Adler LA, Spencer T, Brown TE, Holdnack J, Saylor K, Schuh K, Trzepacz PT, Williams DW, Kelsey D;

J Clin Psychopharmacol |29 (1), 44-50 (Feb 2009)

This randomized, double-blind, placebo-controlled, 6-month trial examined the efficacy and safety of once-daily morning-dosed atomoxetine in adult patients with attention-deficit/hyperactivity disorder (ADHD) and the efficacy of atomoxetine in ameliorating symptoms through the evening hours. Patients received once-daily atomoxetine (n = 250) or placebo (n = 251) in the morning for approximately 6 months. The efficacy measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version, Clinical Global Impressions-ADHD-Severity of Illness, and Adult ADHD Quality of Life Scale. Overall, 94 patients randomized to atomoxetine and 112 patients randomized to placebo completed the study. On the AISRS total score, Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version evening index total score, Clinical Global Impressions-ADHD-Severity of Illness score, and Adult ADHD Quality of Life Scale total score, atomoxetine was statistically superior to placebo at the 10-week and 6-month time points. From the visitwise analysis, the mean (SD) AISRS total scores for atomoxetine decreased from 38.2 (7.5) at baseline to 21.4 (12.3) at the 6-month end point compared with 38.6 (7.0) to 25.8 (13.2) for placebo (P = 0.035). Nausea, dry mouth, fatigue, decreased appetite, urinary hesitation, and erectile dysfunction were the treatment-emergent adverse events reported significantly more often with atomoxetine. Discontinuations due to adverse events were 17.2% and 5.6% for atomoxetine and placebo, respectively (P<0.001). Once-daily morning-dosed atomoxetine is efficacious for treating ADHD in adults when measured 10 weeks and 6 months after initiating treatment. Atomoxetine demonstrated significant efficacy that continued into the evening. Adverse events were similar to previous trials.

2. Revisão da literatura sobre a comorbidade do transtorno do déficit de atenção e hiperatividade com transtornos alimentares.

Nazar, Bruno Palazzo et al.

Rev. Bras. Psiquiatr. 2008, v. 30, n. 4, pp. 384-389.

OBJETIVO: De acordo com os estudos de prevalência de comorbidades, até 70% dos adultos com transtorno do déficit de atenção e hiperatividade apresentam pelo menos uma comorbidade psiquiátrica, ocasionando dificuldades diagnósticas e terapêuticas, bem como um maior prejuízo funcional. Existem poucos estudos sobre a comorbidade entre transtorno do déficit de atenção e hiperatividade e transtornos alimentares. O objetivo deste estudo foi realizar uma revisão da literatura sobre a comorbidade transtorno do déficit de atenção e hiperatividade/transtornos alimentares, realizando uma análise crítica dos dados encontrados.

MÉTODO: Procedeu-se a uma revisão sistemática da literatura por meio de pesquisa bibliográfica de artigos publicados no período de 1980 a 2008, utilizando as bases de dados Medline, Lilacs, SciELO, ISI e PsycINFO.

RESULTADOS: Foram identificados 14 artigos, sendo cinco estudos de prevalência de comorbidades, quatro relatos de casos, três estudos caso-controle, um estudo de avaliação de sintomas de transtorno do déficit de atenção e hiperatividade e de transtornos alimentares e um sobre as possíveis causas da associação entre transtorno do déficit de atenção e hiperatividade e transtornos alimentares. Os artigos identificados evidenciaram maior risco de desenvolvimento de transtornos alimentares, especialmente bulimia nervosa, em mulheres portadoras de transtorno do déficit de atenção e hiperatividade. As taxas de bulimia nervosa encontradas nos grupos com transtorno do déficit de atenção e hiperatividade variaram de 1% a 12%, enquanto que nos grupos controle foram de 0% a 2%.

CONCLUSÕES: Embora pareça existir uma relação entre transtorno do déficit de atenção e hiperatividade e transtornos alimentares, a escassez de trabalhos existentes, com metodologias variadas e pequenas amostras avaliadas não permitem a generalização dos resultados.

3. No Adverse Effects of Psychostimulants on Brain Development

Philip Shaw, MD, PhD, from the National Institute of Mental Health, in Bethesda, Maryland

Am J Psychiatry. 2009; 166:58-63

Psychostimulants do not appear to affect the development of brain structure in children with attention-deficit/hyperactivity disorder (ADHD), a new longitudinal imaging study suggests.
The first prospective study to examine whether psychostimulant treatment in young patients with ADHD is associated with differences in the development of the cerebral cortex showed that there were few differences between ADHD subjects taking stimulants and their untreated counterparts. In addition, there were no differences in clinical outcomes between the 2 groups.
"Essentially what we found is that over time there was very little difference in how the cortex developed, whether kids were treated with psychostimulants or not," principal investigator Philip Shaw, MD, PhD, from the National Institute of Mental Health, in Bethesda, Maryland, told Medscape Psychiatry.

Big Concern
According to Dr. Shaw, the impetus for the study came from evidence suggesting that psychostimulant use in children may slow physical growth.
However, he added, subsequent longer-term follow-up examining the impact of these medications on physical development suggests the slowed effect is limited to the initial stages of treatment and that children treated with these agents may ultimately catch up to their untreated peers.
Nevertheless, he added, the initial suggestion that psychostimulants may have a negative impact on height and weight gain in developing children was a "big concern," prompting the researchers to question whether these drugs may have a similar effect on the brain.
For the study, investigators examined changes in cortical thickness based on 2 neuroanatomic scans in 43 subjects with ADHD. Their mean age was 12.5 years at the time of the first scan and 16.4 years at the time of the second.
The scans of 19 subjects with ADHD not treated with psychostimulants were compared with an age-matched group of 24 individuals with ADHD who were treated with these medications. In addition, researchers further compared scans of the entire study cohort with 620 scans of 294 typically developing youths without ADHD.

No Clinical Differences
There were some areas of the brain, including the left dorsolateral prefrontal cortex and motor strip, where there was a significant difference between the 2 study groups.
In addition, said Dr. Shaw, the study showed that children who were on medication tended to have a trajectory of brain development that more closely resembled that of the typically developing comparison group.
In contrast, subjects who were not on stimulants tended to differ more in cortical development compared with their typically developing teenage peers. However, said Dr. Shaw, this finding must be interpreted with caution.
"This does not mean stimulants improve the brain. It is very important to note that there was no difference in clinical outcomes between children with ADHD who were and were not on stimulant medication. These imaging findings are subtle, so subtle in fact that they affect only a very small proportion of the brain, and whatever they mean, we know that they did not translate into clinical differences," said Dr. Shaw.
He added that these findings should not be used to inform treatment decisions.
"There are many excellent treatment studies that have been done that inform the treatment of ADHD. This was not a treatment study. It was designed strictly to look at the potential impact of these medications on the developing brain, and so the findings are not clinically relevant," he said.
Nevertheless, he added, the study does send a reassuring message that stimulant medications do not appear to adversely affect the developing brain.

4. Methylphenidate and amphetamine do not induce cytogenetic damage in lymphocytes of children with ADHD.

Witt KL, Shelby MD, Itchon-Ramos N, Faircloth M, Kissling GE, Chrisman AK, Ravi H, Murli H, Mattison DR, Kollins SH.

National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services

J Am Acad Child Adolesc Psychiatry. 2008 Dec ; 47(12):1375-83.

OBJECTIVE: In response to previously published findings of methylphenidate-induced chromosomal changes in children, this study was designed to determine whether methylphenidate- or amphetamine-based drugs induce chromosomal damage (structural aberrations, micronuclei, and sister chromatid exchanges) in peripheral blood lymphocytes of children with attention-deficit/hyperactivity disorder after 3 months of continuous treatment.

METHOD: Stimulant drug-naïve subjects, 6 to 12 years of age, in good overall health, and judged to be appropriate candidates for stimulant therapy based on rigorously diagnosed ADHD using DSM-IV criteria, were randomized into two open-label treatment groups (methylphenidate or mixed amphetamine salts). Each subject provided a blood sample before initiation of treatment and after 3 months of treatment. Pretreatment and posttreatment frequencies of chromosomal aberrations, micronuclei, and sister chromatid exchanges were determined for each subject.

RESULTS: Sixty-three subjects enrolled in the study; 47 subjects completed the full 3 months of treatment, 25 in the methylphenidate group and 22 in the amphetamine group. No significant treatment-related increases were observed in any of the three measures of cytogenetic damage in the 47 subjects who completed treatment or the 16 subjects who did not.

CONCLUSIONS: Earlier findings of methylphenidate-induced chromosomal changes in children were not replicated in this study. These results add to the accumulating evidence that therapeutic levels of methylphenidate do not induce cytogenetic damage in humans. Furthermore, our results indicate that amphetamine-based products do not pose a risk for cytogenetic damage in children.

5. Early head injury and attention deficit hyperactivity disorder: retrospective cohort study.

Keenan HT, Hall GC, Marshall SW.
Department of Pediatrics, University of Utah, Salt Lake City.

BMJ. 2008 Nov 6; 337:a1984. Doi: 10.1136/bmj.a1984

OBJECTIVE: To explore the hypothesis that medically attended head injury in young children may be causal in the later development of attention deficit hyperactivity disorder.

DESIGN: Retrospective cohort study.

SETTING: Health improvement network database (1988-2003), a longitudinal UK general practice dataset.

PARTICIPANTS: All children registered in the database from birth until their 10th birthday.

MAIN OUTCOME MEASURES: Risk of a child with a head injury before age 2 developing attention deficit hyperactivity disorder before age 10 compared with children with a burn injury before age 2 and children with neither a burn nor a head injury.

RESULTS: Of the 62 088 children who comprised the cohort, 2782 (4.5%) had a head injury and 1116 (1.8%) had a burn injury. The risk of diagnosis of attention deficit hyperactivity disorder before 10 years of age after adjustment for sex, prematurity, socioeconomic status, and practice identification number was similar in the head injury (relative risk 1.9, 95% confidence interval 1.5 to 2.5) and burn injury groups (1.7, 1.2 to 2.5) compared with all other children.

DISCUSSION: Medically attended head injury before 2 years of age does not seem to be causal in the development of attention deficit hyperactivity disorder. Medically attended injury before 2 years of age may be a marker for subsequent diagnosis of attention deficit hyperactivity disorder.