Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial

<p>Abstract</p> <p>Background</p> <p>Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis.</p> <p>Methods</p> <p>Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale - Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS).</p> <p>Results</p> <p>A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01).</p> <p>Conclusions</p> <p>There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://www.clinicaltrials.gov/</url>: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00932529">NCT00932529</a></p

Switching among antipsychotics in everyday clinical practice: focus on ziprasidone

Objectives: This article addresses points to consider when switching patients to the second-generation antipsychotic (SGA), ziprasidone, in everyday clinical practice: 1) the pharmacologic properties of the pre-switch antipsychotic and of ziprasidone; 2) switch and dosing strategies to ensure maintenance or attainment of efficacy; 3) recognition and management of possible rebound effects of the pre-switch medication discontinuation; 4) recognition and management of potential side effects of ziprasidone; and 5) education and support for patients/caregivers concerning correct ziprasidone administration. Methods: A Medline search (up to July 7, 2010) identified studies in which adult patients with schizophrenia were switched to ziprasidone from another antipsychotic. In addition, based on their extensive clinical experience, an expert faculty of European psychiatrists provided advice on identifying patients who may be appropriate candidates for switching to ziprasidone, and on establishing optimal strategies for switching to ziprasidone in everyday clinical practice. Results: Data from 10 studies, in which 1395 patients were switched to ziprasidone, showed that switching from first-generation antipsychotics (FGAs) or SGAs generally resulted in maintenance or improvement of efficacy across all studied symptom domains, improvements in tolerability, and acute and long-term benefits regarding cardiometabolic parameters, including body weight. Maintenance of efficacy is most likely to be achieved using a plateau cross-titration strategy, with a rapid uptitration of ziprasidone to a dose range of 60 to 80 mg administered twice daily with food. Temporary coadministration of benzodiazepines, anticholinergics, or beta-blockers should be considered for the management of potential rebound effects. Conclusion: Optimal switching of patients with schizophrenia from FGAs or SGAs to ziprasidone requires careful attention to differences in the pharmacological profiles of the pre-switch medication and of ziprasidone, which may impact efficacy and tolerability. Good communication between the clinician and patient/caregiver about the goals of switching, the importance of adherence to the chosen switch strategy, and the correct administration of ziprasidone are essential. © Postgraduate Medicine

Practical guidance for prescribing ziprasidone in acute manic or mixed episodes of bipolar I disorder

Limited information is available on the clinical issues and strategies for optimal clinical usage of ziprasidone in the treatment of adult patients with acute manic or mixed episodes of bipolar disorder. Areas covered: To address those issues, information from clinical trials addressing the efficacy and tolerability of ziprasidone in acute bipolar mania was reviewed and supplemented with the input from an expert faculty of European psychiatrists with extensive experience in treating patients with bipolar mania, both in clinical trials and in everyday clinical practice. Expert opinion: Effective use of oral ziprasidone in the treatment of acute bipolar mania requires rapid titration to doses in the range 120 - 160 mg/day and administration with meals of ≥ 500 kcal. As in the clinical trials, temporary short-term use of benzodiazepines (in particular lorazepam for agitation or temazepam for insomnia) could be advisable. Available evidence from randomized clinical trials in combination with clinical experience supports the use of ziprasidone as one of the first-line effective and safe treatments for acute manic or mixed episodes associated with bipolar I disorder. © 2011 Informa UK, Ltd

Individualizing antipsychotic treatment selection in schizophrenia: characteristics of empirically derived patient subgroups

Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients with schizophrenia. Information on 39 variables was collected. Multiple component analysis was used to identify dimensions that explained the variance between patients. Three axes, accounting for 99% of the variance, were associated with disease severity (64%), socioeconomic status (27%) and patient autonomy (8%). These dimensions discriminated between six discrete patient subgroups, identified using ascending hierarchical classification analysis. The six subgroups differed regarding educational level, illness severity, autonomy, symptom presentation, addictive behaviors, comorbidities and cardiometabolic risk factors. Subgroup 1 patients had moderately severe physician-rated disease and addictive behaviours (23.2%); Subgroup 2 patients were well-integrated and autonomous with mild to moderate disease (6.7%); Subgroup 3 patients were less well-integrated with mild to moderate disease, living alone (11.2%); Subgroup 4 patients were women with low education levels (5.4%), Subgroup 5 patients were young men with severe disease (36.8%); and Subgroup 6 patients were poorly-integrated with moderately severe disease, needing caregiver support (16.7%). The presence of these subgroups, which require confirmation and extension regarding potentially identifiable biological markers, may help individualizing treatment in patients with schizophrenia