Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leponex (clozapine) is an atypical neuroleptic indicated in severe schizophrenia, launched in France in December 1991. The safety and efficacy data pertaining to 1,062 patients treated on a compassionate needs basis between May 1989 and December 1991 constitute the first French experience on the drug. The results of an interim analysis pertaining to 602 patients, i.e. available data on 03-15-1992, generally collected on a retrospective basis, by means of a specific questionnaire are reviewed. The population included patients with severe and long-standing schizophrenia i.e. 15.71 +/- 9.3 years, resistant to usual neuroleptic therapy (90.86% of cases), and rarely with a history of intolerance to this class (2.49%). The indication was in the majority of the cases a paranoid schizophrenia (67.2%). The mean maintenance daily dose was 419 mg/d (+/- 152). Overall, with respect to associated drugs, neuroleptics were recorded in 16.4%, another psychotropic drug in 44.7% and symptomatic treatments for extrapyramidal disorders in 21.3% of patients. Of interest is the fact that, for those patients started on Leponex more recently, the drug is more often prescribed on a single basis. Leponex was stopped in 24.3% for the following reasons: adverse events 10.6%, lack of efficacy 6%, non compliance 3.8%, other reasons 3.8%. The adverse event profile is consistent with the literature data, taking into account the fact that certain adverse events were more commonly described: fatigue of lower limbs 11.8%, leucocytosis 19.8% and eosinophilia 4.3%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clozapine (Leponex) in France]. 133 58

Several developments in serotonin neuropharmacology have implications for psychiatric disorders and have already begun to impact their treatment. Selective inhibitors of serotonin uptake, which enhance serotonergic function by preventing the removal of serotonin from the synaptic cleft via the membrane transporter, have been introduced for the treatment of depression and may be effective in other disorders. Precursor loading can increase serotonin concentrations in the synaptic cleft, and tryptophan--which has been available in health food stores and drug stores--had become increasingly used for self-medication of depression, insomnia, and premenstrual syndrome. Conversion to serotonin is not the major metabolic pathway for tryptophan, and large increases in other tryptophan metabolites (such as quinolinic acid, a substance that is excitotoxic at high concentrations) accompany small increases in extracellular serotonin. The recent epidemic of the eosinophilia-myalgia syndrome associated with tryptophan now appears due to a trace contaminant in the product from a single manufacturer. A major advance in serotonin pharmacology has been the elucidation of serotonin receptor heterogeneity. At least seven receptor subtypes (5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, 5-HT3, 5-HT4) have been identified in brain. Direct-acting agonists and antagonists can have selective affinity for specific receptor subtypes. Selective activation of 5-HT1A receptors seems to cause anxiolytic and possibly antidepressive effects. Selective antagonists of 5-HT2 or 5-HT3 receptors may be useful in treating anxiety and schizophrenia. Drugs that enhance serotonergic function suppress aggression in animals, but the specific receptor subtypes involved are not known. The advances being made in serotonin pharmacology will help define the role of this brain neurotransmitter in psychiatric and other disorders and can be expected to lead to further therapeutic advances.
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PMID:Role of serotonin in therapy of depression and related disorders. 167 51

This report describes a 48-year-old caucasian male with schizophrenia who developed hepatitis, hyperglycemia, pleural effusion, eosinophilia, hematuria and proteinuria early in clozapine treatment which resolved on drug discontinuation. The literature on similar cases is reviewed.
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PMID:Hepatitis, hyperglycemia, pleural effusion, eosinophilia, hematuria and proteinuria occurring early in clozapine treatment. 966 91

Besides the well-known adverse effects of clozapine, such as granulocytopenia, tiredness and hypersalivation, acute pancreatitis is known to be a very rare complication of the drug. In the literature a total of five case reports have been published so far. We report a case of asymptomatic pancreatitis subsequent to clozapine treatment at therapeutic doses in a 38-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient was rehospitalized after an acute exacerbation of the psychosis subsequent to an attempt to change medication on an outpatient basis. Treatment with clozapine was initiated again. During phases of progressively increasing the clozapine dose, serum levels of amylase and lipase were increased; after maintaining daily doses of clozapine of 300 mg and/or 600 mg the pancreatic enzymes normalized quickly within a few days. The patient did not report any pancreas-related complaints, nor did specific diagnostic studies produce any indicative result, only a minor thickening of the head and body of the pancreas in the ultrasound. It is assumed that the phenomenon of subclinical, asymptomatic pancreatitis during increasing dosage of clozapine occurs more often than previously supposed. The monitoring of serum amylase levels during slow increase in clozapine is recommended; if leukocytosis or eosinophilia is present, the possibility of even a subclinical and asymptomatic pancreatitis should be considered.
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PMID:Asymptomatic pancreatitis associated with clozapine. 1033 68

A case of clozapine-induced toxic hepatitis in a 49-year old woman with schizophrenia is described. The daily clozapine dose was clinically titrated to 300 mg. Subsequently, the patient experienced lethargy and anorexia, and fever, eosinophilia, leucocytosis and abnormal liver parameters were found. The serum concentration of clozapine was 8595 nmol/l, and treatment was discontinued. After eight days, the condition stabilised, and low-dose clozapine treatment was successfully reinstituted with serum monitoring (TDM).
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PMID:[Clozapine-induced toxic hepatitis]. 1130 64

Clozapine, the first atypical antipsychotic, is indicated for the treatment of therapy-resistant schizophrenia. It needs to be monitored closely because of its well-known potential side-effects, especially agranulocytosis. We present a case of a middle-aged woman with chronic schizophrenia, who was treated with clozapine and developed a clinical syndrome of asymptomatic pancreatitis and eosinophilia within the fifth week of treatment. Asymptomatic pancreatitis has rarely been reported up to now and is not recognized as a typical side-effect of clozapine. In our opinion, pancreatic enzymes should be monitored especially in the first 6 weeks of clozapine treatment.
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PMID:The development of a clinical syndrome of asymptomatic pancreatitis and eosinophilia after treatment with clozapine in schizophrenia: implications for clinical care, recognition and management. 1250 44

The strategy in the choice of antipsychotic agent must take into account the hepatic tolerance according to non-negligible incidence of liver disorders among psychiatric population (presence of risk factors like alcoholism, drugs of abuse intake, polymedication including potentially hepatotoxic drugs.). More than 1 000 drugs have been listed as being responsible of hepatic side effects; 16% of these agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in biological or/and clinical hepatotoxicity. For these reasons, some psychotropic agents have been withdrawn of the pharmaceutical market like alpidem or medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic drugs, has been withdrawn recently, as well. Isolated elevations of hepatic enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%) but also with other classes of neuroleptic agents, as well. On the contrary, clinical hepatitis have been more rarely described with neuroleptic drugs like phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of hepatotoxicity is based on biological parameters (elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis, jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical diagnosis and the research of its origin may include many investigations like abdominal ultrasonogram and percutaneous liver biopsy. The present article describes the cases of hepatic disorders reported with AAD (Atypical Antipsychotic Drugs), which are available in France (amisulpride, clozapine, olanzapine, risperidone). This new pharmacological class of antipsychotic drugs has showed great interest to improve negative symptoms of schizophrenia and to reduce disabling side effects like dystonia. According to the bibliographic data available, the following points and information must be clinically taken into account. Frequency of hepatic troubles: according to the bibliographic data, AAD appeared generally well tolerated in most cases. The frequency of hepatic troubles remains in general very low or rare. The cases published were observed with clozapine, olanzapine and risperidone. Nevertheless, some authors have observed higher frequency of hepatic enzymes elevation with some AAD. In an investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical observations, asymptomatic biological disorders of the hepatic function are generally described but cytolytic or cholestatic hepatitis were reported, as well. Symptomatic hepatic dysfunctions were, sometimes, associated with other disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check-up may be relevant in case of significant side-effect outcome. Delay time before the hepatic episode: hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. These delay times are very similar to those observed with other psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the responsible agent: all cases were reversible after the AAD withdrawal except with one patient (39 years old) treated by clozapine (350 mg/day) who developed a fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases, the AAD was withdrawn after the hepatic episode according to the significant risk of irreversible alteration. Nevertheless, normalization of hepatic enzymes has been described despite AAD maintenance at the same dosage or after dosage reduction. Rechallenge of clozapine after a first episode was performed for three patients, only one redeveloped a new hepatic disorder. According to different authors, special care is required if maintenance or rechallenge of the agent is indispensable after a first episode of isolated hepatic enzyme elevation (i.e resistance or intolerance to other treatments). In this case, biological and clinical supervision has to be carefully scheduled, which demands a satisfactory compliance from the patient. On the contrary, in case of clinical hepatotoxicity, rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to phenothiazine drugs, no information is available on the respective rule of the agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been reported, suggesting a possible immuno-allergic mechanism. Presence of risk factors: risk factors have been retrieved, in some observations, like high daily dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of hepatic disorders like Gilbert syndrome. Special care is advisable with these patients. As hepatotoxicity has been observed after surdosage (or suicide attempt), a hepatic check-up has to be performed in these clinical situations. Co-medication with hepatotoxic drugs may increase the risk as it has been suggested. In many observations, co-medication made difficult the incrimination of the AAD in the hepatic disorders outcome. Monotherapy has the great advantage to make easier the withdrawal of the responsible agent and its substitution. As drugs of abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they represent a probable factor of risk. Moreover, their detection is fundamental during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is mainly based on the chronology between agent introduction and hepatic disorder onset but other causes must be excluded. Bibliographic data analysis greatly contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article emphasized the limits of bibliographic review to compare drugs towards tolerance. Most of the bibliographic data were case-reports for which it was sometimes difficult to provide absolute evidence of the responsibility of the agent. Moreover, spontaneous notification to health national administration is rarely systematic, in particular with isolated elevation of hepatic enzymes, and even more rarely published in international reviews. Nevertheless, according to the present data available in the literature, systematic and regular hepatic survey does not seem necessary in absence of risk factors. As for other side effects, which may occur more or less rapidly, great advantages may be obtained from psycho-education programs associating the patients in order to detect the first symptoms. Because little long-term hepatic follow-up comparing AAD is available, controlled studies should be carried out to precise the frequency and the risk factors (covariables) to prevent hepatitis outcome.
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PMID:[Hepatic tolerance of atypical antipsychotic drugs]. 1250 67

Clozapine has proven effective in reducing morbidity and suicidality in chronic non-remitting patients with schizophrenia. Occasionally, despite good therapeutic response, clozapine must be stopped due to dangerous side effects such as agranulocytosis. Drug-induced eosinophilia is a non-dose-dependent side effect of clozapine. In cases of mild increments of eosinophils and if the patient is asymptomatic, there is no need to make an immediate decision. However, if the increment is severe and producing symptoms, withdrawing the probable causative drug is warranted. There is a possible association between eosinophilia and myocarditis, a life-threatening condition. The efficacy of corticosteroid therapy in the treatment of eosinophilia has not been clearly established. We present a case report where switching from clozapine to quetiapine maintained the improvement in clinical status, after remittance of eosinophilia.
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PMID:Clozapine-induced eosinophilia and switch to quetiapine in a patient with chronic schizophrenia with suicidal tendencies. 1766 12

Clozapine is associated with a number of side effects and careful monitoring of them is a very important aspect of management of the patients receiving the same. Common side effects of clozapine are sedation, sialorrhoea, weight gain etc. Rarely clozapine is also associated with eosinophilia. Here we present a case of schizoaffective disorder who was receiving clozapine and developed eosinophilia during the initial weeks of treatment with clozapine which came down to baseline after a few weeks of continuation of therapy. Although there are reports of eosinophilia developing in course of treatment with clozapine among patients suffering from schizophrenia but this may be the first case of eosinophilia associated with clozapine use in case of schizoaffective disorder.
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PMID:Clozapine induced eosinophilia. 2177 49

Clozapine is the best treatment option in several clinical circumstances, including treatment-resistant schizophrenia, non treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. However, clozapine is associated with many serious side effects. Furthermore, monitoring requirements, i.e., frequent blood draws and frequent visits, discourage clozapine use. Therefore, the drug is underused. The only way to avoid the underuse of clozapine is full awareness of its side effects and competence to minimize them. The aim of the paper is reviewing the safety profile of clozapine and the suggested strategies in the management of its side effects, including neutropenia, eosinophilia, seizures, myocarditis, weight gain, diabetes, metabolic syndrome, hypersalivation, fever, constipation, ileus, urinary incontinence, sweating. The neuropsychiatric side effects of clozapine are not discussed in this review.
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PMID:Clozapine safety, 35 years later. 2212 92


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