Cecilia Huang

Broadened Use Of Atypical Antipsychotics: Safety, Effectiveness, And Policy Challenges

Atypical antipsychotic medications are increasingly used for a wide range of clinical indications in diverse populations, including privately and publicly insured youth and elderly nursing home residents. These trends heighten policy challenges for payers, patients, and clinicians related to appropriate prescribing and management, patient safety, and clinical effectiveness. For clinicians and patients, balancing risks and benefits is challenging, given the paucity of effective alternative treatments. For health care systems, regulators, and policymakers, challenges include developing the evidence base on comparative risks and benefits; defining measures of treatment quality; and implementing policies that encourage evidence-based practices while avoiding unduly burdensome restrictions.

Premature Mortality Among Adults With Schizophrenia in the United States

IMPORTANCE Although adults with schizophrenia have a significantly increased risk of premature mortality, sample size limitations of previous research have hindered the identification of the underlying causes. OBJECTIVE To describe overall and cause-specific mortality rates and standardized mortality ratios (SMRs) for adults with schizophrenia compared with the US general population. DESIGN, SETTING, AND PARTICIPANTS We identified a national retrospective longitudinal cohort of patients with schizophrenia 20 to 64 years old in the Medicaid program (January 1, 2001, to December 31, 2007). The cohort included 1,138,853 individuals, 4,807,121 years of follow-up, and 74,003 deaths, of which 65,553 had a known cause. MAIN OUTCOMES AND MEASURES Mortality ratios for the schizophrenia cohort standardized to the general population with respect to age, sex, race/ethnicity, and geographic region were estimated for all-cause and cause-specific mortality. Mortality rates per 100,000 person-years and the mean years of potential life lost per death were also determined. Death record information was obtained from the National Death Index. RESULTS Adults with schizophrenia were more than 3.5 times (all-cause SMR, 3.7; 95% CI, 3.7-3.7) as likely to die in the follow-up period as were adults in the general population. Cardiovascular disease had the highest mortality rate (403.2 per 100,000 person-years) and an SMR of 3.6 (95% CI, 3.5-3.6). Among 6 selected cancers, lung cancer had the highest mortality rate (74.8 per 100,000 person-years) and an SMR of 2.4 (95% CI, 2.4-2.5). Particularly elevated SMRs were observed for chronic obstructive pulmonary disease (9.9; 95% CI, 9.6-10.2) and influenza and pneumonia (7.0; 95% CI, 6.7-7.4). Accidental deaths (119.7 per 100,000 person-years) accounted for more than twice as many deaths as suicide (52.0 per 100,000 person-years). Nonsuicidal substance-induced death, mostly from alcohol or other drugs, was also a leading cause of death (95.2 per 100,000 person-years). CONCLUSIONS AND RELEVANCE In a US national cohort of adults with schizophrenia, excess deaths from cardiovascular and respiratory diseases implicate modifiable cardiovascular risk factors, including especially tobacco use. Excess deaths directly attributable to alcohol or other drugs highlight threats posed by substance abuse. More aggressive identification and management of cardiovascular risk factors, as well as reducing tobacco use and substance abuse, should be leading priorities in the medical care of adults with schizophrenia.

Stimulants and Cardiovascular Events in Youth with Attention-Deficit/Hyperactivity Disorder

OBJECTIVE This study examined associations between stimulant use and risk of cardiovascular events and symptoms in youth with attention-deficit/hyperactivity disorder and compared the risks associated with methylphenidate and amphetamines. METHOD Claims were reviewed of privately insured young people 6 to 21 years old without known cardiovascular risk factors (n = 171,126). A day-level cohort analysis evaluated the risk of cardiovascular events after a diagnosis of attention-deficit/hyperactivity disorder in relation to stimulant exposures. Based on filled stimulant prescriptions, follow-up days were classified as current, past, and no stimulant use. Endpoints included an emergency department or inpatient diagnosis of angina pectoris, cardiac dysrhythmia, or transient cerebral ischemia (cardiac events) or tachycardia, palpitations, or syncope (cardiac symptoms). RESULTS There were 0.92 new cardiac events and 3.08 new cardiac symptoms per 1,000,000 days of current stimulant use. Compared with no stimulant use (reference group), the adjusted odds ratios of cardiac events were 0.69 (95% confidence interval 0.42-1.12) during current stimulant use and 1.18 (95% CI 0.83-1.66) during past stimulant use. The corresponding adjusted odds ratios for cardiac symptoms were 1.18 (95% CI 0.89-1.59) for current and 0.93 (95% CI 0.71-1.21) for past stimulant use. No significant differences were observed in risks of cardiovascular events (2.14, 95% CI 0.82-5.63) or symptoms (1.08, 95% CI 0.66-1.79) for current methylphenidate use compared with amphetamine use (reference group). CONCLUSIONS Clinical diagnoses of cardiovascular events and symptoms were rare and not associated with stimulant use. The results help to allay concerns over the cardiovascular safety of stimulant treatment for attention-deficit/hyperactivity disorder in young people without known pre-existing risk factors.

Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia.

OBJECTIVE The authors compared the effectiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with evidence of treatment-resistant schizophrenia in routine clinical practice. METHOD U.S. national Medicaid data from 2001 to 2009 were used to examine treatment outcomes in a cohort of patients with schizophrenia and evidence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched cohort that initiated a standard antipsychotic (N=3,123). Interventions were new initiation of clozapine or a standard antipsychotic medication, defined as no exposure to the new medication in the prior 365 days. The primary outcome was hospital admission for a mental disorder. Secondary outcomes included discontinuation of the index antipsychotic, use of an additional antipsychotic, incidence of serious medical conditions, and mortality. RESULTS Initiation of clozapine was associated with a significantly decreased rate of psychiatric hospital admission (hazard ratio=0.78, 95% CI=0.69-0.88), index antipsychotic discontinuation (hazard ratio=0.60, 95% CI=0.55-0.65), and use of an additional antipsychotic (hazard ratio=0.76, 95% CI=0.70-0.82). Clozapine was associated with significantly increased incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ratio=1.63, 95% CI=0.98-2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ratio=1.40, 95%CI=1.09-1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ratio=2.50, 95% CI=0.97-6.44). CONCLUSIONS In adults with schizophrenia and evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsychotic was associated with greater effectiveness on several important outcomes. Increasing the judicious use of clozapine is warranted together with vigilance to prevent and detect serious medical adverse effects.

The asian pharmacoepidemiology network (AsPEN): Promoting multi-national collaboration for pharmacoepidemiologic research in Asia

Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden Medical Research Collaborating Center, Seoul National University Hospital/Seoul National University College of Medicine, Seoul, South Korea Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA Department of Medicine, Division of Pharmacoepidemiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA Department of Medical Informatics, School of Medicine, Hamamatsu University, Shizuoka, Japan Department of Pharmacoepidemiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Institute of Clinical Pharmacy and Pharmaceutical Sciences, and Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan Department of Preventative Medicine, College of Medicine, Seoul National University, Seoul, South Korea Korea Institute of Drug Safety and Risk Management, Seoul, South Korea Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia Duke Clinical Research Institute, Durham, NC, USA Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Karolinska University Hospital, Stockholm, Sweden Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, South Korea Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA

Multi-country rapid adverse drug event assessment: the Asian Pharmacoepidemiology Network (AsPEN) antipsychotic and acute hyperglycaemia study.

To undertake a multi‐country study to investigate the risk of acute hyperglycaemia with antipsychotic use.

Patterns and Correlates of Tic Disorder Diagnoses in Privately and Publicly Insured Youth

OBJECTIVE This study examined the prevalence and demographic and clinical correlates of children diagnosed with Tourette disorder, chronic motor or vocal tic disorder, and other tic disorders in public and private insurance plans over the course of a 1-year period. METHOD Claims were reviewed of Medicaid (n = 10,247,827) and privately (n = 16,128,828) insured youth (4-18 years old) focusing on tic disorder diagnoses during a 1-year period. Rates are presented for children with each tic disorder diagnosis overall and stratified by demographic characteristics and co-identified mental disorders. Mental health service use, including medications prescribed, and co-existing psychiatric disorders were also examined. RESULTS In Medicaid-insured children, rates of diagnosis per 1,000 were 0.53 (95% confidence interval [CI] 0.51-0.55) for Tourette disorder, 0.08 (95% CI 0.07-0.08) for chronic motor or vocal tic disorder, and 0.43 (95% CI 0.41-0.44) for other tic disorders. In privately insured children, comparable rates were 0.50 (95% CI 0.49-0.52), 0.10 (95% CI 0.10-0.11), and 0.59 (95% CI 0.58-0.61). In 1 year, children diagnosed with tic disorders also frequently received other psychiatric disorder diagnoses. Compared with privately insured youth, children under Medicaid diagnosed with Tourette disorder had higher rates of attention-deficit/hyperactivity disorder (50.2% versus 25.9%), other disruptive behavior (20.6% versus 5.6%), and depression (14.6% versus 9.8%) diagnoses and higher rates of antipsychotic medication use (53.6% versus 33.2%). CONCLUSIONS Despite similarities in annual rates of tic disorder diagnoses in publicly and privately insured children, important differences exist in patient characteristics and service use of publicly and privately insured youth who are diagnosed with tic disorders.

Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study

BackgroundLithium inhibits glycogen synthase kinase-3, an enzyme implicated in the pathogenesis of dementia.AimsTo examine the association of lithium and dementia risk in a large claims-based US cohort of publicly insured older adults with bipolar disorder.MethodThe cohort included individuals ≥50 years diagnosed with bipolar disorder who did not receive dementia-related services during the prior year. Each follow-up day was classified by past-year cumulative duration of lithium use (0, 1-60, 61-300 and 301-365 days). Dementia diagnosis was the study outcome. Anticonvulsants commonly used as mood stabilisers served as a negative control.ResultsCompared with non-use, 301-365 days of lithium exposure was associated with significantly reduced dementia risk (hazard ratio (HR) = 0.77, 95% CI 0.60-0.99). No corresponding association was observed for shorter lithium exposures (HR = 1.04, 95% CI 0.83-1.31 for 61-300 days; HR = 1.07, 95% CI 0.67-1.71 for 1-60 days) or for any exposure to anticonvulsants.ConclusionsContinuous lithium treatment may reduce dementia risk in older adults with bipolar disorder.

Pre-existing cardiovascular conditions and pharmacological treatment of adult ADHD†‡

Stimulants and atomoxetine should generally not be used or used only with caution in adults with pre‐existing cardiovascular conditions. The extent to which pre‐existing cardiovascular conditions influence initiation of these ADHD medications in adults is not known.

The Quality of Medication Treatment for Mental Disorders in the Department of Veterans Affairs and in Private-Sector Plans

OBJECTIVE The quality of mental health care provided by the U.S. Department of Veterans Affairs (VA) was compared with care provided to a comparable population treated in the private sector. METHODS Two cohorts of individuals with mental disorders (schizophrenia, bipolar disorder, posttraumatic stress disorder, major depression, and substance use disorders) were created with VA administrative data (N=836,519) and MarketScan data (N=545,484). The authors computed VA and MarketScan national means for seven process-based quality measures related to medication evaluation and management and estimated national-level performance by age and gender. RESULTS In every case, VA performance was superior to that of the private sector by more than 30%. Compared with individuals in private plans, veterans with schizophrenia or major depression were more than twice as likely to receive appropriate initial medication treatment, and veterans with depression were more than twice as likely to receive appropriate long-term treatment. CONCLUSIONS Findings demonstrate the significant advantages that accrue from an organized, nationwide system of care. The much higher performance of the VA has important clinical and policy implications.