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

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