1. Efficacy of osmotic-release oral system (OROS) methylphenidate for mothers with attention-deficit/hyperactivity disorder (ADHD): preliminary report of effects on ADHD symptoms and parenting.

Chronis-Tuscano A, Seymour KE, Stein MA, Jones HA, Jiles CD, Rooney ME, Conlon CJ, Efron LA, Wagner SA, Pian J, Robb AS.

University of Maryland, Department of Psychology, College Park, MD 20742, USA.

J Clin Psychiatry. 2008 Dec; 69(12):1938-47. Epub 2008 Dec 2.

OBJECTIVE: A preliminary study to examine the efficacy of osmotic-release oral system (OROS) methylphenidate for attention-deficit/hyperactivity disorder (ADHD) symptoms and parenting behaviors in mothers with ADHD who had children with ADHD.

METHOD: Participants included 23 mother-child dyads in which both were diagnosed with DSM-IV ADHD. Mothers underwent a 5-week, double-blind titration (placebo, 36 mg/day, 54 mg/day, 72 mg/day, 90 mg/day) to an optimal dose of OROS methylphenidate, followed by random assignment to 2 weeks of placebo or their maximally effective dose. Primary outcome measures included maternal ADHD symptoms (Conners' Adult ADHD Rating Scale) and parenting (Alabama Parenting Questionnaire). Secondary outcomes included side effects ratings. Data were collected from December 2004 until August 2006.

RESULTS: During Phase 1, mothers reported significant decreases in inattention (p < .001) and hyperactivity/impulsivity (p < .01) with increases in OROS methylphenidate dose. As dose increased, significant reductions in inconsistent discipline (p < .01) and corporal punishment use (p < .005) were also demonstrated. During Phase 2, small effects on inattention (d = 0.46) and hyperactivity/impulsivity (d = 0.38) were found for those randomly assigned to medication versus placebo. In addition, medium to large medication effects were found on maternal involvement (d = 0.52), poor monitoring/supervision (d = 0.70), and inconsistent discipline (d = 0.71), with small effects on corporal punishment (d = 0.42). During both phases, few adverse effects were noted.

CONCLUSIONS: OROS methylphenidate was well tolerated and was associated with significant improvement in maternal ADHD symptoms and parenting. Variable effects on parenting suggest that behavioral interventions may be necessary to address impairments in parenting among adults with ADHD.

2. MAOA is associated with methylphenidate improvement of oppositional symptoms in boys with attention deficit hyperactivity disorder.

Guimarães AP, Zeni C, Polanczyk G, Genro JP, Roman T, Rohde LA, Hutz MH.

Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Int J Neuropsychopharmacol. 2009 Jun; 12(5): 709-14. Epub 2009 Mar 24.

The monoamine oxidase A (MAOA) gene has been extensively related to aggressive, impulsive and violent behaviours. Previous studies have documented the improvement of oppositional symptoms in attention deficit hyperactivity disorder (ADHD) patients with methylphenidate (MPH). However, the effect of the MAOA gene in response to MPH has not been investigated. A sample of 85 boys from an ADHD outpatient service was genotyped for the MAOA-uVNTR polymorphism. The outcome measure was the parent-rated oppositional subscale of the Swanson, Nolan and Pelham Scale - version IV. The scale was applied by child psychiatrists blinded to genotype at baseline and in the first and third months of treatment. A significant interaction between the presence of MAOA high-activity genotype and treatment with MPH over time on oppositional scores was detected during the 3 months' treatment (n=85, F2,136=4.83, p=0.009). These results suggest an effect of the MAOA-uVNTR high-activity genotype on the improvement of oppositional symptoms with MPH treatment.

3. Behavioral, neurocognitive and treatment overlap between attention-deficit/hyperactivity disorder and mood instability.

Skirrow C, McLoughlin G, Kuntsi J, Asherson P.
Expert Rev Neurother. 2009 Apr; 9(4):489-503.

Attention-deficit/hyperactivity disorder (ADHD) is a common and debilitating psychiatric disorder characterized by symptoms of inattention, impulsivity and motor restlessness. Consistently noted alongside these symptoms is mood instability in the form of irritability, volatility, swift changes in mood, hot temper and low frustration tolerance. The current diagnostic classification systems do not include mood instability as a core aspect of ADHD, but rather as an associated feature of the disorder. However, the literature suggests that overlapping cognitive deficits and neuroanatomical substrates may underlie both the classical ADHD symptoms and mood instability. Furthermore, common neurotherapeutic interventions in the form of stimulant medications or atomoxetine may help to alleviate both types of symptoms when they co-occur. This research suggests that mood instability and symptoms of ADHD may be interlinked and that mood instability may be better understood as a core feature of the ADHD syndrome.

4. Prospective, naturalistic, pilot study of open-label atomoxetine treatment in preschool children with attention-deficit/hyperactivity disorder.

Ghuman JK, Aman MG, Ghuman HS, Reichenbacher T, Gelenberg A, Wright R, Rice S, Fort C.
Department of Psychiatry, University of Arizona, Tucson, Arizona 85724-5002, USA.
J Child Adolesc Psychopharmacol. 2009 Apr; 19(2):155-66.

OBJECTIVE: The aim of this study was to report preliminary data regarding effectiveness and tolerability of atomoxetine in 3- to 5-year-old preschool children with attention-deficit/hyperactivity disorder (ADHD).
METHODS: Nine boys and 3 girls (mean age = 5.0 +/- 0.72 years) diagnosed with ADHD were treated with atomoxetine in an open-label pilot study. Atomoxetine was gradually titrated to a maximum dose of 1.8 mg/kg per day.
RESULTS: There was a significant effect of time from baseline to end point on the parent-rated hyperactivity/impulsivity Swanson Nolan and Pelham (SNAP-IV-HI) subscale ratings (F[9, 11] = 6.32, p < 0.0001). The mean difference between the baseline and end-point parent SNAP-IV-HI scores was 10.2 +/- 7.3 (p = 0.0005). The rate of positive response (defined as at least a 30% reduction in the end-point parent SNAP-IV-HI scores and a Clinical Global Impressions-Improvement [CGI-I] rating of Much Improved or Very Much Improved) was 75%. The Children's Global Assessment Scale scores improved significantly over time [F(9, 11) = 6.24 p < 0.001]. The mean end-point daily dose of atomoxetine was 1.59 +/- 0.3 mg/kg. A high proportion (66.7%) of the preschoolers experienced side effects with atomoxetine. Side effects of defiance, tantrums, aggression, and irritability were most disconcerting to parents, and gastrointestinal complaints were the most commonly reported adverse effects. One child was terminated from the study due to "chest ache." There were no changes in weight, height, or cardiovascular measures.
CONCLUSION: This open-label pilot study provides preliminary evidence of effectiveness and tolerability of atomoxetine for treating ADHD in preschool children, although double-blind, randomized, placebo-controlled studies are needed to confirm this

5. Methylphenidate has positive hypocholesterolemic and hypotriglyceridemic effects: new data;

Charach G, Kaysar N, Grosskopf I, Rabinovich A, Weintraub M;

Journal of Clinical Pharmacology 49 (7), 848-51 (Jul 2009)

Many psychotropic drugs may affect plasma lipids profile and their metabolism, with carbamazepine being the best known among them. Methylphenidate is a piperidine derivative structurally related to amphetamines and acts as a central nervous system stimulant. Its effect on lipid metabolism has not been investigated. The authors evaluated how methylphenidate affects the lipid profile in the plasma of patients diagnosed as having attention-deficit hyperactivity disorder (ADHD). All consecutive patients undergoing treatment for ADHD at the Adolescent Psychiatric Clinic (2003-2007) were enrolled. Blood samples for total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A, apolipoprotein B, and lipoprotein (a) (Lp(a)) were collected before starting treatment and after 3 months of continuous treatment. Forty-two patients (22 men), median age 16, participated. The median total cholesterol count decreased by 9 mg/dL (P<.0002), LDL-C decreased by 5.0 mg/dL (P<.016), and triglycerides decreased by 8.0 mg/dL (P<.016). Changes in the levels of HDL-C, apolipoprotein A, and apolipoprotein B were nonsignificant, and Lp(a) levels decreased by 2.0 mg/dL (P<.0007). Methylphenidate improves the lipid profile by decreasing total cholesterol, triglycerides, LDL-C, and Lp(a).