective prediction of benzodiazepine cessation.

Views of general practitioners and benzodiazepine users on benzodiazepines : a qualitative analysis

Effectively assisting benzodiazepine users to cease use requires a greater understanding of general practitioners’ (GPs)and benzodiazepine users’ views on using and ceasing benzodiazepines. This paper reports the findings from a qualitative study that examined the views of 28 GPs and 23 benzodiazepine users (BUs) in Cairns, Australia. A semistructured interview was conducted with all participants and the information gained was analysed using the Consensual Qualitative Research Approach, which allowed comparisons to be made between the views of the two groups of interviewees. There was commonality between GPs and BUs on reasons for commencing benzodiazepines, the role of dependence in continued use, and the importance of lifestyle change in its cessation. However, several differences emerged regarding commencement of use and processes of cessation. In particular, users felt there was greater need for GPs to routinely advise patients about non-pharmacological management of their problems and potential adverse consequences of long-term use before commencing benzodiazepines. Cessation could be discussed with all patients who use benzodiazepines for longer than 3 months, strategies offered to assist in management of withdrawal and anxiety, and referral to other health service providers for additional support. Lifestyle change could receive greater focus at all stages of treatment.

Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines

Adjuvant use of nutritional and herbal medicines has potential to increase the efficacy of synthetic pharmaceuticals, and perhaps also decrease their side-effects by allowing lower doses to be prescribed. We evaluated current evidence for adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines; and explored novel future areas of research. The paper also critiques current evidence for co-administration of St. John’s wort with synthetic antidepressants. We performed a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane database, China National Knowledge Infrastructure and the Chinese Science Citation Database. Search results were supplemented by a review of reference lists and a forward search using the Web of Science. Where possible we calculated effect sizes. Encouraging evidence exists for the use of omega-3 fatty acids, SAMe, folic acid and l-tryptophan adjuvantly with antidepressants to enhance response and improve efficacy. Various nutrients also have emerging evidence as effective adjuncts with antipsychotics and mood stabilizers. While some evidence supports nutritional adjuvancy with various psychopharmacotherapies, adjuvant use of herbal therapies has not been sufficiently studied to warrant standard clinical application. This remains a promising area of research via robust, safety-conscious studies.

Amorphous Mesoporous Iron Aluminophosphate Catalyst for the Synthesis of 1,5-Benzodiazepines

A simple and versatile method for the synthesis of 1,5-benzodiazepines from o-phenylenediamine and ketones in the presence of solvents and under solvent-free conditions that used an amorphous mesoporous iron aluminophosphate as catalyst was developed. High yields with excellent selectivity were obtained with a wide variety of ketones under mild reaction conditions. The catalyst had the advantages of ease of preparation, ease of handling, simple recovery, reusability, non toxicity, and being inexpensive.

Substance misuse in young people in Ireland - a focus on benzodiazepines

Benzodiazepines are a class of drugs that are prescribed for the treatment of anxiety and insomnia. Due to the powerful tolerance that can develop as a result of sustained use, benzodiazepines can also be dependence-forming. Benzodiazepine dependence can occur from prescribed and from recreational use, and is a significant issue for young people. The consequences of benzodiazepine dependence include cognitive and learning impairment, depressive symptoms, and increased suicide risk. Despite these risks, the nature of youth benzodiazepine use has not been explored to the same extent as other drugs. A review of existing Irish literature revealed that benzodiazepines are one of the five most recreationally-used drugs among young people. Analyses of young people attending a treatment centre indicated that young attendees from urban areas were more likely to be referred to the centre because of benzodiazepines than rural attendees. Further examination of the centre’s attendees showed that regular benzodiazepine users experienced more paranoia, loss of interest in sport, and pallor than non-regular users. Analysis of benzodiazepine prescribing to young people revealed that approximately one in seven young people were prescribed benzodiazepines for periods greater than recommended by national guidelines. Young benzodiazepine users discussed in interviews that they took benzodiazepines to escape from negative feelings and that they are generally taken in a social setting. Further interviews with youth counsellors and general practitioners highlighted that both family and community attitude to benzodiazepine use can impact on a young person’s benzodiazepine usage. Suggestions for reducing benzodiazepine use such as psychological alternatives to medication, public awareness campaigns and prescribing restrictions are provided. Future research can elaborate upon this work to determine other methods of reducing youth benzodiazepine use and the damage that it causes to the young people themselves, but also to their families, their community, and society at large.

Economic evaluation of benzodiazepines versus cognitive behavioural therapy among older adults with chronic insomnia

L’insomnie, commune auprès de la population gériatrique, est typiquement traitée avec des benzodiazépines qui peuvent augmenter le risque des chutes. La thérapie cognitive-comportementale (TCC) est une intervention non-pharmacologique ayant une efficacité équivalente et aucun effet secondaire. Dans la présente thèse, le coût des benzodiazépines (BZD) sera comparé à celui de la TCC dans le traitement de l’insomnie auprès d’une population âgée, avec et sans considération du coût additionnel engendré par les chutes reliées à la prise des BZD. Un modèle d’arbre décisionnel a été conçu et appliqué selon la perspective du système de santé sur une période d’un an. Les probabilités de chutes, de visites à l’urgence, d’hospitalisation avec et sans fracture de la hanche, les données sur les coûts et sur les utilités ont été recueillies à partir d’une revue de la littérature. Des analyses sur le coût des conséquences, sur le coût-utilité et sur les économies potentielles ont été faites. Des analyses de sensibilité probabilistes et déterministes ont permis de prendre en considération les estimations des données. Le traitement par BZD coûte 30% fois moins cher que TCC si les coûts reliés aux chutes ne sont pas considérés (231$ CAN vs 335$ CAN/personne/année). Lorsque le coût relié aux chutes est pris en compte, la TCC s’avère être l’option la moins chère (177$ CAN d’économie absolue/ personne/année, 1,357$ CAN avec les BZD vs 1,180$ pour la TCC). La TCC a dominé l’utilisation des BZD avec une économie moyenne de 25, 743$ CAN par QALY à cause des chutes moins nombreuses observées avec la TCC. Les résultats des analyses d’économies d’argent suggèrent que si la TCC remplaçait le traitement par BZD, l’économie annuelle directe pour le traitement de l’insomnie serait de 441 millions de dollars CAN avec une économie cumulative de 112 billions de dollars canadiens sur une période de cinq ans. D’après le rapport sensibilité, le traitement par BZD coûte en moyenne 1,305$ CAN, écart type 598$ (étendue : 245-2,625)/personne/année alors qu’il en coûte moyenne 1,129$ CAN, écart type 514$ (étendue : 342-2,526)/personne/année avec la TCC. Les options actuelles de remboursement de traitements pharmacologiques au lieu des traitements non-pharmacologiques pour l’insomnie chez les personnes âgées ne permettent pas d’économie de coûts et ne sont pas recommandables éthiquement dans une perspective du système de santé.

A residue close to ?1 loop F disrupts modulation of GABAA receptors by benzodiazepines while their binding is maintained

Benzodiazepines act at the major isoforms of GABA type A receptors where they potentiate the current evoked by the agonist GABA. The underlying mechanism of this potentiation is poorly understood, but hypothesized to be related to the mechanism that links agonist binding to channel opening in these ligand activated ion channels. The loop F of the ?(1) and the ?(2) subunit have been implicated in channel gating, and loop F of the ?(2) subunit in the modulation by benzodiazepines. We have identified the conservative point mutation Y168F located N-terminally of loop F in the ?(1) subunit that fails to affect agonist properties. Interestingly, it disrupts modulation by benzodiazepines, but leaves high affinity binding to the benzodiazepine binding site intact. Modulation by barbiturates and neurosteroids is also unaffected. Residue ?(1) Y168 is not located either near the binding pockets for GABA, or for benzodiazepines, or close to the loop F of the ?(2) subunit. Our results support the fact, that broader regions of ligand gated receptors are conformationally affected by the binding of benzodiazepines. We infer that also broader regions could contribute to signaling from GABA agonist binding to channel opening.

Synthesis and in vitro characterization of radioiodinatable benzodiazepines selective for type 1 and type 2 cholecystokinin receptors

Radiolabeled antagonists of specific peptide receptors identify a higher number of receptor binding sites than agonists and may thus be preferable for in vivo tumor targeting. In this study, two novel radioiodinated 1,4-benzodiazepines, (S)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea (9) and (R)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea (7), were developed. They were characterized in vitro as high affinity selective antagonists at cholecystokinin types 1 and 2 (CCK(1) and CCK(2)) receptors using receptor binding, calcium mobilization, and internalization studies. Their binding to human tumor tissues was assessed with in vitro receptor autoradiography and compared with an established peptidic CCK agonist radioligand. The (125)I-labeled CCK(1) receptor-selective compound 9 often revealed a substantially higher amount of CCK(1) receptor binding sites in tumors than the agonist (125)I-CCK. Conversely, the radioiodinated CCK(2) receptor-selective compound 7 showed generally weaker tumor binding than (125)I-CCK. In conclusion, compound 9 is an excellent radioiodinated nonpeptidic antagonist ligand for direct and selective labeling of CCK(1) receptors in vitro. Moreover, it represents a suitable candidate to test antagonist binding to CCK(1) receptor-expressing tumors in vivo.