Pharmacopsychiatria最新文献

A follow-up of patients under lithium-prophylaxis in a psychiatric neurological practice over a period of eight years is presented. It allowed for the evaluation of the therapeutic results of 54 of a total of 65 patients with affective psychoses. 32 patients remained free from any further episodes of illness (average duration of treatment 3.8 years). In another 14 patients (average duration of treatment 2.9 years) further episodes occurred but with obviously milder symptomatics. 8 patients (average duration of treatment 4.5 years) had to be considered as non-responders. This result largely consists with reports by other authors. Failures were mainly due to non compliance or diagnostic errors. The small number of patients stopping the prophylaxis without approval of the therapist (5 out of 65 patients) may be attributed to a rigid preselection of patients and to the fact that the conditions for a good patient compliance are more favourable in the practice with its tight and continuous doctor - patient relationship than in a typical out-patient department. Intoxications or other lithium-induced complications did not occur. Generally side effects could be well controlled and/or were tolerated by the patients. Discontinuance of therapy due to side effects was necessary in 3 cases.

High-affinity binding of the tricyclic antidepressant drug, 3H-imipramine, has been demonstrated in the brain of various species including man. These specific binding sites have many of the characteristics to be expected for the specific site of action of a drug and appear to be associated with the neuronal uptake mechanism for serotonin. Chronic administration of tricyclic antidepressant drugs or the prolonged application of other antidepressant therapies, such as electroshock and sleep-deprivation, resulted in decreases in the density of 3H-imipramine binding sites. Apparently identical 3H-imipramine binding sites have been found in blood platelets from a variety of species including man. Clinical studies have shown that untreated severely depressed patients have a lower density of binding sites in their platelets than control volunteers. Longitudinal studies of these patients indicate that the density of 3H-imipramine binding sites tends not to change during treatment with tricyclic antidepressant drugs and the subsequent recovery from depression. 3H-imipramine binding in brain and platelets is proposed as a new biological marker in depression and as a useful research tool in biochemical and clinical pharmacological studies in affective disorders.

The dexamethasone suppression test (DST) was developed from the neuroendocrine research strategy to provide indirect information about the integrity of the limbic system in patients with endogenous depression (ED). Abnormal test results occur in close temporal relationship to clinical episodes of ED, but not during the intervals between episodes. The neuroendocrine disinhibition revealed by the test is not a trait marker of individuals predisposed to develop ED. A standardized DST procedure has been established and can be applied in outpatient or inpatient routine clinical practice, with good sensitivity (50-65%) and high specificity (96%). The conditional probability principles of interpreting the test results are discussed and the effect of prevalence on the predictive value of the test results is emphasized. The DST should not be used as a screening test for all psychiatric patients but should be reserved for cases where clinical indications for its use are present. These indications include diagnostic confirmation of ED, monitoring the response to treatment, prediction of relapse or new episodes, and possibly prediction of suicide risk in patients with ED. The test may be especially useful in the diagnostic assessment of patients with difficult or confusing presentations of ED such as catatonia, depressive pseudodementia, depression in adolescents or children, "masked" depression, depression complicated by a personality disorder, and schizoaffective depression.

The psychopharmacological profile and mechanism of action of ten atypical novel and potential antidepressive drugs (AD) have been investigated. It has been shown that they form a pharmacologically heterogeneous group. Some of them may be considered as central 5-hydroxytryptamine (5-HT) antagonists. Two typical AD, amitriptyline and doxeprine, turned out to be potent 5-HT antagonists also. These observations justify the conclusion that these drugs rather block than facilitate 5-HT neurotransmission. Some data indicate that 5-HT antagonists can shift the balance between the noradrenergic and serotoninergic systems in favour of the former. Both atypical and typical AD when administered chronically, induce effects not observed after single-dose treatment. The effects observed indicate that the chronic administration of AD leads to the development of the increased responsiveness (or activation) of the noradrenergic system.

The effect of chlorpromazine (CPZ) was studied at four different doses in a group of 10 normal subjects. Blood levels of CPZ were assayed by gas chromatography and showed wide interindividual variations. Spontaneous brain electrical activity (EEG) was recorded from 8 leads and submitted to spectral analysis. Evoked responses (ER) to flashes, pattern reversals and clicks were averaged, and measured by their amplitude and variability. Several subjects presented marked side-effects (responders, R) and showed differences in many EEG parameters with respect to subjects without side-effects (non-responders, NR). A cluster analysis permitted to distinguish very clearly these two groups of subjects. The differences in the effects of CPZ between the R and NR groups involved mainly EEG, and appeared with a systematic topography over the scalp. Within the R group, many differences were observed as a function of the dose of CPZ; they consisted mainly in a decrease of alpha and an increase of theta activity in the EEG, decrease of amplitude and increase of variability in the ER measures. These modifications had also a typical topography over the scalp. Finally, many variables of EEG (relative power only) were correlated with plasma level of CPZ, while no such correlation appeared for ER. These results are discussed in terms of individual sensitivity to drugs, relationships between EEG parameters and plasma level, and topographical differences in the effect of CPZ.

Lithium effects have been observed on various aspects of the behaviour of fish, and in particular upon social aggregation, aggression, visual and lateral line sensory perception, memory, and alcohol tolerance. The results of these studies are reviewed and the findings related to a model of lithium action based upon attenuation of sensory information processing.

In an open study the cholinolytic biperiden was administered to 10 severely depressed inpatients in an average dose of 12 mg per day for 30 days. Patients were classified according to the International Classification of Diseases, the research Diagnostic Criteria and the Newcastle Scale. A significant improvement was demonstrated in the global score of the Hamilton Depression Scale (p less than 0.001). Especially the factors retardation (p less than 0.001) and agitation (p less than 0.001) and the items depressed mood (p less than 0.001), initial insomnia (p less than 0.05), work and interest (p less than 0.001) and gastrointestinal symptoms (p less than 0.001) could favorably be influenced. Nevertheless, biperiden treatment had to be discontinued after three weeks in two patients because of a paranoid syndrome in one case and symptoms of inner restlessness and disturbances of vital feelings in the other case. There was a positive correlation between the clinical response and the cortisol non-suppressability to dexamethasone prior to the study (p less than 0.03). These results taken together with other findings from the literature suggest that cholinergic mechanisms may have an important impact on the pathogenesis of certain forms of depression.