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

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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    • "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.
    BMC Psychiatry 09/2014; 14(1):253. DOI:10.1186/s12888-014-0253-4 · 2.21 Impact Factor
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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.
    Clinical Psychopharmacology and Neuroscience 08/2014; 12(2):128-36. DOI:10.9758/cpn.2014.12.2.128
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    • "Mood stabilizers might be used by patients diagnosed with other psychiatric diagnoses, such as schizophrenia, and this presents a possible confounder, as the prevalence of diabetes is increased in patients with schizophrenia [25]. We are not aware of data from Norway on the use of mood stabilizers in schizophrenia, and data from other countries vary widely [26,27] so it is difficult to know how important this confounder may be. Of probable greater importance is the ability of antipsychotics to induce diabetes [28]. "
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    ABSTRACT: Background Studies have shown a correlation between bipolar disorder and diabetes mellitus. It is unclear if this correlation is a part of common pathophysiological pathways, or if medication for bipolar disorder has negative effects on blood sugar regulation. Methods The Norwegian prescription database was analyzed. Prescriptions for lithium, lamotrigine, carbamazepine and valproate were used as proxies for bipolar disorder. Prescriptions for insulin and oral anti-diabetic agents were used as proxies for diabetes mellitus. We explored the association between medication for bipolar disorder and diabetes medication by logistic regression Results We found a strong association between concomitant use of medication to treat diabetes mellitus and mood stabilizers for the treatment of bipolar disorder. Females had a 30% higher risk compared to men of being treated for both disorders. Persons using oral anti-diabetic agents had higher odds of receiving valproate than either lithium or lamotrigine. Use of insulin as monotherapy seemed to have lower odds than oral anti-diabetic agents of co-prescription of mood stabilizers, compared to the general population. Conclusions This study showed a strong association between the use of mood stabilizers and anti-diabetic agents. The association was stronger among women than men.
    BMC Medicine 11/2012; 10(1):148. DOI:10.1186/1741-7015-10-148 · 7.25 Impact Factor
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