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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clozapine (Clozaril), a tricyclic dibenzodiazepine, causes fewer extrapyramidal side effects than do other antipsychotic drugs. Because it can induce agranulocytosis, however, clozapine is indicated only for schizophrenia that is not responsive to other therapies. To describe the drug's effects on mortality, we compared rates of various causes of death in 67,072 current and former clozapine users. We linked data from a national registry of clozapine recipients to the National Death Index and Social Security Administration Death Master Files, obtained death certificates, and calculated mortality rates for underlying causes of death using standardization to adjust for age, sex, and race. During 1991-1993, there were 396 deaths in 85,399 person-years for patients ages 10-54 years. Mortality was lower during current clozapine use than during periods of non-use. Mortality from suicide was decreased in current clozapine users by comparison with past users [rate ratio (RR) = 0.17; 95% confidence interval (CI) = 0.10-0.30]. During clozapine use, there were elevations in mortality rates for less common causes of death, including pulmonary embolism (RR for current exposure compared with past clozapine use = 5.2) and respiratory disorders (RR = 2.9). Clozapine appears to reduce mortality in severe schizophrenics, mostly by decreasing suicide rates.
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PMID:Mortality in current and former users of clozapine. 934 68

Since schizophrenia is not a rare occurrence and is often chronic, the general practitioner and internist providing primary care should also be informed on new developments in treatment with neuroleptics. A major new form of treatment is provided by the so-called atypical neuroleptics which, however, in terms of their receptor specificity are not a uniform group, and have only a few properties in common. A prototype of this group is clozapine (Leponex), which has a good antipsychotic effect and virtually no action on the extrapyramidal motor system (EPS). Whether clozapine is also capable of improving the primary negative symptoms of schizophrenia (e.g. flattering of affect, reduction of drive, cognitive disorders, etc.) has not yet been ascertained. On account of the rare but possibly fatal agranulocytosis it may induce, it may be prescribed only when certain safety precautions are taken. Risperidone (Risperdal) has similar efficacy against the classical positive symptoms, with no action on the EPS (up to a medium dosage), and has no hematological effects. Other atypical neuroleptics have recently become available: quetiapine, olanzapine and sertindole. They have at least some of the advantages of clozapine but a very low risk of producing hematological effects. However, before they are widely used in the doctor's practice, further clinical experience is needed.
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PMID:[Atypical neuroleptics--the future of schizophrenia treatment?]. 952 41

Since its introduction to the United States in 1990, the benefits of clozapine use have been repeatedly validated. Clozapine remains the only antipsychotic with proven efficacy in treatment-resistant schizophrenia. Because clozapine has been part of the psychiatric pharmacopeia for considerably less time than neuroleptics, which have dominated the field for over 4 decades, its underutilization may be partly attributed to a lack of experience in managing associated side effects. Most side effects associated with clozapine are typical of antipsychotics in general, and with clozapine, these side effects are typically benign, tolerable, and manageable. It is conceivable that there remains a concern over the risk of agranulocytosis. However, the mandatory blood monitoring carried out through the Clozaril National Registry has considerably reduced the incidence of fully developed cases of agranulocytosis from premarketing values of approximately 1% to 2% to current values of 0.38% and virtually prevented mortalities. These values are likely to decrease further with the application of cytokine augmentation therapy among patients developing blood dyscrasias. Many side effects of clozapine are observed early after treatment onset and are greatly reduced by dose adjustments. Appropriate management of side effects will facilitate a maximization of the benefits of clozapine treatment. Clearly, the benefits of clozapine therapy far outweigh its risks.
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PMID:Maximizing clozapine therapy: managing side effects. 1081 12

Clozapine is the only antipsychotic agent that is effective in treatment-resistant schizophrenia. Despite its superior efficacy to chlorpromazine and the fact that it has fewer extrapyramidal side effects than conventional antipsychotics do, clozapine is relatively underused. This may be due in part to a lack of appreciation of clozapine's favorable risk-benefit ratio in many patients. In addition, clozapine is only indicated for use in patients who fail to respond adequately to standard antipsychotic treatment. Treatment with clozapine considerably improves psychiatric well-being and reduces readmission to the hospital and reduces family burden in many severely ill patients. However, clozapine is associated with severe side effects, including weight gain, tachycardia, sedation, seizures, and agranulocytosis. These risks must be weighed against the risks associated with schizophrenia (e.g., suicide). The death rate attributed to clozapine-induced agranulocytosis has been low, a fact that is largely attributable to safety measures such as the Clozaril National Registry. Determining the optimal dosage for each patient will maximize the benefits of treatment while reducing side effects. In some patients, monitoring plasma levels of drug may aid in optimizing treatment. The optimal plasma level of clozapine is 200 to 350 ng/mL. This usually corresponds to a daily dose of 200 to 400 mg, although dosage must be individualized. If patients improve significantly during treatment with clozapine, they should continue to be treated with clozapine and should be withdrawn from this treatment only when medically warranted. Psychotic relapse rates may be as high as 80% among patients switched from clozapine to other novel antipsychotic agents.
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PMID:Optimizing treatment with clozapine. 954 38

Clozapine (Clozaril) is an atypical antipsychotic agent used to treat schizophrenia refractory to other pharmacological agents. This report describes an accidental clozapine overdose. The half-life of clozapine in this patient was determined from two blood levels, one obtained on admission and the second 10.5 hours later. The calculated half-life of 8.11 hours is consistent with published levels for single doses and suggests an apparent stability in clozapine elimination half-life in the face of overdose. The maximum clozapine blood level attained was probably among the highest nonfatal levels reported. The patient recovered fully following hospital admission for monitoring and supportive care. This case report illustrates the usefulness of following the time course of the changes in blood level at selected time intervals, as well as the importance of entertaining a diagnosis of drug overdose in patients presenting with acute mental status changes.
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PMID:A clozapine overdose with markedly elevated serum levels. 998 6

1. Many patients with refractory schizophrenia remain undertreated and are at great risk for serious consequences of their illness, up to and including suicide. 2. Clozaril is the only antipsychotic medication proven to be effective in treating refractory schizophrenia. It is particularly effective in reducing violence associated with assaults and suicide. 3. Nurses can be very instrumental in working with resistant systems, treating clinicians, and patients by recommending Clozaril therapy for refractory schizophrenia.
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PMID:Refractory schizophrenia: what works pharmacologically? 1002 3

Clozapine (Clozaril) is a new, powerful, costly anti-psychotic medicine, with a possible serious side effect (agranulocytosis) that entails weekly blood monitoring. In a three hundred bed state mental hospital that is allotted thirty clozapine slots (high costs effectively rationing this drug), a woman with schizophrenia responds minimally to this medication. Her attending physician wishes to withdraw the medicine and give it to another patient with schizophrenia on the ward who might have a better response. The woman's family threatens to make a public outcry. Both the attending physician and the family ask the HEC for a consult.
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PMID:Clozapine rationing in a state mental hospital: reviewing a HEC's case consultation. 1013 Sep 76

In clinical trials of dopamine-blocking antipsychotics, significant adverse events may occur in healthy volunteers at dose levels that are well tolerated by schizophrenic patients. Because of these differences in tolerability, bioequivalence and pharmacokinetic studies of antipsychotics should be performed in schizophrenic patients rather than in healthy volunteers. When clozapine is the drug being investigated, pharmacokinetic and bioequivalence studies should be carried out in real-life dosage conditions because the half-life of clozapine increases with multiple doses. Under real-life conditions, the evaluation of multiple doses of clozapine in a population of schizophrenic patients can provide direct therapeutic relevance to bioavailability findings. This article discusses patient recruitment and informed consent in pharmacokinetic trials of schizophrenia, issues in studying antipsychotic agents in healthy volunteers versus schizophrenic patients, and a bioequivalency study of Clozaril (Novartis Pharmaceuticals) and generic clozapine (Creighton [Sandoz]) in schizophrenic patients.
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PMID:Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients. 1130 42

Clozapine has been the treatment of choice for patients with refractory schizophrenia. Generic clozapine has recently become available, because of a waiver of the usual criteria for establishing bioequivalence. However, there are biopharmaceutical, bioavailability, and clinical concerns related to the generic formulation raised by both clinicians and academic researchers. We conducted a prospective, randomized, crossover study to evaluate steady-state pharmacokinetics, pharmacodynamics, and tolerability of generic clozapine (Zenith Goldline Pharmaceuticals) versus Clozaril (Novartis Pharmaceuticals) in schizophrenic patients. A preliminary report of the pertinent bioavailability results is presented here. Despite comparable mean plasma concentration-time curves, significant differences were found in the primary pharmacokinetic parameters of the 2 formulations in almost 40% of patients. Such intraindividual differences raise the issue of average bioequivalence versus individual bioequivalence and the implication for interchangeability of different clozapine formulations. The decision to switch a patient from branded to generic clozapine should be made on an individual basis with special emphasis on clinical outcome, and patients should be monitored closely during the transition.
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PMID:Branded versus generic clozapine: bioavailability comparison and interchangeability issues. 1130 44

Innovation in atypical antipsychotic agents continues with new preparations of available drugs as well as novel agents. In this article, we provide an update on these novel products by reviewing information from a computerised literature search, recent abstracts and discussions with industry representatives. A generic formulation of clozapine is now available. It may be less well absorbed and/or less effective than Clozaril, although evidence is conflicting. A fatty acid amide derivative of clozapine is in early development. A liquid formulation of risperidone is currently available, which may be a useful treatment for psychotic agitation as well as a preferable alternative to tablets for some patients. A depot formulation is in development for the long-term management of psychosis. An orally disintegrating tablet formulation of olanzepine is a useful alternative to standard tablets. A short-acting injectable formulation of the drug is in development for psychotic agitation. Sachets and slow-release formulations of quetiapine are in development. Ziprasidone, a recently launched agent, is available in tablet form for schizophrenia/schizoaffective disorder, psychotic depression and mania. A short-acting injectable formulation is in development for psychotic agitation. Aripiprazole (tablets) and iloperidone (tablets and depot injection) are two antipsychotics in development for schizophrenia/schizoaffective disorder (available information regarding iloperidone is very limited). These new formulations and agents should broaden options for the treatment of psychosis.
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PMID:Advances in atypical antipsychotics for the treatment of schizophrenia: new formulations and new agents. 1194 8


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