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


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.

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    • "Due to the severity of schizophrenia, many patients do not recover with one antipsychotic drug and, consequently, it is common practice to try different combinations of drugs. There are, however, few studies analyzing the benefit or risk of combination treatment with ⩾2 antipsychotic drugs [Schumacher et al. 2003; Tapp et al. 2003; Ganguly et al. 2004; Broekema et al. 2007; Kreyenbuhl et al. 2007a, 2007b; Megna et al. 2007; Lee and Walker, 2008; Pandurangi and Dalkilic, 2008; Tranulis et al. 2008]. Since antipsychotic drugs may cause severe side effects such as cognitive and emotional blunting, acute and chronic extrapyramidal side effects, torsade de pointes, weight gain and metabolic syndrome [Jeste and Caligiuri, 1993; Raschi et al. 2013], these drugs should be used with utmost care and only when really needed. "
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    ABSTRACT: To assess the prevalence of concomitant use of two or more antipsychotic drugs and other psychotropic drugs in the Swedish population. Data for this observational cohort study were collected from the Swedish Prescribed Drug Register including all dispensed drugs to the entire Swedish population (9.4 million inhabitants). We identified all individuals with at least one dispensed prescription of antipsychotic drug during January to June 2008. After 12 months, a second exposure period was chosen. Individuals who were dispensed two or more antipsychotic drugs in both periods were considered long-time users of antipsychotic polypharmacy. In 2008, 1.5% of the Swedish population was dispensed antipsychotic drugs, the majority (75%) using only one antipsychotic drug. Out of individuals who were dispensed 2 or more antipsychotic drugs during the first period, 62% also was also dispensed at least 2 antipsychotic drugs during the second period. A total of 665 different unique combinations were used in 2008. Individuals prescribed two or more antipsychotic drugs during both periods were more often dispensed anxiolytics and sedatives than those who were dispensed only one antipsychotic drug. Elderly were dispensed antipsychotic drugs much more often than younger persons. In Sweden, 25% of patients dispensed antipsychotic drugs receive a combination of two or more antipsychotic drugs. Individuals who are dispensed antipsychotic polypharmacy are more often dispensed anxiolytics and sedatives than those prescribed only one antipsychotic drug. Long-term observational studies are needed to assess the efficacy and safety of such combinations.
    Full-text · Article · Jun 2015 · Therapeutic Advances in Psychopharmacology
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    • "Potential consequences of APP include greater adverse effect burden (Gallego et al. 2012b; Jerrell & McIntyre, 2008; McIntyre & Jerrell, 2008), higher total antipsychotic doses (Bingefors et al. 2003; Elie et al. 2009; Hung & Cheung, 2008) and treatment cost (Rupnow et al. 2007; Stahl & Grady, 2006). In adults, APP is used in an effort to enhance or accelerate antipsychotic efficacy, treat symptoms other than psychosis (Pandurangi & Dalkilic, 2008) or reduce the dose of the first antipsychotic without loss of overall efficacy (Correll & Gallego, 2012). APP also commonly occurs during antipsychotic cross-titration and after an aborted antipsychotic switch (Stahl & Grady, 2004). "
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    ABSTRACT: Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n = 58 041, range 68-23 183) reported on APP in youth [mean age = 13.4 ± 1.7 yr, 67.1 ± 10.2% male, 77.9 ± 27.4% treated with second-generation antipsychotics (SGAs)]. Data collected in these studies covered 1993-2008. The most common diagnoses were attention-deficit hyperactivity disorder (ADHD; 39.9 ± 23.5%) and conduct disorder/oppositional defiant disorder (CD/ODD; 33.6 ± 24.8). In studies including predominantly children (mean age = <13 yr, N = 5), the most common diagnosis were ADHD (50.6 ± 25.4%) and CD/ODD (39.5 ± 27.5%); while in studies with predominantly adolescents (mean age = ⩾13 yr, N = 7) the most common diagnoses were schizophrenia-spectrum disorders (28.6 ± 23.8%), anxiety disorders (26.9 ± 14.9%) and bipolar-spectrum disorders (26.6 ± 7.0%), followed closely by CD/ODD (25.8 ± 17.7). The prevalence of APP among antipsychotic-treated youth was 9.6 ± 7.2% (5.9 ± 4.5% in child studies, 12.0 ± 7.9% in adolescent studies, p = 0.15). Higher prevalence of APP was correlated with a bipolar disorder or schizophrenia diagnosis (p = 0.019) and APP involving SGA+SGA combinations (p = 0.0027). No correlation was found with APP definition [⩾1 d (N = 10) vs. >30-⩾90 d (N = 5), p = 0.88]. Despite lacking safety and efficacy data, APP in youth is not uncommon, even in samples predominantly consisting of non-psychotic patients. The duration, clinical motivations and effectiveness of this practice require further study.
    Preview · Article · May 2013 · The International Journal of Neuropsychopharmacology
    • "Various studies have looked into different aspects of polypharmacy, e.g., incidence, prevalence, rationality, profile of subjects receiving polypharmacy etc.[456] Two reviews on the use of polypharmacy concluded that despite strong recommendation by experts to employ monotherapy whenever possible, the prevalence of antipsychotic polypharmacy (APP) has greatly increased, particularly since the advent of the Second Generation Antipsychotics (SGA).[78] There was very few studies have evaluated the prescription pattern and the issue of polypharmacy in psychiatric patients from India. "
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    ABSTRACT: To study the prescription pattern of psychotropic drugs in a Tertiary Care Hospital in Eastern India with special reference to polypharmacy. A total of 411 patients were included in the study through systematic sampling. Patients were diagnosed by a Consultant Psychiatrist before inclusion in the study using a semi-structured interview schedule based on the International Classification of Disease (ICD), classification of mental and behavioral disorders, 10th version). The most recently prescribed psychopharmacological medication of those patients was studied. A checklist to assess the pattern of prescription and evaluate reasons of polypharmacy was filled up by the prescribing consultant. About 76.6% of the patients received polypharmacy in the index study. Males were more exposed to polypharmacy compared to women (80.93% vs. 70.85%). Gender and diagnosis had a predictive value with regard to the polypharmacy. Polypharmacy was more common in organic mental disorders (F0), psychoactive substance abuse disorders (F1), psychotic disorders (F2), mood disorders (F3) and in childhood, and adolescent mental disorders (F9). Most frequently, antipsychotic drugs were prescribed followed by tranquilizers/hypnotics and anticholinergics. Antidepressants (35.13%) were more commonly prescribed as monotherapy. Anticholinergics (100%) and tranquilizers/hypnotics (96.7%) were the drugs more commonly used in combination with other psychotropics. The three most common reasons for prescribing polypharmacy were augmentation (43.8%) of primary drug followed by its use to prevent adverse effects of primary drug (39.6%) and to treat comorbidity (34.9%). Polypharmacy is a common practice despite the research based guidelines suggest otherwise. More vigorous research is needed to address this sensitive issue.
    No preview · Article · May 2013 · Indian Journal of Pharmacology
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