Reducing Attention-deficit/hyperactivity Disorder Symptoms Research Articles

Comparative Pharmacodynamics and Plasma Concentrations of d-threo-Methylphenidate Hydrochloride After Single Doses of d-threo-Methylphenidate Hydrochloride and d,l-threo-Methylphenidate Hydrochloride in a Double-Blind, Placebo-Controlled, Crossover Laboratory School Study in Children With Attention-Deficit/Hyperactivity Disorder

Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dextro-levo). The initial commercial formulation eliminated the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo isomer methylphenidate (d-MPH) rather than the l-threo isomer (l-MPH) is responsible for the clinical effects in children with attention-deficit/hyperactivity disorder (ADHD). This study compared the efficacy of acute equimolar doses of d-MPH and dl-MPH in reducing ADHD symptoms over an 8-hour period in a laboratory school setting and investigated the relationship of efficacy to plasma levels of MPH. Thirty-two children with ADHD enrolled in this double-blind, placebo-controlled, crossover study, and 31 completed the study. On seven separate occasions separated by at least 6 days, the children received a single morning dose of d-MPH (2.5, 5, or 10 mg), d,l-MPH (5, 10, or 20 mg), or placebo and then were observed in a laboratory classroom setting for 8 hours. At specified intervals, blinded observers rated behavior, and the children performed a computerized math test. The plasma levels of MPH were related to the response to study medication. The safety profiles of the two formulations were compared. For both formulations, the responses to both MPH preparations were dose related, the plasma concentrations of l-MPH were negligible and of d-MPH were indistinguishable, and clinical efficacy was highly correlated with plasma concentrations of d-MPH. The efficacy of the d-isomer was equivalent to the racemic preparation in reducing ADHD symptoms and increasing academic productivity. The efficacy of MPH resides in the d-isomer. The elimination of the l-isomer does not diminish the efficacy of an acute dose of methylphenidate.

A potential natural treatment for attention-deficit/hyperactivity disorder: evidence from a national study.

We examined the impact of relatively "green" or natural settings on attention-deficit/hyperactivity disorder (ADHD) symptoms across diverse subpopulations of children. Parents nationwide rated the aftereffects of 49 common after-school and weekend activities on children's symptoms. Aftereffects were compared for activities conducted in green outdoor settings versus those conducted in both built outdoor and indoor settings. In this national, nonprobability sample, green outdoor activities reduced symptoms significantly more than did activities conducted in other settings, even when activities were matched across settings. Findings were consistent across age, gender, and income groups; community types; geographic regions; and diagnoses. Green outdoor settings appear to reduce ADHD symptoms in children across a wide range of individual, residential, and case characteristics.

Polymorphisms of the dopamine transporter gene: influence on response to methylphenidate in attention deficit-hyperactivity disorder.

Attention deficit-hyperactivity disorder (ADHD) is a very common and heterogeneous childhood-onset psychiatric disorder, affecting between 3% and 5% of school age children worldwide. Although the neurobiology of ADHD is not completely understood, imbalances in both dopaminergic and noradrenergic systems have been implicated in the origin and persistence of core symptoms, which include inattention, hyperactivity, and impulsivity. The role of a genetic component in its etiology is strongly supported by genetic studies, and several investigations have suggested that the dopamine transporter gene (DAT1; SLC6A3 locus) may be a small-effect susceptibility gene for ADHD. Stimulant medication has a well-documented efficacy in reducing ADHD symptoms. Methylphenidate, the most prescribed stimulant, seems to act mainly by inhibiting the dopamine transporter protein and dopamine reuptake. In fact, its effect is probably related to an increase in extracellular levels of dopamine, especially in brain regions enriched in this protein (i.e. striatum). It is also important to note that dopamine transporter densities seem to be particularly elevated in the brain of ADHD patients, decreasing after treatment with methylphenidate. Altogether, these observations suggest that the dopamine transporter does play a major role in ADHD. Among the several polymorphisms already described in the SLC6A3 locus, a 40 bp variable number of tandem repeats (VNTR) polymorphism has been extensively investigated in association studies with ADHD. Although there are some negative results, the findings from these reports indicate the allele with ten copies of the 40 bp sequence (10-repeat allele) as the risk allele for ADHD. Some investigations have suggested that this polymorphism can be implicated in dopamine transporter gene expression in vitro and dopamine transporter density in vivo, even though it is located in a non-coding region of the SLC6A3 locus. Despite all these data, few studies have addressed the relationship between genetic markers (specifically the VNTR) at the SLC6A3 locus and response to methylphenidate in ADHD patients. A significant effect of the 40 bp VNTR on response to methylphenidate has been detected in most of these reports. However, the findings are inconsistent regarding both the allele (or genotype) involved and the direction of this influence (better or worse response). Thus, further investigations are required to determine if genetic variation due to the VNTR in the dopamine transporter gene is able to predict different levels of clinical response and palatability to methylphenidate in patients with ADHD, and how this information would be useful in clinical practice.

Treatment of ADHD with methylphenidate may sensitize brain substrates of desire

Aims. Currently, methylphenidate (MPH, trade name Ritalin) is the most widely prescribed medication for attention deficit/hyperactivity disorder (ADHD). We examined the ability of repeated MPH administration to produce a sensitized appetitive eagerness type response in laboratory rats, as indexed by 50-kHz ultrasonic vocalizations (50-kHz USVs). We also examined the ability of MPH to reduce play behavior in rats which may be partially implicated in the clinical efficacy of MPH in ADHD. Design. 56 adolescent rats received injections of either 5.0 mg/kg MPH, or vehicle each day for 8 consecutive days, and a week later received a challenge injection of either MPH or vehicle. Measurements. Both play behavior (pins) and 50-kHz USVs were recorded after each drug or vehicle administration. Results. MPH challenge produced a substantial 73% reduction in play behavior during the initial treatment phase, and during the last test (1 week post drug), 50-kHz USVs were elevated approximately threefold only in animals with previous MPH experience. Conclusions. These data suggest that MPH treatment may lead to psychostimulant sensitization in young animals, perhaps by increasing future drug-seeking tendencies due to an elevated eagerness for positive incentives. Further, we hypothesize that MPH may be reducing ADHD symptoms, in part, by blocking playful tendencies, whose neuro-maturational and psychological functions remain to be adequately characterized.

Family coherence and ADHD.

A lack of perseverance, poor attention, and poorly modulated behaviour are important criteria of Attention Deficit Hyperactivity Disorder (ADHD). Instructions often must be repeated, sometimes even by different family members, before a child with ADHD attends and complies. The hyperkinetic child might cause less disruption in families with high coherence. Families of 15 boys (aged 6 to 12 years) diagnosed with ADHD using the Mannheim Parent's Interview and the teacher's form of the Conners scale were compared with a matched healthy control group of 15 boys. Parents completed a form assessing the family's cooperation and childrearing practices. Intrafamilial coherence seems to have little positive association with the family's characteristics, especially for boys with Attention Deficit Hyperactivity Disorder. Low coherence among family members may reduce ADHD symptoms and may have protective effects on children with ADHD.

Socioeconomic Status as a Moderator of ADHD Treatment Outcomes

To explore whether socioeconomic status (SES) variables moderate treatment response of attention-deficit/hyperactivity disorder (ADHD) to medication management (MedMgt), behavioral treatment (Beh), combined intervention (Comb), and routine community care (CC). The MTA Cooperative Group's intent-to-treat (ITT) analyses were repeated, covarying for composite Hollingshead SES, education, occupation, income, and marital status. Individual SES variables were more informative than the composite Hollingshead Index. Treatment response of children from less educated households paralleled ITT outcomes: no significant difference was found between Comb and MedMgt (both better than Beh and CC) for core ADHD symptoms. However, children from more educated families showed superior reduction of ADHD symptoms with Comb. For oppositional-aggressive symptoms, children from blue-collar, lower SES households benefited most from Comb, whereas those from white-collar, higher SES homes generally showed no differential treatment response. Household income and marital status failed to influence outcomes. Controlling for treatment attendance attenuated the moderating effects of the SES variables only for MedMgt. Investigators are encouraged to use independent SES variables for maximal explanation of SES effects. Clinicians should prioritize target symptoms and consider the mediating role of treatment adherence when determining an ADHD patient's optimal intervention plan.

A Pilot Controlled Trial of Transdermal Nicotine in the Treatment of Attention Deficit Hyperactivity Disorder

Summary: Objective: To test the hypothesis that transdermal nicotine would be efficacious for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD).Method: This was a double-blind, placebo-controlled, randomized, pilot trial that compared the effects of daily transdermal nicotine (5 mg/16 hrs) to placebo in children and adolescents with ADHD. There was a three-day washout period of all psychotropic medication followed by a one-week treatment period.Results: All 10 subjects enrolled (six males, four females; mean age = 10 years, SEM = 0.8) completed the study. As assessed by the 48-item Conners Parent Rating Scale at endpoint and during the trial, there was a significantly greater reduction in ADHD symptoms on “Learning Problems” and “Hyperactivity” subfactors. Nausea, stomach ache, itching under patch and dizziness were the most frequently reported adverse effects associated with transdermal nicotine.Conclusions: While the results of this study support previous research indicating that nicotinic receptor modulation may be a potentially useful strategy for the treatment of ADHD, therapeutic uses of nicotine are limited due to side effects. Thus, future research should investigate ways of improving the therapeutic index of nicotinic ligands in the treatment of ADHD, such as testing selective nicotinic antagonists alone or in combination with cholinergic agonists.

ADHD Treatment Strategies Linked to Life-Cycle Stage

ADHD Treatment Strategies Linked to Life-Cycle Stage

Ziprasidone vs haloperidol in sequential IM/oral treatment of acute schizophrenia

To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD).In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global Impression of Improvement (CGI-I) scale.Two hundred patients were randomized. Modafinil produced significant reductions in ADHD-RS-IV total scores at school (n = 128; mean change ± SD: −17.5 ± 13.1 points) compared with placebo (n = 66; −9.7 ± 10.3 points; p < .0001). Similarly, modafinil reduced ADHD-RS-IV total scores at home compared with placebo (−17.6 ± 13.3 versus −7.5 ± 11.8 points; p < .0001). Fifty-two percent of patients randomized to modafinil and 18% of those randomized to placebo met prestudy criteria for responder on the CGI-I (p < .0001). Randomization to modafinil was associated with significantly more insomnia, headache, decreased appetite, and weight loss than randomization to placebo, but discontinuation attributed to adverse events did not differ statistically between treatment groups (modafinil, 5%; placebo, 6%).Modafinil was well tolerated and reduced ADHD symptoms at school and home compared with placebo.

Behavioral Treatment of Attention-Deficit Hyperactivity Disorder in the Classroom

Contingency management procedures have been successfully applied in a variety of school settings to treat children with Attention-Deficit Hyperactivity Disorder (ADHD). The present study investigated the efficacy of response-cost contingencies alone and in combination with directed-rehearsal procedures for managing the classroom behavior and academic productivity of two boys with ADHD. A within-subject reversal design with multiple-baseline components across academic work periods (i.e., reading and language) was employed to evaluate each child's behavior and academic performance. Response-cost contingencies led to marked improvements in each student's task-related attention and a reduction in other ADHD symptoms. Response-cost effects on academic productivity and differential effects associated with directed-rehearsal contingencies were equivocal. In addition to promoting greater attention to independent seat-work, response-cost procedures have the potential to affect other important areas of classroom functioning such as behavioral control during teacher lectures.