Attention-deficit/hyperactivity Disorder Drugs Research Articles

Attention-Deficit/Hyperactivity Disorder Drugs and Growth: An Italian Prospective Observational Study

This study was conducted to assess the long-term effect of methylphenidate (MPH) or atomoxetine (ATX) on growth in attention-deficit/hyperactivity disorder (ADHD) drug-naïve children. The study was an observational, post-marketing, fourth phase study. Data on height and weight were collected at baseline and every 6 months up to 24 months. Both ATX and MPH lead to decreased height gain (assessed by means of z-scores); the effect was significantly higher for ATX than for MPH. At any time, height z-score decrease in the ATX group was higher than the corresponding decrease observed in the MPH group, but the difference was significantly relevant only during the first year of treatment. An increment of average weight was observed both in patients treated with MPH and in those treated with ATX. However, using Tanner's percentile, a subset of patients showed a degree of growth lower than expected. This negative effect was significantly higher for ATX than for MPH. We conclude that ADHD drugs show a negative effect on linear growth in children in middle term. Such effect appears more evident for ATX than for MPH.

Adults with ADHD: use and misuse of stimulant medication as reported by patients and their primary care physicians

This study investigated the agreement on treatment for attention-deficit/hyperactivity disorder (ADHD) between adults with ADHD and the primary care physicians responsible for their treatment. Adults with ADHD and the primary care physicians responsible for their ADHD treatment completed a survey. The κ-statistic assessed physician-patient agreement on ADHD treatment variables. The eligible sample consisted of 274 patients with confirmed current or previous psychopharmacological treatment for ADHD and the physicians responsible for their treatment. We received 159 questionnaires (58.0 %) with sufficient information from both sources. There were no significant differences between participants and nonparticipants (N = 115) on ADHD sample characteristics. Participants' mean age was 37.6 years, and 75 (47.2 %) were females. There was high agreement for current pharmacological treatment for ADHD, current and last ADHD drug prescription, treatment for substance use, and misuse of stimulant medication. Agreement for nonpharmacological treatment for ADHD and treatment termination because of the side effects was low. A minority of participants from both sources reported misuse of stimulant medication. There was a moderate correlation between the physicians' clinical judgment and patients' self-report on current functioning. The study showed that primary care physicians and their patients agreed on the pharmacological but not the nonpharmacological, treatments given. They also agreed on patients' current functioning. Physicians and patients reported low levels of misuse of stimulant medication. The results show that pharmacological treatment for adults with ADHD can be safely undertaken by primary care physicians.

Dissociations between cognitive and motor effects of psychostimulants and atomoxetine in hyperactive DAT-KO mice

Psychostimulants such as amphetamine and methylphenidate, which target the dopamine transporter (DAT), are the most frequently used drugs for the treatment of hyperactivity and cognitive deficits in humans with attention deficit hyperactivity disorder (ADHD). While psychostimulants can increase activity in healthy subjects, they exert a "paradoxical" calming effect in humans with ADHD as well as in hyperactive mice lacking the dopamine transporter (DAT-KO mice). However, the mechanism of action of these drugs and their impact on cognition in the absence of DAT remain poorly understood. This study was conducted to investigate the effects of psychostimulants and noradrenergic and serotonergic drugs on cognition in DAT-KO mice and normal (WT) littermates. We used a recently developed behavioral apparatus, the automated H-maze. The H-maze involves the consecutive learning of three different rules: delayed alternation, nonalternation, and reversal tasks. Treatment of WT animals with the psychostimulants replicated the behavior observed in untreated DAT-KO mice while "paradoxically" restoring cognitive performances in DAT-KO mice. Further investigation of the potential involvement of other monoamine systems in the regulation of cognitive functions showed that the norepinephrine transporter blocker atomoxetine restored cognitive performances in DAT-KO mice without affecting hyperactivity. In contrast, the nonselective serotonin receptor agonist 5CT, which antagonizes hyperactivity in DAT-KO mice, had no effect on cognitive functions. Taken together, these data allow dissociation of the locomotor and cognitive effects of ADHD drugs and suggest that the combination of DAT-KO mice with the automated H-maze can constitute a powerful experimental paradigm for the preclinical development of therapeutic approaches for ADHD.

Association of childhood attention-deficit/hyperactivity disorder with atopic diseases and skin infections? A matched case-control study using the General Practice Research Database

BackgroundData to support the hypothesis of a relationship between attention-deficit/hyperactivity disorder (ADHD) and allergies are conflicting. ObjectiveTo assess whether children with ADHD are more likely to have a history of atopic disorders, skin infections, and medical prescriptions than children without ADHD. MethodsWe conducted a nested case-control study among boys using the UK General Practice Research Database (GPRD). Cases were defined as children with first-time diagnosis of ADHD who were treated with methylphenidate. Four controls who had neither ADHD nor ADHD drug prescriptions in their medical records were matched to each case on age and general practice. ResultsWe identified 884 boys with a first-time diagnosis of drug-treated ADHD and 3,536 controls. The independent odds ratios adjusted for age and presence of low birth weight or preterm delivery were 1.4 (95% confidence interval [CI], 1.2-1.7; P < .001) for a medical history of asthma, 1.5 (95% CI, 1.3-1.9; P < .001) for impetigo, and 1.5 (95% CI, 1.3-1.7; P < .001) for any antihistamine drug prescriptions. Other exposures that were more common in cases than controls, though not independently, were cow's milk intolerance and any prescription from the drug categories antiasthmatics, respiratory corticosteroids, topical steroids, antibacterials, or antifungals. ConclusionDespite possible limitations inherent to observational studies, this study lends support to the emerging evidence that childhood ADHD is associated with atopic diseases and impetigo. Further interdisciplinary research is needed to understand the underlying mechanisms and to evaluate targeted preventive, diagnostic, and therapeutic interventions.

Overdose of Drugs for Attention-Deficit Hyperactivity Disorder: Clinical Presentation, Mechanisms of Toxicity, and Management

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.

Association between ADHD drug use and injuries among children and adolescents

To study the association between attention deficit hyperactivity disorder (ADHD) drug use and the incidence of hospitalization due to injuries. A random sample of 150,000 persons (0-18 years) was obtained from the Dutch PHARMO record linkage system. An ADHD medication cohort as well as an up to six age/sex/index date sampled control cohort with no history of ADHD drug use was formed. Differences in incidence of hospitalization due to injuries were stratified for age and sex and compared prior, during and after exposure on ADHD drugs. The overall incidence of hospital admissions for injuries was two times higher in the ADHD medication cohort [incidence rate ratios (IRR) 2.2 (95 % CI 1.6-2.9)]. The incidence rate for injuries during exposure to ADHD drugs was lower in the exposed period compared to the period prior to ADHD drug use, although the difference was not statistically significant [IRR 0.68 (95 % CI 0.29-1.60)]. The relative risk for injuries was almost five times higher in the ADHD medication cohort among those who concomitantly used other psychotropics [IRR 4.8 (95 % CI 1.4-16.9)]. Risk for injuries was highest in 12-18 years olds. Children and adolescents using ADHD medication showed a twofold risk for hospital admissions for injuries. ADHD drug use might diminish the increased injury risk, but still overall risk is higher than in age/sex sampled children and adolescents without treatment with ADHD drugs. Use of ADHD and concomitant psychotropics increases the risk for injuries compared to only ADHD drug use.

Predictive Ability for Drug Use in Sub-Clinical Students with Attention Deficit Hyperactivity Disorder by Questionnaire Survey

Dear Editor, I read with interest the article by Bayrami et al., reporting the predictive ability of drug use for subjects with attention deficit hyperactivity disorder (ADHD) symptoms (1). The target 361 subjects were sampled randomly from 5129 university students, and a cross-sectional survey was conducted by using a questionnaire. Recently, Lichtenstein et al. conducted a follow-up study to know the effect of medication for 25,656 ADHD patients on criminality (2). They concluded that the use of medication for ADHD reduces significantly the risk criminality. These two surveys contain completely different population from the viewpoint on the severity of ADHD. Although Bayrami et al. mentioned that there was a positive relationship between ADHD symptoms and drug use, a further study is needed to make a finalconclusion. First, their study is a cross-sectional study, and cause-effect relationship cannot be defined. Second, the target subjects are composed mainly of healthy young population, and clinical diagnosis of ADHD has not been made. Third, Pearson's moment correlation coefficient using scores from the questionnaire on ADHD and addiction acknowledgment scale score or Mac Andrew alcoholism scale scores showed under 0.4. This means that the relationship is not so strong, although a significant relationship was observed. This fact was also clarified by the multiple regression analysis, which was presented in Tables 2 and 3. Adjusted square values of R (multiple correlation coefficients) were under 0.16, which meant that each explanation rate was under one-sixthof all the variance. Before describing the predictive ability as they conducted, I recommend to describe the characteristics of the target university students. By this process, trace ability of their results by other researchers would improve. In anyway, there is a need for more studies to conclude the effect of ADHD symptoms on drug use including alcoholism.

ENTRY IN THE ADHD DRUGS MARKET: WELFARE IMPACT OF GENERICS AND ME-TOO'S.

Recent decades have seen a growth in treatments for attention deficit hyperactivity disorder (ADHD) including many branded and generic drugs. In the early 2000's, new drug entry dramatically altered market shares. We estimate a demand system for ADHD drugs and assess the welfare impact of new drugs. We find that entry induced large welfare gains by reducing prices of substitute drugs, and by providing alternative delivery mechanisms for existing molecules. Our results suggest that the success of follow-on patented drugs may come from unanticipated innovations like delivery mechanisms, a factor ignored by proposals to retard new follow-on drug approvals.

The past, present and future of psychiatric diagnosis

The past, present and future of psychiatric diagnosis

5,7-Dihydroxy-6-methoxy-4'-phenoxyflavone, a derivative of oroxylin A improves attention-deficit/hyperactivity disorder (ADHD)-like behaviors in spontaneously hypertensive rats

Oroxylin A, a major flavonoid in Scutellaria baicalensis, has been shown to alleviate attention-deficit/hyperactivity disorder (ADHD)-like behaviors in the spontaneously hypertensive rat (SHR) model of ADHD. As part of our continuing effort to discover effective ADHD drug candidates, we synthesized a number of oroxylin A derivatives and characterized their biological activities. Among all oroxylin A analogs, compound 7-7 (5,7-dihydroxy-6-methoxy-4'-phenoxyflavone) showed the most remarkable inhibition of dopamine reuptake alike methylphenidate, a dopamine transporter (DAT) blocker and typical drug for ADHD, and oroxylin A. It did not influence norepinephrine reuptake unlike atomoxetine, a selective norepinephrine inhibitor. Moreover, compound 7-7 reduced hyperactivity, sustained inattention and impulsivity in the SHR as measured by the open field, Y-maze and electro-foot shock aversive water drinking tests, respectively. Most drugs that enhance brain dopamine levels (e.g. DAT blockers like cocaine and methylphenidate) produce behavioral effects like those of stimulants causing them to be abused. However, the repeated treatment of compound 7-7 failed to elicit locomotor sensitization in rats, and neither produced conditioned place preference response nor maintained self-administration behavior. Altogether, the present study suggests the promising therapeutic value of compound 7-7 as an ADHD drug. Furthermore, compound 7-7 may be considered as an alternative therapy to psychostimulant ADHD treatments (e.g. amphetamine and methylphenidate) for which use has been deemed controversial due to their abuse liability.

Assessing the toxicity and associated costs among pediatric patients admitted with unintentional poisonings of attention-deficit/hyperactivity disorder drugs in the United States

Background. Attention-deficit/hyperactivity disorder (ADHD) is widespread, with a national (United States) prevalence of nearly 10%. The 2011 changes in the diagnostic criteria will likely further increase the prevalence of this disorder. Little is known about the incidence of toxicity from unintentional poisonings of ADHD medications. This study attempted to determine the incidence of these ingestions and the corresponding financial impact in the United States. Methods. Four geographically different centers were chosen. Subjects with unintentional poisonings due to ADHD medications were included if the admission dates were between 2000 and 2002 (cohort A) or between 2009 and 2010 (cohort B). Using data from the participating hospitals and the number of monitored beds in each corresponding county, data were extrapolated on a national (United States) level. Results. Sixty-three subjects were admitted at four hospitals (18, cohort A and 45, cohort B). The crude incidence rate ratio increased in the later time frame as compared to that in the earlier time frame (incidence rate ratio, 3.13; 95% CI, 1.80–5.68; p < 0.0001). The median (IQR) charges per patient, adjusted for inflation, were $4780 ($3,895–$8,287) and $5912 ($3,432–$9,433) for cohorts A and B, respectively (p = 0.57). If the subjects in the participating counties were only admitted to the participating hospitals, the annual charges, extrapolated throughout the United States for the two periods, would be $2,419,016 and $8,129,538, respectively. If the subjects were evenly distributed across all pediatric monitored beds in a given county, the annual charges extrapolated throughout the United States for the two periods would be $5,694,232 and $24,126,640, respectively. Conclusion. The incidence of unintentional poisonings from ADHD drugs is increasing and is associated with a significant cost.

Relationship between attention deficit hyperactivity disorder and alcohol dependence: a genetic view.

Dear Editor, Attention deficit hyperactivity disorder (ADHD), is a common, highly heritable childhood-onset psychiatric disorder affecting 2% – 6% of children worldwide. The recent paper examines the effects of child and adult ADHD symptoms in adults among male students on adult addiction acknowledgment and alcoholism potential (1). This article is an original study which provides that adult ADHD and child ADHD predict addiction acknowledgment while child ADHD and impulsivity predict alcohol potential. These findings add new evidence about prediction of adolescent and adult drug abuse and use by early ADHD. However, the biological mechanism of the relationship between ADHD and substance problems is still unclear. One of the important mechanisms is genetic correlation due to shared genetic loci. First, it has been shown that both ADHD and alcohol dependence have strong genetics components. Twin and adoption studies have indicated that ADHD has high heritability in the range of 75% – 91% (2), while family, twin, and adoption studies have revealed that genetic and environmental factors and their interactions contribute to the development of alcohol dependence, with a heritability of more than 50% (3). Second, ADHD has been found to be highly comorbid with nicotine dependence and alcohol dependence. Segregation analysis has provided multigenerational evidence of cosegregation among ADHD, nicotine dependence, and alcohol dependence, while linkage analysis has suggested several regions on human chromosomes with pleiotropic effects on ADHD and alcohol dependence (4). For example, significant linkages at 4q13.1 - 13.2 and 5q31 - 33 for ADHD has been implicated in alcohol dependence and nicotine dependence (4). Third, genetic association studies have suggested several genes which are responsible for both ADHD and alcohol dependence. For example, it has been reported associations between the dopamine transporter (DAT) gene polymorphisms and human disorders including ADHD and alcohol dependence (5). The variants of the dopamine D2 receptor gene (DRD2) has been found to be associated with alcoholism, drug dependency, obesity, smoking, pathological gambling, ADHD, Tourette syndrome, as well as other related compulsive behaviors (6). The tachykinin receptor 1 (TACR1) gene has been reported to be associated with bipolar disorder and alcoholism as well as ADHD (2). However, parts of the associations are not strong and the results are not always consistent due to biologic mechanisms (genetic heterogeneity, gene-gene interactions and gene-environment interactions etc.) and spurious mechanisms (inadequacies of genomic markers, type 1 error, limited sample sizes and power, cohort and age effects, and bias etc.). In addition, some other genes, such as the nicotinic receptor CHRNA5-A3-B4 subunit genes, do not contribute to the common genetic predisposition of ADHD and alcohol dependence (2, 7). In short, the current results not only support previous studies about the relationship between ADHD and alcohol and drug dependence but also provide further evidence on prediction of future substance dependence in adulthood through early ADHD (1). However, the sample size for the current study is relative small; therefore the results need further investigation using large sample and confirmation in other populations. In addition, further genetic and epigenetic study to identify the disease-causing variants including gene-environment interactions in ADHD and alcohol dependence would have promise for understanding the pathogenesis of these comorbity psychiatric disorders, predicting the risks and developing potential treatments for ADHD and alcohol dependence.

Management of adult attention deficit hyperactivity disorder in UK primary care: a survey of general practitioners.

BackgroundCompared to existing literature on childhood attention deficit hyperactivity disorder (ADHD), little published adult data are available, particularly outside of the United States. Using General Practitioner (GP) questionnaires from the United Kingdom, this study aimed to examine a number of issues related to ADHD in adults, across three cohorts of patients, adults who received ADHD drug treatment in childhood/adolescence but stopped prior to adulthood; adults who received ADHD drug treatment in childhood/adolescence and continued treatment into adulthood and adults who started ADHD drug treatment in adulthood.MethodsPatients with a diagnosis of ADHD and prescribed methylphenidate, dexamfetamine or atomoxetine were identified using data from The Health Improvement Network (THIN). Dates when these drugs started and stopped were used to classify patients into the three cohorts. From each cohort, 50 patients were randomly selected and questionnaires were sent via THIN to their GPs.GPs returned completed questionnaires to THIN who forwarded anonymised copies to the researchers. Datasets were analysed using descriptive statistics.ResultsOverall response rate was 89% (133/150). GPs stated that in 19 cases, the patient did not meet the criteria of that group; the number of valid questionnaires returned was 114 (76%). The following broad trends were observed: 1) GPs were not aware of the reason for treatment cessation in 43% of cases, 2) patient choice was the most common reason for discontinuation (56%), 3) 7% of patients who stopped pharmacological treatment subsequently reported experiencing ADHD symptoms, 4) 58% of patients who started pharmacological treatment for ADHD in adulthood received pharmacological treatment for other mental health conditions prior to the ADHD being diagnosed.ConclusionThis study presents some key findings relating to ADHD; GPs were often not aware of the reason for patients stopping ADHD treatment in childhood or adolescence. Patient choice was identified as the most common reason for treatment cessation. For patients who started pharmacological treatment in adulthood, many patients received pharmacological treatment for comorbidities before a diagnosis of ADHD was made.

Current pharmacotherapy of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder in children and adults characterized by a persistent pattern of impulsiveness, inattention and hyperactivity. It affects about 3-10% of children and 2-5% of adolescents and adults and occurs about four times more commonly in boys than girls. The cause of ADHD is unknown, but it has strong genetic and environment components. The first-line treatment options for ADHD include behavioral therapy, pharmacotherapy with stimulants or both. Methylphenidate and amphetamine salts are the stimulant drugs of choice for ADHD treatment. Amphetamines act by increasing presynaptic release of dopamine and other biogenic amines in the brain. Methylphenidate inhibits the reuptake of dopamine and norepinephrine and therefore its pharmacology is identical to that of amphetamines. Lisdex-amfetamine is a prodrug of dextroamphetamine with low feasibility for abuse. Atomoxetine, a selective norepinephrine reuptake inhibitor, is an alternative, non-stimulant drug for ADHD but it is less efficacious than stimulants. Stimulants are generally safe but are associated with adverse effects including headache, insomnia, anorexia and weight loss. There is increased awareness about serious cardiovascular and psychiatric adverse events with ADHD drugs including concern for growth suppression in children. Stimulants have a high potential for abuse and dependence, and should be handled safely to prevent misuse and abuse.

Increased Locomotor Activity and Non-Selective Attention and Impaired Learning Ability in SD Rats after Lentiviral Vector-Mediated RNA Interference of Homer 1a in the Brain

Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD.

Patient preferences and willingness-to-pay for ADHD treatment with stimulants using discrete choice experiment (DCE) in Sweden, Denmark and Norway

Background: The choice between different attention-deficit/hyperactivity disorder (ADHD) medications depends on different drug attributes. Economic evaluations of drugs often disregard the utility of other attributes compare with the drugs’ efficacy. Aims: The aim of this study was to assess patient's preferences and elicit willingness-to-pay (WTP) for different drug attributes in the treatment of ADHD. Methods: 285 patients (117 parents for children below 15 years, 52 adolescents 15–17 years and 116 adults aged 18 years and above) from Sweden, Denmark and Norway completed a questionnaire concerning their ADHD drug treatment, and answered questions on their preferences using a discrete choice experiment (DCE). Included attributes were effectiveness, side-effects, dosing and price. Results: Effectiveness was the most important attribute, followed by side-effects and the number of dosings per day (all P < 0.001). The estimated monthly WTP for a drug generating full effectiveness, no side-effects and once-daily dosing was €790 for adolescents and €360 for adults. The estimated WTP for ADHD drugs with characteristics similar to existing drugs on the market was higher or in line with market prices (€37–180 for adolescents and €16–80 for adults). Regarding experience with current treatment, 19% of all patients in the study reported good functioning during the morning, day and evening. Conclusions: The gap between the monetary valuation of existing products and an optimally valued product suggest that there is room for improvements in the clinical management of ADHD. The results suggest that DCE is a method that can be used to value not only hypothetical scenarios but also can be used to value and distinguish between real-life scenarios.

Drug Treatment Patterns of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents in Germany: Results from a Large Population-Based Cohort Study

Despite a substantial increase in total methylphenidate (MPH) prescriptions in Germany over the last 20 years, and the introduction of modified release MPH (MR MPH) and atomoxetine (ATX), remarkably little is known about treatment patterns of attention- deficit/hyperactivity disorder (ADHD) in individual patients. Usage patterns of ADHD drugs in children and adolescents in Germany were analyzed using data from one large German health insurance including >7,200,000 members. Of those, 6210 ADHD patients newly diagnosed in 2005 were followed for a maximum of 4 years. Kaplan-Meier estimates were calculated for onset and discontinuation of ADHD drug treatment. Predictors of time until drug treatment initiation were assessed by Cox regression. During follow-up, 52.0% of ADHD subjects (53.4% of boys, 47.5% of girls) received ADHD drug treatment. The majority of them (91.6%) were started on MPH, with immediate release MPH (IR MPH) being the initial treatment choice in 75.3%. In these subjects, change to drug treatment with MR MPH in the first year occurred in 48% by switch or addition. Significant predictors of drug treatment were behavioral and emotional disorders (HR=1.13; 95% CI 1.03-1.24) and a diagnosis of ADHD with conduct disorder (HR=1.21, 95% CI 1.12-1.32), whereas young age showed a protective effect. After 6, 12, and 24 months of treatment initiation, 22.4%, 43.4%, and 66.3% of treated girls, and 17.8%, 36.1%, and 54.1% of treated boys had discontinued ADHD treatment. Drug treatment of ADHD was relatively common in Germany and more frequent in boys than in girls. IR MPH was the predominant treatment choice at treatment initiation. Approximately 20% of treated subjects discontinued drug treatment within the first 6 months, with girls stopping drug treatment earlier than boys. The reasons for early drug discontinuation need to be further explored.

Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder

Social isolation of rodents (SI) elicits a variety of stress responses such as increased aggressiveness, hyper-locomotion, and reduced susceptibility to pentobarbital. To obtain a better understanding of the relevance of SI-induced behavioral abnormalities to psychiatric disorders, we examined the effect of SI on latent learning as an index of spatial attention, and discussed the availability of SI as an epigenetic model of attention deficit hyperactivity disorder (ADHD). Except in specially stated cases, 4-week-old male mice were housed in a group or socially isolated for 3–70 days before experiments. The animals socially isolated for 1 week or more exhibited spatial attention deficit in the water-finding test. Re-socialized rearing for 5 weeks after 1-week SI failed to attenuate the spatial attention deficit. The effect of SI on spatial attention showed no gender difference or correlation with increased aggressive behavior. Moreover, SI had no effect on cognitive performance elucidated in a modified Y-maze or an object recognition test, but it significantly impaired contextual and conditional fear memory elucidated in the fear-conditioning test. Drugs used for ADHD therapy, methylphenidate (1–10mg/kg, i.p.) and caffeine (0.5–1mg/kg, i.p.), improved SI-induced latent learning deficit in a manner reversible with cholinergic but not dopaminergic antagonists. Considering the behavioral features of SI mice together with their susceptibility to ADHD drugs, the present findings suggest that SI provides an epigenetic animal model of ADHD and that central cholinergic systems play a role in the effect of methylphenidate on SI-induced spatial attention deficit.

The Over-prescription of Ritalin for Suspected Cases of ADHD

Methylphenidate (Ritalin), the current leading form of treatment for Attention Deficit Hyperactivity Disorder (ADHD), has seen a dramatic increase in prescription rate over the past ten years. No contemporary biological basis for ADHD diagnosis results in physicians making their diagnoses based on behavioural symptoms such as hyperactivity and inability to focus. Considering that these symptoms are behaviours that anyone may express at one point in their life, the risk of over-diagnosis of the disease increases. This may subsequently lead to over-prescription of Ritalin. This paper aims to evaluate and identify the causes and effects of Ritalin over-prescription. Key literature on ADHD reveals that the diagnostic criteria for ADHD has undergone various modifications since the disease was first identified; therefore, different experts may have different opinions on what are regarded as symptoms of the disorder. Furthermore, recent research has demonstrated that Ritalin can increase cognitive performance in both healthy individuals and in ADHD patients. Such data indicates that Ritalin has the potential to be abused by healthy individuals looking to increase their cognitive performance. Correspondingly, Ritalin has been reported to be used by college students to boost their academic performance. In addition, the over-prescription of Ritalin raises several ethical issues: as children are the most common age group to be diagnosed with the disease, critics question whether prescribing a drug for a behaviourally based diagnosed disease is appropriate; also it is thought that the drug may affect the originality and creativity of the children which may hinder their personal development. While alternative behavioural therapy is available for the disorder, it tends to be more expensive and time-consuming than a drug prescription; this may explain why Ritalin remains the dominant form of treatment. This paper concludes that the prescription of drugs for ADHD should be cautioned and that more time and resources should be invested on developing consistent diagnostic criteria as well as potential alternative treatments to drugs for the disorder.

347 Increasing Prevalence of ADHD Drug Toxicity

Study Objective: In recent years, the number of children diagnosed with attention Deficit Hyperactivity Disorder (ADHD) has increased. It is not known if the increased prescribing practices of drugs used to treat ADHD is associated with an increased rate of toxicologic admissions following unintentional ingestion of these medications.