clozapine and Hypotension--Orthostatic

Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System Diseases; Clozapine; Dibenzothiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Health Status; Humans; Hypotension, Orthostatic; Olanzapine; Pirenzepine; Quality of Life; Quetiapine Fumarate; Receptors, Cholinergic; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Sleep Wake Disorders; Treatment Refusal; Weight Gain

Clozapine is an atypical neuroleptic agent given when schizophrenia is resistant to other neuroleptic drugs. Its use is restricted because of the risk of agranulocytosis, which appears in 1% of cases and therefore necessitates frequent WBC counts. We cite the only 2 surveys of the treatment of adolescents with clozapine and report our experience. We treated 7 boys and 6 girls between the ages of 14-17 years (mean 16.6) with clozapine after failure of all other neuroleptic agents tried. Our usual dose was 300 mg/day, for an average of 245 days. In only 2 patients was improvement only partial. In 1 treatment had to be stopped because of symptomatic orthostatic hypotension which appeared 36 hours after the drug was started. In our opinion, clozapine should be considered when severe schizophrenia in adolescents is refractory to other neuroleptic agents, provided the WBC count is monitored.

Topics: Adolescent; Age of Onset; Clozapine; Drug Monitoring; Female; Humans; Hypotension, Orthostatic; Leukocyte Count; Male; Schizophrenia

Cardiovascular side effects of clozapine are not uncommon, but few systematic studies of these effects have been performed. In this study, we reviewed data on the electrocardiographic (ECG) abnormalities in patients treated with clozapine.. Sixty-one patients treated with clozapine were selected from the Seoul National University Hospital Treatment-Resistant Schizophrenia Clinic. A retrospective chart review was conducted to identify ECG abnormalities and cardiovascular side effects.. The prevalence of ECG abnormalities in patients who had been using antipsychotics other than clozapine was 13.6% at baseline, which increased significantly to 31.1% after commencement of clozapine treatment. Among the 53 patients without baseline ECG abnormalities, 13 showed new-onset ECG abnormalities after using clozapine. Normal ECG under previous antipsychotic medication reduced the risk of new-onset ECG abnormalities, whereas increased age was found to increase the risk. The occurrence of orthostatic hypotension or tachycardia was not related to the development of ECG abnormalities. Most of the newly developed abnormalities had little clinical significance, and they tended to occur during the initial phase of treatment. In 10 patients, ECGs normalized despite the continued use of clozapine. Clozapine increased corrected QT interval (QTc) in a dose-dependent fashion; however, the clinical significance of this observation is uncertain. Pathologic prolongation of QTc was found to be rare.. Although a substantial portion of patients treated with clozapine developed ECG abnormalities, most of the abnormalities were benign and did not hinder further treatment.

Topics: Adolescent; Adult; Antipsychotic Agents; Arrhythmias, Cardiac; Clozapine; Comorbidity; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Diseases; Humans; Hypotension, Orthostatic; Male; Middle Aged; Prevalence; Regression Analysis; Retrospective Studies; Sex Factors; Tachycardia

Topics: Adult; Antipsychotic Agents; Benzamides; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypotension, Orthostatic; Male; Moclobemide; Monoamine Oxidase Inhibitors; Schizophrenia; Schizophrenic Psychology; Tyramine

Topics: Adult; Clozapine; Drug Therapy, Combination; Fludrocortisone; Humans; Hypotension, Orthostatic; Male; Schizophrenia; Schizophrenia, Paranoid

Severe orthostatic and cardiorespiratory dysregulation may occur during institution of clozapine therapy both during concomitant benzodiazepine medication and on reinstitution of clozapine after a washout period. Extensive medical and neurological workup before and after the trials can nevertheless be normal. The absence of similar previous reactions to other drugs, adhering to monotherapy with clozapine, increasing dosage slowly or performing a single test for orthostatic reactions after initiating clozapine are insufficient precautionary measures. Cardiorespiratory complications can occur without the challenge of assuming an erect position but appear to otherwise run an initial course similar to that of severe orthostatic reactions. A significantly abnormal response to testing for orthostatic reactions may be established, but only during the period of vulnerability to cardiorespiratory dysregulation. Repeated testing for this predisposition during the first weeks of clozapine therapy is suggested.

Topics: Adult; Cardiovascular System; Clozapine; Humans; Hypotension, Orthostatic; Male; Respiration

The relationship between antipsychotic effect and side effects and plasma levels of clozapine were investigated in 26 patients. A significant linear correlation was found between dosage and plasma levels of clozapine. All patients were clearly improved. The degree of improvement was independent of the plasma levels in an average range of plasma levels (100 ng/ml-800 ng/ml). Sedation and orthostatic dysregulation occurred most pronounced on the third day of treatment. There was no relationship between plasma levels and these symptoms. After prolonged treatment the degree of both symptoms diminished. The development of tolerance of symptoms is concluded.

Topics: Adolescent; Adult; Clozapine; Dibenzazepines; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Psychotic Disorders; Sleep

Topics: Adolescent; Appetite; Clozapine; Dibenzazepines; Humans; Hypotension, Orthostatic; Stimulation, Chemical