Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008.

OBJECTIVE: This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices. METHODS: Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007. RESULTS: In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies-clonidine, guanfacine, and bupropion-was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing. CONCLUSIONS: FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit.

Trends in attention deficit hyperactivity disorder ambulatory diagnosis and medical treatment in the United States, 2000-2010.

OBJECTIVES: Because of several recent clinical and regulatory changes regarding attention deficit-hyperactivity disorder (ADHD) in the United States, we quantified changes in the diagnosis of ADHD and its pharmacologic treatment from 2000 through 2010. METHODS: We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to examine aggregate trends among children and adolescents younger than 18 years of age. We also quantified how diagnosis and treatment patterns have evolved on the basis of patient and physician characteristics and the therapeutic classes used. RESULTS: From 2000 to 2010, the number of physician outpatient visits in which ADHD was diagnosed increased 66% from 6.2 million (95% confidence interval 5.5-6.9M) to 10.4 million visits (95% confidence interval 9.3-11.6 million). Of these visits, psychostimulants have remained the dominant treatment; they were used in 96% of treatment visits in 2000 and 87% of treatment visits in 2010. Atomoxetine use decreased from 15% of treatment visits upon product launch in 2003 to 6% of treatment visits by 2010. The use of potential substitute therapies-clonidine, guanfacine, and bupropion-remained relatively constant (between 5% and 9% of treatment visits) during most of the period examined. During this period, the management of ADHD shifted away from pediatricians and towards psychiatrists (from 24% to 36% of all visits) without large changes in illness severity or the proportion of ADHD treatment visits accounted for by males (73%-77%). CONCLUSIONS: In 10 years, the ambulatory diagnosis of ADHD increased by two-thirds and is increasingly managed by psychiatrists. The effects of these changing treatment patterns on children's health outcomes and their families are unknown.

Impact of FDA drug risk communications on health care utilization and health behaviors: a systematic review.

OBJECTIVE: To review literature on the impact of The Food and Drug Administration (FDA) drug risk communications on medication utilization, health care services use, and health outcomes. DATA SOURCES: The authors searched MEDLINE and the Web of Science for manuscripts published between January 1990 and November 2010 that included terms related to drug utilization, the FDA, and advisories or warnings. We manually searched bibliographies and works citing selected articles and consulted with experts to guide study selection. STUDY SELECTION: Studies were included if they involved an empirical analysis evaluating the impact of an FDA risk communication. DATA EXTRACTION: We extracted the drug(s) analyzed, relevant FDA communication(s), data source, analytical method, and main outcome(s) assessed. RESULTS: Of the 1432 records screened, 49 studies were included. These studies covered 16 medicines or therapeutic classes; one third examined communications regarding antidepressants. Most used medical or pharmacy claims and a few rigorously examined patient-provider communication, decision making, or risk perceptions. Advisories recommending increased clinical or laboratory monitoring generally led to decreased drug use, but only modest, short-term increases in monitoring. Communications targeting specific subpopulations often spilled over to other groups. Repeated or sequential advisories tended to have larger but delayed effects and decreased incident more than prevalent use. Drug-specific warnings were associated with particularly large decreases in utilization, although the magnitude of substitution within therapeutic classes varied across clinical contexts. CONCLUSIONS: Although some FDA drug risk communications had immediate and strong impacts, many had either delayed or had no impact on health care utilization or health behaviors. These data demonstrate the complexity of using risk communication to improve the quality and safety of prescription drug use, and suggest the importance of continued assessments of the effect of future advisories and label changes. Identifying factors that are associated with rapid and sustained responses to risk communications will be important for informing future risk communication efforts.

Trends in use of second-generation antipsychotics for treatment of bipolar disorder in the United States, 1998-2009.

OBJECTIVE: The authors examined trends in the use of second-generation antipsychotics for treatment of bipolar disorder before and after the U.S. Food and Drug Administration's approval in 2000 of olanzapine for use in treating acute manic episodes of bipolar disorder. METHODS: The IMS Health National Disease and Therapeutic Index was used to derive monthly patient treatment visits between January 1998 and December 2009 by individuals 18 and older with a diagnosis of bipolar disorder who were treated with one or more pharmacotherapies. RESULTS: The percentage of treatment visits in which a second-generation antipsychotic was prescribed increased from 18% in 1998 to 49% in 2009. Use of mood stabilizers and first-generation antipsychotics declined substantially. In the 12 months after approval of olanzapine for bipolar disorder, its use increased by 92%, and use of other second-generation antipsychotics increased by 42%. CONCLUSIONS: Second-generation antipsychotics are increasingly used for bipolar disorder, and their effectiveness compared with therapeutic alternatives merits further research.

National trends in ambulatory asthma treatment, 1997-2009.

BACKGROUND: Despite reductions in morbidity and mortality and changes in guidelines, little is known regarding changes in asthma treatment patterns. OBJECTIVE: To examine national trends in the office-based treatment of asthma between 1997 and 2009. PARTICIPANTS AND DESIGN: We used the National Ambulatory Care Survey (NAMCS) and the National Disease and Therapeutic Index™ (NDTI), nationally representative audits of office-based physicians, to examine patients diagnosed with asthma less than 50 years of age. MEASUREMENTS: Visits where asthma was diagnosed and use of six therapeutic classes (short-acting ß(2) agonists [SABA], long-acting ß(2) -agonists [LABA], inhaled steroids, antileukotrienes, anticholinergics, and xanthines). RESULTS: Estimates from NAMCS indicated modest increases in the number of annual asthma visits from 9.9 million [M] in 1997 to 10.3M during 2008; estimates from the NDTI suggested more gradual continuous increases from 8.7M in 1997 to 12.6M during 2009. NAMCS estimates indicated declines in use of SABAs (from 80% of treatment visits in 1997 to 71% in 2008), increased inhaled steroid use (24% in 1997 to 33% in 2008), increased use of fixed dose LABA/steroid combinations (0% in 1997 to 19% in 2008), and increased leukotriene use (9% in 1997 to 24% in 2008). The ratio of controller to total asthma medication use increased from 0.5 (1997) to a peak of 0.7 (2004). In 2008, anticholinergics, xanthines, and LABA use without concomitant steroids accounted for fewer than 4% of all treatment visits. Estimates from NDTI corroborated these trends. CONCLUSIONS: Changes in office-based treatment, including increased inhaled steroid use and increased combined steroid/long-acting ß(2)-agonist use coincide with reductions in asthma morbidity and mortality that have been demonstrated over the same period. Xanthines, anticholinergics, and increasingly, LABA without concomitant steroid use, account for a very small fraction of all asthma treatments.

Maternal Schistosomiasis japonica is associated with maternal, placental, and fetal inflammation.

Schistosomes infect ∼40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial in Schistosoma mansoni did not detect this association. We conducted an observational study among 99 pregnant women living in an area of Schistosoma japonicum endemicity in the Philippines. We enrolled women at 32 weeks gestation and measured S. japonicum and geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1ß), and cord (IL-1ß and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1ß, and TNF-α production by syncytiotrophoblasts was independently associated with decreased birth weight (both P < 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.