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Biomedical subjects

B Shopsin

Publications and source records attributed to B Shopsin.

At least 19 recordsLinked to original sources

Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double-blind comparison.

Clozapine is a unique compound belonging to a relatively new group of antipsychotic agents, the dibenzazepines. To our knowledge, the present study represents the first double-blind, controlled comparison recorded in the United States. The data suggest that clozapine in the present population of newly admitted, acutely psychotic schizophrenic individuals, and in the doses employed, was more effective in overall improvement response, discharge rate, and ameliorating discrete symptoms across the different objective rating scales used than was chlorpromazine (Thorazine) hydrochloride. Placebo was ineffective. Unlike chlorpromazine, no extrapyramidal reactions occurred in those patients ingesting clozapine. Clozapine was also beneficial in reversing abnormal involuntary motor movements. It is an excellent anxiolytic and hypnotic agent. Sedation, hypotension, and hypersalivation are among the more common side effects observed.

Acute Disease

HLA antigen and affective disorders: a report and critical assessment of histocompatibility studies.

The distribution of 50 HLA antigens, of the A, B and C loci, was investigated in 38 affectively ill Caucasian patients of Eastern European Jewish ancestry. The frequencies found were compared to those of a control population matched for race as well as geographic and ethnic-religious origins. Results indicate that a negative association exists between affective disorders and Cw3 and also suggests a similar negative association between such disorders and A9. A positive association with Bw16, Bw22 and Cw1 is also indicated; Bw16 was increased in those patients with no family history of psychological illness. A review of the available literature in this area shows a glaring lack of agreement among the studies. Methodological problems exist which are likely to contribute to the variable and conflicting results and might make comparison of data irrelevant. The lack of agreement of data among the studies may also indicate that no HLA disease association exists but rather reflect the existence of a defective gene in the HLA complex but not a part of the HLA system. Additional population and family studies are required before any definitive statements can be made.

Bipolar Disorder

Dopamine receptor stimulation in the treatment of depression: piribedil (ET-495).

ET-495, a putative central dopamine receptor stimulant, was givem to endogenously depressed individuals, all of whom were largely unresponsive to previous drug treatment. The drug exhibited a rapid and, in some cases, a pronounced antidepressant effect. This effect was short-lived, however, and, within a brief period, depression returned accompanied by a consistent syndrome of anger, irritability, hostility and poor temper control. In one individual with a bipolar history, the induction of a paranoid psychosis and auditory hallucinosis occurred. While the data suggests a role for dopamine in the symptomatic relief of depression in man, they also imply that this monoamine cannot, in and of itself, be considered as the primum movens in either the action of other (established) antidepressant drugs, or as underlying depressive illness.

Adjustment Disorders

Enhancement of the antidepressant response to L-tryptophan by a liver pyrrolase inhibitor: a rational treatment approach.

In an open preliminary investigation, pre- and concomitant treatment with a liver pyrrolase inhibitor allopurinol to depressed male outpatients receiving L-tryptophan suggests a rational approach to treatment with this serotonin precursor. The combination is both safe and apparently effective; the rapidity of response in some patients underscores the clinical effects. Implications are that serotonin, or rather an excess in serotonin, is involved in the symptomatic relief of depressions in man.

Adult

Penfluridol: an open phase III study in acute newly admitted hospitalized schizophrenic patients.

An open study was carried out in 17 acutely ill, newly admitted, floridly psychotic schizophrenic patients to a city hospital in New York. Penfluridol was given on a daily basis up to doses of 120 mg and patients were rated objectively by means of different psychometric evaluations; vital signs were monitored daily as were side effects. The drug was found to be a rapid acting, well-tolerated, and highly effective antipsychotic agent within the population of patients explored and within the dose range used. It was particularly effective in acutely agitated floridly paranoid schizophrenics; a statistically significant impact was achieved by 7 days and usually within 72 h after initiating treatment. The drug appears unique in that (1) its effects are realized without the untoward and usually troublesome effects of nonspecific sedation attendant upon the use of many other 'neuroleptic' medications, and (2) even within the relatively high doses used it produced no hypotensive effects. It is concluded that this appears to be a unique antipsychotic agent and a potentially important addition to the treatment armamentarium of both acute and chronic schizophrenic individuals.

Acute Disease

Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients.

Hospitalized bipolar and unipolar endogenously depressed patients who showed an antidepressant response to the monoamine oxidase (MAO) inhibitor, tranylcypromine sulfate, relapsed (ie, depression returned) when relatively small doses of parachlorophenylalanine (PCPA) were added for brief periods. Considered together with our findings that PCPA similarly reversed the antidepressant effects of the tricyclic drug, imipramine hydrochloride, implications are (1) serotonergic mechanisms are likely involved in the antidepressant effects of both the tricyclic drugs and MAO inhibitors in man and (2) this indolamine may also play a role in the endogenous clinical state of depression.

Bipolar Disorder

Genetics of affective disorders. I. Familial incidence study of bipolar, unipolar and schizo-affective illnesses.

47 affectively ill psychiatric patients and their first-, second- and third-degree relatives were investigated by means of an interview and pedigree analysis to determine the incidence of psychiatric illness in their families. The percentage of psychiatric illness appeared greatest in families of bipolar and schizo-affective probands and least in families of unipolar depressives. In addition, we observed that often within a particular family constellation, more than one type of psychiatric illness (i.e., bipolar manic-depression, schizophrenia, alcoholism, etc.) was present. Morbidity risks varied from one affected family to another, indicating that the genetic risk components for some families are greater than for others. These findings are suggestive of multifactorial genetic disease but other genetic models are considered.

Affective Symptoms

Genetics of affective disorders. II. Morbidity risk and genetic transmission.

Morbidity risk and genetic transmission data on a small population of bipolar, unipolar and schizo-affective outpatients suggest a possible genetic overlap between bipolar and schizo-affective patients. There is a conspicuous absence of a homologous illness in the relatives of schizo-affective probands, although the incidence of schizophrenia was higher in these relatives as compared to the relatives of either bipolar or unipolar probands. The data, although tentative because of the relatively small numbers involved, suggest a multifactorial mode of transmission in some affective illnesses. These disease entities appear familial rather than 'genetically transmitted'. There are select families who show the heritable genetic penetrance previously recorded for these mental disorders.

Adult

Exploration of affective illness.

This report deals with a series of experimental approaches carried out in clinical studies to attempt to examine the role of amines in relationship to affective state and the mode of action of thymoleptic agents. Attempts have been made to examine enzymes, amines and other metabolites in biological fluids to assess the role of catecholamines and indoleamines in these disorders. Synthesis inhibitors were employed in studies where antidepressant drug-induced remission was initiated and the effect of two inhibitors was assessed on the clinical state. The results are presented and discussed in regard to the significance of the role of serotonin in depressive states and the action of thymoleptic agents.

Adult

Effects of tranylcypromine on 5-HT uptake and its interaction with PCPA on rat brain 5-HT.

The effect of p-chlorophenylalanine-treatment in rats receiving chronic treatment with tranylcypromine on brain serotonin and 5-hydroxyindoleacetic acid levels was examined. This treatment schedule was similar to that followed in depressed patients undergoing treatment with the monoamine oxidase inhibitor. PCPA completely obviated the elevation in serotonin and further reduced 5-HIAA levels of animals treated chronically with tranylcypromine. These effects correlated with PCPA-induced reversal in the clinical improvement achieved by tranylcypromine. In in vitro studies, tranylcypromine was found to inhibit 5-HT uptake into synaptosomes with a minimal action on the spontaneous release of the amine.

Animals

Monoamine oxidase inhibitors: potential for drug abuse.

Both the amphetamines and MAO inhibitors share common clinical and pharmacological properties, namely, (i) to clinically induce euphoriant-stimulating type and psychotomimetic effects in certain individuals, and (ii) to increase, albeit by different mechanisms, the amount of functionally available neurotransmitter (catecholamines and indoleamines) at the receptor site. The present data now indicate that, like the amphetamines, the use of MAO inhibitors can be clinically associated with dependence-tolerance. Perhaps these clinical findings will converge with other clinical-biochemical data in helping to define the specific amine(s) responsible for not only the clinical effects of these drugs but also the etiopathogenesis of major psychiatric illnesses such as the affective disorders and schizophrenia.

Amphetamines

Clinical studies with dopamine-receptor stimulants.

Oral administration of ET-495 was found to cause worsening of psychiatric status in 4 out of 7 schizophrenic patients, and to induce a paranoid state and a syndrome of auditory hallucinosis in 2 non-schizophrenics. These observations were compatible with the hypothesized role of dopamine in schizophrenia. However, these psychotogenic effects were far less dramatic than those noted in other studies with amphetamine, methylphenidate or L-Dopa. Possible explanations for this differing psychotogenic potency of receptor stimulators versus presynaptic agonists are presented. Intravenous ET-495 and apomorphine did not show psychotogenic effects.

Adult

Psychoactive drugs in mania. A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol.

Lithium carbonate, haloperidol, and chlorpromazine hydrochloride were compared in a double-blind controlled study with severely ill hospitalized manics. Lithium carbonate and haloperidol produced a highly significant improvement of manic symptoms without sedation. Although producing considerable sedation, chlorpromazine did little to alter the underlying mania qualitatively. Qualitative differences between lithium carbonate and haloperidol indicate that, while haloperidol has a more dramatically rapid impact on behavior-motor activity, lithium carbonate acted more evenly on the entire manic picture, with total normalization realized during active treatment. The majority of lithium carbonate-treated patients met discharge criteria at study termination, but not the patients receiving either neuroleptic drug. The rating scales are not sensitive enough to monitor manic psychopathology; this accounts for the lack of statistically significant differences among drug groups at treatment termination, despite the widely disparate discharge rates.

Adult

Rebound phenomena in manic patients following physostigmine. Preliminary observations.

The authors have administered physostigmine intravenously to three hospitalized manic patients on a double-blind basis. All three individuals showed clinical change both during and after the physostigmine period, which can be clearly delineated into three distinct phases. The behavioral modifications occurring during the physostigmine run did not qualitatively alter the underlying mania. The authors focus on 'rebound' phenomena, or post-physostigmine changes, as a possible clinical index with which chemically to characterize the initial state of amine imbalance responsible for a given affective illness. The data are considered consistent with an adrenergic-dopaminergic-cholinergic balance hypothesis of affective disorders, and may provide a relevant link in understanding the interface or crossover between manic and schizo-affective illness.

Bipolar Disorder