Polypharmacy with second-generation antipsychotics: a review of evidence.

Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
Journal of psychiatric practice 12/2008; 14(6):345-67. DOI: 10.1097/01.pra.0000341890.05383.45
Source: PubMed

ABSTRACT The objective of this study was to review the prevalence of polypharmacy with second-generation antipsychotics (SGAs) in clinical practice, pharmacological reasons for such practice, and the evidence for and against such polypharmacy.
Clinical trial reports, case reports, and reviews were identified by a PubMed literature search from 1966 through October 2006, with retrieved publications queried for additional references. We excluded reports on augmentation with non-antipsychotic medications and polypharmacy involving combinations of SGAs and first-generation (conventional) antipsychotics (FGAs) or combinations of two FGAs. We identified 75 reports concerning SGA polypharmacy, from which we extracted data on study design, sample size, medications, rating scales, outcome, and conclusions. Data from randomized controlled trials and larger case series are presented in detail and case reports are briefly discussed.
Polypharmacy with SGAs is not uncommon, with prevalence varying widely (3.9% to 50%) depending on setting and patient population, despite limited support from blinded, randomized, controlled trials or case reports that employed an A-B-A (monotherapy-combination therapy-monotherapy) design and adequate dosing and duration of treatment. Rather than prohibiting or discouraging co-prescription of SGAs, needs of patients and clinicians should be addressed through evidence-based algorithms. Based on unmet clinical needs and modest evidence from case reports, combinations of two SGAs may merit future investigation in efficacy trials involving patients with schizophrenia who have treatment-resistant illness (including partial response) or who are responsive to treatment but develop intolerable adverse effects. Other areas that may merit future research are efficacy of SGA polypharmacy for schizophrenia accompanied by comorbid conditions (eg, anxiety, suicidal or self-injurious behavior, aggression) and for reducing length of stay in acute care settings.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    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.
    Schizophrenia Research 04/2012; 138(1):18-28. DOI:10.1016/j.schres.2012.03.018 · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although common in psychiatric practice, reasons for antipsychotic polypharmacy (APP) have remained unclear. Single-site, semi-structured interview study of prescribers at a psychiatric teaching hospital inquiring about APP attitudes and behaviors, including frequency, preferred combinations, rationale and concerns. Forty-four prescribers reported using APP in 17.0 ± 10.0% of antipsychotic-treated patients. Although clinicians themselves initiated APP in only 23.3 ± 27.0% of cases, they did not attempt conversion to antipsychotic monotherapy in 40.9 ± 37.7%, despite reported successful conversion in 28.0 ± 30.8% of cases. The following reasons justified most APP (0-10): cross-titration (9.2 ± 1.4), failed clozapine trial (8.2 ± 2.2), randomized controlled evidence (8.0 ± 2.0), and clozapine intolerance (7.7 ± 2.6). Prescribers felt "moderately" (5.0 ± 1.9) concerned about APP (0-10), mostly due to chronic side effects (7.6 ± 2.0), lack of evidence (7.1 ± 2.2), non-adherence risk (6.7 ± 2.3) and mortality risk (6.7 ± 3.2), while increased cost (4.9 ± 2.5) and higher total antipsychotic dose (4.2 ± 2.9) ranked lowest. Comparing high with low APP prescribers (>10% vs. ≤ 10% of patients; mean: 36.1 ± 19.8 vs. 3.4 ± 3.4, p<0.0001), no differences emerged on 25/26 ratings regarding APP justification and 9/9 ratings regarding concerns. In a multivariate analyses, only attending status (OR=10.3, p=0.0043) and endorsing a specific APP preference (OR=21.4, p=0.011) predicted APP use >10% (r(2):0.35, p<0.0001), yet no uniformly preferred APP strategy emerged. High APP prescribers had more clinical experience, less concerns about APP and more likely a preferred APP choice, although no overall preferred strategy emerged. Otherwise, high and low APP prescribers shared attitudes toward APP. Both had inherited most of their APP cases and were reluctant to convert patients to antipsychotic monotherapy.
    Schizophrenia Research 03/2011; 131(1-3):58-62. DOI:10.1016/j.schres.2011.02.016 · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to review the roles of antioxidants in the pathophysiology of schizophrenia, whether the properties of ginkgo can ameliorate symptoms of this illness, and evaluate available literature to test this assumption. This review is based upon published works on antioxidants and ginkgo. A primary electronic search for meta-analysis on the usage of ginkgo or its derived products in schizophrenia was conducted using Pubmed, Cochrane Library, EMBASE, CINAHL, PsycINFO and AMED. Inclusion criteria were: criteria-based diagnosis of schizophrenia, randomized case assignment, use of ginkgo as an add-on therapy, and assessment using standardized rating scales to measure the state of psychopathology for negative and total symptoms of schizophrenia. Additionally, a detailed review was undertaken to investigate if antioxidants are involved in development of psychotic symptoms in schizophrenia. The six studies that fulfilled the selection criteria were constituted of 466 cases on ginkgo and 362 cases on placebo. They all used the Scale for the Assessment of Negative Symptoms (SANS) to measure negative symptoms, and the Scale for the Assessment of Positive Symptoms (SAPS) or the Brief Psychiatric Rating Scale (BPRS) to measure total symptoms. Difference between ginkgo and control groups from their pre- and post-trial scores and its pooled standard deviation were used to compute standardized mean difference (SMD). Ginkgo as an add-on therapy to antipsychotic medication produced statistically significant moderate improvement (SMD=-0.50) in total and negative symptoms of chronic schizophrenia. Ginkgo as add-on therapy ameliorates the symptoms of chronic schizophrenia. The role of antioxidants in pathogenesis of schizophrenia has also been explored.
    The International Journal of Neuropsychopharmacology 09/2009; 13(2):257-71. DOI:10.1017/S1461145709990654 · 5.26 Impact Factor