Prevalence and correlates of antipsychotic polypharmacy: A systematic review and meta-regression of global and regional trends from the 1970s to 2009

The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA.
Schizophrenia Research (Impact Factor: 4.43). 04/2012; 138(1):18-28. DOI: 10.1016/j.schres.2012.03.018
Source: PubMed

ABSTRACT To assess the prevalence and correlates of antipsychotic polypharmacy (APP) across decades and regions.
Electronic PubMed/Google Scholar search for studies reporting on APP, published from 1970 to 05/2009. Median rates and interquartile ranges (IQR) were calculated and compared using non-parametric tests. Demographic and clinical variables were tested as correlates of APP in bivariate and meta-regression analyses.
Across 147 studies (1,418,163 participants, 82.9% diagnosed with schizophrenia [IQR=42-100%]), the median APP rate was 19.6% (IQR=12.9-35.0%). Most common combinations included first-generation antipsychotics (FGAs)+second-generation antipsychotics (SGAs) (42.4%, IQR=0.0-71.4%) followed by FGAs+FGAs (19.6%, IQR=0.0-100%) and SGAs+SGAs (1.8%, IQR=0.0-28%). APP rates were not different between decades (1970-1979:28.8%, IQR=7.5-44%; 1980-1989:17.6%, IQR=10.8-38.2; 1990-1999:22.0%, IQR=11-40; 2000-2009:19.2% IQR=14.4-29.9, p=0.78), but between regions, being higher in Asia and Europe than North America, and in Asia than Oceania (p<0.001). APP increased numerically by 34% in North America from the 1980s 12.7%) to 2000s (17.0%) (p=0.94) and decreased significantly by 65% from 1980 (55.5%) to 2000 (19.2%) in Asia (p=0.03), with non-significant changes in Europe. APP was associated with inpatient status (p<0.001), use of FGAs (p<0.0001) and anticholinergics (<0.001), schizophrenia (p=0.01), less antidepressant use (p=0.02), greater LAIs use (p=0.04), shorter follow-up (p=0.001) and cross-sectional vs. longitudinal study design (p=0.03). In a meta-regression, inpatient status (p<0.0001), FGA use (0.046), and schizophrenia diagnosis (p=0.004) independently predicted APP (N=66, R(2)=0.44, p<0.0001).
APP is common with different rates and time trends by region over the last four decades. APP is associated with greater anticholinergic requirement, shorter observation time, greater illness severity and lower antidepressant use.

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    ABSTRACT: Objective This large nationwide study describes the prevalence and predictors of long-term antipsychotic polypharmacy among patients with schizophrenia. Methods A register-based longitudinal study of all people in Finland, who had at least one hospitalization due to schizophrenia during the years 2000–2007 and who were alive on March 1, 2007. Entry to the cohort was defined from the first hospitalization for schizophrenia during the years 2000–2007, and the date of assessment of antipsychotic polypharmacy was March 1, 2007. We studied separately chronic (N = 8,037) and recent onset (N = 8,046) schizophrenia patients. Antipsychotic polypharmacy was defined as overlapping of two or more filled prescriptions of antipsychotics for over 60 days. Results In a total 16,083 patients with schizophrenia the prevalence of antipsychotic polypharmacy was 46.2 % (N = 7,436, mean age 47.5 years, male 55 %). The longer the duration of schizophrenia, the more common the antipsychotic polypharmacy. Long index hospitalization and being male significantly associated with antipsychotic polypharmacy among all schizophrenia patients. Especially, in chronic schizophrenia patients, the previous use of benzodiazepine like agents was associated with antipsychotic polypharmacy, but the use of antidepressants associated with less frequent antipsychotic polypharmacy. Conclusions Antipsychotic polypharmacy was widely prevalent among patients with schizophrenia and it was associated with long hospitalizations and long duration of illness. Benzodiazepine use was associated with increased risk and antidepressant use with decreased risk of antipsychotic polypharmacy when the effect of other clinical and socioeconomic factors was adjusted. Research is needed of risks and benefits of antipsychotic polypharmacy and augmentation of antipsychotic with other psychoactive drugs.
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    ABSTRACT: INTRODUCTION: Antipsychotic polypharmacy (APP), the concomitant use of ≥ 2 antipsychotics, is common in clinical practice. Prior reviews have focused on the efficacy of APP, but no systematic review exists regarding the safety and tolerability of this practice. AREAS COVERED: A systematic review of adverse effects associated with APP was conducted to prepare this review; case series with ≥ 2 patients, chart reviews, naturalistic, database, cohort and randomized studies that reported on the association between APP in general or specific APP combinations and global or specific adverse effect were included. Methodological limitations of available studies are discussed and recommendations for clinicians and future research are provided. EXPERT OPINION: Across mostly small and uncontrolled studies, APP has been associated with increased global side effect burden, rates of Parkinsonian side effects, anticholinergic use, hyperprolactinemia, sexual dysfunction, hypersalivation, sedation/somnolence, cognitive impairment and diabetes. Effects on akathisia and mortality were inconclusive. Although some combinations, particularly aripiprazole augmentation of an agent with greater side effect burden, may reduce weight gain, dyslipidemia, hyperprolactinemia and sexual dysfunction, APP should remain a last-resort treatment option after monotherapy, switching and non-antipsychotic combinations have failed. More data are needed to further inform the individualized risk-benefit evaluation of APP.
    Expert Opinion on Drug Safety 05/2012; 11(4):527-42. DOI:10.1517/14740338.2012.683523 · 2.74 Impact Factor
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    ABSTRACT: Antipsychotic polypharmacy (APP) is common in the treatment of schizophrenia spectrum disorders. The literature indicates that APP is related to patient, illness, and treatment variables that are proxy measures for greater illness acuity, severity, complexity, and chronicity. The largely unknown relative risks and benefits of APP need to be weighed against the known risks and benefits of clozapine for treatment-resistant patients. To inform evidence-based clinical practice, controlled, high-quality antipsychotic combination and discontinuation trials are necessary to determine the effectiveness, safety, and role of APP in the management of severely ill patients with insufficient response to antipsychotic monotherapy.
    The Psychiatric clinics of North America 09/2012; 35(3):661-81. DOI:10.1016/j.psc.2012.06.007 · 1.87 Impact Factor


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