Attention-Deficit/Hyperactivity Disorder and antidepressants and prescription medications: A pilot study

Background. Attention Deficit-Hyperactivity Disorder (AD/HD) diagnosis in children and adolescents has been on the rise over the last couple of decades and a multitude of studies have been conducted in an aim to better understand the disease. Literature has explored the role of several factors suspected of contributing to development of the disease, including: prenatal smoking exposures, environmental exposures, and low-birth weight. However, there is very limited reporting of fetal/infant exposure to antidepressants and prescription medications and the long-term behavioral outcomes, namely development of AD/HD. The purpose of this study was to evaluate the relationship between mother's exposure to prescription medications and/or antidepressants around the time of conception, during pregnancy, or while breastfeeding and the development of Attention-Deficit/Hyperactivity Disorder in offspring. Methods. Secondary analysis of data from a case-control study was performed. Exposure histories were collected for the mother and offspring. Data were collected using a secure, confidential, self-report, online survey to evaluate the relationship between antidepressant and/or prescription medication exposure and the development of AD/HD. The period of exposure to these drugs was defined as: around the time of conception, during pregnancy, or while breastfeeding. Cases were defined as a child who had been diagnosed with AD/HD. Controls were defined as a child who had not been diagnosed with AD/HD. Results. Prescription medication and antidepressant medication exposures around the time of conception, during pregnancy, or while breastfeeding were not associated with development of AD/HD. However, traumatic brain injury (OR=2.77 (1.61–4.77)) and preterm birth (OR=1.48 (1.04–2.12)) were identified as potential risk factors. These results support existing literature on AD/HD, but future work must be undertaken to better evaluate fetal/infant medication exposures and long-term behavioral outcomes.^

The association of allergies and attention deficit hyperactivity disorder in children

To investigate the association between allergies and attention deficit hyperactivity disorder (ADHD), a case-control study was conducted using the National Longitudinal Survey of Youth population. Cases were between the ages of 4 and 11 years and were classified either by a maternal-reported diagnosis or by the Behavior Problems Index Hyperactivity Scale. Controls were chosen from the same age group but had a score of less than 14 on the overall Behavior Problems Index. A history of allergies was considered positive if any of the following conditions were reported as requiring treatment by a doctor or other health professional: asthma, allergic conditions, or food allergies. A strong association was observed between allergies and a maternal-reported diagnosis while controlling for demographic, socioeconomic, perinatal, and environmental factors (adjusted odds ratio = 2.85 (95% CI = 1.49-5.42)). Other risk factors found to be important risk factors for a diagnosis of ADHD were gender (male), gestational age ($<$36 weeks), and maternal education ($\leq$high school). No association between allergies and cases classified as ADHD based on the hyperactivity symptom scale was observed. This study confirms other studies that reported an allergy/ADHD association in diagnoses populations. Further investigation confirming the association and explanation of the reasons and underlying mechanisms of the observed association is warranted. These studies should use validated diagnostic criteria for the diagnosis of ADHD symptoms and allergies, adequate sample sizes, and control for confounding. ^

Attention-deficit hyperactivity disorder symptoms and lead exposure in children: A systematic review of literature

Blood lead levels > 10 µg/dL are known to affect various areas of the brain that influence behavior and cause many other health problems in children. As a result, the Centers for Disease Control and Prevention (CDC) set the blood lead action level at 10 µg/dL. However, recent research provides evidence that blood lead levels <10 µg/dL also may lead to behavioral problems in children. With the recent increase in diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD) in children in the U.S. it is important to determine possible environmental toxins such as lead that may play a role in causing ADHD symptoms. The aim of this systematic review of the literature was to identify recent published studies that examine an association between blood lead levels < 10 µg/dL and ADHD symptoms in children in order to summarize their findings and describe major gaps in the literature. Although available research is limited, the articles reviewed indicate that blood lead at levels much below the CDC action level of 10 µg/dL may affect a child's level of attention, hyperactivity, impulsivity and ADHD diagnosis. Additional prospective research is warranted in order to inform the revision of current blood lead action levels as well as better elucidate the relationship between lead and ADHD diagnoses.^

Selective effects of methylphenidate in attention deficit hyperactivity disorder: A functional magnetic resonance study

Functional MRI revealed differences between children with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls in their frontal–striatal function and its modulation by methylphenidate during response inhibition. Children performed two go/no-go tasks with and without drug. ADHD children had impaired inhibitory control on both tasks. Off-drug frontal–striatal activation during response inhibition differed between ADHD and healthy children: ADHD children had greater frontal activation on one task and reduced striatal activation on the other task. Drug effects differed between ADHD and healthy children: The drug improved response inhibition in both groups on one task and only in ADHD children on the other task. The drug modulated brain activation during response inhibition on only one task: It increased frontal activation to an equal extent in both groups. In contrast, it increased striatal activation in ADHD children but reduced it in healthy children. These results suggest that ADHD is characterized by atypical frontal–striatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.

Molecular Genetic Basis of Opposite Gene by Environment Interactions in Reading Disability and Attention Deficit/Hyperactivity Disorder

The goal of this study is to better understand the genetic basis of Reading Disability (RD) and Attention Deficit Hyperactivity Disorder (ADHD) by examining molecular G x E interactions with parental education for each disorder. Research indicates that despite sharing genetic risk factors, RD and ADHD are influenced by different types of G x E interactions with parental education - a diathesis stress interaction in the case of ADHD and a bioecological interaction in RD. In order to resolve this apparent paradox, we conducted a preliminary study using behavioral genetic methods to test for G x E interactions in RD and the inattentive subtype of ADHD (ADHD-I) in the same sample of monozygotic and dizygotic Colorado Learning Disabilities Research Center same-sex twin pairs (DeFries et al., 1997), and our findings were consistent with the literature. We posited a genetic hypothesis for this opposite pattern of interactions, which suggests that only genes specific to each disorder enter into these opposite interactions, not the shared genes underlying their comorbidity. This study sought to further investigate this paradox using molecular genetics methods. We examined multiple candidate genes identified for RD or related language phenotypes and those identified for ADHD for G x E interactions with parental education. The specific aims of this study were as follows: 1) partition known risk alleles for RD and/or related language phenotypes and ADHD-I into those which are pleiotropic and non-pleiotropic by testing each risk allele for association with both RD and ADHD-I, 2) explore the main effects of parental education on both RD and ADHD-I, 3) address G-E correlations, and 4) conduct exploratory G x E interaction analyses in order to test the genetic hypothesis. Analyses suggested a number of pleiotropic genes that influence both RD and ADHD; however, results did not remain after correcting for multiple comparisons. Although exploratory G x E interaction findings were not significant after multiple comparison correction, results suggested a G x E interaction in the bioecological direction with KIAA0319, parental education, and ADHD-I. Given the limited power in the current study, replication of these findings with larger samples is necessary.

Relationship Maintenance in Couples with a Partner Who Has Attention Deficit Hyperactivity Disorder

The body of research on the relationship functioning of adults with attention deficit hyperactivity disorder (ADHD) is relatively small; the aim of the present study is to advance our understanding of this topic. It has been estimated that three to ten percent of children and one to five percent of adults have impairing symptoms of ADHD, which is a total of 4 million children and 4-5 million adults in the U.S. (Wender, 2000). A recent prevalence study found that approximately 4.4% of adults in the U.S. meet the criteria for a diagnosis of ADHD (Kessler et al., 2006). Children with ADHD show innate temperamental characteristics, usually inattentiveness, distractibility, impulsivity, restlessness, demandingness, hyperreactivity, low tolerance for frustration, temperoutbursts, bossiness and stubbornness, and mood lability, along with an innate proclivity for academic underachievement. It has been estimated that one- to two-thirds of children with ADHD have symptoms that continue into adulthood, and for 40-50% of these adults, these symptoms are serious enough to cause impairment in functioning (Everett & Everett, 1999; Wender, 2000). Research suggests that the majority of cases are transmitted genetically, but some may be due to exposure to environmental toxins such as lead. Consumption of excess sugar or allergies to food may exacerbate or mimic ADHD symptoms in some children, but they are not a cause of ADHD (Wender, 2000). One hypothesized cause of the symptoms associated with ADHD is a deficit in the brain's executive functioning (Barkley & Gordon, 2002). Executive functioning can be conceptualized as the ability to inhibit, organize, and plan behaviors. Barkley and Gordon (2002) define it as the abilityto self-direct and regulate behaviors toward future goals, including social behaviors and goals. Other research suggests that executive functioning consists of inhibition, control of interference, verbal and nonverbal working memory, emotional regulation, attention, verbal fluency, visual scanning, and processing speed. Studies have shown impairments in these areas among adults with ADHD (Barkley & Gordon, 2002; Barkley, Murphy & Kwasnik, 1996; Goldstein, 2002).

Adult attention-deficit/hyperactivity disorder and nicotine withdrawal: a qualitative study of patient perceptions

Background: Nicotine use has been reported to ameliorate symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Furthermore, adults with ADHD have a relatively high prevalence of cigarette smoking and greater difficulty abstaining from smoking. Overall, though, there is scant literature investigating the beliefs, perceptions and experiences of smokers with ADHD regarding smoking cessation and withdrawal. Methods: Our participants (n = 20) fulfilling criteria for ADHD and a past or current dependence from nicotine were recruited from the in- and outpatient clinic of the Zurich University Psychiatric Hospital and the Psychiatric Services Aargau (Switzerland). We conducted in-depth interviews to explore their motivations to quit, past experiences with and expectations about quitting using a purposeful sampling plan. The sample was selected to provide diversity in relation to level of nicotine dependence, participation in a smoking-cessation program, gender, age, martial status and social class. Mayring’s qualitative content analysis approach was used to evaluate findings. Results: Adult smokers with ADHD had made several attempts to quit, experienced intense withdrawal symptoms, and relapsed early and often. They also often perceived a worsening of ADHD symptoms with nicotine abstinence. We identified three motives to quit smoking: 1) health concerns, 2) the feeling of being addicted, and 3) social factors. Most participants favored a smoking cessation program specifically designed for individuals with ADHD because they thought ADHD complicated their nicotine withdrawal and that an ADHD-specific smoking cessation program should address specific symptoms of this disorder. Conclusions: Since treatment initiation and adherence associate closely with perception, we hope these findings will result in better cessation interventions for the vulnerable subgroup of smokers with ADHD. Keywords: ADHD, Nicotine, Withdrawal, Subjective, Qualitative, Narrative

An n-of-1 trial service in clinical practice: Testing the effectiveness of stimulants for attention-deficit/hyperactivity disorder

OBJECTIVE. We sought to describe the clinical use of n-of-1 trials for attention-deficit/hyperactivity disorder in publicly and privately funded family and specialized pediatric practice in Australia. METHODS. We used a within-patient randomized, double-blind, crossover comparison of stimulant (dexamphetamine or methylphenidate) versus placebo or alternative stimulant using 3 pairs of treatment periods. Trials were conducted from a central location using mail and telephone communication, with local supervision by the patients' clinicians. PATIENTS. Our study population included children with clinically diagnosed attention-deficit/ hyperactivity disorder who were aged 5 to 16 years and previously stabilized on an optimal dose of stimulant. They were selected because treatment effectiveness was uncertain. MAIN OUTCOME MEASURES. Our measures included number of patients recruited, number of doctors who used the service, geographic spread, completion rates, response rate, and post-n-of-1 trial decisions. RESULTS. Forty-five doctors across Australia requested 108 n-of-1 trials, of which 86 were completed. In 69 drug-versus-placebo comparisons, 29 children responded better to stimulant than placebo. Immediately posttrial, 19 of 25 drug-versus-placebo responders stayed on the same stimulant, and 13 of 24 nonresponders ceased or switched stimulants. In 40 of 63 for which data were available, posttrial management was consistent with the trial results. For all types of n-of-1 trials, management changed for 28 of 64 children for whom information was available. DISCUSSION. Attention-deficit/hyperactivity disorder n-of-1 trials can be implemented successfully by mail and telephone communication. This type of trial can be valuable in clarifying treatment effect when it is uncertain, and in this series, they had a noticeable impact on short-term management.

Responding to interpersonal and physically provoking situations in classrooms: emotional intensity in children with attention deficit hyperactivity disorder

The present research investigated the emotional functioning of children with and without Attention Deficit Hyperactivity Disorder (ADHD), in order to examine the relationships between emotional intensity and classroom-based responses to physically and interpersonally provoking situations. Seventy children (35 with ADHD and 35 without ADHD) in Years 3–8 participated and were matched on age, gender, grade, and school class. Each child was observed individually in the classroom over two 20-min periods. The Responses to Interpersonal and Physically Provoking Situations Observation Schedule was used to record the frequency and severity of responses and the triggers for these during the observational periods. Children later rated their emotional intensity in response to hypothetical scenarios on the Emotional Intensity Scale for Children. Results revealed children with ADHD displayed significantly more frequent and severe challenging and solitary off-task behaviours, and significantly more frequent vocalisations and severe interactional off-task behaviours. For triggers, environmental and teacher-initiated distractions were significantly more frequently observed in children with ADHD. There were no differences in ratings of emotional intensity between children with and without ADHD, although a number of significant and meaningful correlations were observed between positive emotional intensity scores and responses and triggers.

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder

Objective To compare the efficacy and safety of two methylphenidate (MPH) formulations—once-daily modified-release MPH (EqXL, Equasym™ XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin®)—and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Methods Children aged 6–12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher’s IOWA Conners’ Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. Results The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (−1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. Conclusions EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.