Pharmakopsychiatrie, Neuro-Psychopharmakologie最新文献

1. We have stressed the detrimental effect that lay publications, T. V. and mass media has had on the pharmacotherapy of anxiety and depressive reactions with benzodiazepines. 2. We have reviewed the scientific literature and found few well documented cases of benzodiazepine dependence if one considers that benzodiazepines are the most prescribed medications. 3. We discussed the possibility that the seizures reported on withdrawal of benzodiazepines used for very long periods, is not a "proof" of a physical dependence, but rather clinical evidence of the well known anticonvulsant effect of benzodiazepines. 4. We have hypothesized that the withdrawal syndromes associated to high dosages of benzodiazepines might have a different neurochemical mechanism to that observed in alcohol and barbiturates withdrawals.

Anxiety has three essential elements: the subjective experience, autonomic symptoms and avoidance behaviour. Various theories are considered which highlight the psychic and somatic aspects of anxiety. Beta-adrenergic receptor blocking drugs have been used with advantage to treat everyday stresses. These include the anxiety produced by the civil disturbances in Northern Ireland, performing surgery, dentistry, musical instruments or speaking in public, as well as examination nerves. The profile of symptoms such as tachycardia, palpitations and tremor which are most likely to respond to beta-blockers are discussed as well as their side-effects. Their mode of action is different from other anxiolytics, with which they can be combined.

It is reasonable to suggest that further understanding of the physiology and the mode of action of the drugs that are most effective in decreasing human anxiety, the BDZ, may provide important clues to the understanding of anxiety. BDZ receptors have recently been discovered in human brain where they have a differential distribution. Good correlations have been obtained between the clinical potency of a series of BDZ and the tightness with which they bind to brain membranes. It has been discovered that BDZ may exert part of their therapeutic action by enhancing the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Thus it appears that some of the actions of diazepam may be a result of increasing the ability of GABA to quiet brain cell activity. A number of endogenous compounds have been discovered that are produced in brain and that may act like BDZ, but at the present time no single candidate has convincingly emerged as the endogenous BDZ. A world-wide search for the endogenous BDZ continues. Finally, a brain structure, the nucleus locus coeruleus, has been proposed as possibly relevant to anxiety-like behavior. Electrical stimulation of this area can produce anxiety-like behavior in monkeys that can be blocked by diazepam. Thus, for the first time in many years, the above-mentioned discoveries have increased hope that significant progress will be made in our understanding of the severe and at times incapacitating mental problem of severe anxiety.

A selective review of findings about the frequency of anxiety, fears, and phobias is presented. It is stressed that caution is necessary in considering the findings of the review because of the ambiguity of the concept anxiety, and numerous methodological problems which beset studies and make comparisons difficult.

The renal function of 46 outpatients from a lithium-clinic was examined in detail during 5 days of hospitalization on a nephrological ward. Lithium medication was stopped seven days before admission. In approximately 25% of the examined patients, a lithium-induced nephropathia must be assumed. Irreversibility of the disturbances cannot be excluded. The characteristic feature of this patient population is to be seen in an exclusive reduction of the renal concentrating ability. Urine osmolality showed a significant negative correlation to the product of duration of treatment times lithium serum concentration. In all patients with a reduced GFR a preexisting kidney disease could be demonstrated. The degree of polyuria was not related to the observed impairment of renal function. On the average it took seven years until a reduced concentration ability became apparent; the minimal time interval was three years. The lithium-associated nephropathy may be characterized as a rather frequently occurring damage of the kidney interstitium being dependent on serum-lithium concentration and duration of treatment. Progress of these pathological changes is obviously very slow and accompanied by only few and mild clinical symptoms. Kidney biopsy in 4 cases revealed focal fibrosis and tubular degeneration as has been described by other authors.

Lithium carbonate was administered during a double-blind crossover experiment lasting 8 weeks, involving 11 healthy volunteers. In psychological tests, no deterioration in mood, performance or memory could be shown. Informal diary entries made by the subjects, however, refer to complaints, particularly relating to vegetative functions, more frequently under lithium medication than during the placebo period. In the interpretation of the findings, it is important to take into account the very high motivation of the subjects.

A representative sample of patients under long-term lithium therapy was examined with respect to performance in reaction task, mood, and attitude toward lithium therapy. Reaction time to simple acoustic or visual stimuli as well as reactivity in complex settings under power- and speed-conditions requiring psychomotoric response represent the bulk of the data. Significant effects of additional medication, sex and duration of lithium therapy are assessed by univariate and multivariate data analysis. A hierarchic cluster analysis results in 5 well interpretable clusters. The clusters, furthermore, demonstrate the importance of attitude and other psychological variable, e.g. morning-/evening-type.

Peripheral blood lymphocytes of 77 patients under lithium-therapy were analyzed with respect to structural chromosomal aberrations. As compared to controls not treated with lithium, no elevation of the frequencies of chromosomal aberrations was found in the patients. Comparable investigations may lead to erroneous conclusions if the higher X-ray load of psychiatric patients is not considered.