Attention-deficit/hyperactivity Disorder Drugs Research Articles

Micronutrients and Diets in the Treatment of Attention-Deficit/Hyperactivity Disorder: Chances and Pitfalls.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric diagnoses in childhood and adolescence. It is characterized by age-inappropriate levels of inattention, impulsivity, and hyperactivity and is associated with long-term academic, social, and mental health problems (1, 2). Both pharmacotherapy and behavior therapy yield short-term symptom reduction in individuals with ADHD. Psychostimulants, in particular, have been shown to improve attention and to decrease activity levels in children in the short term. However, their impact on academic performance and quality of life is low (3, 4), and initial symptomatic effects are not usually sustained on long-term follow-up (5, 6). The unproven long-term efficacy of commonly used ADHD drugs, together with concerns in regard to adverse effects of medication, which can be as serious as growth retardation and severe cardiovascular events (7, 8), has led to a search for alternative treatment options.

Illicit Stimulant Use among Medical Students in Riyadh, Saudi Arabia.

This study aims to assess the prevalence of illicit use of stimulants and attention deficit hyperactivity disorder (ADHD) among a sample of medical students at the main universities in Riyadh, Saudi Arabia and their motivation for use. We examine the association between the use of stimulants and the students' academic performance. We also look into the possible adverse consequences of illicit stimulant use among students.The competitive nature of medical school might place the students at a higher risk of using stimulant drugs illicitly. Acquiring these stimulants illegally has become easier since the diagnosis and treatment of ADHD have risen. We are unaware of any other study exploring the prevalence of and motivation for illicit use of stimulants among medical students in Riyadh.A cross-sectional web-based survey was the study design we chose as we were targeting medical students in three governmental medical colleges in Riyadh, Saudi Arabia. The total sample population of 1,177 participants was divided into the three following groups: no previous use of stimulant drugs (Group 1), illicit use (Group 2), and medical use (Group 3). Of the 1,177 medical students, 29 (2.46%) were found to be using stimulants illicitly; 39 (3.31%) were using the stimulants medically as they had been diagnosed with ADHD. The ability to prolong study time was reported as the most common motive for illicit use by many students.The present study contributes to the literature by casting light on this serious issue in Riyadh. More educational effort is needed to promote awareness about the adverse effects of ADHD drugs and their illicit use among students.

Regional analysis of UK primary care prescribing and adult service referrals for young people with attention-deficit hyperactivity disorder.

Approximately 20% of children with attention-deficit hyperactivity disorder (ADHD) experience clinical levels of impairment into adulthood. In the UK, there is a sharp reduction in ADHD drug prescribing over the period of transition from child to adult services, which is higher than expected given estimates of ADHD persistence, and may be linked to difficulties in accessing adult services. Little is currently known about geographical variations in prescribing and how this may relate to service access. To analyse geographic variations in primary care prescribing of ADHD medications over the transition period (age 16-19 years) and adult mental health service (AMHS) referrals, and illustrate their relationship with UK adult ADHD service locations. Using a Clinical Practice Research Datalink cohort of people with an ADHD diagnosis aged 10-20 in 2005 (study period 2005-2013; n = 9390, 99% diagnosed <18 years), regional data on ADHD prescribing over the transition period and AMHS referrals, were mapped against adult ADHD services identified in a linked mapping study. Differences were found by region in the mean age at cessation of ADHD prescribing, range 15.8-17.4 years (P<0.001), as well as in referral rates to AMHSs, range 4-21% (P<0.001). There was no obvious relationship between service provision and prescribing variation. Clear regional differences were found in primary care prescribing over the transition period and in referrals to AMHSs. Taken together with service mapping, this suggests inequitable provision and is important information for those who commission and deliver services for adults with ADHD.

Clinically Significant Drug-Drug Interactions with Agents for Attention-Deficit/Hyperactivity Disorder.

This article provides an overview of the pharmacokinetic drug-drug interactions (DDIs) for agents prescribed for attention-deficit/hyperactivity disorder (ADHD). Polypharmacy in the treatment of patients with ADHD leads to high exposures to DDIs and possibly adverse safety outcomes. We performed a systematic search of DDI reports for ADHD agents in Embase and Medline. We also searched for agents in the pharmacological pipeline, which include (1) mazindol, molindone and viloxazine, which were previously prescribed for other indications; (2) centanafadine and AR-08, never before approved; and (3) two extracts (Polygala tenuifolia extract and the French maritime pine bark extracts). The identified literature included case reports, cross-sectional, cross-over and placebo-controlled studies of patient cohorts and healthy volunteers. The DDIs were classified as follows: ADHD agents acting as perpetrators, i.e., affecting the clearance of co-prescribed agents (victim drugs), or ADHD agents being the victim drugs, being affected by other agents. Ratios for changes in pharmacokinetic parameters before and after the DDI were used as a rough estimate of the extent of the DDI. Alcohol may increase plasma dextroamphetamine concentrations by presystemic effects. Until studies are done to orient clinicians regarding dosing changes, clinicians need to be aware of the potential for cytochrome P450 (CYP) 2D6 inhibitors to increase amphetamine levels, which is equivalent to increasing dosages. Atomoxetine is a wide therapeutic window drug. The CYP2D6 poor metabolizers who do not have CYP2D6 activity had better atomoxetine response, but also an increased risk of adverse effects. CYP2D6 inhibitors have been used to increase atomoxetine response in CYP2D6 extensive metabolizers. Guanfacine is mainly metabolized by CYP3A4, which can be induced and inhibited. The package insert recommends that in guanfacine-treated patients, after adding potent CYP3A4 inducers, the guanfacine dose should be doubled; after adding potent CYP3A4 inhibitors the guanfacine dose should be halved. Based on a phenobarbital case report and our experience with CYP3A4-metabolized antipsychotics, these correction factors may be too low. According to two case reports, carbamazepine is a clinically relevant inducer of methylphenidate (MPH). A case series study suggested that MPH may be associated with important elevations in imipramine concentrations. Due to the absence of or limitations in the data, no comments for clinicians can be provided on the pharmacokinetic DDIs for clonidine, centanafadine, mazindol, molindone, AR-08, P. tenuifolia extract and the French maritime pine bark extracts. According to currently available data, clinicians should not expect that ADHD drugs modify each other's serum concentrations. A summary table for clinicians provides our current recommendations on pharmacokinetic DDIs of ADHD agents based on our literature review and the package inserts; whenever it was possible, we provide information on serum concentrations and dose correction factors. There will be a need to periodically update these recommendations and these correction factors as new knowledge becomes available.

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.

Druggable genome in attention deficit/hyperactivity disorder and its co-morbid conditions. New avenues for treatment

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with only symptomatic care available. Genome-wide association (GWA) studies can provide a starting point in the search for novel drug targets and possibilities of drug repurposing. Here, we explored the druggable genome in ADHD by utilising GWA studies on ADHD and its co-morbid conditions. First, we explored whether the genes targeted by current ADHD drugs show association with the disorder and/or its co-morbidities. Second, we aimed to identify genes and pathways involved in the biological processes underlying ADHD that can be targeted by pharmacological agents. These ADHD-associated druggable genes and pathways were also examined in co-morbidities of ADHD, as commonalities in their aetiology and management may lead to novel pharmacological insights. Strikingly, none of the genes encoding targets of first-line pharmacotherapeutics for ADHD were significantly associated with the disorder, suggesting that FDA-approved ADHD drugs may act through different mechanisms than those underlying ADHD. In the examined druggable genome, three loci on chromosomes 1, 4 and 12 revealed significant association with ADHD and contained nine druggable genes, five of which encode established drug targets for malignancies, autoimmune and neurodevelopmental disorders. To conclude, we present a framework to assess the druggable genome in a disorder, exemplified by ADHD. We highlight signal transduction and cell adhesion as potential novel avenues for ADHD treatment. Our findings add to knowledge on known ADHD drugs and present the exploration of druggable genome associated with ADHD, which may offer interventions at the aetiological level of the disorder.

Cardiovascular Effects of Drugs Used to Treat Attention-Deficit/Hyperactivity Disorder: Part 1: Epidemiology, Pharmacology, and Impact on Hemodynamics and Ventricular Repolarization.

Attention-deficit/hyperactivity disorder (ADHD) is a clinical syndrome characterized by persistent inattention, impulsivity, and hyperactivity. It is most commonly encountered in children and adolescents but may persist into adulthood. A variety of psychostimulant and nonpsychostimulant medications have proven to be successful in reducing inattention, impulsivity, and hyperactivity in those with ADHD. Psychostimulants used to treat ADHD include methylphenidate and related drugs and various amphetamine preparations. Non-psychostimulant medications used to treat ADHD include atomoxetine and two alpha-2 adrenergic agonists: guanfacine extended-release and clonidine extended-release. The psychostimulants and atomoxetine have been shown, on average, to increase heart rate by 3-10 beats/min, systolic blood pressure by 3-8 mm Hg, and diastolic blood pressure by 2-14 mm Hg. These drugs may also delay ventricular repolarization. The alpha-2 adrenergic agonists may reduce heart rate and blood pressure. For these reasons, there is concern about the safety of psychostimulant and nonpsychostimulant medications in patients with ADHD. In part 1 of this review, we discuss the epidemiology and natural history of ADHD, describe the pharmacology of drugs used to treat ADHD, and discuss in detail studies assessing the effects of ADHD drugs on blood pressure, heart or pulse rate, and electrocardiographic indices of ventricular repolarization.

Potential Explanations for Increasing Methylphenidate Use in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder in Germany From 2004 to 2013.

Despite a decreasing population of children and adolescents, the cumulative total amount of dispensed methylphenidate (MPH), the first-choice treatment of attention-deficit/hyperactivity disorder (ADHD) in this age group, has increased dramatically in Germany. We investigated potential reasons for this increase such as changes in the ADHD prevalence over time and other potential explanations including the cumulative amount of dispensed MPH per person. Based on German claims data, we calculated standardized annual ADHD prevalence rates, proportions of ADHD cases treated with MPH and/or psychotherapy, and mean cumulative defined daily doses of ADHD drugs for 3- to 17-year-old children and adolescents from 2004 to 2013. The ADHD prevalence increased continuously from 2004 to 2011 and remained stable thereafter. In ADHD cases, there was little variation in the proportion of individuals treated with drugs and in the frequency of psychotherapeutic treatment during the whole study period. The annual cumulative mean amount of MPH defined daily doses increased by approximately 30% from 2004 to 2008. Our analyses suggest that the increase in MPH use in Germany was mainly influenced by an increasing ADHD prevalence and increasing amounts of dispensed MPH per person.

Associations between Attention-Deficit Hyperactivity Disorder (ADHD) Treatment and Patient Nutritional Status and Height.

Attention-deficit hyperactivity disorder (ADHD) has been found to co-occur frequently with obesity, although the reasons for this association are unknown. The aim of this study was to compare the nutritional profile of a Brazilian cohort of ADHD patients with that of the general population and to analyze the association between ADHD drug treatment (with methylphenidate), nutritional status, and height of these individuals. In the first phase of the study, we designed the nutritional and height profile of 93 ADHD patients (5.1 to 13.8 years old) and compared it to a control group. In the second phase, we analyzed the association of the use of methylphenidate with nutritional status and height. The results showed that the prevalence of overweight/obesity was statistically higher in the cohort of ADHD patients compared to controls (40.9% vs. 34.7%; P < 0.05). After treating ADHD patients with methylphenidate, a statistically significant decrease in the BMI z-score was observed (0.695 vs. 0.305; P < 0.01). On the other hand, no significant impact on height was detected after treatment (0.189 vs. 0.248; P = 0.298). In conclusion, the results suggest that the use of methylphenidate in patients who have ADHD and obesity is relevant not only for controlling ADHD symptoms but also for improving the nutritional status of these individuals. Moreover, the treatment did not affect the patients' height.

The Atxn7-overexpressing mice showed hyperactivity and impulsivity which were ameliorated by atomoxetine treatment: A possible animal model of the hyperactive-impulsive phenotype of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder characterized by varying levels of hyperactivity, inattention, and impulsivity. Patients with ADHD are often classified as (1) predominantly hyperactive-impulsive, (2) predominantly inattentive, and (3) combined type. There is a growing interest in developing specific animal models that would recapitulate specific clinical forms of ADHD, with the goal of developing specific therapeutic strategies. In our previous study, we have identified Ataxin-7 (Atxn7) as a hyperactivity-associated gene. Here, we generated Atxn7 overexpressing (Atxn7 OE) mice to investigate whether the increased Atxn7 expression in the brain correlates with ADHD-like behaviors. Quantitative real-time polymerase chain reaction and immunofluorescence confirmed overexpression of the Atxn7 gene and protein in the prefrontal cortex (PFC) and striatum (STR) of the Atxn7 OE mice. The Atxn7 OE mice displayed hyperactivity and impulsivity, but not inattention. Interestingly, treatment with the ADHD drug, atomoxetine (3 mg/kg, intraperitoneal), attenuated ADHD-like behaviors and reduced Atxn7 gene expression in the PFC and STR of these mice. These findings suggest that Atxn7 plays a role in the pathophysiology of ADHD, and that the Atxn7 OE mice can be used as an animal model of the hyperactive-impulsive phenotype of this disorder. Although confirmatory studies are warranted, the present study provides valuable information regarding the potential genetic underpinnings of ADHD.

What stops practitioners discussing medication breaks in children and adolescents with ADHD? Identifying barriers through theory-driven qualitative research

National and international guidelines on the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents call for annual reviews to assess continuing need for medication by considering brief periods without medication, referred to as ‘Drug holidays’. However, drug holidays are reactively initiated by families, or recommended by practitioners if growth has been suppressed by medication rather than proactively to check the need. There is little evidence of planned, practitioner-initiated drug holidays from methylphenidate. The aim of this study was to identify what stops practitioners from routinely discussing planned drug holidays from methylphenidate with children, adolescents, and their parents. Practitioners involved in shared-care prescribing for children and adolescents with ADHD in one UK County were included. Interviews with 8 general practitioners (GPs) and 8 Child and Adolescent Mental Health Service (CAMHS) practitioners were conducted. Transcripts were analysed qualitatively against the components of the Capability–Opportunity–Motivation–Behaviour (COM-B) model. Possible interventions for increasing prescribers’ engagement with planned drug holidays were considered in response. Multiple barriers to practitioner engagement in planned drug holidays from methylphenidate were identified. Capability, in terms of knowledge and skills, was not a barrier identified for CAMHS practitioners but was for GPs. Opportunity was a main barrier for both groups, who reported lack of time and the absence of educational material about drug holidays. Motivation was more complex to define, with CAMHS practitioners questioning the need for drug holidays and GPs being more accepting due to worries about long-term medication side effects as well as cost savings. ‘Education’ and ‘enablement’ interventions were identified as key activities targeting all three components, which could feasibly increase uptake of practitioner-initiated planned drug holidays from methylphenidate. The application of the COM-B system identified a number of key barriers to practitioner engagement with drug holidays in children and adolescents with ADHD. Accordingly, a number of interventions could be developed to facilitate change. For example, educating and training GPs about ADHD management and drug holidays, and developing a decision aid to help families make informed decisions about whether or not to implement drug holidays could be used.

Attention-deficit/hyperactivity disorder - unifying mechanism involving antioxidant therapy: Phenolics, reactive oxygen species, and oxidative stress

Reactive oxygen species (ROS) and oxidative stress (OS) play roles in Attention-Deficit/Hyperactivity Disorder (ADHD), as also in Alzheimer’s disease (AD), Parkinson’s disease (PD), Dementia, Schizophrenia (SCZ), Multiple Sclerosis (MS), Huntington’s Disease (HD), and Depression. Various sources, including oxidases, serve as generators of ROS-OS, such as mitochondria, NADPH, cytochromes P450, monoamines, ET metal complexes, G72 gene, and microglia. Diverse types of antioxidants (AOs) exert a positive influence on the harmful effects. Methylphenadate (MPH) is a widely favored drug for ADHD; however, there is considerable ROS-OS and AO action is less clear. Nevertheless, a proposal for the AO action is offered. MPH’s dopaminergic action provides additional support for quinone formation, similar to dopamine. There are appreciable numbers of phenol and phenolic ether drugs, as for AD (1) and PD (2). A unifying mechanism based on ET-ROS-OS-AO is involved. Other possible influential aspects are discussed in a multifaceted approach.

Pharmacoepidemiology of Tourette and Chronic Tic Disorders in Sweden 2005-2013.

Monitoring "real world" dispensation patterns over time is important to build the evidence base for safe and efficient use of psychotropic drugs. In this study, we aimed to comprehensively examine the patterns of psychotropic drug dispensations in patients with Tourette and chronic tic disorders (TD/CTD) in Sweden between 2005 and 2013. A cohort of 6979 TD/CTD patients was identified through the Swedish National Patient Register. Their drug dispensation patterns, collected in the Swedish Prescribed Drug Register, were examined between July 1, 2005 and December 31, 2013. Frequencies of drug dispensations were further stratified by gender and comorbidities. Additionally, differences in the patterns of dispensation in children and adolescents versus adults in the last year of the follow-up were examined, as well as the time trends of the dispensations over the 8-year study period. A total of 5299 (75.9%) TD/CTD patients were dispensed at least one drug during the study period. The most frequently dispensed medications were attention-deficit/hyperactivity disorder (ADHD) drugs (53.8%), antidepressants (50.7%), hypnotics/sedatives (41.7%), and antipsychotics (41.5%). Most of the medicated patients (72.1%) were dispensed more than one drug during the study period. Patterns of dispensation varied according to patient's gender, associated comorbidities, and age group. Dispensation of quetiapine and aripiprazole, antiadrenergics, ADHD drugs, antiepileptics, and hypnotics/sedatives and anxiolytics (particularly the nonbenzodiazepine types) significantly increased over time, whereas dispensation of antidepressants, typical antipsychotics, and benzodiazepine-based anxiolytics significantly decreased over the study period. Long-term monitoring of these drug dispensation patterns and the study of both their beneficial and adverse effects is warranted.

Novel and rapid LC-MS/MS method for quantitative analysis of methylphenidate in dried blood spots.

Development and validation of a novel, sensitive, specific and rapid dried blood spots (DBS)-LC-MS/MS method for methylphenidate (MPH), an attention-deficit hyperactivity disorder drug. Methodology & results: Protein precipitation with acetonitrile was used to extract MPH from the DBS cards. Chromatographic separation was achieved on a Zorbax C18 column using an isocratic mobile phase composed of acetonitrile and 5mM ammonium formate buffer (20:80, v/v) at a flow rate of 0.5ml/min. MPH was quantified over a linear range of 200-25,000pg/ml. The clinical DBS-LC-MS/MS method was successfully validated as per the US FDA's Bioanalytical Method Validation Guidance to support an ongoing pediatric pharmacokinetic study.

Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies.

Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies.

A Novel Drug for ADHD

People with attention-deficit/hyperactivity disorder (ADHD) can have >300 mutations in glutamate network genes, including 79 mutations found to be

The Prevalence of ADHD Patients among Pediatric Dentists in Israel and Knowledge of Dental and Behavioral Aspects of Treating Them.

There are no clear guidelines for managing the dental treatment of children with attention deficit hyperactivity disorder (ADHD). The use of sedation in combination with chronic ADHD medication use is also not well defined. This study surveyed the prevalence of ADHD children, management techniques and knowledge of pharmacologic therapies of these children among Israeli dentists. A specially designed questionnaire was distributed to all Israeli dentists attending a national conference in 2016. Of the 160 dentists who attended the conference, 96 completed the survey (60% response rate), and they included 46 (51%) pediatric dental specialists and 50 (49%) general dental practitioners. The medications Ritalin and Concerta were most familiar to the respondents (98.9%). Eighty-seven (91.1%) of the practitioners responded that their ADHD patients take their usual doses of any drug for treating ADHD symptoms, regardless of whether or not the dentists intended to use sedatives. The practitioners invented their own behavior management techniques with varying degrees of success. There are no specific guidelines for the most effective pharmacologic protocol (co-administration of ADHD drugs and dental sedatives) or behavior management techniques for the provision of optimal dental care to children with ADHD.

Differentiating physicochemical properties between NDRIs and sNRIs clinically important for the treatment of ADHD

BackgroundDrugs available for treating attention-deficit hyperactivity disorder (ADHD) are mainly selective norepinephrine (sNRIs) and dual norepinephrine-dopamine (NDRIs) reuptake inhibitors. The major problem of sNRIs lines in their delayed onset of action and partial- or non-responses, which makes NDRIs distinguished in drug efficacy. Understanding of the differential binding modes of these 2 types of drugs to their corresponding targets can give great insights into the discovery of privileged drug-like scaffolds with improved efficacy. So far, no such study has been carried out. MethodsA combinatorial computational strategy, integrating homology modeling, molecular docking, molecular dynamics (MD) and binding free energy calculation, was employed to analyze the binding modes of 8 clinically important ADHD drugs in their targets. ResultsBinding modes of 2 types of ADHD drugs (sNRIs and NDRIs) in their targets was identified for the first time by MD simulation, and 15 hot spot residues were discovered as crucial for NDRIs' binding in hNET and hDAT. Comparing to sNRIs, a clear reduction in the hydrophobic property of NDRIs' one functional group was observed, and the depth of drugs' aromatic ring stretched into the pocket of both targets was further identified as key contributors to drugs' selectivity. ConclusionsThe hydrophobic property of NDRI ADHD drugs' one functional group contributes to their selectivity when bind hNET and hDAT. General significanceThese results provide insights into NDRI ADHD drugs' binding mechanisms, which could be utilized as structural blueprints for assessing and discovering more efficacious drugs for ADHD therapy.

Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps in "Impulsive" SHR/NCrl and Wistar Rats.

Impulsivity, the predisposition to act prematurely without foresight, is associated with a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of impulsive behavior may help decipher the complex etiology and neurobiological factors of disorders marked by impulsivity. To identify potential genetic factors of impulsivity, we examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug-responsive transcripts whose mRNA levels were altered following treatment (in SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with methylphenidate and/or atomoxetine increased choice of the large, delayed reward in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of Nr4a2, Btg2, and Homer2, genes with previously described roles in neuropsychiatric disorders characterized by impulsivity. While further studies are required, we dissected potential genetic factors that may influence impulsivity by identifying genetic overlaps in the PFC of "impulsive" SHR/NCrl and Wistar rats. Notably, these are also drug-responsive transcripts which may be studied further as biomarkers to predict response to ADHD drugs, and as potential targets for the development of treatments to improve impulsivity.

Preliminary Evidence of an Association Between ADHD Medications and Diminished Bone Health in Children and Adolescents.

The US Centers for Disease Control and Prevention estimate that 3.5 million children use psychotropic drugs for attention-deficit hyperactivity disorder (ADHD). With an increase in use of these types of drugs, thorough understanding of their potential side effects on the growing skeleton is needed. The purpose of this study was to determine whether there is an association between use of ADHD medication and diminished bone health. Three waves of the National Health and Nutrition Examination Survey public-use data set, collected from 2005 through 2010, were compiled for this study (N=5315). Bone health was measured using dual-energy x-ray absorptiometry scans, which were performed for participants aged 8 to 17 years to determine bone mineral density (BMD) for 3 regions: (1) total femur; (2) femoral neck; and (3) lumbar. Use of ADHD medications was determined by self-reported responses to questions regarding prescription drug use, which were answered by either the respondent or the respondent's parent or guardian. Multiple statistical techniques were used to produce estimates of association between ADHD medication use and z score age and sex standardized BMD measures, including survey adjusted univariate, survey adjusted multiple linear regression, and generalized estimating equations with a propensity-matched subsample (N=1967). Multivariate models adjusted for covariates including time period, age, sex, race/ethnicity, family income to poverty ratio, and total number of prescription medications. Conservative estimates of the difference in standardized BMD measures between the ADHD medication group and the nonmedicated group range from -0.4855 (±0.27; P<0.001) for total femoral, -0.4671 (±0.27; P<0.001) for femoral neck, and -0.3947 (±0.29; P<0.01) for lumbar. Significantly more children on ADHD medications versus match subjects on no medication had BMDs with in osteopenic range (38.3% vs. 21.6%, P<0.01). The findings suggest that there are real and nontrivial differences in BMD for children and adolescents taking ADHD medications, as compared with similar children not taking any prescription medications. Prescribing physicians and parents should be aware of potential bone health risks associated with these medications. Level III-case-control study.