Antipsychotic Prescribing Pathways, Polypharmacy, and Clozapine Use in Treatment of Schizophrenia

Psychiatric services (Washington, D.C.) (Impact Factor: 2.41). 03/2013; 64(6). DOI: 10.1176/
Source: PubMed


To ensure optimal care for patients with schizophrenia, antipsychotic medications must be appropriately prescribed and used. Therefore, the primary objectives of this study were to identify and describe pathways for antipsychotic prescribing, assess the consistency of observed pathways with treatment guidelines, and describe variability across facilities.

Data from Veterans Affairs administrative data sets from fiscal year (FY) 2003 to FY 2007 were gathered for analysis in this retrospective cohort study of antipsychotic prescribing pathways among 13 facilities across two regional networks. Patients with a new episode of care for schizophrenia or schizoaffective disorder in FY 2005 were identified, and antipsychotic prescribing history was obtained for two years before and after the index diagnosis. Demographic characteristics and distribution of comorbidities were assessed. Median medical center rates of polypharmacy were calculated and compared with Fisher's exact test.

Of 1,923 patients with a new episode of schizophrenia care, 1,003 (52%) had complete data on prescribing pathways. A majority (74%) of patients were prescribed antipsychotic monotherapy, and 19% received antipsychotic polypharmacy. Of patients receiving antipsychotic polypharmacy, 65% began polypharmacy within 90 days of starting any antipsychotic treatment. There was a fourfold difference in polypharmacy across facilities. Antipsychotic polypharmacy was not associated with geographic location or medical center patient volume. Clozapine utilization was low (0%-2%).

Retrospective examination of longitudinal prescribing patterns identified multiple antipsychotic prescribing pathways. Although most patients received guideline-concordant care, antipsychotic polypharmacy was commonly used as initial treatment, and there was substantial variability among facilities. Study findings suggest the utility of secondary data to assess treatment adaptation or switching for practical clinical trials.

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    • "It should be noted that our results do not provide information on the risks and benefits of initiating antipsychotic polypharmacy in patients with schizophrenia. They do suggest, however, that since it may be difficult to get patients off antipsychotic polypharmacy once it has become a sustained treatment strategy, trials of clozapine and injectable antipsychotics should precede consideration of antipsychotic polypharmacy (Brissos et al., 2014;Constantine et al., 2010Constantine et al., , 2013Goren et al., 2013;Kales et al., 1999;Tandon, 2011). Of note, a recent analysis of outcomes of Medicaid beneficiaries with schizophrenia noted that those on clozapine monotherapy had better outcomes than those on antipsychotic polypharmacy (Velligan et al., 2015). "
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    ABSTRACT: Despite little evidence to support its use and practice guidelines discouraging the practice, antipsychotic polypharmacy is widely prevalent in schizophrenia. This randomized controlled trial studied the effects of switching patients stable on two antipsychotic medications to one antipsychotic medication. 104 adult outpatients with schizophrenia from 7 community mental health centers clinically stable on concurrent treatment with 2 antipsychotics were randomly assigned to stay on polypharmacy or to switch to antipsychotic monotherapy. Participants were followed for 1-year with assessments of symptoms and side effects occurring every 60days (7 total assessments). We examined differences in time trajectories in symptoms (PANSS, CGI) and side effects (EPS, metabolic, other) as a function of group assignment (switch vs. stay) and time, using intention-to-treat analysis. Participants who switched to antipsychotic monotherapy experienced greater increases in symptoms than stay patients. These differences emerged in the second 6months of the trial. All-cause discontinuation rates over the 1-year trial were higher in the switch-to-monotherapy group than in the stay-on-polypharmacy group (42% vs. 13%; p<0.01). There were no differences in change over time in any of the side effect measures, except that stay patients experienced a greater decrease in Simpson Angus total scores than switch patients. Clinicians should be cautious in switching patients with chronic schizophrenia who are stable on 2 antipsychotics to one antipsychotic. Given the challenges in discontinuing antipsychotic polypharmacy, adequate trials of evidence-based treatments such as clozapine and long-acting injectable antipsychotics should be undertaken in inadequately responsive schizophrenia patients before moving to antipsychotic polypharmacy. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Jun 2015 · Schizophrenia Research
    • "Most guidelines strongly advise clozapine as a third trial antipsychotic. About 30% of patients with schizophrenia are treatment-resistant and therefore eligible for clozapine treatment (Meltzer, 1997; Robinson et al., 1999), but clozapine prescription rates are seriously low across Europe and the USA (Gören et al., 2013; Stroup et al., 2014), resulting in a theoretical delay of 47.7 months (Howes et al., 2012). Because clozapine is a last resort, its underuse is an impediment to improving outcomes for patients. "
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    ABSTRACT: Underuse of the antipsychotic clozapine for schizophrenia is an impediment to improving outcomes for patients. Because of its possible severe side effects, including granulocytopenia or even agranulocytosis, clozapine treatment entails regular WBC monitoring, which can be a major drawback for patients and practitioners. The HemoCue WBC DIFF system is a point-of-care device using capillary blood sampling which provides WBC counts with differentials, including granulocytes. We investigated if capillary sampling instead of conventional venous sampling might diminish the burden for patients and practitioners and motivate them to continue clozapine treatment. A randomized cross-over trial design was used to compare the two sampling methods. Patients׳ subjective experiences of various aspects of blood sampling were rated on a 10-cm visual analogue scale (VAS). Patients and practitioners were also asked if they had any preference for venous or capillary sampling and patients were asked if the sampling method influenced their motivation to continue clozapine treatment. Seventy-three patients were included in this study. Three dropped out before completion. The VAS ratings on all five aspects and the total burden experienced showed a consistent pattern favouring capillary blood sampling (p<0.001). This pattern was more pronounced for inpatients than for outpatients. Patients strongly preferred capillary testing (p<0.001). The method used moderately influenced their motivation for clozapine therapy. In this study patients tolerated capillary blood testing with a point-of-care device better than traditional venous sampling at a laboratory and practitioners also preferred it. Using this method might therefore boost clozapine prescription rates. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.
    No preview · Article · Dec 2014 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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    ABSTRACT: Second generation antipsychotics (SGAs) are widely used for post-traumatic stress disorder (PTSD), although without strong evidence base. With substantial numbers of veterans returning from Iraq/Afghanistan conflicts with PTSD, it is important to characterize the extent of SGA use and identify associated factors. We determined time trends and patient characteristics associated with the use of SGAs in veterans with PTSD, without comorbid schizophrenia or bipolar disorders, using the Department of Veterans Affairs national administrative data 2003-2010. Among 732 085 veterans with PTSD, 27.6% received an intentional trial of an SGA in 2003-2010. The annual number treated with SGAs almost doubled (45 268 to 84 197, p < 0.001), while prescribing rates decreased (28.6% to 21.5%, p < 0.001). In multivariate analyses, African Americans (odds ratio (OR) = 1.07, 95%confidence interval (CI) = 1.06-1.09) and Hispanics (OR = 1.13, 95%CI = 1.10-1.17) were more likely to receive SGAs than Whites. Strongest clinical associations were with prior diagnosis of depression (OR = 1.96; 95%CI = 1.94-1.99), substance use disorders (OR = 1.86; 95%CI = 1.84-1.88), and other anxiety disorders (OR = 1.27; 95%CI = 1.26-1.29) (all p - < 0.0001) as well as cardiovascular risk factors. Veterans previously deployed to Iraq/Afghanistan had lower likelihood of SGA receipt. Substantial regional differences were demonstrated (South > Northeast; Midwest and West < Northeast; p < 0.0001); regional administrative units (veterans integrated service networks) contributed minimally to regional differences. Post-traumatic stress disorder population growth is driving substantial increases in SGA use. Decreasing rates of the Department of Veterans Affairs prescribing may be due to integrated system-wide mechanisms (e.g., national practice guidelines), although regional variations remain prominent. These analyses provide foundational steps for identifying modifiable provider-level and organization-level determinants of SGA prescription in this growing population. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
    Full-text · Article · Jan 2014 · Pharmacoepidemiology and Drug Safety
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