The main objective of this thesis is to describe the epidemiology of long term BZD use as well as its long term consequences. This thesis is structured into three sections: In section one, the... Show moreThe main objective of this thesis is to describe the epidemiology of long term BZD use as well as its long term consequences. This thesis is structured into three sections: In section one, the correlates of BZD use, new use, chronic use, inappropriate use, and BZD dependence severity are investigated. The possible influence of the prescribing physicians on patient BZD use is also considered. In section two, the focus is on the physiological consequences of long-term BZDs use on the HPA axis and the ANS. In section three, cognitive effects of BZDs in long-term users are addressed Show less
This thesis describes different ways of exploring the pharmacological and therapeutic effects of novel GABA-ergic and GABA-like agents in humans. Systematic pharmacodynamic evaluations, using well... Show moreThis thesis describes different ways of exploring the pharmacological and therapeutic effects of novel GABA-ergic and GABA-like agents in humans. Systematic pharmacodynamic evaluations, using well-characterised positive controls, can confirm or refute the unique pharmacological properties of GABAA-subtype selective drugs in healthy volunteers. Such studies can help to predict dosing regimens and therapeutic advantages of these drugs. The distribution of different GABAA-receptor subtypes provides clues for their functional relevance. This knowledge can be used to optimise the desirable and undesirable effect profiles of selective GABA-ergic drugs. Very little is still known about the pathophysiological relevance of GABA-systems in CNS-disorders, although GABA-ergic treatments are in use for a wide range of clinical conditions. The availability of novel compounds with well defined pharmacological characteristics can clarify the involvement of these mechanisms in normal or abnormal physiology. This thesis hopes to show that carefully designed studies, using a range of CNS-measurement that reflect different GABAergic systems, can aid in the development of new GABA-ergic drugs, and help to unravel the role of the different GABA-ergic systems in health and disease. Show less
Because of the problems associated with chronic benzodiazepine use, there is impetus to prevent and reduce chronic benzodiazepine use. The overall aim was to develop a 'tailor-made' intervention in... Show moreBecause of the problems associated with chronic benzodiazepine use, there is impetus to prevent and reduce chronic benzodiazepine use. The overall aim was to develop a 'tailor-made' intervention in order to reduce chronic use. Before developing tailored patient education, it is first of all important to know which psychosocial factors predict benzodiazepine cessation. The computer-tailored intervention should target and change these determinants. The thesis showed that benzodiazepine users had a greater intention to quit and were more likely to quit their benzodiazepine intake if they perceived many positive consequences of cessation, while at the same time perceiving few negative consequences. In addition, higher self-efficacy was associated with cessation. These determinants were translated into intervention texts on the computer. The computer programme produced single-tailored letters and multiple-tailored letters. Single-tailored letters consisted of one letter of advice and multiple-tailored letters consisted of three different letters with a one-month interval. The multiple-tailored letters took into account the changes in benzodiazepine use over time. The results showed that tailored letters were twice as effective as non-tailored letters in quitting benzodiazepine use, especially in the case of patients who were already intending to quit. We found, however, no differences between single and multiple-tailored letters. Show less
The aim of this thesis was to contribute to better care for suicide attempters by studying several aspects of their assessment and management. In the first part of the thesis, the role of... Show moreThe aim of this thesis was to contribute to better care for suicide attempters by studying several aspects of their assessment and management. In the first part of the thesis, the role of guidelines was studied resulting in suggestions for improvement. In the second part, the role of factors is studied that, as experience in clinical practice suggests may hamper proper assessment and management. From the studies in part 1, it was concluded that the available evidence suggests that guidelines for the assessment and management of suicide attempters differ to a large extent with respect to their content, that only a minority can be recommended based on an evaluation of their quality, and that they are probably not implemented properly. This leads to a plea to update the Dutch guideline, made 15 years ago, and to develop procedures that may promote implementation. From the studies of part 2, it was concluded that professionals should be alert on patients forgetting relevant aspects of the assessment. Furthermore, although a systematic assessment in the hospital is comparable to a reassessment at home, for a subgroup of patients there is concern about their condition after discharge, and their tendency to forget the arrangements made for treatment after discharge from the hospital. So, additional strategies to the assessment in the hospital should be developed. In the Appendix, recommendations are given regarding development and implementation of guidelines for assessment and management of suicide attempters. Show less
