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: 3.92). 04/2012; 138(1):18-28. DOI: 10.1016/j.schres.2012.03.018
Source: PubMed


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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    • "The use of antipsychotic polypharmacy (APP), defined as the concurrent use of two or more antipsychotic agents, is increasing in clinical practice although treatment guidelines and supporting evidence for APP's safety and efficacy are lacking [1]. According to a comprehensive metaanalysis , the world-wide prevalence of APP is 19.6% [2]. Medicaid data show that the frequency of American patients with schizophrenia on APP increased from 3.3% in 1999 to 13.7% by 2004 [3]. "
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    ABSTRACT: Objective: In China, maintenance treatment for clinically stable patients with schizophrenia is usually provided by primary care physicians, but their prescribing patterns have not been studied. This study examined the frequency as well as demographic and clinical correlates of antipsychotic polypharmacy (APP) and its impact on quality of life (QOL) in patients with schizophrenia treated in primary care in China. Method: A total of 623 community-dwelling patients from 18 randomly selected primary care services were interviewed. Patients' socio-demographic and clinical characteristics, including number of hospitalizations, antipsychotic drug-induced side effects, and QOL were recorded using a standardized protocol and data collection procedure. Results: The rate of APP prescription was 31% (193/623). Of the patients on APP, 89.6% received 2 antipsychotics, 10.4% received 3 or more antipsychotics. Clozapine (35.6%) was the most commonly prescribed second generation antipsychotic (SGA), while perphenazine (17.8%) was the most commonly prescribed first generation antipsychotic (FGA). Multiple logistic regression analyses revealed that patients on APP were more likely to receive SGAs and anticholinergics, had fewer hospitalizations, younger age of onset, and higher doses of antipsychotics. There were no significant differences between the two groups in any of the QOL domains. Conclusions: Approximately a third of Chinese patients with schizophrenia in primary care receive APP. Further examination of the rationale and appropriateness of APP and its alternatives is warranted.
    Full-text · Article · Nov 2015 · International journal of clinical pharmacology and therapeutics
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    • "Many newer agents or approaches have been the focus of TRS studies with the hope of having similar efficacy to clozapine but better tolerability and safety – although, on average, other medications seem less effective than clozapine [8,9]. Whilst clozapine is the only licensed drug for TRS, clinicians do often try other approaches such as poly-pharmacy and high dose prescribing [10] before its prescription with an average 47.7 months delay in use of clozapine [11]. Up to 30% of people whose illness has been designated as resistant to treatment will have an inadequate response to clozapine and more interventions may be indicated [12]. "
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    ABSTRACT: Background Schizophrenia is a common serious mental health condition which has significant morbidity and financial consequences. The mainstay of treatment has been antipsychotic medication but one third of people will have a `treatment resistant¿ and most disabling and costly illness. The aim of this survey was to produce a broad overview of available randomised evidence for interventions for people whose schizophrenic illness has been designated `treatment resistant¿.Method We searched the Cochrane Schizophrenia Group¿s comprehensive Trials Register, selected all relevant randomised trials and, taking care not to double count, extracted the number of people randomised within each study. Finally we sought relevant reviews on the Cochrane Library and investigated how data on this subgroup of people had been presented.ResultsWe identified 542 relevant papers based on 268 trials (Average size 64.8 SD 61.6, range 7¿526, median 56 IQR 47.3, mode 60). The most studied intervention is clozapine with 82 studies (total n¿=¿6299) comparing it against other anti-psychotic medications. Cognitive behavioural therapy (CBT), electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) supplementing a standard care and risperidone supplementation of clozapine has also been extensively evaluated within trials. Many approaches, however, were clearly under researched. There were only four studies investigating combinations of non-clozapine antipsychotics. Only two psychological approaches (CBT and Family Rehabilitation Training) had more than two studies. Cochrane reviews rarely presented data specific to this important clinical sub-group.Conclusions This survey provides a broad taxonomy of how much evaluative research has been carried out investigating interventions for people with treatment resistant schizophrenia. Over 280 trials have been undertaken but, with a few exceptions, most treatment approaches - and some in common use - have only one or two relevant but small trials. Too infrequently the leading reviews fail to highlight the paucity of evidence in this area ¿ as these reviews are maintained this shortcoming should be addressed.
    Full-text · Article · Sep 2014 · BMC Psychiatry
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    • "It could be inferred that the rate of antipsychotic polypharmacy has decreased and that the rate of atypical antipsychotic use has increased. The reason for this trend is not clear, but it is possible that the replacement of typical antipsychotic polypharmacy (typical antipsychotics+typical antipsychotics) with atypical antipsychotic monotherapy due to greater efficacy and less EPS is associated with the use of atypical antispsychotics.15) Another remarkable finding from the present study is the marked change in the antipsychotic prescription pattern over a relatively short period of time. "
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    ABSTRACT: Objective This study investigated the prescription patterns for Korean patients with schizophrenia with a particular focus on antipsychotic polypharmacy. All data were gathered from patients presenting at 41 tertiary university hospitals and 8 secondary hospitals. Methods Data from three multicenter studies conducted in Korea were retrospectively reviewed and integrated to identify patients with schizophrenia who had their antipsychotic medication switched to paliperidone extended-release between 2008 and 2009. The rates for antipsychotic polypharmacy, combined use of different antipsychotic classes with a special focus on atypical antipsychotics, and psychotropic polypharmacy using benzodiazepines, mood stabilizers, and other relevant drugs were identified. Results Of the 851 Korean patients analyzed in this study, 20.4% (n=173) had been prescribed antipsychotic polypharmacy. Of the 678 patients receiving antipsychotic monotherapy, 6.9% (n=47) were prescribed a typical antipsychotic and 93.1% (n=631) were prescribed an atypical antipsychotic. Of the 173 patients receiving a combination of antipsychotic drugs, only 6.4% (n=11) had been prescribed polypharmacy with typical antipsychotics, while 46.82% (n=81) were prescribed atypical+atypical antipsychotics or typical+atypical antipsychotics. The highest co-prescription rates for other psychotropic drugs in conjunction with antipsychotics included benzodiazepines (30.3%), anticholinergic drugs (28.8%), antidepressants (13.3%), β-blockers (10.1%), and mood stabilizers (8.7%). Conclusion The present findings demonstrate that the rate of antipsychotic polypharmacy is relatively low in Korea and that Korean clinicians prefer to prescribe atypical, rather than typical, antipsychotic drugs. This suggests that there is a distinct prescription pattern in Korea that is focused on antipsychotic polypharmacy.
    Full-text · Article · Aug 2014 · Clinical Psychopharmacology and Neuroscience
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