Change In Attention-deficit/hyperactivity Disorder Symptoms Research Articles

The influence of sex on the course and psychiatric correlates of ADHD from childhood to adolescence: A longitudinal study

Little is known about the influence of sex on the course of attention-deficit/hyperactivity disorder (ADHD) and its comorbid psychiatric conditions. The purpose of this study was to examine the effect of sex on the course and psychiatric correlates of ADHD from childhood into adolescence. Two identically designed, longitudinal, case-control family studies of male and female probands with and without ADHD and their siblings were combined. All subjects were blindly assessed with structured diagnostic interviews. Among subjects with a lifetime history of ADHD (n = 471, mean age 11.5 +/- 4.3 years at baseline), we used linear growth curve models to estimate the effect of time on the change in ADHD symptoms, and whether this effect differed by sex. We also we examined the effect of sex on the association between ADHD and the longitudinal progression of comorbid psychopathology using structural equation models. We found no evidence that sex moderated the effect of age on ADHD symptoms; in both genders, age exhibited a similar effect on the decline of ADHD symptoms. However, the female sample demonstrated greater stability in comorbid psychopathology from childhood into adolescence. Furthermore, we found that the stability of comorbid psychopathology in females remained significant after accounting for the correlation between adolescent psychopathology and adolescent ADHD. In males, childhood and adolescent comorbid psychopathology were no longer correlated when adolescent ADHD was taken into account. Our findings indicate that while the course of ADHD across childhood and adolescence did not differ between males and females, patterns of psychiatric comorbidity were conditional on sex. Future studies should explicitly test how sex modifies the associations between ADHD and risk factors and ADHD and associated functional outcomes.

Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study

Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD. To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children. The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners' questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study. FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners' questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2. A subgroup of eight patients (four in each group) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement, particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, total Conners' subscales. A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control. The data of the present study also supported n-3 PUFA safety and tolerability, but limited changes were noted in the FA profile in French Canadians with ADHD.

Medication Effects on Symptoms of Attention-Deficit/Hyperactivity Disorder in Children with Fetal Alcohol Spectrum Disorder

Attention-deficit/hyperactivity disorder (ADHD) may be the most common mental health disorder in children with fetal alcohol spectrum disorders (FASD). Despite this, little information is available regarding the effectiveness of ADHD treatment in this population. This study, conducted within a clinical service, aimed to assess the impact of medication on symptoms of ADHD in children with FASD by determining (a) the extent of change in ADHD symptoms with medication, and (b) whether differences in improvement are seen between symptom domains. Data were extracted from the medical records of 27 children with FASD who had been referred to an ADHD medication service at the Alberta Children's Hospital in Canada. Participants were primarily male and ranged in age from 5 years 6 months to 14 years 5 months. Teacher MTA-SNAP-IV scores were the primary outcome measure. Baseline, best, and change scores across three symptom domains (inattention, hyperactivity/impulsivity, and opposition/defiance) were determined. A total of 41 medication trials was conducted. More children obtained normalized best scores for hyperactivity/impulsivity (n = 18) and opposition/defiance (n = 19) than for inattention (n = 9) across medication trials. These findings suggest that inattention may be less responsive to ADHD medication. Replication in larger samples with a placebo-controlled design is required.

Association Study of 10 Genes Encoding Neurotrophic Factors and Their Receptors in Adult and Child Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder that often persists into adolescence and adulthood and is characterized by inappropriate levels of inattention, hyperactivity, and/or impulsivity. Genetic and environmental factors are believed to be involved in the continuity of the disorder as well as in changes in ADHD symptomatology throughout life. Neurotrophic factors (NTFs), which participate in neuronal survival and synaptic efficiency, are strong candidates to contribute to the neuroplasticity changes that take place in the human central nervous system during childhood, adolescence, and early adulthood and might be involved in the genetic predisposition to ADHD. We performed a population-based association study in 546 ADHD patients (216 adults and 330 children) and 546 gender-matched unrelated control subjects with 183 single nucleotide polymorphisms covering 10 candidate genes that encode four neurotrophins (NGF, BDNF, NTF3, and NTF4/5), a member of the cytokine family of NTFs (CNTF), and their receptors (NTRK1, NTRK2, NTRK3, NGFR, and CNTFR). The single-marker and haplotype-based analyses provided evidence of association between CNTFR and both adulthood (p = .0077, odds ratio [OR] = 1.38) and childhood ADHD (p = 9.1e-04, OR = 1.40) and also suggested a childhood-specific contribution of NTF3 (p = 3.0e-04, OR = 1.48) and NTRK2 (p = .0084, OR = 1.52) to ADHD. Our data suggest that variations in NTFs might be involved in the genetic susceptibility to ADHD, support the contribution of the CNTFR locus as a predisposition factor for the disorder, and suggest that NTF3 and NTRK2 might be involved in the molecular basis of the age-dependent changes in ADHD symptoms throughout life span.

Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder—A preliminary tolerability and efficacy study

The primary treatment for attention-deficit/hyperactivity disorder (ADHD) has been psychostimulants. Recently developed nonpsychostimulant treatments have allowed certain patients to switch from a psychostimulant to a nonpsychostimulant. However, the outcomes of such switches have not been systematically studied. The purpose of this pilot study was to assess treatment tolerance and efficacy during a cross-taper transition from methylphenidate or amphetamine to atomoxetine among children and adolescents with ADHD. This pilot study was conducted in patients (aged 6-17 years) with incomplete responses (failure to obtain full reduction/elimination of symptoms) or intolerance of adverse events (AEs) during psychostimulant treatment. Patients continued ongoing psychostimulant treatment during the first week of the study. Transition to atomoxetine began by administering atomoxetine 0.5 mg/kg . d plus full-dose psychostimulant for 1 week, followed in the second week by 1.2 mg/kg . d atomoxetine plus half-dose psychostimulant. Patients remained on 1.2 mg/kg . d atomoxetine monotherapy for the remaining 5 weeks. This stepwise transition was enacted due to the difference in pharmacodynamics between the psychostimulants and atomoxetine. Applying a stepwise cross-titration allowed for better control of ADHD symptoms during the intervening period. Change in ADHD symptoms, as measured by the mean change in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), was assessed from baseline to end point. Of the 62 subjects enrolled in the study, 39 (62.9%) were diagnosed as ADHD-combined type. Similar proportions were receiving methylphenidate (51.6%) and amphetamine (48.4%). Slightly more wished to switch due to inadequate response (53.2%) than intolerability (46.8%). Nine subjects discontinued at various times during the course of the study (patient or parent/caregiver decision [4], AE [2], protocol violation [2], and lack of efficacy [1]). Mean (SD) ADHDRS-IV-Parent:Inv total scores (n = 59, last-observation-carried-forward) improved significantly from baseline (visit 2) to an end point (32.1 [10.5] vs 22.6 [14.0]; P < 0.001). Of the 58 subjects answering in the atomoxetine monotherapy phase, 38 (65.5%) reported a preference for atomoxetine treatment over their previous psychostimulant. Tolerability results were as follows: 26 (44.1%) of 59 patients reported >or=1 AE, the most common being somnolence (4 [6.8%]), fatigue (3 [5.1%]), decreased appetite (3 [5.1%]), cough (3 [5.1%]), headache (3 [5.1%]), and contact dermatitis (2 [3.4%]). No clinically severe AEs were reported. Both mean (SD) diastolic (2.4 [7.8] mm Hg; P = 0.031) and systolic (2.4 [7.9] mm Hg; P = 0.029) blood pressures increased significantly from baseline to end point. Electrocardiography revealed a significant increase in mean (SD) heart rate (9.2 [11.6] bpm; P < 0.001) and a corresponding decrease in mean (SD) RR interval (-77.8 [98.2] ms; P < 0.001). Statistically significant, but mild, increases in diastolic pressure and heart rate were observed. These children and adolescent patients were successfully switched from methylphenidate or amphetamine to atomoxetine treatment, with resulting improvement in ADHD symptom severity from baseline in this pilot study.

Symptoms of Attention-Deficit/Hyperactivity Disorder Following Traumatic Brain Injury in Children

We investigated changes in inattentive and hyperactive symptoms over 2 years following traumatic brain injury (TBI) in relation to preinjury attention-deficit/hyperactivity disorder (ADHD), injury, and socioeconomic status (SES) variables. Postinjury stimulant medication treatment was also documented. Of 175 consecutive patients of ages 5 to 15 years with acute TBI, 148 consented, including 114 without preinjury ADHD (mean age, 10.0 years, SD = 2.76) and 34 with preinjury ADHD (mean age 10.36 years, SD = 2.75). The Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version, was administered at baseline and at 6, 12, and 24 months post-injury to assess the presence of nine core inattentive and nine hyperactive symptoms and associated impairment. The baseline assessment was performed within 1 month post-injury to establish preinjury diagnosis. Nonlinear change in inattentive symptoms in patients without preinjury ADHD contrasted with higher and more stable symptom levels in children with preinjury diagnosis, including the cubic trend (chi2(1) = 6.23, p = .0126). There was also a significant interaction of group x gender effect (chi2(1) = 4.08, p = .0435) as males had higher numbers of inattentive symptoms than females in the preinjury ADHD group. Change in hyperactive symptoms over time also differed by group, including both linear (chi2(1) = 5.42, p = .0199) and cubic trends (chi2(1) = 8.91, p = .0029), reflecting greater and more frequent fluctuations in children without preinjury ADHD. Socioeconomic level also contributed to change in hyperactive symptoms as reflected by the interaction of SES and linear time (chi2(1) = 6.91, p = .009), as well as quadratic time (chi2(1) = 4.90, p = .027). Occurrence of ADHD diagnosed post-injury ranged from 14.5% (12 months) to 18.3% (24 months) in the group without preinjury ADHD compared with a range from 86.4% (12 months) to 96.2% (6 months) in children with preinjury ADHD. In children without preinjury ADHD, SES was the only patient variable that predicted onset of ADHD, t(110) = -2.85, p = .0052. Treatment with stimulant medication post-injury was more frequently associated with preinjury ADHD (39% vs 7% of children without preinjury ADHD), p< .0001 (Fisher exact test). Children with preinjury ADHD who were treated pre-injury with stimulant medication had fewer total symptoms at 24 months post-injury relative to untreated patients with preinjury ADHD (F[1,14] = 3.93, p = 0.069, Cohen's d = 1.28). Change in ADHD symptoms after TBI varies with preinjury diagnosis, reflects injury severity in children without preinjury ADHD, and is treated with stimulant medication mainly in those patients with preinjury ADHD.

Case Series: Evaluation of a Behavioral Sleep Intervention for Three Children With Attention-Deficit/Hyperactivity Disorder and Dyssomnia

Objective: The authors conducted a preliminary evaluation of a behavioral sleep intervention for children with attention-deficit/hyperactivity disorder (ADHD) and dyssomnia delivered via distance treatment. Method: Three children (1 male, 2 females; aged 6-10 years) with ADHD and dyssomnia participated in a 5-week manualized intervention. Using a non-concurrent multiple baseline design, the children were randomly assigned to a 1-, 2-, or 3-week baseline and then received the 5-week intervention. Sleep problems were assessed daily by both objective and subjective measures. Measures of problematic nighttime behaviors and daytime ADHD symptoms were also obtained weekly. Results: After 5 weeks, a clinically significant decrease was found in the severity of the children’s dyssomnia. No changes in ADHD symptoms were noted. Gains were generally maintained at the 3-month follow-up. Parents perceived the intervention as being “helpful” to “very helpful.” Conclusion: Based on the initial data, this intervention shows promise as an effective and feasible treatment.

Comparison of Parent and Teacher Reports of Attention-Deficit/Hyperactivity Disorder Symptoms from Two Placebo-Controlled Studies of Atomoxetine in Children

The validity of parent reports regarding children's attention-deficit/hyperactivity disorder (ADHD) symptoms has been questioned. This study assessed whether parent reports were as sensitive as teacher reports to document change in ADHD symptoms during clinical trials with atomoxetine. Data were compared from two randomized, double-blind, placebo-controlled clinical trials of atomoxetine using different versions (parent or teacher) of the same rating scale (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV [parent or teacher] Version: Investigator Administered and Scored - ADHD RS). Exclusion criteria included history of bipolar disorder, psychosis, seizures, alcohol abuse, or positive drug screen. Patients (6-16 years old) were treated with atomoxetine (titrated to a maximum dose of 1.8 mg/kg/day) administered once daily for up to 7 weeks. Parent and teacher ratings were compared using an analysis of covariance (ANCOVA) model. The analysis (n = 318) showed that treatment effects (mean change, baseline to endpoint) were similar between parent and teacher ratings (total, p = .762; inattention, p = .519; hyperactive/impulsive, p = .955). Effect sizes also were similar based on total scores (parent ratings = .69; teacher ratings = .63). Parent reports are as sensitive as teacher reports in assessing the efficacy of long-acting pharmacologic treatment for ADHD in children during clinical trials using the nonstimulant atomoxetine.

Bupropion SR in Adolescents With Comorbid ADHD and Nicotine Dependence: A Pilot Study

Bupropion SR has been shown to be effective for the treatment of nicotine dependence in adults. This open-label pilot study was designed to examine the feasibility and preliminary tolerability of bupropion SR in adolescents with nicotine dependence. Sixteen adolescents aged 12 to 19 years were enrolled in the study. Eleven of the 16 participants also had comorbid attention-deficit/hyperactivity disorder (ADHD). Participants were titrated over 1 week to bupropion SR 150 mg b.i.d. and maintained at this dosage for 6 weeks. Participants also received two brief smoking cessation counseling sessions. Nine participants received at least 4 weeks of medication. There was a significant decrease in the average number of cigarettes smoked (p <.00) and carbon monoxide levels (p =.04) over the course of treatment. Intent-to-treat analysis showed that 31.25% of the adolescents were completely abstinent (5/16) after 4 weeks of taking bupropion SR. Participants' weight did not change significantly during the study (p =.55). There was a no significant change in ADHD symptoms during the study (p =.1). Bupropion SR along with brief counseling may be safe and potentially efficacious for adolescents with nicotine dependence with and without ADHD. Smoking cessation trials in adolescents need to focus on strategies to increase retention for optimal effect.