Vinod S. Bhatara

Association of Attention Deficit Hyperactivity Disorder and Gestational Alcohol Exposure: An Exploratory Study.

Objective and methods: To explore association between prevalence of ADHD and levels of risk for gestational alcohol exposure, the authors reviewed the charts of 2,231 youth referred for fetal alcohol spectrum disorders. Participants were categorized into four groups by different levels of risk for gestational alcohol exposure. For each group, the prevalence rates of ADHD and other selected disorders were determined. Results: The disorder ranking first in overall prevalence was ADHD (41%), followed by learning disorder (17%) and oppositional-defiant/conduct disorder (16%). Prevalence rates of ADHD across the groups generally were high risk > some risk > unknown risk > no risk. Conclusion: The frequency distribution of ADHD cases was according to the levels of risk for gestational alcohol exposure. These results add to a growing body of evidence supporting an association between ADHD and prenatal alcohol exposure. Findings need to be confirmed by definitive studies on ADHD and gestational alcohol exposure.

Patterns and determinants of antipsychotic prescribing in children and adolescents, 2003–2004

ABSTRACT Objectives: This study examined patterns and determinants of antipsychotic prescribing in children and adolescents receiving outpatient care in the United States. Methods: Antipsychotic prescribing practices for patients younger than 20 years were examined using the 2003–2004 National Ambulatory Medical Care Survey and the outpatient department portion of the 2003–2004 National Hospital Ambulatory Medical Care Survey. The analysis focused on outpatient visits involving 11 typical and six atypical antipsychotic agents. National visit estimates were used to characterize the nature and extent of antipsychotic prescribing for patients younger than 20 years. Multiple logistic regression analysis was applied to visits involving children and adolescents to examine the need, predisposing, and enabling factors associated with antipsychotic prescribing. Results: Antipsychotic medications were prescribed in two million outpatient visits annually involving children and adolescents, representing 1% of overall visits by children and adolescents in 2003–2004. Most (99%) of these visits involved prescribing of atypical agents. The most frequently prescribed atypical agents were risperidone, quetiapine, and aripiprazole. The majority of the visits involving antipsychotic medications in children were seen in patients over 9 years, males, and whites. Factors positively associated with antipsychotic prescribing in children and adolescents included age over 9 years, diagnoses (bipolar disorder, psychoses, depression, disruptive behavior, and anxiety), and visits to specialists. Private insurance was negatively associated with antipsychotic prescribing. Conclusions: Although the findings were based on cross-sectional analyses of outpatient visit data, the study revealed that atypical antipsychotic medications are being commonly and extensively prescribed to children and adolescents despite the relatively limited scientific evidence to support their pediatric use. Well-designed studies are urgently needed in children and adolescents to address atypical antipsychotic use for a variety of psychiatric disorders.

Mood stabilizers in children and adolescents.

OBJECTIVE The efficacy of mood stabilizers in children and adolescents has not been studied adequately. This article will review existing studies and highlight some important issues in designing future studies on these agents. METHOD Electronic databases including Medline, Psycholnfo, and CRISP were searched for data in children receiving compounds that have mood-stabilizing properties in adults. RESULTS Some open clinical data and an extremely modest amount of controlled research data suggest lithium, carbamazepine, and valproate may be effective mood stabilizers in children and adolescents. There are no controlled data on other potential mood stabilizers in children. CONCLUSIONS The disorders that may be responsive to mood stabilizers are among the most morbid in child psychiatry. More studies are needed to clarify the efficacy of these compounds in children and adolescents and to provide a rational basis for choosing among them.

National trends in concomitant psychotropic medication with stimulants in pediatric visits: Practice versus knowledge

Objectives: (1) To examine U.S. national trends in the use of concomitant pharmacotherapy with the stimulant class of psychotropic drugs in youth; and (2) to present these trends in the context of (a) extant safety and efficacy data, and (b) overall trends in concomitant pharmacotherapy with psychotropic drugs for youth. Methods: Prescribing data for youths under age 18 years from National Ambulatory Medical Surveys from 1993 to 1998 were analyzed. The visits were categorized into monotherapy (only one psychotropic prescribed) and concomitant pharmacotherapy (>1 psychotropic prescribed). The proportions of these groups were computed as a percentage of all visits during which a psychotropic medication was prescribed. Differences in proportions between surveys were analyzed to determine trends. Results: Between 1993-94 and 1997-98, the proportions of visits for concomitant pharmacotherapy in association with the stimulant class increased nearly five-fold. This increase paralleled an overall increase in the proportion of visits involving prescription of more than one psychotropic medication among youth. Conclusions: The growth in concomitant pharmacotherapy with the stimulants class has out-paced the increase in safety/efficacy data to inform the use of this practice, resulting in a mismatch between trends in prescribing and growth in knowledge. A simultaneous trend of note is the overall increase in the use of concomitant pharmacotherapy with all psychotropic drugs in youth. Controlled trials are particularly needed to support commonly used combinations of stimulants with antidepressants in youth. In the absence of definitive data, clinical guidelines based on expert consensus and limited data are available and are useful.

Resistance To Thyroid Hormone: Implications for Neurodevelopmental Research On the Effects of Thyroid Hormone Disruptors

Thyroid hormones are essential for normal behavioral, intellectual, and neurological development. Congenital hypothyroidism, if not treated, can result in irreversible mental retardation, whereas thyroid diseases with more moderate impairment of thyroid function, such as resistance to thyroid hormone, cause less severe intellectual and behavioral abnormalities, including attention deficit hyperactivity disorder. There is increasing evidence that exposure to certain synthetic compounds, including dioxins and polychlorinated biphenyls (PCBs), during the perinatal period can also impair learning, memory, and attentional processes in offspring. Animal and human studies suggest that exposure to these environmental toxicants impair normal thyroidfunction. Although the precise mechanisms of action of the adverse effects these toxicants have on neurodevelopment have not yet been elucidated, it is possible that they are partially or predominantly mediated by alterations in hormone binding to the thyroid hormone receptor. The convergence of studies that examine the neurodevelopmental consequences of moderate impairment of thyroid function, such as is found in resistance to thyroid hormone, with those studies that demonstrate the adverse behavioral and cognitive effectsof perinatal exposure to dioxins and PCBs serves to generate new hypotheses to test in a research setting. Such studies may provide new insights into the basic pathogenesis of developmental neurotoxicity following exposure to thyroid-disrupting synthetic compounds.

Concomitant antipsychotic prescribing in US outpatient settings

BACKGROUND Clinicians use concomitant antipsychotic therapy for management of psychotic disorders despite a paucity of evidence for this practice. OBJECTIVE To examine national patterns and determinants of concomitant antipsychotic therapy. METHODS Concomitant antipsychotic therapy was defined as simultaneous use of 2 or more antipsychotic agents. Prescription data from the 2003-2004 National Ambulatory Medical Care Survey and the outpatient department portion of the 2003-2004 National Hospital Ambulatory Medical Care Survey were used to characterize the prescribing of concomitant antipsychotic therapy and antipsychotic monotherapy (defined as use of a typical or atypical agent). Multiple logistic regression was applied to antipsychotic visits to examine the determinants of concomitant antipsychotic therapy based on patient and provider characteristics. RESULTS Overall, concomitant antipsychotic therapy was documented in 9% of the visits involving antipsychotic agents, and monotherapy in 91% of the visits. The use of atypical agents, namely risperidone, olanzapine, and quetiapine, was common in both forms of therapy. Concomitant therapy was frequently used for psychoses and bipolar disorder. Logistic regression revealed that the odds of receiving concomitant antipsychotic therapy were higher for patients younger than 65 years, with greatest odds (odds ratio=6.52) for patients 40 to 64 years old. Having a diagnosis of psychosis quadrupled (odds ratio=4.33) the odds of receiving concomitant antipsychotic therapy. Physicians in metropolitan areas were more likely (odds ratio=2.17) to use concomitant antipsychotic therapy than physicians in non-metropolitan areas. CONCLUSIONS Concomitant antipsychotic therapy continues to be prevalent and extensive in outpatient settings. With the use of concomitant antipsychotic therapy as a quality of care measure, there is a need to optimize prescribing of these potent combinations.

A Review of the Case for Neonatal Thyrotropin Screening in Developing Countries: The Example of India

BACKGROUND Infantile hypothyroidism, either caused by iodine-deficiency disorder (IDD) or congenital hypothyroidism (CH), is the worlds leading cause of preventable mental retardation. Such hypothyroidism has virtually been eliminated in the developed world by salt iodization and neonatal thyroid screening. However, most developing countries do not have neonatal thyroid screening programs. Using India as an example, we review the case for newborn screening in the developing world. METHODS A literature review on infantile hypothyroidism in India was conducted and three Indian thyroid experts were queried about their views on neonatal screening in India. RESULTS Iodine nutrition improved markedly in India during the 1990s; 49% of the households are now using adequately iodized salt. The control of IDD is still insufficient in India. Nationally representative data on neonatal screening in India are not available, but two regional studies have been published. One study (n = 12,407) measured cord blood thyrotropin and the other (n = 25,244) measured filter paper thyroxine. These studies reported difficult socioeconomic and organizational barriers to the implementation of neonatal screening in India. DISCUSSION It is time for India to make neonatal thyroid screening and mandatory iodization of salt a priority and develop a comprehensive infantile hypothyroidism policy. Prioritization of infantile hypothyroidism prevention is justified by its high frequency, sensitivity of screening in detecting both IDD and CH, adverse consequences of missing diagnosis at birth, high effectiveness of prevention, severity of disability from hypothyroidism, cost effectiveness of prevention, and lack of a clinical method of diagnosis near birth.

Concurrent Use of Stimulants and Second-Generation Antipsychotics Among Children With ADHD Enrolled in Medicaid

OBJECTIVE This study examined the prevalence of and factors associated with concurrent use of long-acting stimulants (LAS) and second-generation antipsychotic agents among children and adolescents with attention-deficit hyperactivity disorder (ADHD). METHODS The study involved retrospective longitudinal analysis of 2003-2007 Medicaid data from four states for children and adolescents between the ages of six and 17 years who were diagnosed as having ADHD and initiated LAS treatment. Concurrent use of LAS and second-generation antipsychotic medications was defined as simultaneous receipt of both medications for at least 14 days. On the basis of the conceptual framework of the Andersen behavioral model, multivariable logistic regression analysis was used to examine predisposing, enabling, and need factors associated with concurrent use. RESULTS Among the 61,793 children who initiated LAS treatment for ADHD, 11,866 (19.2%) received LAS and second-generation antipsychotics concurrently for at least 14 days. Overall, the average length of concurrent use was 130±98 days. Multivariable logistic regression revealed that concurrent use was higher among boys, blacks, and foster care children compared with their respective counterparts. Comorbid psychiatric conditions, including disorders that are not approved indications for second-generation antipsychotic use, were associated with concurrent use of LAS and second-generation antipsychotics. CONCLUSIONS Almost one in five children and adolescents who initiated LAS also received second-generation antipsychotics concurrently for at least 14 days. Approved and nonapproved indications of second-generation antipsychotics influenced concurrent use in pediatric ADHD.

Pharmacotherapy with Atomoxetine for US Children and Adolescents

BACKGROUND Atomoxetine, a non-stimulant medication, was approved for treatment of Attention Deficit/ Hyperactivity Disorder (ADHD) in 2002. However, there is a paucity of recent practice-based national data on the use of atomoxetine. This article compares the use of atomoxetine with that of stimulant medications in outpatient treatment of U.S. children and adolescents, and examines the predictors of atomoxetine use in this population. METHODS The 2003-2004 National Ambulatory Medical Care Survey and the outpatient department portion of the 2003-2004 National Hospital Ambulatory Medical Care Survey were used to determine the utilization of atomoxetine and stimulants in youth<20 years. Bivariate analyses were used to examine the use of atomoxetine relative to that of stimulant medications in children and adolescents (n=1,133). Multiple logistic regression analysis was applied to visits involving youths with ADHD to examine predictors of atomoxetine use (n=1,361). RESULTS An estimated 14.51 million visits involving psychotropic agents resulted in prescription of atomoxetine and stimulants during the years 2003 and 2004. The percentage of visits for atomoxetine, as a proportion of all psychotropic visits, was nearly 10% (versus 40% for stimulants). Analyses of visits involving atomoxetine and stimulants revealed age- and region-based differences in the use of atomoxetine. Among children with ADHD, approximately 15% of outpatient visits resulted in prescription of atomoxetine; and stimulant medications were prescribed in nearly 61% of these visits. Examination of predictors of ADHD treatments (atomoxetine vs. stimulants) revealed no variations in the use of atomoxetine across sex, race, psychiatric comorbidity, primary care status, and metropolitan location. However, atomoxetine was preferred in 10-to-14 year old children, and in patients with private insurance. Physicians in the Northeast region were less likely to prescribe atomoxetine than physicians in the South. CONCLUSIONS Although stimulant drugs remain the most frequently prescribed class of psychotropic medications for ADHD in children and adolescents, atomoxetine has emerged as the leading stimulant alternative. Preferential use of atomoxetine in age group 10-to-14 years needs to be further evaluated. Additionally, the role of several factors, including patient preferences, physician-related factors, and psychiatric comorbidity warrant further investigation. Data on differential safety and efficacy of atomoxetine and stimulants are needed to optimize pharmacotherapy in children.

Health care consequences of black-box warnings for antidepressants in the United States and Canada.

Health care consequences of black-box warnings for antidepressants in the United States and Canada Saurabh Nagar, B.Pharm., Sandhya Mehta, B.Pharm., Vinod Bhatara, M.D., M.S., Rajender Aparasu, M. Pharm., Ph.D.* Department of Clinical Sciences and Administration, College of Pharmacy, University of Houston, Texas Medical Center, 1441, Moursund Street, Houston, TX 77030-3407, USA University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57105