A randomized controlled trial of pemoline for attention-deficit/hyperactivity disorder in substance-abusing adolescents

OBJECTIVE: In adolescents with substance use disorder (SUD), comorbid attention-deficit/hyperactivity disorder (ADHD) is associated with greater severity of substance abuse, conduct problems, and worse treatment outcomes. Although many controlled trials have established the efficacy of psychostimulants, including pemoline, for ADHD in children and adolescents, none have been conducted in adolescents with SUD. This randomized, placebo-controlled trial, conducted between 1996 and 2000, evaluated the safety and efficacy of pemoline on substance abuse and conduct problems. METHOD: Sixty-nine adolescents (aged 13-19) with conduct disorder (CD), SUD, and ADHD were recruited from the community and randomly assigned to a 12-week clinical trial of pemoline (n = 35) or placebo (n = 34), titrated over 4 weeks to a single morning dose of 75 to 112.5 mg as tolerated. RESULTS: Pemoline had greater efficacy than placebo for ADHD as determined by significantly more Clinician's Global Impression-Improvement (CGI-I) ratings of 1 (very much improved) or 2 (much improved) at the study endpoint (n = 69; p <.05). There was also greater reduction in ADHD severity on the parent-rated Conners Hyperactivity-Impulsivity scale in pemoline-treated study completers compared to placebo-treated completers (pemoline, n = 17; placebo, n = 16; p <.01), but no difference between groups in the intent-to-treat analysis (n = 68; p <.13). Substance use did not decline in either group, and there was no difference between groups in baseline to study endpoint change in substance use or CD symptoms. Overall, pemoline was well tolerated, demonstrating a good safety profile and no elevation in liver enzyme levels. CONCLUSIONS: Pemoline was efficacious for ADHD but did not have an impact on CD or substance abuse in the absence of specific treatment for SUD.     

Prevalence of attention-deficit/hyperactivity disorder in a community sample of older adolescents

OBJECTIVE: To study the prevalence and correlates of attention-deficit/hyperactivity disorder (ADHD) in a community sample of older adolescents. METHOD: From 1986 to 1988, 3,419 seventh, eighth, and ninth graders were screened with the Center for Epidemiologic Studies-Depression Scale. The top decile scorers and a random sample of the remainder were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children. These data are from the second wave of interviews (N = 490, mean age = 18.65). RESULTS: The weighted prevalence of DSM-III-R ADHD was 1.51% (males: 2.62%, females: 0.54%). Significant associations (p < .05) were found for gender (male), comorbid affective disorders, baseline undesirable life events, and fewer than two biological parents at baseline. Family cohesion (p = .058) is inversely associated with ADHD. For subjects not meeting the age-at-onset criterion, 1.94% met the eight symptom criteria, and females (3.2%) were more prevalent than males (0.3%). CONCLUSIONS: ADHD remains a problem in this sample of older adolescents and is often comorbid with affective disorders. A significant number report eight ADHD symptoms but do not meet the age-at-onset criterion. This group deserves research attention.     

Tic disorders: Administrative prevalence and co-occurrence with attention-deficit/hyperactivity disorder in a German community sample

Coexistence of tics and attention-deficit/hyperactivity disorder (ADHD) has important clinical and scientific implications. Existing data on the co-occurrence of tic disorders, Tourette Syndrome (TS), and ADHD are largely derived from small-scale studies in selected samples and therefore heterogeneous. The Nordbaden project captures the complete outpatient claims data of more than 2.2 million persons, representing 82% of the regional population in 2003. Based upon the number of diagnosed cases of tic disorders, TS, and ADHD, we determined 12-months administrative prevalence rates as well as rates of co-occurrence. Both tic disorders and ADHD were diagnosed most often in the age group 7–12 years (any tic disorder: 0.8%; ADHD: 5.0%). With increasing age, the administrative prevalence difference in favor of males disappeared, with tic disorders being somewhat more frequently reported in females than males in the age groups above 30 years. The highest rate of ADHD co-occurring with tic disorders was found in adolescents (age 13–18 years, 15.1%). Tic disorders were observed in 2.3% of patients with ADHD. Administrative prevalence rates of tic disorders and TS were substantially lower compared to rates found in community-based epidemiological studies, suggesting that a large number of cases remain undetected and untreated under present conditions of routine outpatient care.     

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized,controlled trial

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment ? placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).     

A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of once-daily OROS methylphenidate (MPH) in the treatment of adults with DSM-IV attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a randomized, 6-week, placebo-controlled, parallel-design study of OROS MPH in 141 adult subjects with DSM-IV ADHD, using standardized instruments for diagnosis. OROS MPH or placebo was initiated at 36 mg/day and titrated to optimal response, depending on efficacy and tolerability, up to 1.3 mg/kg/day. RESULTS: Treatment with OROS MPH was associated with clinically and statistically significant reductions in DSM-IV symptoms of inattention and hyperactivity/impulsivity relative to subjects treated with placebo. At endpoint, 66% of subjects (n = 44) receiving OROS MPH and 39% of subjects (n = 29) [corrected] receiving placebo attained our a priori definition of response of much or very much improved on the Clinical Global Impression-Improvement scale plus a >30% reduction in Adult ADHD Investigator System Report Scale score. OROS MPH was associated with small but statistically significant increases in systolic blood pressure (3.5 +/- 11.8 mm Hg), diastolic blood pressure (4.0 +/- 8.5 mm Hg), and heart rate (4.5 +/- 10.5 bpm). CONCLUSIONS: These results show that treatment with OROS MPH in daily doses of up to 1.3 mg/kg/day was effective in the treatment of adults with ADHD. Because of the potential for increases in blood pressure and heart rate, subjects receiving treatment with MPH should be monitored for changes in blood pressure parameters during treatment.     

Parent-teacher concordance for DSM-IV attention-deficit/hyperactivity disorder in a clinic-referred sample

OBJECTIVE: To examine concordance between parent and teacher reports of DSM-IV attention-deficit/hyperactivity disorder (ADHD) and its symptoms. METHOD: Parents and teachers of 74 clinically referred children were interviewed using the ADHD module of the Diagnostic Interview Schedule for Children. Parent-teacher agreement for the diagnosis of ADHD and its subtypes, as defined in DSM-IV, as well as parent-teacher concordance of in-school ADHD symptoms, was examined. RESULTS: Agreement between parents and teachers was found to be relatively poor, with virtually no agreement for individual ADHD subtypes. Diagnoses based on either parent or teacher report frequently yielded a diagnosis of either inattentive or hyperactive-impulsive subtype of ADHD. However, when cross-informant data were used to form diagnoses, these subtypes became relatively rare, with most cases meeting criteria for ADHD combined type. In addition, parent reports of in-school behavior were more highly correlated with their own reports of their child's behavior at home than with teacher reports of their child's behavior in school. CONCLUSIONS: These data suggest that the diagnosis of ADHD inattentive or hyperactive-impulsive subtype based on data from a single informant may be of questionable validity, and they point to the importance of using multiple informants when diagnosing this disorder in clinically referred samples.     

Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study.

BACKGROUND: Data remain limited on treatment strategies for adults with attention-deficit/hyperactivity disorder (ADHD). This study evaluated the efficacy and safety of an extended-release, once-daily formulation of bupropion (XL) in the treatment of adults with ADHD. METHODS: This multisite, placebo-controlled, 8-week prospective trial evaluated 162 adult patients diagnosed with ADHD (combined and inattentive types). Subjects were treated with up to 450 mg/day of bupropion XL. The primary efficacy endpoint was the proportion of ADHD responders (defined as at least a 30% reduction in the investigator-rated ADHD Rating Scale score) at week 8 (last observation carried forward [LOCF]). RESULTS: Bupropion XL responders (53%) exceeded placebo responders (31%) (p =.004 at week 8) with a significantly greater proportion of bupropion XL responders as early as week 2 (p = .01). Treatment effect size calculated for the ADHD Rating Scale total score was .6. Bupropion XL appeared to provide sustained benefit throughout the day compared with placebo (morning p =.033, afternoon p =.004, evening p = .024). Bupropion XL was safe and well tolerated, with no serious or unexpected adverse events and a low rate of drug-related study discontinuation (5%). CONCLUSIONS: The results from this multisite study indicate that bupropion XL is an effective and well-tolerated nonstimulant treatment for adult ADHD.     

Association of attention-deficit/hyperactivity disorder symptoms with levels of cigarette smoking in a community sample of adolescents

OBJECTIVE: Research on the association of attention-deficit/hyperactivity disorder (ADHD) with cigarette smoking has primarily occurred within samples of clinically referred youths. This paper reports the association of ADHD symptoms with smoking practices in a community sample of adolescents. METHOD: Confidential self-report surveys were completed by 1,066 tenth-grade students enrolled in five public high schools who were taking part in a longitudinal study of biobehavioral predictors of adolescent smoking adoption. A well-standardized measure of ADHD inattention and hyperactivity-impulsivity symptoms, as well as demographic and social risk factors, were examined in relation to three levels of cigarette smoking: (1) never having smoked, (2) ever having smoked, and (3) current smoking (having smoked a cigarette within the past 30 days). RESULTS: Regarding lifetime cigarette use, approximately 43% of students had ever smoked. Among those who had ever smoked, approximately 31% of students were current smokers. Ever having smoked was associated with family (odds ratio [OR] = 2.49, confidence interval [CI] = 1.85, 3.36) and peer smoking (OR = 4.05, CI = 3.07, 5.33) and clinically significant ADHD inattention symptoms (OR = 3.39, CI = 1.53, 7.54). Current smoking was also associated with peer smoking (OR = 2.99, CI = 1.72, 5.20) and clinically significant ADHD inattention symptoms (OR = 2.80, CI = 1.20, 6.56). CONCLUSION: Clinically significant ADHD symptoms should be taken into account when identifying adolescents at risk to smoke, since those with problematic inattention may be more likely to experiment with smoking and to become regular tobacco users.     

Scaffolding the attention-deficit/hyperactivity disorder brain using transcranial direct current and random noise stimulation: A randomized controlled trial

ObjectiveImproving symptomology and cognitive deficits in neurodevelopmental disorders is a crucial challenge. We examined whether neurostimulation protocols, which have been shown to yield long-term effects when combined with cognitive training, could benefit children with Attention-deficit/hyperactivity-disorder (ADHD), the most common neurodevelopmental disorder in childhood.MethodsWe used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD, who received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or random noise stimulation (tRNS) over the bilateral dlPFC, while completing executive functions training.ResultsFor our primary outcome, tRNS yielded a clinical improvement as indicated by the reduced ADHD rating-scale score from baseline, and in comparison to the changes observed in tDCS. The effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, tRNS improved working memory compared to tDCS, and a larger tRNS effect on ADHD rating-scale was predicted for those who showed the greatest improvement in working memory.ConclusionsWe found that our intervention can have a lasting effect, rather than a merely immediate effect as was shown for in previous medical interventions in ADHD.SignificanceOur results provide a promising direction toward a novel intervention in ADHD.     

Psychopathology in females with attention-deficit/hyperactivity disorder: a controlled, five-year prospective study.

BACKGROUND: Despite the importance of understanding the long-term outcome of children with attention-deficit/hyperactivity disorder (ADHD), the available literature is predominantly based on male samples. This study estimated the lifetime burden of comorbid psychopathology in a large sample of girls with and without ADHD followed up over five years. METHODS: We conducted a blind, five-year prospective longitudinal study of girls with (n=140) and without (n=122) ADHD, aged 6-18 years at baseline, consecutively ascertained from either community pediatricians or psychiatrists at an academic medical center. At the five-year follow-up, 123 (88%) and 112 (92%) of the ADHD and control children, respectively, were re-assessed at a mean age of 16.7 years. Psychiatric disorders were assessed using blinded structured diagnostic interviews. RESULTS: At follow-up, females with ADHD were at significantly higher risk than controls to manifest disruptive behavior, mood and anxiety disorders, and substance dependence. The magnitude of increased risk was greatest for major depression and oppositional-defiant disorder, followed by substance dependence and anxiety disorders. CONCLUSIONS: These prospective follow-up findings documenting high morbidity associated with ADHD extend to females previously reported findings in male samples and underscore the importance of early recognition and intervention efforts for youth with ADHD of both genders.     

Full syndrome and subthreshold attention-deficit/hyperactivity disorder in a Korean community sample: comorbidity and temperament findings

Objective  The main objective of this study was to investigate the comorbid disorders and temperamental profiles of full syndrome and subthreshold attention-deficit/hyperactivity disorder (ADHD). Method  A sample of 2,493 students was randomly selected from six representative elementary schools in Seoul, Korea. Among 245 children with full syndrome and subthreshold ADHD diagnosed by the diagnostic interview schedule for children-4th version, parents of 185 subjects (mean age 9.0 ± 1.7 years) and of a random sample of 185 age- and gender-matched non-ADHD children have completed the parent’s version of the children behavior checklist (CBCL) and the juvenile temperament and character inventory (JTCI). Results  The prevalence rates of full syndrome and subthreshold ADHD were, respectively, 5.90% (95% confidence interval = 4.74–7.06) and 9.00% (95% confidence interval = 7.58–10.41). Subthreshold ADHD cases did not differ from full syndrome ADHD in any JTCI profile, showing high novelty seeking/low persistence/low self-directedness than controls. Subthreshold ADHD also showed increased risk for externalizing disorders and higher scores in eight CBCL scales (somatic complaints, anxious/depressed, social problems, attention problems, delinquent behaviors, aggressive behaviors, externalizing problems and total behavioral problems) compared to the controls. Conclusions  These results support the clinical relevance of subthreshold ADHD in Asian culture. Increased clinical awareness for children with subthreshold ADHD is needed.     

Atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: a 6-week, randomized, placebo-controlled, double-blind trial in Russia

The objective of the study was to compare the efficacy and tolerability of once-daily atomoxetine (≤1.8 mg/(kg day) with those of placebo in children and adolescents (aged 6–16 years) with attention-deficit/hyperactivity disorder [ADHD (DSM-IV)]. This randomized, placebo-controlled, double-blind trial was conducted in Russia. The primary efficacy measure was baseline-to-end point changes in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv) total score. Tolerability measures included treatment-emergent signs and symptoms (TESS), laboratory values and weight. Compared with patients in the placebo group (n = 33), patients treated with atomoxetine (n = 72) with a mean final dose of 1.4 mg/kg showed significantly greater improvement in ADHDRS-IV-Parent:Inv total score (least-squares mean: atomoxetine, –15.8; placebo, –11.4; p = 0.013). The most common TESS in the atomoxetine group included anorexia [atomoxetine, n = 13 (18.1%); placebo, n = 2 (6.1%)], somnolence, n = 11 versus n = 3 (15.3% vs. 9.1%, respectively), abdominal pain n = 9 versus n = 1 (12.5% vs. 3.0%, respectively) and nausea, n = 8 versus n = 1 (11.1% vs. 3.0%, respectively). Seven patients in the atomoxetine group and two in the placebo group experienced clinically important weight loss during the study (≥7% from baseline; mean change, kg: atomoxetine, –0.6; placebo, 0.1; p = 0.032). Atomoxetine is efficacious in improving ADHD symptoms in children and adolescents. Atomoxetine treatment may be associated with a numerically higher incidence of anorexia, somnolence, abdominal pain and nausea, as well as statistically greater losses in body weight.     

Home-based parent training for school-aged children with attention-deficit/hyperactivity disorder and behavior problems with remaining impairing disruptive behaviors after routine treatment: a randomized controlled trial

The objective is to investigate the effectiveness of home-based behavioral parent training for school-aged children with attention-deficit/hyperactivity disorder (ADHD) and behavior problems with remaining impairing disruptive behaviors after routinely offered treatments in clinical practice. In a randomized controlled study including 73 referred children with ADHD and impairing disruptive symptoms after routine clinical pharmacotherapy and/or clinic-based parent training had been tried or, at least, offered, home-based behavioral parent training (n?=?26) was compared to a waiting list (n?=?23) and a care-as-usual home-based treatment (n?=?24). It was unknown to families which of the home-based treatments that they received. Using mixed models for repeated measures, we examined the effectiveness on the primary outcome measure of children’s severity of disruptive behaviors and on a number of secondary outcome measures [the degree to which parents experienced the disruptive behaviors as troublesome, ADHD symptoms, oppositional-defiant disorder (ODD) symptoms, and internalizing problems]. Compared to the waiting list, children receiving home-based parent training improved significantly more regarding severity of disruptive behaviors (ES?=?0.75), ADHD symptoms (ES?=?0.89), ODD symptoms (ES?=?0.65), and internalizing problems (ES?=?0.60). Compared to care-as-usual, home-based parent training was more effective in reducing disruptive behaviors (ES?=?0.57), ADHD symptoms (ES?=?0.89), and ODD symptoms (ES?=?0.88). Significantly more reduction of children’s internalizing problems was not found. In conclusion, children with ADHD and residual behavioral problems after routine treatment may benefit from home-based behavioral parent training.

     

Parental psychopathology and offspring attention-deficit/hyperactivity disorder in a nationwide sample

ObjectiveTo study the associations between a wide range of parental psychiatric disorders and offspring attention-deficit/hyperactivity disorder (ADHD).MethodThis study is based on a nested case–control design. The association between parental registered psychiatric diagnoses and offspring ADHD was examined adjusting for socioeconomic and prenatal factors. Data was linked from Finnish nationwide registers. The cases (n = 10,409) were all the children born between years 1991 and 2005 in Finland and diagnosed with ADHD by the end of 2011. Four controls without ADHD (n = 39,124) were matched for every case by sex, age and place of birth. Main outcomes were adjusted odds ratio (aOR) for parental diagnosis of cases vs controls. Analyses were further stratified by sex. Disorders diagnosed before and after birth were analyzed separately.ResultsThe odds ratio for ADHD increased when only mother (aOR 2.2, 95% CI 2.0–2.3), only father (aOR 1.7, 95% CI 1.6–1.8) and both parents (aOR 3.6, 95% CI 3.3–4.0) were diagnosed. Maternal diagnosis showed stronger association than paternal. The weight of association between several parental disorders and offspring ADHD were similar. Maternal psychopathology overall showed stronger associations with girls than boys with ADHD. The diagnoses registered after birth did not show stronger association than the diagnoses registered before. Conclusions: Maternal psychopathology showing stronger association than paternal implies that environmental factors or their interaction with genetic factors partly mediates the risk of parental psychopathology. Similar associations between several maternal psychiatric disorders and offspring ADHD points towards the need for investigating some common mother-related risk factors.     

Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials

Aim: The aim of this study was to systematically review the efficacy, acceptability and tolerability of bupropion in comparison to placebo. Only randomized‐controlled trials were included in the meta‐analysis. Methods: MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in October 2010. Study populations comprised adults with any subtype of attention‐deficit hyperactivity disorder, attention‐deficit disorder, hyperkinetic disorder, minimal brain dysfunction, minimal cerebral dysfunction or minor cerebral dysfunction. Efficacy outcomes were pooled mean changed scores of the ADHD rating scale (ADHD‐RS) and the overall response rates. The overall discontinuation rate was considered as the measure of acceptability. Results: A total of 349 participants (n for bupropion treatment = 175) in five published randomized, controlled trials were included. Bupropion sustained‐ or extended‐release was the experimental treatment in all studies. The pooled mean changed score of the ADHD‐RS of the bupropion‐treated group was greater than that of the placebo‐treated group with a weighted mean difference (95%CI) of 5.08 (3.13–7.03). The overall response rate of the bupropion‐treated group was significantly greater than that of placebo‐treated groups with a relative risk (95%CI) of 1.67 (1.23–2.26). However, the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events were not significantly different between groups with a relative risk (95%CI) of 1.11 (0.71–1.72) and 0.87 (0.08–9.79), respectively. Conclusion: The evidence suggests that bupropion is superior to placebo and effective for the treatment of ADHD in adults. However, its acceptability and tolerability were not significantly higher than those of placebo.     

Efficacy of methylphenidate in children with attention-deficit hyperactivity disorder and learning disabilities: a randomized crossover trial

OBJECTIVE: To determine whether children with attention-deficit hyperactivity disorder (ADHD) and learning disabilities respond differently to methylphenidate (MPH) compared with children with ADHD only. METHODS: We conducted a prospective, double-blind, placebo-controlled, randomized, 2-week crossover trial of MPH, during which response to MPH was assessed. Learning ability was appraised using the Wide Range Achievement Test, Revised (WRAT-R), for English-speaking students and the Test de rendement pour francophones for French-speaking students. The study was conducted at the Douglas Hospital, a McGill University-affiliated teaching hospital in Montréal. Ninety-five children, aged 6-12 years, who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for ADHD participated in the study, which ran from 2001 to 2004. The outcome measure used was the Consensus Clinical Response, an indicator of the degree of clinical improvement shown when taking MPH. RESULTS: The proportion of children with learning disabilities who responded to MPH (55%) was significantly smaller (chi(2)1 = 4.5, p = 0.034) than the proportion of children without learning disabilities who responded adequately to MPH (75%). This difference was mainly because of children with mathematics disability being particularly unresponsive to MPH (chi(2)1 = 4.5, p = 0.034). Children with reading disability did not show this pattern of poor response (chi(2)1 = 1.0, p = 0.33). CONCLUSION: Children with ADHD and comorbid learning disability tended to respond more poorly to MPH. In particular, children with disability in mathematics responded less to MPH than those without disability in mathematics. Additional therapy may be indicated for this group of patients.