نافذه

التفاوت العرقي في استخدام مضادات الذهان غير النمطية بين المحاربين القدماء
المصدر: المجلة الأمريكية للطب النفسي
Am J Psychiatry 160: 1822, Oct.2003
Racial Disparity in the Use of Atypical Antipsychotic Medications Among Veterans
Laurel A. Copeland, M.P.H., Ph.D., John E. Zeber, M.H.A., Marcia Valenstein, M.D., M.S., and Frederic C. Blow, Ph.D.
OBJECTIVE: This study assessed the current state of antipsychotic prescription practices regarding race among veterans receiving care through the Department of Veterans Affairs. METHOD: The authors examined pharmacy records over a 12-month period for all veterans with schizophrenia and antipsychotic prescriptions in fiscal year 1999. They used logistic regression analysis to assess the effect of race on the use of various atypical antipsychotic agents. Analytic models controlled for age, sex, comorbid substance use, bipolar disorder, and other psychosis. RESULTS: The sample of 69,787 veterans with schizophrenia was 61.3% white, 30.1% African American, and 8.5% Hispanic. Among them, 39% had prescriptions for conventional antipsychotics, 37% for atypical antipsychotics, and 23% for both atypical and conventional antipsychotics. Use of any atypical agent during the year was less likely for Hispanic veterans (55%) than for two other groups (both 61%). When examining specific medications in a multivariate model, the authors found that African American and Hispanic veterans were much less likely to receive clozapine than were white veterans. CONCLUSIONS: Overall use of atypical antipsychotics was slightly less common for African American and Hispanic veterans with schizophrenia than for white patients. However, use of clozapine, the first choice for refractory illness and possibly uniquely effective for patients with comorbid substance abuse, did vary greatly by race. This may reflect concern over serious side effects, such as loss of white blood cells and fluctuations of serum glucose levels, or patient preference.

لمعالجة الداعمة للفصام باستخدام الريسبيريدون أو الهالوبيلايدول: حصيلة عامين
المصدر:المجلة الأمريكية للطب النفسي
\ Am J
Psychiatry 160:1412 Aug.2003

Maintenance Treatment of Schizophrenia withM

Risperidone or Haloperidol: 2-Year Outcomes
Stephen R. Marder, M.D., Shirley M. Glynn, Ph.D., William C. Wirshing, M.D., Donna A. Wirshing, M.D., Doreen Ross, Clifford Widmark, M.D., Jim Mintz, Ph.D., Robert P. Liberman, M.D., and Karen E. Blair, M.S.
OBJECTIVE: Most controlled studies comparing second-generation and conventional antipsychotics have focused on the acute treatment of schizophrenia. The authors compared symptom outcomes, side effects, and social adjustment in stable schizophrenia outpatients who received 2 years of maintenance treatment with risperidone or haloperidol. METHOD: This was a 2-year, randomized, double-blind comparison of 6 mg of risperidone versus haloperidol in 63 patients with stabilized DSM-IV schizophrenia. Study patients also received 15 months of standard behavioral skills training or enhanced training with a case manager who promoted patients’ use of their skills in the community. RESULTS: The risk of psychotic exacerbations and the risk of leaving the study were similar for both drug treatment groups. However, patients who received both risperidone and the enhanced community-based skills training were more likely to remain in the study than those in the other treatment groups. Patients demonstrated significant improvement in score on the Brief Psychiatric Rating Scale over time with both medications. There were no between-group differences in cluster scores for thought disturbance, hostile-suspiciousness, and withdrawal-retardation. A significant between-group difference favoring risperidone was found for the anxious-depression cluster. Risperidone resulted in significantly greater reductions in tremor and akathisia and greater improvements in most items on the SCL-90-R. CONCLUSIONS: When compared with patients given a low dose of haloperidol, risperidone-treated patients experienced similar improvements in positive and negative symptoms and similar risks of psychotic exacerbations. However, risperidone-treated patients appeared to feel subjectively better, as indicated by less anxiety and depression and fewer extrapyramidal side effects.

هل يؤثر الكلوزابين والهالوبيريدول على مستوى الكفاءة الاجتماعية والمقدرة على حل المشكلات
المصدر: المجلة الأمريكية للطب النفسي
Am J Psychiatry 161:367 Feb.2004

Do Clozapine and Risperidone Affect Social Competence
and Problem Solving?
Alan S. Bellack, Ph.D., Nina R. Schooler, Ph.D., Stephen R. Marder, M.D., John M. Kane, M.D., Clayton H. Brown, Ph.D., and Ye Yang, M.S.
OBJECTIVE: The purpose of this investigation was to evaluate the effects of clozapine and risperidone on social skill and problem solving in patients with schizophrenia. METHOD: The Wisconsin Card Sorting Test and the Maryland Assessment of Social Competence were administered at baseline, week 17, and week 29 of a multisite clinical trial. RESULTS: Despite evidence of clinical improvement with both medications, there was virtually no medication effect on either social competence or problem solving. CONCLUSIONS: These findings underscore the circumscribed nature of symptomatic improvement in the broader spectrum of clinical outcomes and suggest that new-generation medications may not be expected to produce substantial changes in social role functioning or social problem-solving capacity in the community. The generalizability of the findings should be viewed cautiously because of the low power of this trial, and replication is warranted.

الكلوزابين كعلاج أول للفصام
المصدر: المجلة الأمريكية للطب النفسي
\\\am J Psychiatry 161:1516 Aug.2003

Clozapine as a First Treatment for Schizophreni

Margaret G. Woerner, Ph.D., Delbert G. Robinson, M.D., Jose Ma. J. Alvir, Dr.P.H., Brian B. Sheitman, M.D., Jeffrey A. Lieberman, M.D., and John M. Kane, M.D.
OBJECTIVE: The authors’ goal was to explore whether clozapine given as the first antipsychotic treatment favorably affects the course of schizophrenia. METHOD: Thirty-four inpatients experiencing their first episode of schizophrenia or schizoaffective disorder were treated first with clozapine and then followed for up to 4 years. In a previous study, the authors followed patients experiencing their first episode of schizophrenia or schizoaffective disorder who were given fluphenazine as the first treatment. In the current study and the previous study, response criteria required sustained remission of positive symptoms. RESULTS: Nineteen of the 34 subjects met response criteria while taking clozapine. The median time to treatment response was 11 weeks (range=2–13). Using survival analysis, the authors determined that the cumulative response rate for the 34 patients was 66.4% at the end of 13 weeks, which is comparable to the response rate to fluphenazine in the previous study. All responses to clozapine occurred by 13 weeks. Eight (42%) of the clozapine responders discontinued clozapine before 6 months, and only six (32%) remained on clozapine for all of their time in the study. CONCLUSIONS: The authors found no benefit for clozapine over conventional antipsychotics for acute treatment of the first episode of schizophrenia or schizoaffective disorder. Long-term benefits could not be studied because of the high rate of early discontinuation of clozapine treatment.

الآراء الشائعة حول دور مستقبلات الدوبامين في آلية تأثير المطمئنات الكبرى في معالجة الفصام
المصدر المجلة التشيكية والسلوفاكية للطب النفسي
Czes. a slov. Psychiatrie, 99,2003 No.7, p.376

Current Opinions on the Role of Dopamine D(2) and D(3) Receptors in the Mechanism of Action of Neuroleptics in the Treatment of Schizophrenia
Dóci I.

Summary:
Mechanism of Action of Neuroleptics in the Treatment of Schizophrenia Although atypical antipsychotics are becoming the treatment of choice for schizophrenia, what makes the antipsychotic „atypical“, is not clear. New Findings based on research using positron emission tomography (PET) were published recently. Schizophrenic patients have increased synaptic dopamine concentrations in the striatum; antipsychotics with high affinity for dopamine D(2) receptors are associated with a substantial increase in D(2) receptor binding; Columbia study provides an important indication of hyperdopaminergic function in schizophrenia; antipsychotic efficacy of atypical antipsychotics has been observed at lower D(2) receptor occupancy rates than with typical neuroleptics. Based on this and other new findings the Schizophrenia research group in Toronto propose than fast dissociation from the D(2) receptor makes an antipsychotic more accomodating of physiological dopamine transmission, permitting an antipsychotic effect without motor side effects. In contrast to the multireceptor hypotheses, the authors predict that the atypical antipsychotic effect can be produced by appropriate modulation of the D(2) receptor alone; the blockade of other receptors is neither necessary nor sufficient.

Effect Size of Symptom Status in Withdrawal of Typical Antipsychotics and Subsequent Clozapine Treatment in Patients With Treatment-Resistant Schizophrenia
David Pickar, M.D., and John J. Bartko, Ph.D.
OBJECTIVE: In light of the efficacy of newer antipsychotic agents and the possibility that drug withdrawal may negatively affect subsequent drug response, concern has arisen that the use of placebo in schizophrenia research may be unethical. This study examines the effect size of symptom exacerbation during drug washout with placebo and the effects of drug washout on the efficacy of subsequent drug treatment. METHOD: Fifty patients with treatment-resistant schizophrenia hospitalized on a research unit participated in a double-blind longitudinal study of the effects of drug washout after chronic treatment with a typical antipsychotic and before prospective treatment with clozapine. Brief Psychiatric Rating Scale (BPRS) scores were analyzed to examine drug effects and effect sizes for baseline treatment with a typical antipsychotic (>6 months treatment), drug washout with placebo (mean=34 days), early treatment with clozapine (mean=42 days, mean dose=345.0 mg/day), and optimal clozapine treatment (mean=83 days, mean dose=450.5 mg/day). RESULTS: Patients’ BPRS total, positive, and negative symptom scores significantly increased during placebo washout, compared with baseline treatment, and significantly decreased with administration of clozapine, compared with placebo washout and baseline treatment. However, 30% of patients showed some symptom improvement during placebo washout. The effect sizes for the BPRS total score were 0.63 for baseline treatment versus placebo washout, 1.10 for optimal clozapine treatment versus placebo washout, and 0.82 for optimal clozapine treatment versus baseline treatment. CONCLUSIONS: Symptom exacerbation induced by drug withdrawal in patients with treatment-resistant schizophrenia did not impede subsequent responsiveness to clozapine. The effect size for clozapine, compared with typical antipsychotics, suggests that the drug-washout longitudinal design is useful for establishing a drug-free baseline and for investigating drug response, while requiring relatively few subjects.

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