Pharmacopsychiatria最新文献

Transitory ataxias have repeatedly been observed and reported in connection with antidepressant medication. However, it is remarkable that exact descriptions of this particular form of ataxia are rarely included. Also, hypotheses concerning the etiology and pathophysiology of these disorders are generally lacking. They are usually given the imprecise designation of "extrapyramidal" ataxias. Two cases are presented here in which therapy-resistant endogenous depressions were treated with maprotiline/dibenzepine and maprotiline/clomipramine, respectively. In both cases, marked neurological side effects in the form of cerebellar ataxia developed. The symptoms, which occurred despite usual dosage, remitted after maprotiline treatment was discontinued for one patient and after dose reduction of both drugs for the other. The atactical and dysmetric symptoms described here are thought to result from a reversible intoxication of mainly cerebellar structures. In an attempt to explain the genesis of these ataxias, a neurophysiological and a neuropharmacological hypothesis are considered and predisposing factors as well as therapeutic consequences are discussed.

Whilst the "effect" of a drug can be observed or deduced from observational data, the concept of "therapeutic efficacy" represents mainly a theoretical construction of a high degree of abstraction which is inconceivable without reciprocal combination with other theoretical constructs. The "therapeutic efficacy" of drugs can be investigated only via clinical-pharmacological or clinical models. Several examples are given. The strength of evidence of models is discussed as well as the necessity to continually test them empirically.

There is some evidence that the early response of schizophrenic patients to neuroleptic treatment is of prognostic value for the subsequent course of treatment. This hypothesis was confirmed in a prospective study. It was demonstrated that already the therapeutic effect on the first day of treatment is of prognostic value, especially with a standardized drug regimen.

The serum dopamine-beta-hydroxylase activity of 134 carefully selected paranoid schizophrenic patients was compared with that of 118 normal controls. Significantly reduced serum DBH activity found in the schizophrenic group in comparison to the control group could not be brought into relationship with the patients' age, nor with neuroleptic treatment. Manic depressive patients showed values similar to the normal control group. It is discussed that mainly genetically determined low serum DBH activity may be related to the hyperdopaminergic pathomechanism of paranoid schizophrenia.

The frequency of disturbances of the liver function, of leucopoiesis, blood pressure and temperature regulation under clozapine in comparison with perazine and haloperidol in 478 patients (partly being treated repeatedly) was investigated by means of case histories of the Psychiatric Clinic of Tübingen from October 1974 up to June 1978. Within the time of the investigation no case of jaundice arose, however non-symptomatic increases of the liver values could be observed. The three drugs did not differ in this respect. Within the time of the investigation no case of agranulocytosis was observed. Only one leucopenia under clozapine, one under perazine, and six under haloperidol occurred. Concerning cardio-vascular effects of the neuroleptic medication, in 4.1% of the patients under clozapine therapy, 4.3% under haloperidol therapy and 10.3% under perazine therapy hypotension could be observed. Under clozapine 15.2% of the patients showed a rise of temperature, under perazine 3.2% and under haloperidol 2.8% of the patients. 83.3% of cases with elevated temperature under clozapine occurred during the first two weeks of treatment.

Amitriptyline N-oxide (AMINO) was given to male Wistar rats orally in single and multiple doses, and the levels of the drug and its main metabolite amitriptyline (AMI) were assayed in blood and brain by HPLC. After the single dose of AMINO (20 mg/kg), the levels of the parent compound and of AMI in the brain were higher than in blood. In the brain Cmax of AMINO and AMI were similar, whereas in the blood Cmax of AMI was considerably lower than that of the parent compound. After chronic treatment with AMINO (10 mg/kg twice daily, at 12 h intervals, for 14 days) the brain level of AMI reached the value of approx. 4 micrograms/g of tissue and remained nearly stable for 12 h after the last dose. Brain Cmax of AMINO was approx. 2 micrograms/g; the drug was eliminated more rapidly than AMI and 24 h after the last dose it was not detectable. The blood level of AMINO exceeded the level of AMI, but the difference was less marked than that observed after a single dose. The brain and blood levels of both drugs were considerably higher than those observed in the acute experiment. When AMI was given to rats chronically (dosage and schedule as above) its blood and brain levels were 2-5 times higher than the corresponding levels of AMI after treatment with AMINO, and its elimination was more rapid. Our results indicate that after oral administration of AMINO to rats AMI is formed in significant amounts, its brain level is high and becomes more stable after chronic treatment.

We examined the influence of single applications of placebo, caffeine (7 mg/kg), and crotylbarbital (2 mg/kg) on reaction and attention performance in 15 volunteers. A newly developed reaction-time apparatus permits the reaction time to be split for differentiation between initiation time and movement time. Moreover, simple and complex attention performance can be quantified. The volunteers were selected as to the dimensions of "introversion/extraversion" and "emotional lability/stability" by means of the Freiburg Personality Inventory. Labile volunteers responded to placebo faster than stables. Caffeine improved mainly the performance of introverted subjects. Crotylbarbital was without influence on the reaction time at the threshold dose applied.

Recent studies report the occurrence of withdrawal reactions in a significant number of patients after long-term use of benzodiazepines, i.e. daily use for one year or more. The abstinence syndrome is partially characterized by anxiety, dysphoria, sleep disturbances and other unspecific symptoms. In addition, some patients experience symptoms, which, so far, have not been described as typical part of a withdrawal syndrome, especially disturbances of sensory perception. The withdrawal syndrome is less acutely distressing than a classical withdrawal syndrome of the barbiturate type, but occasionally it can show a protracted course.

Present methodological problems in assessing the clinical efficacy of putative antidepressants require testing of various new strategies. The approach presented by the authors allows "natural" clinical treatments to be evaluated scientifically; double-blind conditions are replaced by other measures of bias control. In this paper, the clinical effectiveness of mianserin in homogenous groups of inpatients with severe endogenous depression is compared with that of maprotiline and amitriptyline. The frequency of change of the respective antidepressant by the physicians in charge as well as patients' self-evaluations based on v. Zerssen's Mood Scale served as outcome criteria. No difference in efficacy was found between maprotiline and amitriptyline, whereas mianserin was significantly less effective. The number of patients complaining of side effects from the two tetracyclic compounds was no less than in the case of amitriptyline. There were, however, qualitative differences; with maprotiline, myoclonic jerks were observed in some cases. The hypothesis that mianserin may possess sedative-anxiolytic rather than antidepressive properties is discussed in conjunction with methodological and theoretical implications.