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)

West Nile Virus (WNV) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. We report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (MGAWN1) targeting the E protein of WNV in a phase 1 study, the first to be performed on humans. A single intravenous infusion of saline or of MGAWN1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volunteers (30 receiving MGAWN1; 10 receiving placebo). Subjects were evaluated on days 0, 1, 3, 7, 14, 21, 28, 42, 56, 91, 120, and 180 by clinical assessments, clinical laboratory studies, electrocardiograms (ECGs), and pharmacokinetic and immunogenicity assays. All 40 subjects tolerated the infusion of the study drug, and 39 subjects completed the study. One serious adverse event of schizophrenia occurred in the 0.3-mg/kg cohort. One grade 3 neutropenia occurred in the 3-mg/kg cohort. Six MGAWN1-treated subjects experienced 11 drug-related adverse events, including diarrhea (1 subject), chest discomfort (1), oral herpes (1), rhinitis (1), neutropenia (2), leukopenia (1), dizziness (1), headache (2), and somnolence (1). In the 30-mg/kg cohort, MGAWN1 had a half-life of 26.7 days and a maximum concentration in serum (C(max)) of 953 microg/ml. This study suggests that single infusions of MGAWN1 up to 30 mg/kg appear to be safe and well tolerated in healthy subjects. The C(max) of 953 microg/ml exceeds the target level in serum estimated from hamster studies by 28-fold and should provide excess WNV neutralizing activity and penetration into the brain and cerebrospinal fluid (CSF). Further evaluation of MGAWN1 for the treatment of West Nile virus infections is warranted.
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PMID:Safety and pharmacokinetics of single intravenous dose of MGAWN1, a novel monoclonal antibody to West Nile virus. 2035 Sep 45

A patient with a 28-year history of schizophrenia was treated with a wide range of antipsychotic medications since diagnosis. She had experienced no clinically significant symptomatic relief until she commenced treatment on clozapine. Her psychotic symptoms, self care, and general sense of well-being improved significantly. After 6 years of successful treatment, she developed leukopenia and clozapine was discontinued. The following issues will be discussed in the article: rechallenge with clozapine following leukopenia during previous therapy and the choice of and haematological monitoring needs with other antipsychotic medications after clozapine-induced blood dyscrasia.
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PMID:Clozapine-induced late leukopenia. 2205 37

Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carbamazepine, and sulfonamide antibiotics, such as sulfamethoxazole. There were no studies at the writing of this article examining the effect of concomitant medications on clozapine blood dyscrasias, and few published reports describing enhanced bone marrow suppression in those taking clozapine. The primary objective of this study was to evaluate the effect of concomitant medications used in a state psychiatric hospital on clozapine-induced blood dyscrasias. This was a retrospective record review of adverse drug reactions reported at an adult inpatient state psychiatric center. The records for a pilot sample of 26 patients with reported clozapine-related adverse drug reactions between January 1, 2007, and June 30, 2009, were reviewed. Fundamental to this study were reported adverse drug reactions defined as 1) substantial drops in white blood cell or absolute neutrophil count (a substantial drop in white blood cell is >3,000 or absolute neutrophil count is >1,500 over a 3-week period); 2) mild leukopenia/granulocytopenia; and 3) moderate-severe leukopenia/granulocytopenia. Concomitant medications were examined for contributions to an increased potential for clozapine-induced blood dyscrasias. Other data collected included demographic information (age, gender, ethnicity), medical and psychiatric diagnoses, dose and duration of medications, and changes in medications. Medications that had a statistically significant impact on the incidence of clozapine-induced blood dyscrasias are reported in this article, as well as the possible duration of medication use prior to induction of an adverse drug reaction.
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PMID:Are clozapine blood dyscrasias associated with concomitant medications? 2163 33

Up until October 2012, Kohnodai Hospital had introduced clozapine treatment for 55 cases of treatment-resistant schizophrenia. In all cases, previous antipsychotic medication was discontinued the day before clozapine administration began. Of the 55 cases, 45(85%)are continuing clozapine administration, and 40 cases (73%) are receiving outpatient treatment. The average dose of clozapine was 373.1 mg/day (SD : 160.5). Clozapine was administered for a month or more in 51 cases (93%). BPRS scores improved 20% or more in a month's administration of clozapine in 18 of the cases (35%). The average clozapine dose in the improvement cases was 176 mg/day. The average BPRS score had significantly decreased from the baseline at months 1, 3, 6, and 12 after the start of clozapine administration. Of the 33 cases receiving clozapine treatment for 12 months or more, BPRS improved 20% or more in 27 (82%). BPRS improved 20% or more for the first time after clozapine administration within a month in 12 cases (44%), 3 months in 8 cases (30%), 6 months in 5 cases (19%), and 12 months in 2 cases (7%). These results suggest that clozapine should be administered continuously for over 6 months at the least and 12 months if possible to evaluate the efficacy of clozapine treatment. Of the 43 cases receiving outpatient clozapine therapy, the average GAF score improved significantly from the time of ward admission to discharge (20.6 and 42.0, respectively). Clozapine had to be discontinued in 2 cases of leukopenia, 2 cases of neutropenia, 1 case of reduced left ventricular ejection due to pericardial effusion, 1 case of drug eruption, and 1 case of marked hunger. When introducing clozapine for treatment-resistant schizophrenia, it is important to administer it as a monotherapy, slowly increase the dosage to reduce side effects, and achieve a treatment effect at the minimum required dosage.
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PMID:[Clinical experience with clozapine in 55 cases of treatment-resistant schizophrenia]. 2422 73

Case. We report a case of catatonia with elevated CK, elevated temperature, and hypoferritinemia after abrupt discontinuation of clozapine in a patient with known proneness to catatonic symptoms. Reinstatement of clozapine therapy was contraindicated due to leukopenia. Neuroleptic malign syndrome could not be ruled out by the administration of quetiapine; this prevented the quick use of other potent D2 antagonists. Some improvement was achieved through supportive therapy, high dose of lorazepam, and a series of 10 ECT sessions. Returning to baseline condition was achieved by a very careful increase of olanzapine. Discussion. Catatonic symptoms in schizophrenia as well as in NMS might be caused by a lack of striatal dopamine (CS) or dopamine D2 antagonism (NMS). CS might be a "special" kind of schizophrenia featuring both hypo- and hyperactivity of dopaminergic transmission. ECT has been described as a "psychic rectifier" or a "reset for the system." The desirable effect of ECT in cases of CS might be dopaminergic stimulation in the striatum and decrease of both the dopaminergic activity in the limbic system and the serotonergic activity on 5-HT2 receptors. The desirable effect of ECT in NMS would be explained by activation of dopaminergic transmission and/or liberation of dopaminergic receptors from the causative neuroleptics.
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PMID:Catatonic dilemma in a 33-year-old woman: a discussion. 2441 11

Benign familial leukopenia (BFL) has been reported in several ethnic groups, including Ethiopians of Jewish origin. To date, there are no reported cases of patients with BFL developing granulocytopenia following administration of neuroleptics. We report a case of a young Ethiopian Jew suffering from schizophrenia, who exhibited premorbid benign reduced white blood cells (WBC) count and developed leukopenia and neutropenia following exposure to typical (zuclopentixol, perphenazine, haloperidol) antipsychotics and the atypical antipsychotic risperidone. The diagnosis of BFL was established and tissue typing of the patient was determined. To the best of our knowledge, this is the first report of leukopenia with neutropenia in an ethnically susceptible (due to BFL) schizophrenia patient following exposure to typical and atypical antipsychotics. HLA typing of this patient was distinct from that reported in patients susceptible to clozapine-induced agranulocytosis. Further extensive investigations including HLA typing in a larger cohort of schizophrenic patients is needed in order to define the association between HLA haplotypes and neuroleptic-induced hematological reactions and to identify the potentially vulnerable individuals.
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PMID:Granulocytopenia associated with neuroleptic therapy in a patient with benign familial leukopenia. 2493 Apr 15

Risperidone is an atypical antipsychotic agent that was originally approved by the United States Food and Drug Adminstration for the treatment of schizophrenia. There are many side effects that are frequently associated with the use of risperidone. These include weight gain, anxiety, extra-pyramidal side effects, and elevated prolactin levels. More infrequently, the use of risperidone has been linked to leukopenia. We will now present the case of a 66-year-old gentleman who developed leukopenia after the initiation of risperidone to control agitation due to delirium. We will review the previous cases of leukopenia associated with risperidone, and will review possible risk factors for the development of leukopenia, based on the reported cases.
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PMID:Leukopenia Associated with Risperidone Treatment. 2855 30

Leukopenia is a known hematological side effect of atypical antipsychotics. We report a case of an antipsychotic-naive patient with schizophrenia who developed leukopenia after a single dose of olanzapine, which worsened during subsequent treatment with risperidone. Normalization of the white blood cell counts occurred within 24 hours of risperidone discontinuation. Possible synergistic mechanisms underlying olanzapine-induced and risperidone-induced leukopenia are discussed. This case highlights the challenges in identifying and managing nonclozapine antipsychotic-induced leukopenia in a susceptible patient.
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PMID:Olanzapine-induced and Risperidone-induced Leukopenia: A Case of Synergistic Adverse Reaction? 2950 83

The U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application Lurasidone (Latuda, Sunovion Pharmaceuticals), an atypical antipsychotic, for the treatment of schizophrenia in adolescents 13-17 years of age. Lurasidone was previously indicated in the U.S. for the treatment of adults with schizophrenia and major depressive episodes with bipolar I disorder as monotherapy. We present a case of a 29-year-old male patient who was hospitalized with thrombocytopenia (WHO grade-3 toxicity) (unlabeled) along with extrapyramidal disorder, gastritis, and hyperprolactinemia within 2-3 months of initiation of tablet lurasidone 80 mg/day (Lurasid, Intas Pharmaceuticals) in bipolar depression. Dechallenge was found to be positive in three reactions except hyperprolactinemia (outcome unknown) during hospital stay. The terms anemia and leukopenia are well labeled/listed with the drug literatures of lurasidone. Thus, this case presents a strong probability of lurasidone to cause myelosuppression/bone marrow depression.
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PMID:Lurasidone Induced Thrombocytopenia: Is it a Signal of Drug Induced Myelosuppression? 2996 79

Clozapine remains the definitive gold standard for treatment-resistant schizophrenia despite limitations in use because of hematological abnormalities. Neutropenia or leukopenia are often treated with interruption of clozapine treatment, frequently resulting in clinical decompensation, hospitalization, increased burden to patient care, and increased risk of suicide. Colony-stimulating factors, including granulocyte colony-stimulating factors and granulocyte-macrophage colony-stimulating factors, are cytokines that stimulate proliferation and differentiation of myeloid precursor cells. Their use in the prevention and treatment of clozapine-associated neutropenia presents an alternative to clozapine discontinuation in certain cases. We present a case report of successful periodic granulocyte-macrophage colony-stimulating factor use with clozapine in a patient with treatment-resistant schizophrenia, as well as discussion of a practical approach to patients with possible clozapine-induced neutropenia or leukopenia.
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PMID:Utilization of G-CSF and GM-CSF as an alternative to discontinuation in clozapine-induced neutropenia or leukopenia: A case report and discussion. 3020 10


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