P300, clinical symptoms, and neuropsychological parameters in acute and remitted schizophrenia: a preliminary report.
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Adult↗
Biomedical subjects
M Gastpar
Publications and source records attributed to M Gastpar.
Clinical correlates of response to DST. The Dexamethasone Suppression test in depression: a World Health Organisation collaborative study.
From 9 centres 293 patients took part in the WHO-collaborative study on Dexamethasone-Suppression-Test (DST) in depression to examine the relationship of psychopathological and psychiatric history information to cortisol-levels and suppression/non-suppression status. Differences between the centres were large and significant on nearly all of the measures. The predictor analyses generally suffered from numerically weak correlations with many variables correlating to sex and age. Therefore analyses of the data were adjusted for centre-, sex-, and age-influences. The best predicting features of cortisol were 'fitful, restless sleep', 'change of bodyweight' and 'affective disorders in blood relatives'. The last 2 items together with 'hypersomnia' and 'ideas of insufficiency' were the best predictors of suppression/nonsuppression status. However, statistical evidence did not seem to be strong enough to describe a typical symptom profile of a depressive cortisol suppressor or nonsuppressor.
Age Factors↗
Postimperative negative variation and skin conductance response in chronic DSM-III-R schizophrenia.
The hypothesis was tested that there are relationships between schizophrenic negative or deficit symptoms, the skin conductance nonresponding and an elevated amplitude of the postimperative negative variation (PINV). These variables were recorded in 16 chronic schizophrenics and 10 healthy controls. Clinical symptoms were assessed by the Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Frankfurt Complaint Questionnaire 3 and Chapman Questionnaire. In the patient group we found a significantly elevated PINV at Fz. Surprisingly, only one patient was a skin conductance nonresponder. PINV amplitude at Fz and the number of skin conductance responses to habituation were not correlated with negative or deficit symptoms inclding anhedonia. The hypothesis thus had to be rejected.
Adult↗
[Central anticholinergic intoxication syndrome. A contribution to the differential diagnosis of exogenous psychoses].
A withdrawal syndrome in a 50-year-old alcoholic subsided within 5 days in response to treatment with doxepin (150 mg/d). But 2 days later he developed auditory hallucinations which were interpreted as alcohol hallucinations, for which he was additionally given haloperidol, 15 mg/d. He then developed early dyskinesia which was treated with 5 mg biperiden i.v. followed by twice 2 mg/d by mouth, while doxepin and haloperidol were continued. 5 days after detoxification there occurred, under this combination of drugs which included two with marked anticholinergic action, an anticholinergic intoxication syndrome characterized by restlessness, optical hallucinations, dysarthritic speech, mydriasis, urinary retention, fever, tachycardia and red, dry skin. After all previous drugs had been discontinued and clomethiazole started, the intoxication syndrome began to regress within 3 days. The case demonstrates the need to consider a central anticholinergic syndrome, which could end fatally, as a possible cause of otherwise unexplained delirium.
Akathisia, Drug-Induced↗
Trimipramine: pharmacological reevaluation and comparison with clozapine.
Trimipramine has been reported to differ from other typical tricyclic antidepressant drugs in several aspects, for instance it does not inhibit neuronal transmitter uptake and does not cause down-regulation of beta-adrenoceptors. Moreover, it may possess antipsychotic activity in schizophrenic patients. In the present investigation it was found that trimipramine did not alter the electrically-induced release of [3H]noradrenaline and [3H]5-hydroxytryptamine, from slices of the cerebral cortex of the rat, in concentrations of less than 1 microM. It did not antagonize the inhibitory effect of noradrenaline and 5-hydroxytryptamine on the release of transmitter, mediated by presynaptic autoreceptors. In radioligand binding studies, D,L-trimipramine showed fairly high affinities (KI 10-60 nM) for some dopamine (DA), noradrenaline and 5-hydroxytryptamine (5-HT) receptor subtypes (5-HT2 receptors = alpha 1A/B-adrenoceptors greater than or equal to D2 receptors), intermediate affinities (300-550 nM) for D1 receptors, alpha 2B-adrenoceptors and 5-HT1C receptors but only low affinities (greater than 1000 nM) for alpha 2A-adrenoceptors, 5-HT1A, 5-HT1D and 5-HT3 receptors. It may thus be classified as an atypical neuroleptic drug. Especially, its affinities for dopamine receptors, alpha 1-adrenoceptors and 5-HT2 receptors closely resembled the values measured for clozapine. The L-enantiomer of trimipramine showed higher affinities for these binding sites than D-trimipramine. The present findings may explain the mechanism of the potential antipsychotic action but not the antidepressant effect of trimipramine.
Animals↗
Trimipramine--an atypical neuroleptic?
Trimipramine and clozapine show some similarities in their receptor binding profiles. Since both have the same affinity for the D2 receptor and since the affinity for this receptor correlates closely with the antipsychotic potency of a drug, an antipsychotic efficacy of trimipramine in acute schizophrenia could be expected. Therefore 28 schizophrenic patients in an acute phase were treated with trimipramine up to 400 mg/d in an open clinical trial. For the whole group of patients the BPRS total score changed from 58 +/- 5 before treatment to 46 +/- 18 at the last rating (p less than 0.05). According to our clinical judgement the patients were divided into three subgroups. Thirteen patients showed a good remission under trimipramine so that they could be discharged on a trimipramine maintenance treatment. They improved on the BPRS from 58 +/- 6 before treatment to 32 +/- 8 at endpoint. Six patients deteriorated during the first week of treatment and had to be withdrawn from the study. Nine patients showed insufficient improvement or became worse after an initial improvement. The observed side-effects (dry mouth, sedation, sweating, increased appetite, constipation, tremor, vertigo) are well known under trimipramine and were therefore expected. Beyond these, one patient developed a cardiac insufficiency. No clinical relevant extrapyramidal side-effects occurred. Since the improvement of florid psychotic symptoms seems to be markedly higher under trimipramine than the one reported under placebo, our results indicate that trimipramine may have an antipsychotic potency.
Acute Disease↗
[Event-related potentials in schizophrenic patients in the acute phase and in remission].
In 15 schizophrenic patients event-related potentials were recorded during an auditory two-tone-discrimination task in the acute phase and after remission. The control group consisted of ten healthy subjects of the same age. The schizophrenic patients showed reduced amplitudes of N1, P2 and P3 and prolonged latencies of N2 and P3 independent of neuroleptic medication and clinical state. We found no differences in the topographical distribution of P3 between schizophrenic patients and controls. The changes of the event-related potentials in the schizophrenic patients may be interpreted as electrophysiological correlates of basic disturbances in information processing in schizophrenia.
Acute Disease↗
[Methadone maintenance as a therapeutic approach in the treatment of opiate dependent patients].
Treatment of opiate addicts is still difficult, and often has only limited success. Methadone therapy offers an alternative, in particular for patients who have repeatedly attempted conventional treatment without success. According to experience in Switzerland, about two-thirds of these patients become medically stable and socially rehabilitated during methadone therapy, or even drug-free in the long term following therapy. The therapy does not consist solely in a daily dose of methadone, but also involves intensive psychosocial care. In Germany, methadone therapy has been under discussion for more than 20 years. In this discussion doubts have been expressed about the criteria used to assess the indications for and the degree of success attained with methadone therapy. In addition, ethical arguments question whether social rehabilitation should be a primary goal of therapy. In order to objectify the discussion, methadone therapy is now being tested in Germany. A social consensus must be sought on goals and strategies in the treatment of opiate addicts.
Follow-Up Studies↗
The Hamilton Depression Rating Scale in a WHO collaborative program.
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Adult↗
High-dose trimipramine in acute schizophrenia. Preliminary results of an open trial.
Trimipramine and clozapine show some similarities in receptor-binding profiles. Both have the same dissociation constant for D2-receptors and marked binding potencies for H1-receptors and muscarinic acetylcholine receptors. Based on these similarities an antipsychotic efficacy of trimipramine might be postulated. To generate hypotheses 15 schizophrenic patients with a BPRS total score of at least 50 were treated with trimipramine up to 400 mg per day. Four patients deteriorated under this treatment and had to be withdrawn from the study between the 4th and the 10th day. One patient stopped participating after the 15th day due to lack of improvement. These drop-outs showed a mean impairment in BPRS total score from 56 at baseline to 66 at endpoint. Ten patients were treated for 4 to 5 weeks successfully and improved on the BPRS from 57 at baseline to 31 at endpoint. High-dose trimipramine was tolerated well. In schizophrenic patients the expected sedative effect was small. One patient developed a modest parkinsonism, no acute dystonia was seen.
Acute Disease↗
Mood (affective) and schizoaffective disorders (section F3): results of the ICD-10 field trial.
Section F3 (affective disorders) of ICD-10 has preserved a high degree of continuity with respect to ICD-9, and a strong convergence towards DSM-III-R affective disorders is evident. Despite this tendency, some categories, like F31, F33 and F36, need further specification. In general, section F3 was adequately accepted by clinicians, easy to use and proved to be user-friendly for a wide variety of psychiatrists with different orientation.
Affect↗
ICD-10 field trial in German-speaking countries--summary, judgement and perspectives.
On the basis of the results of the field trial, the most important classificatory innovations of ICD-10, together with their advantages and disadvantages are described. The initial good acceptance of the new system could be further improved by structural modifications, such as a uniform and systematic description of the individual diagnostic categories. Criticism of content was focused on affective and neurotic disorders and adult personality disorders. When it is introduced, the psychiatric chapter of ICD-10 will surpass most of the hitherto existing psychiatric classification systems in size, differentiation and international testing.
Adolescent↗
Biological study of alcohol dependence syndrome with reference to ethnic difference: report of a WHO Collaborative Study.
Inherited deficiency of acetaldehyde dehydrogenase type I (ALDH-I) was found in 43% (50/117) of normals, 33% (27/82) of schizophrenics, but only 4% (5/113) of alcoholics among Japanese. The ALDH-I deficiency was never found, however, in 146 mostly schizophrenic subjects from Europe (Basel, Moscow, Zagreb), Australia (Nedlands), India (Lucknow), Morocco (Casablanca) and Mexico (Mexico City). It was demonstrated that ALDH-I deficiency produces the flushing syndrome which inhibits the development of drinking habit and alcohol dependence syndrome.
Alcoholism↗
Clinical originality and new biology of trimipramine.
Trimipramine differs from other antidepressant drugs in a number of ways. Although trimipramine shares equivalent efficacy with doxepin, imipramine, maprotiline and amitriptyline, as evidenced by double-blind studies, it possesses a different side-effect profile. Trimipramine is considered to be less cardiotoxic, and data presented in this paper support its minimal effect on orthostatic hypotension, as compared with clomipramine. In addition, trimipramine has less epileptogenic potential than other antidepressants such as imipramine, amitriptyline and maprotiline. Besides this different side-effect profile, trimipramine exerts differing effects on neurotransmitter functions and their reuptake. For example, trimipramine does not inhibit reuptake of noradrenaline and serotonin, and does not down-regulate beta 1-adrenoceptors. Furthermore, in common with lithium, trimipramine produces enhancement of antidepressant action in treatment-resistant depressed patients. There is evidence that trimipramine enhances the sensitivity of cortical neurons to noradrenaline after prolonged administration and may also increase the activity of serotonin neurons.
Depressive Disorder↗
WHO pilot study on the validity of imipramine platelet receptor binding sites as a biological marker of endogenous depression. A preliminary report on the initial evaluation phase of a World Health Organization Collaborative Study.
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Blood Platelets↗
Thrombosis of cerebral veins following intravenous application of clomipramine.
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Cerebral Veins↗
L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression.
In an open study 25 depressed patients were treated with L-5-hydroxytryptophan (L-5-HTP) either alone or in combination with a peripheral decarboxylase inhibitor. The therapeutic efficacy of L-5-HTP was considered as equal to that of traditional antidepressants. There was no difference in efficacy between the two treatments. Best results were obtained in patients with an anxious-agitated depressive syndrome and in patients with an endogenous depression if the illness had been acute. The onset of action was rapid (within 3 or 5 days). Gastrointestinal side effects proved to be dose-dependent and occurred more frequently in patients receiving L-5-HTP alone, whereas psychopathological side effects (especially acute anxiety states) have mainly been reported in patients receiving L-5-HTP in combination with a peripheral decarboxylase inhibitor.
5-Hydroxytryptophan↗
Acetylation of maprotiline and desmethylmaprotiline in depressive patients phenotyped with sulfamidine, debrisoquine, and mephenytoin.
A gas chromatographic/mass spectrometric method (using either electron impact or chemical ionisation with methane or ammonia) is described for the quantitative analysis of maprotiline (MP, Ludiomil), N-acetylmaprotiline (AcMP) and N-acetyldesmethylmaprotiline (AcDMP) in whole blood or plasma. In two groups (A and B) of 82 and 53 depressive patients treated clinically with MP for 10 and 21 days, respectively, plasma and whole blood MP was monitored during the treatment. In group A, all subjects were phenotyped with debrisoquine and mephenytoin, and 44 with sulfamidine. 5 patients were poor metabolizers of debrisoquine and 2 of mephenytoin; 18 subjects were fast acetylators of sulfamidine. Traces of AcMP were found only in two patients. AcDMP was present in levels below 2 ng/ml in the plasma of most of the patients in group A. In group B, AcDMP levels between 2.4-14.6 ng/ml of whole blood were found in 9 patients. The mass spectral data suggest the presence of another, unknown MP metabolite interfering partly with the analysis of AcDMP. The presence of AcDMP seemed not to be related to the phenotype of the patients as determined by the pharmacogenetic tests.
Acetylation↗