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The newer atypical antipsychotics have gained prominence as first-line oral agents to treat severe agitation, but their use in the psychiatric emergency service (PES) setting has been limited because of the unavailability of parenteral formulations. The advent of parenteral formulations of atypical antipsychotics, beginning with ziprasidone in 2002, might afford an alternative treatment option.
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The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events. Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.
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All treated lymphocyte cultures showed a statistically significant increase in SCE frequency and a significant decrease in PRI values (p<0.001). The combined effect of the drugs induced similar or more intense results, without reaching levels indicating synergistic action.
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Health related quality of life (HRQL) has become an important outcome measure in the treatment of psychiatric disorders. This long-term observational study examined ziprasidone-induced improvement in satisfaction with HRQL in schizophrenia patients treated under real-world conditions.
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This case of ziprasidone- and lithium-induced NMS is of probable cause, as determined by the Naranjo probability scale. The patient presented with symptoms consistent with NMS 4 days after initiation of ziprasidone and lithium. The majority of NMS cases present with the core features of hyperthermia, muscle rigidity, and elevated CK levels. Other frequently seen symptoms include altered mental status, tachypnea, tachycardia, elevated WBC count, hypotension, diaphoresis, and myoglobinuria. Our patient presented with 2 of the core symptoms, but did not develop muscle rigidity at any time. NMS criteria include muscle rigidity as one of the major presenting symptoms. Recent literature suggests that perhaps NMS due to novel antipsychotics presents with less muscle rigidity than is seen with traditional agents due to their lower affinity for the dopamine D2 receptor.
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One of the major challenges in the design of double-blind flexible-dosing clinical trials comparing active drugs is the selection of dosing regimens that are equivalent across drugs. This study uses data from the CATIE schizophrenia trial to evaluate the hypothesis that drugs that were dosed somewhat higher in the trial than in typical practice would show greater efficacy and more side effects, especially at high capsule levels, than drugs that were dosed at lower relative strengths.
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Medication outcome literature in schizophrenia across racial-ethnic groups is sparse, with inconsistent findings. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study provided an opportunity for exploratory analyses of racial-ethnic outcomes. The study objective was to examine race-ethnicity outcomes for CATIE's main outcome (study discontinuation) and secondary outcomes.
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We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine.
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The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE).
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Little has been published regarding the pharmacokinetics of the intramuscular (IM) formulation of Ziprasidone. The authors report results from 2 early phase I studies in healthy volunteers: a trial of single 5-, 10-, or 20-mg IM doses of ziprasidone in 24 subjects and an open-label 3-way crossover trial of 5-mg intravenous (IV), 5-mg IM, and 20-mg oral ziprasidone in 12 subjects. Absorption of IM ziprasidone was rapid (Tmax < 1 hour). The IM pharmacokinetic profile was consistent between studies and linear, with dose-related increases in exposure observed. The mean IM elimination t(1/2) was short and approximately 2.5 hours. The mean bioavailability for the 5-mg IM ziprasidone dose was approximately 100%. Adverse events were generally mild to moderate, and no subjects were discontinued from the study. No significant effects on renal function or other laboratory values were noted. These results support the use of IM ziprasidone in treating acutely agitated patients with schizophrenia.
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There were 81 patients who were treated with ziprasidone and matched with 81 healthy controls in this open-label trial. The functions were evaluated by Continuous Performance Test (CPT) and Color Word Test (CWT) at baseline and eight weeks later. Between two groups the functions were compared at the two time points, and in patients group those were compared prior to and post treatment.
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Ziprasidone use increased rapidly among patients with schizophrenia after FDA approval, which suggests that both patients and providers remain eager to try new antipsychotic medications. Earlier dissemination was associated with clinical factors, such as comorbid diabetes, and with nonclinical factors, such as race or ethnicity. Differences by race diminished over time. The underlying processes and implications for affected patient groups are unclear.