Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients

Article Abstract:

Almost all antipsychotic drugs (neuroleptics) used to treat schizophrenic patients work by blocking dopamine receptors. Clozapine is a clinically proven antipsychotic that is classified as atypical since it is presumed to work by other mechanisms. Clozapine has been shown to relieve psychotic symptoms among many schizophrenic patients who have not responded well to standard neuroleptic treatment. In order to investigate possible interactions between concentrations of clozapine in the blood and therapeutic response, 20 male and 9 female hospitalized, adult schizophrenic patients who did not improve with standard neuroleptic treatment were given approximately 400 milligrams a day of clozapine for one month. At the onset of the study, clinical evaluations of patients' symptoms were made, followed by weekly assessments. Daily blood-samples were collected and plasma was analyzed with high-performance liquid chromatography. Plasma values of clozapine and its metabolite norclozapine were analyzed statistically so that concentrations could be computed. Patients were classified as responders if they demonstrated quantitative improvements in symptoms. Data analysis revealed that 37.9 of the patients who had not responded to other neuroleptics responded well to clozapine. A significant relationship was shown to exist between clozapine plasma concentration and symptom response. The threshold plasma concentration necessary for symptom improvement was found to be 350 nanograms per milliliter. Sixty-four percent of the patients with concentration levels greater than threshold were responders. Only 22 percent of the patients with concentration levels below threshold demonstrated any symptom reduction. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Dosage and administration, Clozapine

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Neuropsychological performance in medicated and unmedicated patients with Tourette's disorder

Article Abstract:

Tourette's syndrome is a neuropsychiatric disorder characterized by obsessive-compulsive behavior and chronic multiple motor and vocal tics. Motor tics include uncontrollable sniffing, snorting, and blinking, while vocal tics include clicks, grunts, barks, coughs and yelps. Tourette's is thought to be caused, in part, by a neurochemical abnormality. The onset of the disease occurs in children aged 1 to 15 years. Coprolalia (compulsive uttering of obscenities) eventually occurs in about 60 percent of all cases. Several neuroleptic (antipsychotic) drugs, administered in low doses, effectively reduce Tourette's symptoms. However, even at low doses, they have been reported to cause adverse side effects, particularly among school-age children, including sedation, poor school performance and decreased motivation. To evaluate the benefits and side-effects of neuroleptic treatment, 96 Tourette's patients between the ages of 6 and 18 years were studied. The patients were divided into two groups matched by age, sex and education: 51 who were taking low doses of neuroleptics and 45 who took no medication. They were given a battery of tests to assess intelligence, memory, achievement, perception and motor and sensory skills. No differences were found between groups on ratings of tics, obsessive-compulsive traits, behavior, or neuropsychological tasks. Almost all children taking neuroleptics reported a notable improvement in Tourette's symptoms. Results suggest that Tourette's patients who take neuroleptics can perform equally as well as nonmedicated patients on educational, intellectual and neuropsychological levels. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Tourette's syndrome, Tourette syndrome

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A prospective analysis of 24 episodes of Neuroleptic Malignant Syndrome

Article Abstract:

Neuroleptic drugs, which have antipsychotic actions, can cause a life-threatening syndrome in a small number of patients. This neuroleptic malignant syndrome (NMS) is a toxic reaction marked by catatonic rigidity, stupor, unstable blood pressure, elevated body heat, profuse sweating, incontinence, and difficult breathing. Twenty patients who had episodes of NMS were evaluated for characteristics. This group experienced all of the above symptoms and, in addition, a frightened facial expression was observed in all cases. Eleven patients later described that this was accompanied by a wish to speak but an inability to do so, which caused an overwhelming sense of impending doom and anxiety. There was also a dramatic drop in serum iron concentration noted in all patients. This may be due to muscle injury caused by the rigidity, as this symptom has been reported after both strenuous exercise and myocardial infarction. The authors believe their data suggest that NMS is dose-related, it may be predisposed by agitation and emotional disorders, it is related to the drugs used to treat these states, and patients with some form of central nervous system compromise are most susceptible. The majority of patients were found to be dehydrated; whether this contributed to the onset of NMS by concentrating the neuroleptic drug or was purely a result of the syndrome itself is unclear. A 20 to 30 percent mortality rate has been associated with this syndrome, but there were no deaths among this study group. The authors suggest that with proper hospital care a good outcome can be expected. (Consumer Summary produced by Reliance Medical Information, Inc.)

Neuroleptic malignant syndrome

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