Editorial: Accumulating Evidence for the Benefit of Micronutrients for Children With Attention-Deficit/Hyperactivity Disorder.

The first paper indicating that a central nervous system stimulant (amphetamine) could be beneficial for children with attention-deficit/hyperactivity disorder (ADHD)-like behavioral symptoms appeared in 1937.1 Over the subsequent 80 years, a range of additional stimulant (methylphenidate) and nonstimulant (atomoxetine, clonidine, guanfacine, and, most recently, viloxazine) drugs have been approved to treat children and adolescents with ADHD. These drug treatments have been the subject of a large number of randomized controlled trails (RCTs). A network meta-analysis found that using clinician ratings, amphetamine, methylphenidate, and atomoxetine were all significantly superior to a placebo.2 These findings suggest that in the short-term at least, these treatments are effective-data are sparse on the efficacy of longer-term drug treatment. However, there are longstanding worries about the use of such drug treatments with children. In particular there are concerns over possible adverse impact on growth. There are also less tangible, but important, concerns of parents as the whether it is appropriate to subject their children to the modification of behavior by drugs.3 For these reasons, there is an urgent need to develop nonpharmacological treatments for children and adolescents with ADHD. One such nonpharmacological treatment is dietary supplementation with micronutrients. In this issue of the Journal, Johnstone et al.4 present a study of micronutrients showing that, under the stringent conditions of an RCT, micronutrients substantially benefit the well-being of young people with ADHD and irritability (risk ratio [RR] = 2.97; 97.5% CI = 1.50-5.90).

Effects of white noise on off-task behavior and academic responding for children with ADHD.

We evaluated the effects of white noise played through headphones on off-task behavior, percentage of items completed, and percentage of items completed correctly for 3 students with attention deficit hyperactivity disorder (ADHD). Headphones plus white noise were associated with decreases in off-task behavior relative to baseline and headphones-only (no white noise) control conditions. Little change in academic responding occurred across conditions for all participants.

Pharmacotherapy for obese adolescents.

The pharmaceutical search to induce weight loss was precipitated by the United States Food and Drug Administration's (FDA) 1959 formal approval of phentermine for short-term weight loss despite limited research supporting its assertions of weight loss. In addition to sympathomimetic amine products like phentermine, other medications considered in this article include herbal products, sibutramine, orlistat, metformin, and rimonabant. The use of pharmacotherapy for morbidly obese adolescents should be part of a comprehensive weight-loss program that recommends diet, exercise, and behavioral modification. Side effects and the possibility of major adverse effects should be remembered when considering use of these products.

Health care costs of adults treated for attention-deficit/hyperactivity disorder who received alternative drug therapies.

BACKGROUND: Many therapies exist for treating adult attention-deficit/hyperactivity disorder (ADHD), also referred to as attention-deficit disorder (ADD), but there is no research regarding cost differences associated with initiating alternative ADD/ADHD drug therapies in adults. OBJECTIVE: To compare from the perspective of a large self-insured employer the risk-adjusted direct health care costs associated with 3 alternative drug therapies for ADD in newly treated patients: extended-release methylphenidate (osmotic release oral system-MPH), mixed amphetamine salts extended release (MAS-XR), or atomoxetine. METHODS: We analyzed data from a US claims database of 5 million beneficiaries from 31 large self-insured employers (1999-2004). Analysis was restricted to adults aged 18 to 64 years with at least 1 diagnosis of ADD/ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 314.0x--attention deficit disorder; 314.00--attention deficit disorder without hyperactivity; or 314.01--attention-deficit disorder with hyperactivity) and at least 1 pharmacy claim for OROS-MPH, MAS-XR, or atomoxetine identified using National Drug Codes. In preliminary analysis, we calculated the duration of index ADHD drug therapy as time from index therapy initiation to a minimum 60-day gap. Because the median duration of index ADHD drug therapy was found to be approximately 90 days, the primary measures were total direct medical plus drug costs and medical-only costs computed over 6 months following therapy initiation. Adults were required to have continuous eligibility 6 months before and 6 months after their latest drug therapy initiation and no ADHD therapy during the previous 6 months. Cost was measured as the payment amount made by the health plan to the provider rather than billed charges, and it excluded patient copayments and deductibles. Medical costs included costs incurred for all-cause inpatient and outpatient/other services. Costs were adjusted for inflation to 2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index. RESULTS: Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P <0.001); the risk-adjusted total direct costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD. CONCLUSIONS: After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on average, slightly lower medical and total medical and drug costs than those treated with MAS-XR or atomoxetine over the 6-month period after drug therapy initiation. Approximately 30% of the cost difference compared with MAS-XR was attributable to 1 high-cost outlier with medical diagnoses for the highest-cost claim that were unrelated to ADHD.

Ergogenic aids: a review of basic science, performance, side effects, and status in sports.

The use of drugs and supplements to enhance performance has become a part of mainstream athletics. Many team physicians and sports medicine practitioners are unfamiliar with the benefits and risks of these products and thus are unable to educate young athletes on this topic. In spite of numerous reports on the health risks of anabolic steroid use, 1 to 3 million Americans have used them. Human growth hormone has been tried by up to 5% of 10th graders, although no scientific study has shown that it is an effective performance-enhancing drug. Amphetamines and similar compounds may be the most widely abused drug in baseball; recently, they have come under increased scrutiny in sport. Erythropoietin is a highly effective aerobic enhancer that has been linked to multiple deaths in cyclists and other endurance athletes. The neutraceutical industry, led by supplements such as creatine, ephedra, and androstenedione, remains unregulated by the Food and Drug Administration and has serious issues with quality and side effects. An understanding of these products is essential for the sports medicine practitioner to provide sound, safe advice to the athlete.

Systemic administration of serotonin 2A/2C agonist improves upper airway stability in Zucker rats.

The effects of [+/-]-2,5-dimethoxy-4-iodoaminophentamine, a serotonin(2A/2C) receptor agonist, on pharyngeal airflow mechanics were examined in isoflurane-anesthetized lean and obese Zucker rats. The pharyngeal pressure associated with flow limitation, maximum inspiratory flow, oronasal resistance, genioglossus muscle activity, and arterial blood pressure (BP) were measured before and after the intravenous administration of the agonist. A robust activation of the genioglossus muscle in all lean and obese rats was associated with decreased upper airway (UA) collapsibility (p < 0.05), unchanged maximum flow, and increased oronasal resistance (p < 0.05) in both groups. The changes in UA mechanics and BP after the drug were similar in lean and obese rats. The serotonin agonist had no effect on UA mechanics in a group of paralyzed (pancuronium bromide) rats, despite similar elevations in BP. There was a smaller decrease (p < 0.05) in UA collapsibility that was also associated with increased upstream resistance when the drug was administered after bilateral hypoglossal nerve transection. We conclude that systemic administration of a serotonin(2A/2C) receptor agonist improves UA collapsibility predominantly, but not exclusively, via stimulation of the hypoglossal nerves and also increases upstream resistance, at least in part, through activation of nonhypoglossal motoneuronal pools innervating the UA muscles.

Parental medication use and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Few studies have examined the risk of childhood acute lymphoblastic leukemia (ALL) associated with parental medication use. As part of a large case-control study conducted by the Children's Cancer Group, we evaluated the association between maternal and paternal medication use and the risk of ALL in offspring. METHODS: Information on selected medication use in the year before and during the index pregnancy was obtained by telephone interview. Participants included 1842 children of 14 years or younger with newly diagnosed and immunophenotypically defined ALL and 1986 individually matched controls. Data were analyzed using logistic regression models and stratified by immunophenotypes of ALL and age at diagnosis of cases. RESULTS: After adjusting for potential confounders and other medication use, we found that maternal use of vitamins (odds ratio [OR] = 0.7, 99% confidence interval [CI]: 0.5-1.0) and iron supplements (OR = 0.8, 99% CI: 0.7-1.0) only during the index pregnancy was associated with a decreased risk of ALL. Parental use of amphetamines or diet pills and mind-altering drugs before and during the index pregnancy was related to an increased risk of childhood ALL, particularly among children where both parents reported using these drugs (OR = 2.8, 99% CI: 0.5-15.6 for amphetamines or diet pills, OR = 1.8, 99% CI: 1.1-3.0 for mind-altering drugs). Stratified analyses showed that maternal use of antihistamines or allergic remedies and parental use of mind-altering drugs were strongly associated with infant ALL, whereas patterns of association between childhood ALL and parental medication use did not influence markedly the immunophenotypic subgroup of ALL. CONCLUSIONS: The findings of this study suggest that certain parental medication use immediately before and during the index pregnancy may influence risk of ALL in offspring.

The use of psychostimulants in the pediatric patient.

The psychostimulant drugs have a long history of safe and effective usage in the treatment of ADHD. They remain the drugs of first choice in this condition. Children with ADHD should be aggressively treated with at least two different classes of psychostimulants before moving to nonpsychostimulant agents. As long as side effects are not troublesome, higher dosages may be used to adequately control the ADHD symptoms, and such high dosages do not impair learning. No evidence shows long-term effects of psychostimulants on growth. Effective use of the psychostimulants is essential for any clinician involved in the treatment of children with ADHD.

[A pharmacological analysis of the central monoaminergic mechanisms of the development of neurogenic stomach damage]. / Farmakologicheskii analiz tsentral'nykh monoaminergicheskikh mekhanizmov razvitiia neirogennogo povrezhdeniia zheludka.

It was found that 3 hours after electrostimulation of the immobilized rats there was observed in addition to destructive lesions in the gastric mucosa a significant decrease of noradrenaline, dopamine, DOPA, homovanillic acid and creatine phosphate levels in the brain tissue involving the hypothalamus and the midbrain surrounding it. The use before the extreme impact of neurotropic agents blocking transmission of the damaging impulses from the site of stimulation of reflexogenic zones through the central adrenergic synapses which activate genome in the nerve cell or prevent depletion of catecholamine stores and disturbance of energy formation processes in the brain tissue protects against the development of neurogenic damage of the stomach.