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Objective: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.Methods: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced–dose-escalation study of MAS XR in adults (≥ 18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mgl day for 1 week, with subsequent titration up to 60 mgl day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-N). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs.Findings: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2±13.04 unit points; PConclusion: Treatment with MAS XR 20–60 mgl day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.

Our analysis compares three approaches to detect the most common drug abused in early adulthood, cannabis: (1) report on direct structured interview; (2) indirect parental report; and (3) urine toxicology screen.We examined data on 207 subjects (36% also met criteria for alcohol abuse; 9% for alcohol dependence) derived from two prospective and ongoing family studies of boys and girls with or without attention-deficit/hyperactivity disorder (ADHD). Assessments relied on the Schedule for Affective Disorders and Schizophrenia (K-SADS-E; under 18 years of age) and on the Structured Clinical Interview for DSM-IV (SCID-IV; over 18 years of age). Urine samples were analyzed with Auccusign DOA5 (on-site screening assay).Ninety-seven percent (97%) of individuals, who reported no use of cannabis within the past month, had a negative urine screening and 79% of individuals, who endorsed cannabis abuse/dependence, had a positive urine screening. The sensitivity of the direct structured interview report was 91%, the specificity 87%, the positive predicting value 67%, and the negative predictive value 97%. Indirect parental reports were found to be less informative on cannabis use than direct report.Direct report of cannabis use, abuse, or dependence during the structured interview is both sensitive and specific when compared to urine toxicology screens and indirect parental reports.

Few studies exist on pharmacological interventions for adolescents with substance use disorders (SUD). To this end, we evaluated the response of bupropion hydrochloride sustained release (SR) in SUD adolescents with comorbid psychopathology (both attention-deficit/ hyperactivity disorder (ADHD) and a mood disorder).Fourteen adolescent outpatients were treated naturalistically and followed openly for 6 months. Adolescents were rated using the Drug Use Screening Inventory--Revised (DUSI-R), ADHD Symptom Checklist, and the Hamilton Rating Scale for Depression (HAM-D). Clinical Global Impression (CGI) Scale scores were obtained for Substance Abuse, ADHD, Anxiety, and Depression. The ratings were completed at baseline, at month 3, and at the 6-month endpoint. Bupropion SR was initiated at 100 mg once-daily and titrated naturalistically to a maximum dose of 400 mg/day.Of the 14 subjects followed, 13 subjects completed 6 months of treatment. At the 6- month endpoint compared to baseline, treatment with bupropion was associated with clinical and significant reductions in DUSI scores (-39%; p0.05), ADHD symptom checklist (-43%; p0.001), HAM-D (-76%; por = 0.001); and reductions in the CGIs for ADHD (por = 0.001), depression (por = 0.001), and substance abuse (p0.05). The mean daily dose of bupropion SR was 315 mg (in divided doses). No significant adverse events were noted during the follow-up period.These naturalistic data suggest that bupropion is well tolerated and may be an effective medication for the treatment of substance abusing adolescents with comorbid mood disorders and ADHD.

ObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; PConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

Background Little is known about the neuropsychological status of youth with bipolar disorder (BPD) or whether cognitive deficits in this population are accounted for by comorbidity with attention deficit/hyperactivity disorder (ADHD). We compared neuropsychological and academic functioning of youth with and without DSM-IV BPD, controlling for effects of comorbid ADHD. Methods Fifty-seven youth with BPD and 46 healthy control subjects were assessed on a battery of clinical neuropsychological measures including subtests from the Wechsler Intelligence Scales for Children and Adults (Third Editions), the Stroop, the Wisconsin Card Sorting Test, the Rey–Osterreith Complex Figure, an auditory working memory Continuous Performance Test, a measure of verbal learning, and the Wide Range Achievement Test-Third Edition. Results Bipolar disorder was associated with impairments on subtests reflecting sustained attention, working memory, and processing speed after controlling for ADHD. Additionally, decrements of moderate effect sizes were found for measures of interference control, abstract problem solving, and verbal learning but did not meet criteria for statistical significance. Conclusions After controlling for ADHD, youth with BPD show neuropsychological deficits similar to impairments found in adults with the disorder. Further studies are needed to understand the clinical implications of these impairments as well as their role in the underlying risk for pediatric BPD.

Objective Few studies have assessed effectiveness and tolerability of stimulants when used for prolonged periods in children with attention-deficit/hyperactivity disorder (ADHD). This article presents final results from an open-label, multisite study of a once-daily formulation of methylphenidate (MPH), OROS® MPH. Method Subjects received OROS MPH (18-54 mg initially, with adjustments based on clinical condition) for up to 24 months. Multiple measures of ADHD symptoms, vital signs, weight, height, and laboratory results were assessed throughout the study period. Results A total of 407 children enrolled in the open-label study and 229 completed the trial. Effectiveness of OROS MPH therapy was maintained throughout the study as indicated by parent and investigator assessments. There was a 26% increase in mean daily dose over the study period, with the majority of the increase occurring during year 1. In general, treatment was well tolerated, with 31 (7.6%) of subjects discontinuing because of adverse events. Minimal effects on growth in height and weight were observed during the study. No clinically significant effects on vital signs or laboratory test parameters were observed. Conclusions Sustained effectiveness of OROS MPH was maintained for up to 24 months with minimal effects on growth, tics, vital signs, or laboratory test values. J. Am. Acad. Child Adolesc. Psychiatry , 2005;44(10):1015-1023.

ObjectiveAssess long-term tolerability and efficacy of once-daily mixed amphetamine salts extended release (MAS XR) for attention-deficit/hyperactivity disorder (ADHD) in adolescents (13–17 years of age).MethodsEfficacy of MAS XR (10–60 mg/day) in 138 adolescents with ADHD was assessed in a 6-month, openlabel, extension study following participation in a 4-week, randomized, placebo-controlled trial of MAS XR. Efficacy was based on ADHD Rating Scale-IV (ADHD-RS-IV) scores and Clinical Global Impressions-Improvement (CGI-I) ratings at end point. Tolerability was based on reported adverse events, physical and laboratory examintions, vital signs, and electrocardiographic measures.FindingsPatients exhibited sustained improvement in ADHD symptoms in this 6-month, open-label study of MAS XR 10–60 mg/day. End point ADHD-RS-IV total score was significantly decreased from baseline (-7.9; PConclusionLong-term MAS XR therapy is generally well tolerated and exerts sustained control of ADHD symptoms in otherwise healthy adolescents.

There has been increasing interest in the developmental origins of substance use disorders (SUDs) in children and adolescents. Because of its early onset, high prevalence and known risk for SUD, attention deficit hyperactivity disorder (ADHD) is a model developmental disorder to evaluate in context to SUDs. A selected review of the literature was undertaken examining ADHD as an antecedent disorder to subsequent SUD. ADHD and its co-occurring comorbid psychopathology increase the risk for cigarette smoking and SUD and is associated with greater SUD severity and chronicity. The treatment of ADHD appears to decrease the risk for cigarette smoking and SUD. ADHD is an important antecedent disorder in children and adolescents worthy of further targeted preventive efforts to diminish the risk for cigarette smoking and SUD.

The purpose of the present study was to examine the potential efficacy, patient acceptability, and feasibility of a novel, cognitive-behavioral therapy (CBT) for adults with attention-deficit hyperactivity disorder (ADHD) who have been stabilized on medications but still show clinically significant symptoms. Thirty-one adults with ADHD and stable psychopharmacology for ADHD were randomized to CBT plus continued psychopharmacology or continued psychopharmacology alone. Assessments included ADHD severity and associated anxiety and depression rated by an independent evaluator (IE) and by self-report. At the outcome assessment, those who were randomized to CBT had lower IE-rated ADHD symptoms (p < .01) and global severity (p < .002), as well as self-reported ADHD symptoms (p < .0001) than those randomized to continued psychopharmacology alone. Those in the CBT group also had lower IE-rated and self-report anxiety (p's < .04), lower IE-rated depression (p < .01), and a trend to have lower self-reported depression (p = .06). CBT continued to show superiority over continued psychopharmacology alone when statistically controlling levels of depression in analyses of core ADHD symptoms. There were significantly more treatment responders among patients who received CBT (56%) compared to those who did not (13%) (p < .02). These data support the hypothesis that CBT for adults with ADHD with residual symptoms is a feasible, acceptable, and potentially efficacious next-step treatment approach, worthy of further testing.

Background The few controlled studies of methylphenidate (MPH) in adults with attention deficit/hyperactivity disorder (ADHD) have reported equivocal results. A previous, pilot study by our group suggested that these results were due to inadequate dosing. Method We conducted a randomized, 6-week, placebo-controlled, parallel study of MPH in 146 adult patients with DSM-IV ADHD using standardized instruments for diagnosis, separate assessments of ADHD, depressive and anxiety symptoms, and a robust average oral daily dose of 1.1 mg/kg/day. Results We found a marked therapeutic response for the MPH treatment of ADHD symptoms that exceeded the placebo response (76% vs. 19%). Treatment was safe and well tolerated. Response to MPH was independent of socioeconomic status, gender, and lifetime history of psychiatric comorbidity. Conclusions These results confirm that robust doses of MPH are effective in the treatment of adult ADHD.

Objective: To evaluate the effects of medications used in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD) on blood pressure and pulse. Method: Subjects were those with DSM-III-R-/DSM-IV-diagnosed ADHD enrolled in placebo-controlled studies of 5 different medications for ADHD. Cardiovascular data from these studies of both stimulants (methylphenidate, amphetamine compounds, pemoline) and nonstimulants (bupropion, desipramine) were reanalyzed for baseline-to-endpoint active-treatment or placebo effects on blood pressure and heart rate. Results: There were 125 subjects with a mean ′ SD age of 39 ′ 9 years. In general, active drug treatment for ADHD compared to baseline was associated with several statistically significant changes in systolic blood pressure (bupropion: +5.9 mm Hg, p

Objective: Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD. Method: Probands with DSM-IV BPD ( n = 57, mean age ± SD = 13.3 ± 2.4 years) and without DSM-IV BPD ( n = 46, 13.6 ± 2.2 years) were studied. Structured psychiatric interviews and multiple measures of SUD were collected. Results: Bipolar disorder was associated with a highly significant risk factor for SUD (32% versus 7%, Z = 2.9, p = .004) that was not accounted for by conduct disorder (adjusted odds ratio = 5.4, p = .018). Adolescent-onset BPD (≥13 years) was associated with a higher risk of SUD compared with those with child-onset BPD (χ 2 1 = 9.3, p = .002). Conclusions: These findings strongly indicate that BPD, especially adolescent onset, is a significant risk factor for SUD independently of conduct disorder.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder that affects all age groups. Recent data on the clinical presentation, comorbidity, neurobiology, and treatment are reviewed. Method: Using the search term ADHD, a selective PubMed review of the clinical literature was undertaken to evaluate recent data relevant to ADHD with attention to a life span perspective of the disorder. Results: A growing literature indicates that ADHD is more persistent than previously thought and has a developmental variability in its presentation. The disorder impairs academic, social, and occupational functioning and is often associated with comorbidity, including cigarette smoking and substance abuse. Considerable evidence suggests that the disorder has a strong genetic component and a biological underpinning; the pathophysiology includes dysfunction in both noradrenergic and dopaminergic systems. Both psychosocial therapy and pharmacotherapy have been shown effective in the treatment of the disorder throughout the life span. The therapeutic effectiveness of pharmacologic agents in the treatment of ADHD has been attributed to noradrenergic and/or dopaminergic effects. Conclusion: ADHD is associated with impairment and comorbidity throughout the life span. Growing evidence suggests the importance of short- and long-term management of the disorder. While the long-term treatment of ADHD is expected to lessen the individual's impairment, the outcome for adults who have received treatment since childhood requires further study.

There is a strong literature supporting a relationship between ADHD and SUD. Clearly, ADHD adolescents with conduct or bipolar disorder as partof their clinical picture are at the highest risk for SUD. ADHD without comorbidity appears to confer an intermediate risk factor for SUD that appears to manifest in young adults and college students. Both family genetic and self-medication influences may be operational in the development and continuation of SUD in ADHD subjects: however, systematic data are lacking. Patients with ADHD and SUD require multi-modal intervention incorporating addiction and mental health treatment. Pharmacotherapy in individuals with ADHD and SUD needs to take into consideration abuse liability, potential drug interactions, and compliance concerns. Although the existing literature has provided important information on the relationship of ADHD and SUD, it also points to a number of areas in need of further study. The mechanism by which untreated ADHD leads toSUD and the risk reduction of ADHD treatment on later SUD, needs to be understood better. The influence of adequateness of treatment of ADHD on later SUD needs to be delineated. Given the prevalence and major morbidity and impairment caused by SUD and ADHD. prevention and treatment strategies for these patients need to be developed and evaluated further.

There is a substantial body of literature documenting the efficacy of multiple unrelated pharmacological agents in attention-deficit hyperactivity disorder (ADHD) individuals throughout the life-cycle. The available literature indicates the important role of psychopharmacological agents in the reduction of the core symptoms of ADHD and associated impairments. The literature documents that stimulants not only improve abnormal behaviours of ADHD, but also improves self-esteem, cognition, and social and family function. However, response varied in different age groups and with certain comorbidities. In addition there is a large body of literature documenting the efficacy of atomoxetine which shows improvement in these same domains. More research is needed on alternative pharmacological treatments and to further evaluate established therapeutics beyond school-aged Caucasian boys. Further, more research is needed on the efficacy of treatment for comorbid ADHD, use of combined medications, and the combination of medication and psychosocial treatment.

Studies of vital signs in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) receiving stimulants indicate a variable effect on blood pressure (BP) and heart rate (HR). We evaluated the longer-term effects on vital signs of once-daily osmotic-release methylphenidate (MPH, Concerta) in children with ADHD.As part of a 1-year open-extension trial, we studied children with ADHD (aged 6-13 years; baseline assessment, n = 432) who were entered into an open-label study of osmotic-release MPH (18-54 mg) for up to 1 year. Subjects' BP and HR were recorded at monthly visits and, when applicable, analyses were by last observation carried forward.Compared to off-drug baseline, osmotic-release MPH was associated with minor clinical, although statistically significant, changes in systolic and diastolic blood pressure (DBP) (3.3 and 1.5 mm Hg, Ps0.001) and HR (3.9 bpm, P0.0001) at 12-month end point. There was no clear dose-response relationship. There was no tolerance to the pressor effects of osmotic-release MPH over the 1-year period. There was an inverse relationship between baseline vital signs and positive change in vital signs at end point.Over a 12-month period, osmotic-release MPH produced minor clinical, although statistically significant, changes in BP and HR in children with ADHD.

Objective To evaluate hepatic enzyme elevations during treatment with olanzapine, divalproex, and their combination. Method Fifty-two children, aged 4 to 18 years, with hepatic enzyme levels measured during treatment with olanzapine ( n = 17), divalproex ( n = 23), or their combination ( n = 12), were identified in the computerized records at a pediatric medical center. Clinical characteristics as well as serial alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were collected. Results Mean and peak hepatic enzyme levels were significantly higher for the combined treatment group compared to the olanzapine or divalproex groups. All 12 patients who received combined treatment had at least one peak enzyme elevation during the treatment. For 42% of these patients, at least one enzyme level remained elevated during the time for which values were available (mean 8 ± 6 months). For those treated with divalproex either alone or in combination, the findings were not explained by variations in divalproex plasma levels. Two patients receiving combined treatment had the combination treatment discontinued because of medical complications (pancreatitis in one and steatohepatitis in the other). Conclusions Combined treatment with olanzapine and divalproex was associated with more elevations of hepatic enzymes than treatment with either agent alone. The long-term significance of this is unknown but warrants study.

Objective To evaluate whether attention-deficit hyperactivity disorder (ADHD) is a risk factor for psychoactive substance use disorders (PSUD), attending to issues of psychiatric comorbidity, family history, and adversity. Method Using assessments from multiple domains, the authors examined 140 ADHD and 120 normal control subjects at baseline and 4 years later. Drug and alcohol abuse and dependence were operationally defined. Results No differences were detected in the rates of alcohol or drug abuse or dependence or in the rates of abuse of individual substances between the groups; both ADHD and control probands had a 15% rate of PSUD. Conduct and bipolar disorders predicted PSUD, independently of ADHD status. Family history of substance dependence and antisocial disorders was associated with PSUD in controls but less clearly so in ADHD probands. Family history of ADHD was not associated with risk for PSUD. ADHD probands had a significantly shorter time period between the onsets of abuse and dependence compared with controls (1.2 years versus 3 years, p Conclusions Adolescents with and without ADHD had a similar risk for PSUD that was mediated by conduct and bipolar disorder. Since the risk for PSUD has been shown to be elevated in adults with ADHD when compared with controls, a sharp increase in PSUD is to be expected in grown-up ADHD children during the transition from adolescence to adulthood.

Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. This study was conducted, in part, to evaluate the single-dose and steady-state pharmacokinetics of atomoxetine in pediatric patients.This was an open-label, dose-titration study in pediatric patients with attention deficit hyperactivity disorder. Eligible patients could elect to participate in a single-dose or steady-state discontinuation pharmacokinetic evaluation including serial plasma sample collection over 24 hours. Plasma concentrations of atomoxetine, 4-hydroxyatomoxetine, and N-desmethylatomoxetine were determined using an atmospheric pressure chemical ionization liquid chromatography/mass spectrometry/mass spectrometry assay. Pharmacokinetic parameters were calculated using noncompartmental analysis.Twenty-one cytochrome P450 2D6 extensive metabolizer patients participated in these single-dose and steady-state pharmacokinetic evaluations. Atomoxetine was rapidly absorbed, with peak plasma concentrations occurring 1 to 2 hours after dosing. Half-life averaged 3.12 and 3.28 hours after a single dose and at steady state, respectively. Minimal accumulation occurred in plasma after multiple twice-daily dosing in extensive metabolizer pediatric patients, as expected based on single-dose pharmacokinetics. As the dose (in mg/kg) increased, proportional increases in area under the curve were observed.The pharmacokinetics of atomoxetine in extensive metabolizer patients were well characterized over a wide range of doses in this study. Atomoxetine pharmacokinetics in pediatric patients and adult subjects were similar after adjustment for body weight.

Practitioners are increasingly called upon to diagnose and treat attention deficit hyperactivity disorder (ADHD) in adults. Although the use of pharmacotherapy in children with ADHD is well studied, the use of drugs for the treatment of adults with ADHD remains less well established. A systematic review of the literature identified 15 studies (n = 482 patients) of stimulants, and 27 studies of nonstimulant medications (n = 1179 subjects) including antidepressants, norepinephrine reuptake inhibitors, antihypertensive agents, amino acids and wake-promoting agents for the treatment of ADHD in adults. Controlled clinical trials in adults showed that stimulants, antidepressants and norepinephrine reuptake inhibitors demonstrated significant short-term improvements in ADHD symptoms compared with placebo. The two longer term trials with methylphenidate in adults confirmed the ongoing effectiveness and tolerability of stimulants. The response to amphetamine and methylphenidate appears to be dose-dependent. Methylphenidate and amphetamine had an immediate onset of action, whereas responses to pemoline, antidepressants and norepinephrine reuptake inhibitors appeared delayed. Controlled data on nicotinic/cholinergic compounds appear promising. Considerable variability was found in the diagnostic criteria for ADHD in adults, drug dosages and response rates between the various studies. Under controlled conditions, the aggregate literature comprised mainly of short-term studies, shows that stimulants, norepinephrine reuptake inhibitors and specific antidepressants had clinically and statistically significant beneficial effects in the treatment of ADHD in adults. Cholinergic agents appear promising. Further studies are necessary to evaluate the long-term effectiveness and tolerability of various agents, functional and neuropsychological outcomes, and the use of various agents in specific subgroups of adults with ADHD.

Adults with substance use disorders (SUD; alcohol or drug abuse or dependence) were evaluated to determine if childhood-onset psychopathology preceded the onset of SUD. Using structured psychiatric interviews, we assessed 47 clinically referred adults with SUD (27 with opioid dependence and 20 with alcohol dependence), with attention to childhood-onset psychopathology. A sequence of psychopathology and SUD was reconstructed using mean diagnosis onset data. Sixty-two percent of the 47 SUD adults (mean age 39.3±6.6 years) had early-onset SUD (defined as ≤18 years) and 38% had late-onset SUD (≥19 years at onset). Psychopathology preceded the onset of SUD in 56% of adults. Attention deficit/hyperactivity disorder, multiple anxiety, and disruptive disorders typically preceded the onset of SUD; in contrast, mood disorders (specifically depressive and bipolar disorders) followed the onset of SUD. The majority of clinically referred adults with SUD had psychopathology that began in childhood, frequently preceding the onset of their SUD. These findings further highlight the importance of targeting antecedent disorders for preventive and early intervention programs aimed at reducing the risk for SUD.

Despite the growing interest in the use of psychotropic medications in preschoolers, little is known about the clinical presentation of young children referred for psychiatric services. We describe the clinical characteristics, psychiatric disorders, and functioning of preschoolers referred for pediatric psychiatry evaluation. Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed on clinically referred youth. Family, social, and overall functioning were assessed at intake. From the pool of 1658 consecutive referrals, we identified 200 children less than or equal to (

The substantial discrepancy in the male-to-female ratio between clinic-referred (10 to 1) and community (3 to 1) samples of children with attention deficit hyperactivity disorder (ADHD) suggests that gender differences may be operant in the phenotypic expression of ADHD. In this study the authors systematically examined the impact of gender on the clinical features of ADHD in a group of children referred to a clinic.The study included 140 boys and 140 girls with ADHD and 120 boys and 122 girls without ADHD as comparison subjects. All subjects were systematically assessed with structured diagnostic interviews and neuropsychological batteries for subtypes of ADHD as well as emotional, school, intellectual, interpersonal, and family functioning.Girls with ADHD were more likely than boys to have the predominantly inattentive type of ADHD, less likely to have a learning disability, and less likely to manifest problems in school or in their spare time. In addition, girls with ADHD were at less risk for comorbid major depression, conduct disorder, and oppositional defiant disorder than boys with ADHD. A statistically significant gender-by-ADHD interaction was identified for comorbid substance use disorders as well.The lower likelihood for girls to manifest psychiatric, cognitive, and functional impairment than boys could result in gender-based referral bias unfavorable to girls with ADHD.

Adolescents and young adults with substance use disorders (SUD) and attention deficit/hyperactivity disorder (ADHD) are increasingly presenting in clinical practice. The overlap and role of treatment for these co-occurring disorders remains unclear. A review of the literature was conducted to highlight and update recent evidence on the overlap of ADHD and SUD, the role of ADHD medication on later SUD, and the treatment of ADHD and SUD in adolescents and young adults. Recent work continues to highlight the high risk for comorbid ADHD in patients with SUD; and conversely, the high risk for SUD developing in ADHD across the lifespan, particularly in the context of comorbid conduct disorder. Although the data remains discordant, it appears that ADHD pharmacotherapy does not increase the risk for SUD. Medication treatment alone does not appear to be particularly effective in treating SUD in currently active substance abusing individuals with ADHD. Structured therapies may be effective in treating adolescents and young adults with ADHD and SUD. Further controlled trials evaluating the sequence and effect of structured psychotherapies and/or ADHD pharmacotherapy on SUD relapse in these groups are warranted.

Objective: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, the use of pharmacotherapeutics remains less established.Methods: A systematic review of the literature identified 15 studies (N = 435 subjects) of stimulants, and 22 studies of non- stimulant medications (N = 421 subjects) including antidepressants, antihypertensives, amino acids, and wake-promoting agents for the treatment of ADHD in adults.Results: Studies with stimulants and antidepressants demonstrated significant short-term improvement in ADHD symptoms compared to placebo in adults. Methylphenidate (MPH) and amphetamine had an immediate onset of action whereas the ADHD response to pemoline and antidepressants appeared delayed. The response to amphetamine and MPH appears to be dose-dependent. Controlled data on nicotonic and noradrenergic compounds appear promising. There was considerable variability In diagnostic criteria, dosing parameters, and response rates between the various studies.Conclusions: Under controlled conditions, the aggregate literature shows that the stimulants and noradrenergic antidepressants had a clinically and statistically significant beneficial effect on treating ADHD in adults.

Background: Because attention-deficit/hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the nature and causes of psychiatric comorbidity in girls and the reason for gender differences in the prevalence of these comorbidities. Methods: Using blinded, structured psychiatric interviews, we studied two groups of boys: 140 ADHD probands and 120 non-ADHD comparisons. These groups had 454 and 368 first-degree biological relatives, respectively. We also studied two groups of girls: 140 ADHD probands and 122 non-ADHD comparisons. These groups had 417 and 369 first-degree biological relatives, respectively. Results: The co-occurrence of ADHD and comorbid psychopathology in families was the same for families ascertained through boy and girl probands. Conclusions: Our results suggest that boys and girls do not differ in the familial risk factors that mediate comorbid psychopathology and the familial aggregation of comorbid disorders in ADHD families. Although this is consistent with prior work suggesting more similarities than differences in the nature of psychiatric comorbidity in ADHD boys and girls, we cannot make strong conclusions, owing to the possibility of cohort effects.

Objective. A new once-a-day methylphenidate (MPH) formulation, Concerta (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed. This study was conducted to determine the safety and efficacy of OROS MPH in a multicenter, randomized, clinical trial. Methods. Children with attention-deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years, were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3 times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd;n = 95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed, and data were analyzed using analysis of variance and Kaplan Meier product limit estimates for time to study cessation. The primary time point for analysis was the last available patient visit using last observation carried forward. Results. Children in the OROS and IR MPH groups showed significantly greater reductions in core ADHD symptoms than did children on placebo. This was true both at the end of week 1 and at the end of treatment on the basis of mean teacher and parent IOWA Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any direct comparisons. Forty-eight percent of the placebo group discontinued early compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively. Conclusions. For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR MPH dosed tid were superior to placebo and were not significantly different from each other.attention-deficit/hyperactivity disorder, methylphenidate, OROS, Concerta.

The unique pattern of comorbidity found in pediatric mania greatly complicates accurate diagnosis, the course of the disorder, and its treatment. The pattern of comorbidity is unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder (ADHD), aggression, and conduct disorder. Clinically, symptoms of mania have been discounted as severe ADHD or ignored in the context of aggressive conduct disorder. This atypicality may lead to neglect of the mood component. The addition of high rates of additional disorders contributes to the severe morbidity, dysfunction, and incapacitation frequently observed in these children. A comprehensive approach to diagnostic evaluation is the keystone to establishing an effective treatment program because response to treatment differs with individual disorders. Recognition of the multiplicity of disorders guides therapeutic options in these often refractory conditions. What was previously considered refractory ADHD, oppositionality, aggression, and conduct disorder may respond after mood stabilization. We review these issues in this article.

The impact of tic disorders on the outcome of attention deficit hyperactivity disorder (ADHD) remains a subject of high scientific and clinical interest. To evaluate the impact of comorbid ADHD and tic disorders from a lifespan perspective, the authors systematically examined data from adults with and without ADHD.They comprehensively evaluated 312 consecutively referred adults with ADHD and 252 comparison subjects without ADHD. Tic disorders were characterized along with a wide range of neuropsychiatric correlates, including other comorbid disorders as well as indexes of function in the domains of school, cognition, and interpersonal functioning.A significantly greater proportion of adults with ADHD (12%) than those without ADHD (4%) had tic disorders. Tic disorders followed a mostly remitting course and had little impact on functional capacities. In addition, tic disorders were not associated with stimulant use.These findings in adults with ADHD confirm and extend previous findings in young subjects with ADHD, documenting that although individuals with ADHD are at greater risk for tic disorders, the presence of tic disorders has a limited impact on ADHD outcome.

Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials demonstrating the effectiveness of compounds used in treatment, particularly nonstimulants. The authors report results from a controlled investigation to determine the anti-ADHD efficacy of bupropion in adult patients with DSM-IV ADHD.This was a double-blind, placebo-controlled, randomized, parallel, 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg b.i.d.) (N=21) to patients receiving placebo (N=19). The authors used standardized structured psychiatric instruments for diagnosis of ADHD. To measure improvement, they used separate assessments of ADHD, depression, and anxiety symptoms at baseline and each weekly visit.Of the 40 subjects (55% male) enrolled in the study, 38 completed the study. Bupropion treatment was associated with a significant change in ADHD symptoms at the week-6 endpoint (42% reduction), which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the subjects receiving bupropion improved, compared to 37% of the subjects receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of the subjects receiving bupropion reported being "much improved" to "very improved," compared to 11% of the subjects receiving placebo.These results indicate a clinically and statistically significant effect of bupropion in improving ADHD in adults. The results suggest a therapeutic role for bupropion in the armamentarium of agents for ADHD in adults, while further validating the continuity of pharmacological responsivity of ADHD across the lifespan.

To study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD).Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responders to treatment were then randomized into a 3-week, controlled discontinuation phase. During this phase, subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depression.Of the 35 subjects enrolled in the study, 32 completed the open phase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusion of the open 6-week study, NT was related to a significant reduction in ADHD (p0.001) and oppositional symptoms (p0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects randomized to placebo (31 versus 21; t = 2.2; p0.04). No significant adverse events were observed, and children were noted to have weight gain during the trial.These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality. This group of children and adolescents tolerated robust dosing of NT well, with few clinical or cardiovascular adverse events.

To assess the validity of adult attention-deficit/hyperactivity disorder (ADHD), we reviewed clinical, family, psychopharmacologic, neurobiological, and outcome studies. We found multiple reports describing adults with clinical features highly reminiscent of the childhood ADHD. These adults, who are impulsive, inattentive, and restless, have the clinical “look and feel” of ADHD children. As with their childhood counterparts, many adults with ADHD suffer from antisocial, depressive, and anxiety disorders. They also show clinically significant impairments—histories of school failure, occupational problems, and traffic accidents. Studies of biological features show correspondences between child and adult cases of ADHD. Both show familial aggregation and a characteristic profile of neuropsychologic deficits; an emerging neuroimaging literature suggests that abnormalities in the same brain regions underlie both the child and adult forms of the disorder. Although these converging lines of evidence support the validity of ADHD in adults, follow-up studies of ADHD children have yielded ambiguous results. This ambiguity is in part due to differences in how researchers define the persistence of ADHD, a problem that suggests future research focus on how best to diagnose ADHD in adulthood.

Stimulants are the most often prescribed psychotropics in children and adolescents, used generally for the treatment of attention deficit /hyperactivity disorder (ADHD). In this article the authors summarize the literature on prevalence of usage, neurobiology, and pharmacology of the stimulants. Recent studies on the use of stimulants in special ADHD populations including preschoolers and adults, and co-occuring neurologic, psychiatric, and substance use disorders are cited. Clinical guidelines for the management of individuals receiving the stimulants are offered, and treatment strategies delineated for ADHD subjects with comorbidity and medication-induced adverse effects are discussed.

An increasing awareness of the importance of comorbidity in psychiatric disorders has emerged. Over the past decade numerous reports on the overlap of attention deficit hyperactivity disorder and depression have been published. A growing number of reports have now addressed the overlap of childhood mania and attention deficit hyperactivity disorder. Clinical, epidemiological and family genetic studies have provided evidence supporting the coexistence of these conditions.

Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials. Recent reports have suggested the potential usefulness of cholinergic agents for ADHD. To this end, the authors completed a controlled study of ABT-418, a novel cholinergic activating agent, for the treatment of adults with ADHD.This was a double-blind, placebo-controlled, randomized, crossover trial that compared a transdermal patch of ABT-418 (75 mg/day) to placebo in adults who met DSM-IV criteria for ADHD. There were two 3-week treatment periods separated by 1 week of washout.Of the 32 subjects enrolled in the study (88% were men; mean age = 40 years, SD = 9), 29 completed the study. At the endpoint of each active arm (last observation carried forward), a significantly higher proportion of subjects was considered improved while receiving ABT-418 than while receiving placebo (40% versus 13%). Similarly, at endpoint there was a significantly greater reduction in ADHD symptom checklist scores (28% versus 15%). Symptoms reflective of attention, and subjects with less severe ADHD, responded more robustly to ABT-418. Treatment with ABT-418 was relatively well tolerated; dizziness and nausea were the most frequently reported adverse effects.The results of this investigation indicate that ABT-418, a nicotinic analog, may be a potentially useful agent for the treatment of ADHD.

Objective To Investigate the effectiveness and tolerability of the atypical neuroleptic risperidone in the treatment of juvenile mania. Method This is a retrospective chart review of outpatients with the diagnosis of bipolar disorder ( DSM-IV ) treated with risperidone at a university center. Response to treatment was evaluated using the Clinical Global Impression Scale (CGI) with separate assessments of mania, psychosis, aggression, and attention-deficit/hyperactivity disorder (ADHD). Results Twenty-eight youths (mean SD age, 10.4 3.8 years) with bipolar disorder (25 mixed and 3 hypomanic) who had been treated with risperidone were identified. These children received a mean dose of 1.7 1.3 mg over an average period of 6.1 8.5 months. Using a CGI Improvement score of ≤2 (very much/much improved) to define robust improvement, 82% showed improvement in both their manic and aggressive symptoms, 69% in psychotic symptoms, but only 8% in ADHD symptoms. Conclusions Although limited by its retrospective nature, this study suggests that risperidone may be effective in the treatment of maric young people and indicates the need for controlled clinical trials of risperidone and other atypical neuroleptics in juvenile mania. J.Am.Acad. Child Adolesc. Psychiatry , 1999, 38(8):960–965.