Pharmakopsychiatrie, Neuro-Psychopharmakologie最新文献

Averaged evoked potentials, expectancy waves and number and amplitude of skin resistance responses to auditory stimuli are found to be significantly smaller in a group of 18 patients with primary depression than in 27 healthy controls. AEP amplitude attenuation is shown not to be an averaging artifact, due to varying response latencies. There are no simple relations between electrocortical and electrodermal parameters, but patients display more significant correlations between these two sets of variable than controls. Amplitude attenuations are interpreted as hyporesponsivity resulting from depressive inhibition. The narrower coupling of variables in the depressed group is viewed as a limitation in physiological plasticity.

Studies on the effects of the d- and l-stereoisomers of tranylcypromine on locomotor activity, aggressive behavior, hindlimb reflexes, head twitches and behaviors produced by reserpine in rats are reviewed. The d-isomer is found to produce stereotypic behavior and head twitches, to enhance extensor hindlimb reflexes, and to alter effects of reserpine on locomotor activity. The l-isomer is shown to enhance vertical and horizontal locomotor activity and to cause aggressive behavior, but failed to influence hindlimb reflexes, effects of reserpine, or to produce head twitches. Biochemical and pharmacological studies suggest that the d-isomer influences mainly tryptaminergic neurotransmission while the l-isomer affects primarily catecholaminergic neurotransmission. It is concluded that tranylcypromine stereoisomers have stereoselective effects on behavior and monoaminergic neurotransmission. The implications of the findings for the notion that the antidepressant effects of tranylcypromine are due to inhibition of MAO are briefly discussed.

In a double-blind trial in depressed outpatients, 80 subjects received either mianserin 30--80 mg daily or diazepam 15--40 mg daily, for 4 weeks. Most patients received 50--60 mg mianserin, or 25--30 mg diazepam, daily after the first week. Mianserin was significantly superior to diazepam in antidepressant efficacy from day 14 to the end of the trial, as measured by the Hamilton Rating Scale for Depression and the Beck Self-Rating Scale, and at day 28 as measured by the Clinical Global Impression. All three measures showed that the mianserin group started the trial with a significantly more severe degree of illness than the diazepam group, but this difference was already reversed by day 14. Side-effects were more frequent with mianserin treatment.

Since the introduction of seizures as a therapy in psychiatry in 1934, much has been learned about the target populations, modes of induction, means to make the treatment safer, and the mechanisms underlying the therapeutic process. The repeated and spaced induction of seizures relieves the symptoms of severe depressive psychoses. The presence of vegetative symptoms is a predictor of good outcome, and brain stem stimulation is a feature of successful treatment. The safest inductions are those using barbiturate and succinylcholine anesthesia, hyperoxygenation, unilateral electrode placements, and minimal inducing currents. Patients with severe depression present neuroendocrine abnormalities, which return to normal with convulsive therapy. Recently, peptides of hypothalamic origin have been identified which have behavioural and mood altering effects. From these experiences, we suggest that the antidepressant efficacy of convulsive therapy results from the increased release and greater penetration into the brain of hypothalamic peptides with behavioral effects.

Tricyclic antidepressant drugs are remarkable in their therapeutic actions. When given acutely they are generally sedating. Then after a lag of 1-3 weeks, they alleviate depressive symptoms. Besides the delayed psychic energizing properties, the immediate apparent sedative actions may have importance for the relief of psychomotor agitation. This article describes influences of the drugs on histamine H1 and alpha-adrenergic receptors which may be of relevance to the energizing effects and relief of psychomotor agitation.

The Unipolar (UP) and Bipolar (BP) forms of affective illness appear not to be genetically and physiologically identical, although the degree of overlap in family and biologic pharmacologic studies is considerable. It appears likely that at least a subgroup of UP illness shares its genetic diathesis with BP illness. The hypothesis of monoamine alterations associated with the affective illnesses has led to studies of genetics of enzymes of monoamine metabolism as observed in peripheral blood, erythrocyte catechol-O-methyl-transferase (COMT), platelet monoamine oxidase (MAO), and plasma dopamine-beta-hydroxylase (DBH). These are under genetic control and show some differences between patients with affective illness and controls, but these differences have not been consistently propagated through families along with the disorder. Linkage of BP illness to markers on the X-chromosome has been reported, but the evidence has internal inconsistencies which must be resolved before the phenomenon can be accepted. Association of BP illness with specific HLA types has also been reported, but efforts at replication have been unsuccessful. Mathematical models of transmission applied to family study data do not consistently support the same mode of transmission when applied to data collected at different centers.

The effects of 20 mg morphine HCL i.m. and the synthetic metenkephalin analogue FK 33-824 (1.25 mg, i.m.) were compared single blind in 8 addicts undergoing withdrawal from chronic heroin misuse. FK 33-824 was found to reduce withdrawal distress in 6 subjects but was less effective than distress in 6 subjects but was less effective than morphine. The effect of FK 33-824 was described as not morphine-like "an intoxication without euphoria". All 8 subjects preferred morphine to FK 33-824 and five stated that they would refuse to take another dose of FK 33-824. This difference in preference, with regard to the two drugs of substitution, may have been due to side-effects of the enkephalin-like compound: a feeling of oppression in the chest and heaviness in muscles.

Besides the well known somnolent and almost delirious states which always imply different mnestic and gnostic disorders also other drug-induced side-effects and complications can be observed during antidepressive treatment. Mnestic blackouts which clinically are more or less inconspicuous but which are always discovered retrospectively occur more often than they are documented. They are rather related to disturbances of engrammation depending on psychotropic drugs than to a disturbance and narrowing of the state of vigilance and consciousness. In order to exemplify a serious psychopathological complication of the altogether rare amential-amnestical syndrom, a casuistic report is presented of a case of a regulated semiconscious state during two weeks, a case of an amential-amnestical attack, and a case of ictal amnestical episode (Ictus amnesticus). The possible etiology and the observed disorders of memory and consciousness are discussed. The following common pathogenetic factors should be considered though the presented three cases have a different psychopathology and probably a different etiology: (1) The specific pharmacodynamics of the individual antidepressive drug, (2) disease related factors inclusing an alteration of the ability of conceiving and of the process of engrammation, (3) an individual vulnerability of neuronal synaptic systems.

Chlorprothixene was the first neuroleptic of the thioxanthene group and was marketed in 1959 under the trade names of Taractan and Truxal. Since then 20 years have passed and the authors were of the opinion that it would be opportune to study the literature published during these 20 years. They perused 801 publications, hereof 542 clinical works. Of these clinical works 109 were suited for statistical analysis. They represented 7109 patients. The other publications comprise 4378 patients which means that all the literature studied consists of a total of 11487 patients. The chlorprothixene proved to be a broad-spectrum neuroleptic with good therapeutic effects. Side effects, especially the extrapyramidal symptoms, appeared only seldom. Among the 11487 patients only 1.02% showed extrapyramidal symptoms and of these only 0.05% had tardive dyskinesias. Sme evidence seems to exist that these are schizophrenic patients showing extrapyramidal symptoms, without having received neuroleptics. It is the authors' opinion that chlorprothixene is still a neuroleptic of topical interest.

The results of a one year treatment with Melperone are reported. 18 mentally retarded female patients with severe aggressive and autoaggressive behaviour had been included in this open study. Six patients suffered from various epileptic seizures. A significant reduction of aggressive and autoaggressive behaviour, measured by the AFGB, was found. The activity of alkaline phosphatase showed a significant tendency towards normalisation. EEG-controls of patients with epileptic seizures showed no increase of epileptic activity in the EEG. No severe side effects were noticed.