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Biomedical subjects

J A Lieberman

Publications and source records attributed to J A Lieberman.

At least 199 records · Page 11Linked to original sources

The Structured Interview for Schizotypy (SIS): a preliminary report.

This article presents a new interview-based research instrument for assessing schizotypal symptoms and signs. The Structured Interview for Schizotypy (SIS), which was developed from experience gained in a large, controlled family study of schizophrenia in the west of Ireland and has been field-tested in three other locations, differs from previously available interviews in that it includes: (1) built-in contextual assessments of the pathological nature of certain symptoms (e.g., suspiciousness or ideas of reference); (2) multiple independently scored items, most with closed response options, per symptom scale; (3) extensive assessment of schizotypal signs; (4) symptom probes designed to make responding positively appear nondeviant; and (5) coverage of potentially relevant symptoms and signs not required in current criteria for schizotypal personality disorder. Schizotypal symptoms can be assessed with high reliability by the SIS. When sufficient variability is present, schizotypal signs are also reliably assessed by the SIS, although the reliability is generally lower than that found for symptoms. In three independent pilot studies, schizotypal symptoms and signs assessed by the SIS appear to discriminate significantly the relatives of schizophrenic patients from relatives of controls.

Adolescent↗

Spastic dysphonia and denervation signs in a young man with tardive dyskinesia.

Pathophysiological theories of tardive dyskinesia (TD) suggest the possibility of structural changes in the central nervous system of patients with TD. This report describes a case of choreoathetoid dyskinesia and spastic dysphonia associated with clinical and electromyographic signs of muscle denervation. The findings of this case suggest that the neurological syndrome originates within basal ganglia nuclei but may also extend to the peripheral neuromuscular system.

Adult↗

The behavioral toxicity of bromocriptine in patients with psychiatric illness.

Dopamine agonists may be useful in the treatment of neuroleptic-induced hyperprolactinemia and movement disorders; it is a treatment approach that has been avoided for fear of inducing or exacerbating psychotic symptoms. The risks of giving dopamine agonists to psychiatric patients have been well documented in the literature. To further evaluate the psychotogenic effects of bromocriptine, a dopamine receptor agonist, we conducted a double-blind study in which 16 psychiatrically stable patients were treated for tardive dyskinesia with neuroleptics plus high doses of bromocriptine (N = 11) or placebo (N = 5) for 10 weeks. The diagnoses included schizophrenia, schizoaffective disorder, and major depression with psychotic features. Patients were evaluated weekly with the Brief Psychiatric Rating Scale and the Clinical Global Impression Scale during the 10-week treatment phase and for 8 weeks after medication was withdrawn. There were no statistically significant differences between active and placebo groups in behavioral ratings at baseline, week 10, and week 18. These results are compared with the findings of previous studies in which bromocriptine was given to psychiatric patients. Although the literature suggests that bromocriptine can induce or exacerbate psychosis in psychiatric patients, this occurs primarily in those with a psychotic diathesis and who are not currently receiving neuroleptic medication. Other important factors include the dose of bromocriptine, duration of treatment, and the clinical state of the patient at the time bromocriptine treatment is initiated. These results suggest that bromocriptine can be safely used in patients at risk for psychotic illnesses as long as patients are clinically stable and maintained on neuroleptics.

Adult↗

Clozapine: guidelines for clinical management.

The advent of antipsychotic drugs represented a milestone in psychotherapeutics. Despite their proven efficacy, antipsychotic drugs are limited by side effects and treatment resistance in some patients. Since the introduction of chlorpromazine and the subsequent development of numerous neuroleptic compounds, there have been no significant qualitative advances in the clinical efficacy of antipsychotic drugs. Clozapine is an experimental neuroleptic with atypical properties. In clinical testing, this agent has shown superior antipsychotic efficacy in treatment-refractory schizophrenics and a more favorable extrapyramidal side effect profile in comparison with standard neuroleptics. Because clozapine represents a potential contribution to our therapeutic armamentarium, this article provides an overview of its pharmacology, efficacy, and methods of clinical utilization.

Clinical Trials as Topic↗

Financing medical education.

As more health care services are being diverted from hospitals to the ambulatory setting, funding for student and resident training in this setting becomes a problem. This paper details the causes of this problem and proposes some financial solutions.

Ambulatory Care↗

Clozapine-induced agranulocytosis: non-cross-reactivity with other psychotropic drugs.

Clozapine, an atypical neuroleptic with unique clinical and preclinical properties, represents a potentially valuable addition to the psychopharmacopeia. Its development and use have been limited by its higher frequency, compared with other pharmacologic treatments, of the potentially fatal side effect of agranulocytosis. This article describes the natural history of five cases of agranulocytosis that occurred in the course of clozapine treatment. The cases were generally uniform as to onset, recovery, and hematologic features. No patient had hematologic reactions to treatment with psychotropic agents before or after clozapine treatment. These findings, along with other work in progress, suggest that clozapine's granulocytoxic effects are produced by a highly specific immune-mediated mechanism.

Adult↗

Prediction of relapse in schizophrenia.

Despite the proven efficacy of neuroleptic drugs in the acute and maintenance pharmacotherapy of schizophrenia, practical methods for identifying patients who require neuroleptic treatment to prevent relapse are lacking. This study evaluated the use of a methylphenidate challenge test to predict the outcome in 34 stable outpatients with schizophrenia receiving neuroleptic treatment. Patients received two infusions, one of methylphenidate and one of placebo, in randomized order one week apart while receiving neuroleptic treatment and again three weeks after drug withdrawal. Behavioral, cardiovascular, and neurologic responses were evaluated before and after infusion under double-blind conditions. Patients were then followed up without medication for 52 weeks or until symptom recurrence. The results indicate that specific measures, including behavioral response to methylphenidate, presence of tardive dyskinesia, and, under specific pharmacologic conditions, tardive dyskinesia, blink-rate, and pulse-rate responses to methylphenidate, are associated with time and propensity to relapse following neuroleptic withdrawal. These measures may be potentially useful in the identification of candidates for neuroleptic withdrawal and/or dosage-reduction treatment strategies.

Adolescent↗

Provocative tests with psychostimulant drugs in schizophrenia.

The psychotogenic effects of psychostimulant drugs have provided a major line of evidence in support of the DA hypothesis of schizophrenia. To evaluate the effects of psychostimulant (PS) drug in schizophrenia and the clinical variables which may influence their expression, we reviewed 36 studies of PS drugs in patients with schizophrenia. Approximately 40% evidence a psychotogenic response to PS administration in doses that are subpsychotogenic in normals. Specific clinical variables appear to modify this response, including diagnosis, degree and type of psychopathology, stage of illness and pharmacologic status at the time of testing. Non-amphetamine-like PS drugs, e.g., methylphenidate, appear to have greater psychotogenic potency than amphetamine-like PS drugs. These results suggest the presence of a subgroup of schizophrenic patients who exhibit psychotic symptom activation with PS in a state dependent or independent fashion. This biologic phenomenon may be clinically exploitable and should be investigated further.

Antipsychotic Agents↗

Neuromuscular effects of monoamine oxidase inhibitors.

The MAOI class of drugs is known to produce neuromuscular effects at therapeutic and toxic doses when given alone or in combination with other drugs. These effects range from muscle tension and twitches in their mild form to forceful myoclonic jerks. These effects may also be part of a more pervasive toxic syndrome that includes autonomic and mental symptoms as well. There is meager direct and substantial indirect evidence that serotonergic mechanisms play a role in mediating the neuromuscular effects of MAOIs. We have hypothesized that MAOIs produce a condition of heightened neuromuscular excitability due to a combination of increased serotonergic tone and central disinhibition of alpha-motor neuron-mediated spinal activity. Further study is needed utilizing objective pharmacologic and neurophysiologic measures.

5-Hydroxytryptophan↗

Tricyclic antidepressant and metabolite levels in chronic renal failure.

Serial blood samples were drawn from 12 patients undergoing hemodialysis who were receiving tricyclic antidepressants (TCAs). Samples were drawn before, during, and after a dialysis session (two to 17 sessions per subject). Samples were analyzed by HPLC before and after hydrolysis with beta-glucuronidase/sulfatase to determine the conjugated and nonconjugated metabolites. Analysis of these data in comparison with those of controls with depression and normal renal function showed that: (1) at steady state, tertiary and secondary amine TCA levels did not differ; (2) levels of the hydroxylated metabolites had greater variability and were somewhat higher at steady state; (3) levels of the conjugated hydroxylated compounds were markedly elevated, reaching 500% to 1500% normal; (4) the time to reach a steady-state level appeared to be slightly increased; and (5) elimination t1/2 s of unconjugated and conjugated drug forms were longer in our patients with normal renal function than those reported in the literature. Levels of the tertiary, secondary, and hydroxylated metabolites were not changed by dialysis, whereas there were substantial decrements in glucuronidated metabolite levels. These findings demonstrate increased concentrations of conjugated drug forms and suggest an abnormal distribution or delayed elimination of unconjugated and conjugated metabolites. These observations may shed some light on the apparent hypersensitivity of these patients to TCA side effects, particularly because glucuronides may exert peripheral pharmacologic effects.

Adult↗

Dexamethasone suppression tests in patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder and major depressive disorder are associated by several lines of evidence. To explore the possible relationship between the two disorders, the authors administered 1-mg dexamethasone suppression tests to 18 patients with obsessive-compulsive disorder and 51 patients with major depressive disorder. None of the obsessive-compulsive patients were classified as nonsuppressors on the basis of a 4:00 p.m. serum cortisol level, whereas 37% of the depressed patients were nonsuppressors. The mean cortisol levels of the two groups differed significantly. Factors that may influence hypothalamic-pituitary-adrenal function, such as age, depressive symptoms, and severity of illness, are discussed in light of these results.

Adolescent↗