Pharmacopsychiatria最新文献

Twenty-eight patients with acute schizophrenic illness received an oral daily dose of 200-800 mg perazine (Taxilan) for 4 weeks. Weekly plasma level determinations showed a constant perazine concentration from day 7 to day 28, whereas the equilibrium level of its metabolite desmethyl perazine was only achieved at day 14; on an average it amounted to twice the level of perazine. Additional measurements were carried out 2 and 4 h after administration of the morning dose on day 14. The maximal increase of the perazine concentration was usually reached after 2 h; though it varied between 7 and 240% of the morning level, a close correlation existed between minimal and maximal levels. The perazine fraction not bound to plasma proteins was found to be 3.1-5.5% on day 21. The percent improvement in target syndromes during 4 weeks of neuroleptic therapy, as documented with the AMDP system, was most marked in those patients who had perazine levels in the 100-230 ng/ml range at day 28; patients with lower or higher levels improved significantly less. Curvilinear relationships also appeared to exist between improvement and free perazine concentration as well as maximal level on day 14. With regard to total scores on the Brief Psychiatric Rating Scale or scores of higher-order factors, no significant relationship between improvement and perazine level was found. The desmethyl perazine concentration did not exhibit a significant relationship to the therapeutic result. The pharmacokinetic parameters investigated seem to have a limited influence on the clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

In a pharmacopsychiatric pilot study 28 patients with an acute schizophrenic illness were treated for 4 weeks with perazine (Taxilan). Research goals in the psychopathological investigation were: (1) to assess the range of efficacy, target symptoms and syndromes of perazine and to compare these results with previous studies; (2) to compare the quality, interrater reliability, and practicability of two instruments of psychopathological assessment (AMDP and BPRS) for measuring change during treatment; (3) to apply new mathematical methods for finding statistically significant changes in symptomatology on the item level as well as on the levels of syndrome and total score; (4) to test whether pre-treatment prediction based on psychopathological evaluation or psychophysiological data is possible. The target symptoms and syndromes of perazine were the "positive" schizophrenic syndromes, above all thought disturbances and delusional phenomena. This result was consistent with a former perazine investigation. The BPRS proved to be a practicable and reliable instrument for a more global evaluation of change in psychopathology. The AMDP seemed to be especially useful for evaluating the homogeneity of a sample and showing differentiated psychopathological profiles. On this scale, changes in symptomatology became statistically apparent more clearly and more quickly on the syndrome level rather than on the level of single items. As to interrater reliability, both scales perform well. Dichotomizing the original scaling may mean a loss of information from both scales (AMDP and BPRS) in their evaluation of change. Hence it seems necessary to introduce new mathematical procedures (e.g., Friedman and Dunn-Rankin tests) into pharmacopsychiatric research.(ABSTRACT TRUNCATED AT 250 WORDS)

During drug development effects on blood cells, metabolism or function of heart and circulation are routinely examined. In case there is evidence of influence on such systems, examinations in clinical pharmacology are done. For the organ central nervous system the same rules should be followed, independently whether a substance is primarily a psychotropic drug or developed for other indications. Besides pharmacopsychological procedures pharmacoelectroencephalography is the most sensitive method to describe drug induced changes on brain function of humans. In event related research (e.g. evoked potentials) it is easier to form hypotheses for the mechanism of reaction after stimulation. About the validity of spontaneous cortical activity, like scalp recorded EEG we have little knowledge. However, a single signal of the spontaneous activity is analyzed into several components, each of which can be influenced differently by various drugs. Important areas of pharmacoelectroencephalography are: 1) Determination of CNS effects on a functional level; judgement whether a pharmacon has a potential for influencing CNS function in comparison to placebo. 2) Characterization of CNS-effects; determination of vigilance changes and classification of the profile in comparison to the EEG-effects of standards. 3) Determination of dose/efficacy and time/efficacy relations; description of kinetic data based on an effect-parameter, in contrast to blood levels; comparison of different galenic formulations; determination of onset and duration of effects; etc. 4) Determination of sleep-wake rhythms; measurement of influence on sleep/waking behaviour in the sleep laboratory or under vigilance controlled conditions during daytime.(ABSTRACT TRUNCATED AT 250 WORDS)

The cardiovascular effects of the antidepressant zimelidine were studied in healthy volunteers ( n = 10) during a period of six days. The following parameters were examined: plasma level of the substance, blood pressure and--by means of ECG echocardiogram, carotid pulse curve and phonocardiogram--heart rate, myocardial contractility parameters, afterload and systemic arterial resistance. At therapeutic plasma levels zimelidine did not cause any significant increase in heart rate at unchanged blood pressure in contrast to classical tricyclic antidepressant. Furthermore, the inotropy parameters e.g. circumferential fibre shortening rate, systolic time intervals, and fibre shortening did not show any alterations after zimelidine. Decreases of peripheral resistance and afterload were negligible.

The authors describe two female patients with bipolar I depression who did not respond to tricyclic antidepressants in their previous depressive episodes and were prophylactic lithium nonresponders. Both patients showed a high pretreatment platelet MAO activity and responded well and rapidly to monoamine oxidase inhibition (MAOI) treatment. These findings suggest that although bipolar depressed patients show a low platelet MAO activity, there may be a subgroup with high enzyme activity. These patients revealed a low tendency to respond to tricyclic antidepressants and showed rapid improvement on MAOI therapy.

Using a double-blind experimental design, two dosage regimens of haloperidol were compared in acutely decompensated, newly admitted schizophrenic patients. Patients in group A (n = 21) received 5 mg haloperidol tablets, patients in group B (n = 20) 15 mg haloperidol tablets. The number of tablets did not exceed six a day but could be varied according to the condition of each patient. On the average patients of group A were prescribed 4.0 tablets, corresponding to 20.0 mg haloperidol a day, and patients of group B 3.9 tablets, corresponding to 58.0 mg haloperidol a day. A significant amelioration of the psychopathology as measured by BPRS were observed in both groups. Between both groups investigated, no differences were found neither with regard to therapeutic efficacy nor to the tolerance of the treatment. Administration of higher oral haloperidol doses cannot be recommended as a standard procedure.

The clinical boundaries of affective disorders have been considerably broadened in the past few years, in part due to therapeutic advances. Many psychotic patients who were formerly considered schizophrenic are now being treated with thymoleptic agents. Clinicians as well as researchers are seeing many patient with mood disturbance in ambulatory settings where anxious, intermittent, masked, and characterological presentations are common. Mood disorders are also being increasingly diagnosed in children, the elderly and in patients in primary care settings. Do these changes in diagnostic practice reflect therapeutic fashion? Are there external validating criteria by which the affective origin of these diverse conditions can be ascertained? In discussing the clinical and research dimensions of these questions, we provide a framework for resolving the methodologic issues involved.

A nation-wide survey on the abuse of benzodiazepines in Switzerland showed an average morbidity (incidence) of 0.0006 per year for isolated abuse of benzodiazepines. The exposure risk was, independently of the benzodiazepine compound used. 0.00002 per prescription. The afflicted population differed demographically in no way from the population of "normal" benzodiazepine consumers, legitimate therapeutic use of a benzodiazepine being the only visible risk factor for development of an abuse. The motivation for abuse, too, was in about 90% of the case self-medication of anxiety and/or insomnia and related symptomatology. Main source of the drug was new prescriptions by the treating physician. The majority of patients were medically in a good state of health and socially well adjusted; 52 out of 180 patients, however, showed negative consequences. Withdrawal syndromes were reported in about one quarter of the detected cases, but detection was mostly due to the increased frequency of prescriptions of confession of the patient. Because of the low frequency of severe negative consequences and the mostly unobtrusive behaviour of the patients, differing in many ways from the accustomed picture of an "abuser of (illicit) drugs", the physician's attitude towards abuse of benzodiazepines was in many cases ambivalent, resulting in a tacit acquiescence and continued prescription. From the data presented it is concluded that the most appropriate measure against abuse of benzodiazepines would be, rather than international control, education of medical professionals and the public, according to internationally accepted medical knowledge and to national law and prescription regulations.

Hypersexuality induced by dopaminergic drug treatment in parkinsonian patients is a rarely reported side-effect. A case history is presented where it occurred together with hyperkinesias while the patient was treated with L-dopa and bromocriptine. An addictive misuse of these drugs complicate the guidance of this patient. Approximately three years after the beginning of hypersexuality he developed several paranoid-hallucinatory psychoses which subsided each time upon dose reduction.