Newcorn JH, Sutton VK, Weiss MD, Sumner CR.
J Am Acad Child Adolesc Psychiatry. 2009 Mar 23.

OBJECTIVE: Clinical experience suggests that some (but not all) patients with attention-deficit/hyperactivity disorder (ADHD) are highly responsive to the nonstimulant atomoxetine. We conducted a retrospective analysis of randomized controlled trials (RCTs) to identify potential baseline (moderator) and on-treatment (mediator) predictors of responses.
METHOD: Data from 6 U.S. RCTs among patients aged 6 to 18 years were pooled (N = 1,069; subjects treated with atomoxetine, n = 618). Subjects were categorized as much improved (>/=40% decrease in ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored total score), minimally improved (25%-<40% decline), or nonresponders (<25% decrease). Logistic regression, analyses of variance, and repeated-measures analyses were used to explore associations between baseline and on-treatment variables, achieving a much improved response at trial endpoint (6-9 weeks).
RESULTS: Forty-seven percent of patients showed a much improved clinical response, and 40% did not respond. Only 13% of the patients had a minimal response. No baseline characteristics predicted achieving a much improved clinical response; the only predictor of achieving this response was being at least minimally improved by treatment week 4 (sensitivity = 81%, specificity = 72%, positive predictive value = 75%, and negative predictive value = 79%).

CONCLUSIONS: Clinical response to atomoxetine was bimodal, with most subjects being either responders who were much improved or nonresponders. There were no demographic or clinical predictors of response. However, subjects who ultimately achieved a much improved response were likely to be at least minimal responders by week 4. The recommendation to consider either augmenting or switching treatment in patients who do not achieve at least this level of response to atomoxetine by 4 weeks offers a method for limiting the extended duration of titration to subjects who are most likely to benefit further, while minimizing the duration of exposure in those less likely to achieve an excellent response.Clinical trials registration information-Evaluation of Continuous Symptom Treatment of ADHD: A Placebo-Controlled Double-Blind Assessment of Morning-Dosed or Evening-Dosed Strattera.

2. Better efficacy for the osmotic release oral system methylphenidate among poor adherents to immediate-release methylphenidate in the three ADHD subtypes.

Chou WJ, Chou MC, Tzang RF, Hsu YC, Gau SS, Chen SJ, Wu YY, Huang YF, Liang HY, Cheng H.
Department of Child Psychiatry, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Psychiatry Clin Neurosci. 2009 Apr; 63(2):167-75.

AIMS: To determine factors for switching to osmotic release oral system methylphenidate (OROS-MPH) among poor adherents to immediate-release methylphenidate (IR-MPH); and to compare the efficacy of OROS-MPH on the three attention-deficit/hyperactivity disorder (ADHD) subtypes in a multi-site prospective observational study in Taiwan.

METHODS: The sample included 240 children with ADHD, aged 6-16 years, who were poor adherents to IR-MPH, 137 of whom were switched to OROS-MPH. The child psychiatrists diagnosed the Diagnostic Statistical Manual of Mental Disorders (4th edition) ADHD subtypes and assessed the medical history, adherence, side-effects, global ADHD severity, and family/school effectiveness. Parents reported their child's behavioral symptoms.

RESULTS: The determinants for an OROS-MPH switch were higher dosage, shorter treatment and thrice-daily administration of IR-MPH, and more severe inattention symptoms. Hyperactivity and oppositional symptoms were greater in the ADHD combined and hyperactive-impulsive subtypes than the inattentive subtype. Switching to OROS-MPH significantly improved behavioral symptoms and family/school measures, and this was most evident in the ADHD-combined group, followed by the ADHD-inattentive group. Inattention influenced not only academic performance, but also overall classroom behaviors and the parent-child relationship, with the latter two also influenced by oppositional symptoms.

CONCLUSIONS: This study suggests better efficacy for the OROS-MPH among poor adherents to IR-MPH; however, its effectiveness varied across the three ADHD subtypes

3. Sleep Problems Common in Children with ADHD

Sleep 2009;32:343-350.

NEW YORK (Reuters Health) Mar 26 - Nonmedicated children with attention deficit/hyperactivity disorder (ADHD) often have sleep disturbances characterized by difficulty falling asleep and short duration of sleep and of REM sleep, Canadian investigators have found.
"Clinicians have reported sleep problems in an estimated 25 to 50% of children with ADHD, and treatment of sleep problems has been shown to improve behavior and decrease the need for stimulant medication in children with ADHD," lead author Dr. Reut Gruber at McGill University told Reuters Health.
"My work is geared toward exploring new avenues of examination to help understand the basic mechanisms associated with ADHD, optimizing treatment, and minimizing unnecessary use of medication," she added.

To compare sleep architecture in children with and without ADHD, the researchers conducted standard overnight multichannel polysomnography evaluations performed at each child's home using a portable polysomnography device. The 15 children with ADHD and 23 normal controls (ages 7 to 11 years) were not taking medications and had not consumed caffeine for at least a week prior to the test.
According to results published in the March 1 issue of Sleep, those with ADHD averaged significantly reduced total sleep time (499 min) compared with the control group (533 min), reduced REM sleep (84 min vs 100 min), and a smaller percentage of REM sleep out of total sleep tie (17% vs 19%).
Parental questionnaire responses indicated significantly more problems with sleep onset delay, sleep anxiety, and insufficient sleep as indicated by daytime sleepiness.
These findings point to a "delayed endogenous circadian pacemaker" in children with ADHD, Dr. Gruber's team maintains.
Currently, Dr. Gruber is evaluating the benefits of light therapy or sleep extension for children with ADHD.
"Over the next 5 years," she continued, "I plan to study the mechanisms underlying the interplay between sleep, behavior and attention in children with ADHD, and to develop sleep-based therapeutic interventions for ADHD."
To that end, she has "obtained specialized equipment for measuring sleep and activity in the child's natural environment, instruments for measuring circadian parameters, as well as specialized software to measure neurobehavioral processes, neurophysiological functioning and to integrate observational and physiological methods."
Until such research is completed, she strongly advises physicians "to assess sleep and signs of daytime fatigue in children with ADHD. If this is the case, depending on the clinical picture, a thorough investigation should be made and recommendations should be tailored to each individual child."

4. Attention-deficit hyperactivity disorder: treatment discontinuation in adolescents and young adults.

McCarthy S, Asherson P, Coghill D, Hollis C, Murray M, Potts L, Sayal K, de Soysa R, Taylor E, Williams T, Wong IC.

Centre for Paediatric Pharmacy Research, School of Pharmacy, University of London and Institute of Child Health, University College London, UK.
Br J Psychiatry. 2009 Mar; 194(3):273-7.

BACKGROUND: Symptoms of attention-deficit hyperactivity disorder (ADHD) are known to persist into adulthood in the majority of cases.
AIMS: To determine the prevalence of methylphenidate, dexamfetamine and atomoxetine prescribing and treatment discontinuation in adolescents and young adults.
METHOD: A descriptive cohort study using the UK General Practice Research Database included patients aged 15-21 years from 1999 to 2006 with a prescription for a study drug. RESULTS: Prevalence of prescribing averaged across all ages increased 6.23-fold over the study period. Overall, prevalence decreased with age: in 2006, prevalence in males dropped 95% from 12.77 per 1000 in 15-year-olds to 0.64 per 1000 in 21-year-olds. A longitudinal analysis of a cohort of 44 patients aged 15 years in 1999 demonstrated that no patient received treatment after the age of 21 years.
CONCLUSIONS: The prevalence of prescribing by general practitioners to patients with ADHD drops significantly from age 15 to age 21 years. The fall in prescribing is greater than the reported age-related decrease in symptoms, raising the possibility that treatment is prematurely discontinued in some young adults in whom symptoms persist.

5. APA 2009: Male Drivers with ADHD Have More Collisions as They Age

May 22, 2009 (San Francisco, California) — Studies have shown that the core symptoms of attention deficit/hyperactivity disorder (ADHD) interfere with safe driving abilities. Although it's known that adolescents with ADHD are more likely to be involved in automobile collisions than teenagers in the general population, older adults with ADHD could also be more prone to more auto accidents than people of similar age without the disorder, according to a study presented here at the American Psychiatric Association (APA) 162nd Annual Meeting.

"Normally, people become better drivers as they age. But we found that collisions for males with ADHD steadily increased as they aged," study investigator Richard Merkel, MD, from the University of Virginia in Charlottesville, told Medscape Psychiatry.

By contrast, collisions tended to decline among older female ADHD drivers as they aged —similar to the trend seen in the general population, according to the new research.
In the study, researchers posted a survey of drivers with ADHD on 5 Web sites, including 1 run by Children and Adults with Attention Deficit/Hyperactivity Disorder, for 6 months.
Two thirds of those who responded did not complete the survey entirely and were eliminated from the study. Of all qualifying surveys, 156 were completed by males and 283 were completed by females who had been diagnosed with ADHD.

Possible Selection Bias?

Overall, the study comprised 142 adolescents (16 to 18 years), 161 young adults (19 to 25 years), and 136 middle-aged people with ADHD (26 to 62 years). Results indicated that in the previous 12 months, 28% reported receiving a citation, 34% reported being involved in an automobile collision, and 44% reported either a citation or collision.

Middle-aged adult male drivers reported 1.1 automobile collisions in the previous year — a number higher than that in the general population. A similar national survey of the general population reported only 0.06 collisions in the previous 24 months, according to Dr. Merkel.

The researchers concluded that long-acting stimulant medication is needed for ADHD drivers; it has been shown that these treatments improve driving ability.
"Most of the people in the survey were not adequately treated, if at all," Dr. Merkel said.

Although the study is an interesting one, at least 1 expert questioned its validity. "Part of the problem with Internet-based surveys is that people self-diagnose with ADHD. And there may be some selection bias in the study. So the people who responded may be more likely to have problems with ADHD, and may thus be more likely to be involved in accidents," said Iqbal Ahmed, MD, from the University of Hawaii in Honolulu, and a member of the APA Scientific Program Committee.

Ahmed conceded that it is entirely likely that drivers with ADHD are more prone to accidents than the general population, as are patients with cognitive disorders. "Still, I would expect that driving in older people, even those with ADHD, would get better with age. So what they're reporting doesn't make sense to me," he said.

Dr. Ahmed noted that attention is an important factor in driving ability: "It certainly makes senses that those with ADHD would have a higher rate of accidents in general," he said.

The study was supported by a grant from Shire Pharmaceutical Co. Dr. Merkel and Dr. Ahmed disclosed no relevant financial relationships.

American Psychiatric Association 2009 Annual Meeting: Abstract NR2-042. Presented May 18, 2009.