Antipsychotic Polypharmacy in Children and Adolescents at Discharge from Psychiatric Hospitalization

Inpatient psychiatric admissions have increased among children and adolescents over the past 2 decades, with hospitalization rates rising from 0.84% to 1.25% over this period.1 In parallel, the use of second-generation antipsychotics (SGAs) in youth has dramatically increased.2-11 This rise in SGA prescribing likely relates to a myriad of factors, including an accumulating evidence base and United States Food and Drug Administration approval for the use of these medications in youth with mood, psychotic, and pervasive developmental disorders12-15 as well as off-label prescribing. However, despite the clinical benefits of these agents, children and adolescents may be more vulnerable to SGA-related adverse effects,16-21 including sedation, drug-induced movement disorders (e.g., dystonic reactions, akathisia), and metabolic abnormalities (e.g., weight gain, dyslipidemia, and glucose intolerance).22 Moreover, adverse effects may also increase health care costs and adversely impact adherence and quality of life. Recent data suggest that a significant population of children and adolescents are treated with more than one antipsychotic concomitantly (i.e., antipsychotic polypharmacy),23 with the majority of regimens including more than one SGA.24,25 However, to date, there are scant data on clinical benefit, safety, or cost-effectiveness of antipsychotic polypharmacy in youth.26,27 The knowledge gap remains, as current evidence is limited to small or uncontrolled studies in adults with psychotic disorders.27 These reports suggest that antipsychotic polypharmacy is associated with increased adverse effects and medical costs yet lacks evidence of clinical benefit, aside from clozapine augmentation in adults with treatment-resistant schizophrenia.26,27 This practice became such a concern that “patients discharged on multiple antipsychotic medication” and “patients discharged on multiple antipsychotic medications with appropriate justification” were among the seven 2010 Hospital-Based Inpatient Psychiatric Services (HBIPS) core measures,28 which remain in the 2013 Joint Commission National Quality Measures.29 Nonetheless, antipsychotic polypharmacy is an enduring clinical practice in adult populations.30,31 Data on the prevalence and predictors of antipsychotic polypharmacy in youth are limited, as the extant data are extracted from studies of antipsychotics in children and adolescents designed to investigate other aims. In this regard, antipsychotic polypharmacy descriptions are primarily derived from studies that were designed to examine adverse effects and treatment duration,21 metabolic changes,32 use and prescribing practices,33,34 and SGA versus first-generation antipsychotic (FGA) dyskinesia risk.35 Although more than a dozen studies have examined antipsychotic treatment patterns between 1993 and 2008,23 few have evaluated antipsychotic polypharmacy. Moreover, only five studies have examined prescribing patterns in inpatient or residential settings21,32-35 and have reported the prevalence of antipsychotic polypharmacy as ranging from 2.9-27%; in these studies, correlates of antipsychotic polypharmacy were bipolar- or schizophrenia-spectrum disorder diagnoses, treatment with anxiolytics or hypnotics, and SGA plus SGA regimens; FGA plus SGA treatment was negatively correlated.23 Three studies used Medicaid data and reported that antipsychotic polypharmacy rates were 4.4-7.1% among youth, and correlates were male sex, older age (adolescent vs child), non-white race, autism, bipolar disorder, conduct disorder, psychotic disorders, and treatment with antidepressants and mood stabilizers; however, these studies—because of the data sources—have limited direct information related to specific clinical characteristics of the populations being studied.24,25,36 Higher rates of antipsychotic prescribing have been documented in children and adolescents with public versus private insurance.4-6,37,38 Moreover, among the Medicaid-insured, rates are higher in youth in foster care.5,25,39 Antipsychotic polypharmacy was also more likely, and occurred for longer durations, in Medicaid-insured youth in foster care.25 Knowledge on predictors of antipsychotic polypharmacy in youth is largely limited to state Medicaid claims data in outpatients, which precludes the examination of payer (e.g., public vs private insurance) as a potential correlate. Importantly, findings from outpatient claims data may have significant limitations in that they may not be applicable to a general child and adolescent inpatient psychiatry setting, a level of care utilized by an increasing number of youth.1 Given the increasing prevalence of antipsychotic polypharmacy and concerns related to increased risks for nonadherence and adverse effects, as well as costs, it is critical to determine the characteristics of youth that increase their vulnerability to be treated with multiple antipsychotics. With these considerations in mind and to address this gap in knowledge, we examined factors potentially associated with increased risk of antipsychotic polypharmacy in a large, mixed-payer population, reviewing demographic and clinical characteristics of all children and adolescents (i.e., not limited to antipsychotic-treated patients) discharged from an inpatient psychiatric facility. Data are scant regarding antipsychotic polypharmacy in pediatric patients, and there are no data regarding predictors of antipsychotic polypharmacy in psychiatrically hospitalized youth.