Nock MK, Kazdin AE, Hiripi E, Kessler RC.
Department of Psychology, Harvard University, Cambridge, MA 02138, USA.

J Child Psychol Psychiatry. 2007 Jul; 48(7):703-13.

BACKGROUND: Oppositional defiant disorder (ODD) is a leading cause of referral for youth mental health services; yet, many uncertainties exist about ODD given it is rarely examined as a distinct psychiatric disorder. We examined the lifetime prevalence, onset, persistence, and correlates of ODD.

METHODS: Lifetime prevalence of ODD and 18 other DSM-IV disorders was assessed in a nationally representative sample of adult respondents (n = 3,199) in the National Comorbidity Survey Replication. Retrospective age-of-onset reports were used to test temporal priorities with comorbid disorders.

RESULTS: Lifetime prevalence of ODD is estimated to be 10.2% (males = 11.2%; females = 9.2%). Of those with lifetime ODD, 92.4% meet criteria for at least one other lifetime DSM-IV disorder, including: mood (45.8%), anxiety (62.3%), impulse-control (68.2%), and substance use (47.2%) disorders. ODD is temporally primary in the vast majority of cases for most comorbid disorders. Both active and remitted ODD significantly predict subsequent onset of secondary disorders even after controlling for comorbid conduct disorder (CD). Early onset (before age 8) and comorbidity predict slow speed of recovery of ODD.

CONCLUSIONS: ODD is a common child- and adolescent-onset disorder associated with substantial risk of secondary mood, anxiety, impulse-control, and substance use disorders. These results support the study of ODD as a distinct disorder. Prospective and experimental studies are needed to further delineate the temporal and causal relations between ODD and related disorders.

2. Atomoxetine Treatment for Pediatric Patients with Attention-Deficit/Hyperactivity Disorder with Comorbid Anxiety Disorder.

Geller D, Donnelly C, Lopez F, Rubin R, Newcorn J, Sutton V, Bakken R, Paczkowski M, Kelsey D, Sumner C.

OBJECTIVE: Research suggests 25% to 35% of children with attention-deficit/hyperactivity disorder (ADHD) have comorbid anxiety disorders. This double-blind study compared atomoxetine with placebo for treating pediatric ADHD with comorbid anxiety, as measured by the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Pediatric Anxiety Rating Scale (PARS).

METHOD: Patients (ages 8-17 years) meeting DSM-IV criteria for ADHD and generalized anxiety disorder, separation anxiety disorder, and/or social phobia were randomized to 12 weeks of atomoxetine (n = 87) or placebo (n = 89). ADHDRS-IV-PI and PARS total scores were analyzed using analysis of covariance last observation carried forward and repeated-measures analyses.

RESULTS: Sixty-six patients in each group completed the study. Mean ADHDRS-IV-PI total score improved significantly for atomoxetine (n = 55; -10.5, SD 10.6) relative to placebo (n = 58; -1.4, SD 8.3; p < .001). Mean PARS total score also improved significantly for atomoxetine (n = 55; -5.5, SD 4.8) relative to placebo (n = 58; -3.2, SD 5.0; p = .011).

CONCLUSIONS: Atomoxetine was efficacious in reducing ADHD symptoms in patients who have ADHD with comorbid anxiety and was well tolerated. There was also a significant reduction in independently assessed anxiety symptoms using both clinician-rated and self-rated measures, which merits further investigation. Results support consideration of atomoxetine for the treatment of ADHD in youths who have ADHD with comorbid anxiety disorder. Clinical trial registration information: The LYBP study, on which this article is based, was not registered at clinicaltrials.gov because the last patient visit occurred before July 1, 2005. Results, however, are publicly posted at lillytrials.com and clinicalstudyresults.org. The unique study ID at both sites is 6477a.

3. High-Dose Atomoxetine Treatment of ADHD in Youths with Limited Response to Standard Doses.

Kratochvil CJ, Michelson D, Newcorn JH, Weiss MD, Busner J, Moore RJ, Ruff DD, Ramsey J, Dickson R, Turgay A, Saylor KE, Luber S, Vaughan B, Allen AJ; THE ATOMOXETINE HIGH-DOSE STUDY GROUP.

J Am Acad Child Adolesc Psychiatry. 2007 Sep; 46(9):1128-1137.

OBJECTIVE: To assess the utility and tolerability of higher than standard atomoxetine doses to treat attention-deficit/hyperactivity disorder (ADHD).

METHOD:: Two randomized, double-blind trials of atomoxetine nonresponders ages 6 to 16 years were conducted comparing continued treatment with same-dose atomoxetine to treatment using greater than standard efficacious doses (study 1: up to 3.0 mg . kg . day; study 2: up to 2.4 mg . kg . day).

RESULTS: The primary outcome measure for both studies was mean ADHD Rating Scale (ADHD RS) total score. For study 1 (N = 122), decreases in ADHD RS total scores were not significantly different between treatment groups (mean change [SD]: continued same dose, -8.9 [11.2]; high dose, -9.8 [13.1]; p = .595). Likewise, for study 2 (N = 125), treatment groups did not differ (mean change [SD]: continued same dose, -6.2 [12.2]; high dose, -8.9 [10.0], p =.110). Tolerability was not significantly different between the continued same-dose and high-dose groups.

CONCLUSIONS: These studies provide evidence that current dose recommendations are appropriate for most patients, suggesting no systematic advantage to increasing atomoxetine doses beyond current guidelines. In both studies, continued treatment, whether at a higher dose or the previous dose, was associated with improved outcomes in patients who demonstrated incomplete/inadequate response to acute ADHD treatment, although without a placebo arm, we cannot rule out the possibility that expectancy played a role in symptom improvement.

4. Long-term effects of methylphenidate transdermal delivery system treatment of ADHD on growth.

Faraone SV, Giefer EE.

J Am Acad Child Adolesc Psychiatry. 2007 Sep; 46(9):1138-47

OBJECTIVE: To examine the long-term effects of the methylphenidate transdermal system (MTS) on the growth of children being treated for attention-deficit/hyperactivity disorder.

METHOD: Height, weight, and body mass index (BMI) were measured in 127 children ages 6 to 12 at longitudinal assessments for up to 36 months of treatment with MTS. These data were compared with norms provided by the Centers for Disease Control and Prevention.

RESULTS: MTS treatment was associated with small but significant delays in growth for height, weight, and BMI. The latter two indices were affected in a dose-dependent manner. Children who had not received prior stimulant therapy and children who entered the study with above-average height, weight, and BMI were most likely to experience growth deficits during the trial. Effects on all parameters of growth were most apparent during the first year of treatment, and attenuated over time.

CONCLUSIONS: Consistent with prior studies of methylphenidate, our results suggest that treatment with MTS can lead to reductions in expected height, weight, and BMI that show some attenuation over the course of treatment. Growth of patients with attention-deficit/hyperactivity disorder treated with MTS should be closely monitored, but in this study, deficits in growth in relation to MTS treatment were not a significant clinical concern for most children.

5. Is age-at-onset criterion relevant for the response to methylphenidate in attention-deficit/hyperactivity disorder?

Reinhardt MC, Benetti L, Victor MM, Grevet EH, Belmonte-de-Abreu P, Faraone SV, Rohde LA.
ADHD Outpatient Program, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

J Clin Psychiatry. 2007 Jul; 68(7): 1109-16

OBJECTIVE: Since DSM-IV criteria for attention-deficit/hyperactivity disorder (ADHD) require that some symptoms causing impairment must be present before 7 years of age, clinicians are faced with a diagnostic and treatment dilemma on how to proceed with late-onset ADHD patients. We aimed to compare the response to methylphenidate between a group of patients fulfilling all DSM-IV ADHD criteria (full ADHD diagnosis) and a group of patients fulfilling all DSM-IV criteria except the age-at-onset criterion (late-onset ADHD).

METHOD: We evaluated 180 children and adolescents (4-17 years old) and 111 adults from our ADHD unit. All ADHD diagnoses were assessed using DSM-IV criteria. Methylphenidate was administered twice daily (8 a.m. and noon), but an extra dose was allowed between 5 and 6 p.m. for children and adolescents needing extra coverage in the evening. The minimum dose was 0.30 mg/kg/day. Response to treatment was assessed in methylphenidate naive subjects using the Swanson, Nolan, and Pelham Scale-version IV (SNAP-IV) at baseline and after 1 month of treatment. Data were collected from January 2000 to January 2006.

RESULTS: In both samples, subjects with the full ADHD diagnosis did not have a better response to methylphenidate at doses around 0.5 mg/kg/day than the late-onset ADHD subjects. In fact, adults with late-onset ADHD had a better response to methylphenidate than adults with the full diagnosis, even after adjustment for confounders (baseline SNAP-IV total score and ADHD types) (children and adolescents: F = 0.865, p = .354; adults: F = 5.760, p = .018).

CONCLUSION: These results concur with recent literature questioning the validity of the DSM-IV age-at-onset criterion for the diagnosis of ADHD and suggest that clinicians should consider implementing methylphenidate treatment for subjects with late-onset ADHD.