- Email: [email protected]
Cochrane schizophrenia group
142
mechanism and that eosinophilia may predict later agranulocytosis. Our study aimed to examine this reported relationship between eosinophilia and subsequent neutropenia and compare the rates of these blood dyscrasias to haloperidol treated patients. Method: Thirty-two clozapine-treated patients have been monitored for a minimum of six months. Rates of eosinophilia and neutropenia were tallied and compared with a matched haloperidol treated group. Results: Of the thirty-two clozapine-treated patients, two patients had baseline eosinophilia and seven patients developed treatment emergent eosinophilia. Neutropenia occurred in three of the thirty-two patients. These results did not differ from the haloperidol control group. Of the fifteen haloperidol treated patients, eosinophilia occurred in two patients (XZ=0.91 p = N.S.). Neutropenia occurred in one patient (X2=0.06 p = N.S.). Only one clozapine treated patient had both neutropenia and eosinophilia. In this case neutropenia preceded eosinophilia by three weeks. Conclusions: Treatment emergent eosinophilia is common in both clozapine and haloperidol treated patients. No significant difference in rates of neutropenia were seen in this patient cohort. No clear relationship between eosinophilia and neutropenia can be established. Eosinophilia's utility as a marker for subsequent neutropenia is probably negligible.
COCHRANE
SCHIZOPHRENIA
GROUP
J. Anderson*, C.E. Adams, J. Mari Department of Adult Psychiatry, Monash Medical Centre, Victoria, Australia The Cochrane Collaboration aims to prepare, maintain and disseminate systematic reviews of health care. Discussions at the Winter Workshop (Switzerland, 1994), led to the formation of the Cochrane Schizophrenia Group (CSG). This paper introduces the interests of the CSG, its work to date and its agenda for 1995-96. The CSG is producing and will maintain a Register of all relevant controlled trials. Hand-searching of many journals (1948-present) is complete and MEDLINE, EMBASE and PsycLIT are being methodically searched. A meeting in New York (5th April 1995), preceding the International Congress on Schizophrenia Research (Warm Springs, USA), will train collaborators in the process of systematic reviewing of trials. Sample protocols for undertaking a systematic review, as well as electronic reviews, will be made available. In 1995-96 an increasing number of systematic reviews relevant to the care of those with schizophrenia will be produced, maintained and disseminated in the Coehrane Database (online early 1995). These summaries of the best available evidence of the effectiveness and efficiency of care will help the decision-making of clinicians, researchers, purchasers and consumers of care. More collaborative effort is needed if this urgent task is to be completed both swiftly and efficiently.
S E R O Q U E L ~ ( I C I 204 636): A N O V E L , ATYPICAL ANTIPSYCHOTIC: EFFICACY AND SAFETY RESULTS FROM TWO P H A S E II, M U L T I C E N T E R , PLACEBOCONTROLLED CLINICAL TRIALS Lisa Arvanitis*, Barbara G. Miller, Chris G.G. Link, and the U S and International S E R O Q U E L Study Groups CNS Clinical Research, ZENECA Pharmaceuticals Group, 1800 Concord Pike, Wilmington, DE 19897, USA Seroquel (ICI 204 636), a dibenzothiazepine with affinity for multiple brain receptors, is a potential atypical antipsychotic agent. Seroquel satisfies pharmacologic criteria considered©juputative predictors of atypicality, i.e., clozapinelike activity: (1) higher affinity for central 5-HT2 receptors than for Dz receptors (IC50=148 and 329nM, respectively); (2) limbic system selectivity as evidenced by depolarization inactivation of A10 dopamine cells after chronic administration; (3) minimal dystonic liability in haloperidol-sensitized and drug-naive monkeys; and (4) transient elevations in prolactin after acute administration. The efficacy and safety of Seroquel were evaluated in two 6-week, multicenter, double-blind, placebo-controlled trials, in which 395 patients with acute exacerbation of schizophrenia were enrolled. Patients were assessed weekly using the BPRS, SANS, and CG1 for efficacy and Simpson Scale and AIMS for extrapyramidal side effects. Seroquel was statistically and clinically superior to placebo across all efficacy variables. There were no differences between treatment groups with regard to extrapyramidal symptoms or plasma prolactin levels. No acute dystonic reactions were noted. These results provide evidence that Seroquel is effective in the treatment of the positive and negative symptoms of schizophrenia and is well-tolerated. Seroquel's atypical profile is further supported by the lack of extrapyramidal symptoms and sustained elevations in plasma prolactin levels. Seroquel is a trademark, the property of Zeneca Limited.
SCHIZOPHRENIA-LIKE HIPPOCAMPAL NEUROPATHY IN RATS: CHANGES IN ACCUMBENS CORE AND SHELL DOPAMINE AFTER HALOPERIDOL TREATMENT M a r k E. Bardgett*, Jamie L. Jackson, John G. Csernansky Department of Psychiatry, Box 8134, Washington University Schoolof Medicine, St Louis, MO 63110 1093, USA Kainic acid (KA) administration to rats produces neuronal injury and loss in the same limbic-cortical brain regions affected in schizophrenia. Many of these brain regions, such as the
mechanism and that eosinophilia may predict later agranulocytosis. Our study aimed to examine this reported relationship between eosinophilia and subsequent neutropenia and compare the rates of these blood dyscrasias to haloperidol treated patients. Method: Thirty-two clozapine-treated patients have been monitored for a minimum of six months. Rates of eosinophilia and neutropenia were tallied and compared with a matched haloperidol treated group. Results: Of the thirty-two clozapine-treated patients, two patients had baseline eosinophilia and seven patients developed treatment emergent eosinophilia. Neutropenia occurred in three of the thirty-two patients. These results did not differ from the haloperidol control group. Of the fifteen haloperidol treated patients, eosinophilia occurred in two patients (XZ=0.91 p = N.S.). Neutropenia occurred in one patient (X2=0.06 p = N.S.). Only one clozapine treated patient had both neutropenia and eosinophilia. In this case neutropenia preceded eosinophilia by three weeks. Conclusions: Treatment emergent eosinophilia is common in both clozapine and haloperidol treated patients. No significant difference in rates of neutropenia were seen in this patient cohort. No clear relationship between eosinophilia and neutropenia can be established. Eosinophilia's utility as a marker for subsequent neutropenia is probably negligible.
COCHRANE
SCHIZOPHRENIA
GROUP
J. Anderson*, C.E. Adams, J. Mari Department of Adult Psychiatry, Monash Medical Centre, Victoria, Australia The Cochrane Collaboration aims to prepare, maintain and disseminate systematic reviews of health care. Discussions at the Winter Workshop (Switzerland, 1994), led to the formation of the Cochrane Schizophrenia Group (CSG). This paper introduces the interests of the CSG, its work to date and its agenda for 1995-96. The CSG is producing and will maintain a Register of all relevant controlled trials. Hand-searching of many journals (1948-present) is complete and MEDLINE, EMBASE and PsycLIT are being methodically searched. A meeting in New York (5th April 1995), preceding the International Congress on Schizophrenia Research (Warm Springs, USA), will train collaborators in the process of systematic reviewing of trials. Sample protocols for undertaking a systematic review, as well as electronic reviews, will be made available. In 1995-96 an increasing number of systematic reviews relevant to the care of those with schizophrenia will be produced, maintained and disseminated in the Coehrane Database (online early 1995). These summaries of the best available evidence of the effectiveness and efficiency of care will help the decision-making of clinicians, researchers, purchasers and consumers of care. More collaborative effort is needed if this urgent task is to be completed both swiftly and efficiently.
S E R O Q U E L ~ ( I C I 204 636): A N O V E L , ATYPICAL ANTIPSYCHOTIC: EFFICACY AND SAFETY RESULTS FROM TWO P H A S E II, M U L T I C E N T E R , PLACEBOCONTROLLED CLINICAL TRIALS Lisa Arvanitis*, Barbara G. Miller, Chris G.G. Link, and the U S and International S E R O Q U E L Study Groups CNS Clinical Research, ZENECA Pharmaceuticals Group, 1800 Concord Pike, Wilmington, DE 19897, USA Seroquel (ICI 204 636), a dibenzothiazepine with affinity for multiple brain receptors, is a potential atypical antipsychotic agent. Seroquel satisfies pharmacologic criteria considered©juputative predictors of atypicality, i.e., clozapinelike activity: (1) higher affinity for central 5-HT2 receptors than for Dz receptors (IC50=148 and 329nM, respectively); (2) limbic system selectivity as evidenced by depolarization inactivation of A10 dopamine cells after chronic administration; (3) minimal dystonic liability in haloperidol-sensitized and drug-naive monkeys; and (4) transient elevations in prolactin after acute administration. The efficacy and safety of Seroquel were evaluated in two 6-week, multicenter, double-blind, placebo-controlled trials, in which 395 patients with acute exacerbation of schizophrenia were enrolled. Patients were assessed weekly using the BPRS, SANS, and CG1 for efficacy and Simpson Scale and AIMS for extrapyramidal side effects. Seroquel was statistically and clinically superior to placebo across all efficacy variables. There were no differences between treatment groups with regard to extrapyramidal symptoms or plasma prolactin levels. No acute dystonic reactions were noted. These results provide evidence that Seroquel is effective in the treatment of the positive and negative symptoms of schizophrenia and is well-tolerated. Seroquel's atypical profile is further supported by the lack of extrapyramidal symptoms and sustained elevations in plasma prolactin levels. Seroquel is a trademark, the property of Zeneca Limited.
SCHIZOPHRENIA-LIKE HIPPOCAMPAL NEUROPATHY IN RATS: CHANGES IN ACCUMBENS CORE AND SHELL DOPAMINE AFTER HALOPERIDOL TREATMENT M a r k E. Bardgett*, Jamie L. Jackson, John G. Csernansky Department of Psychiatry, Box 8134, Washington University Schoolof Medicine, St Louis, MO 63110 1093, USA Kainic acid (KA) administration to rats produces neuronal injury and loss in the same limbic-cortical brain regions affected in schizophrenia. Many of these brain regions, such as the