Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder

Previous work has shown that adolescent hyperactivity patients are significantly more likely to smoke than controls. To determine whether this pattern persists in adults, we studied a series of 71 patients (55 males, 16 females; mean age ±SD: 33.9 ± 11.4 years) diagnosed with ADHD. Of the males, 23 (42%) were current smokers, 7 (13%) were ex-smokers, and 25 (45%) were never smokers. Comparable figures for males in the general population in 1991, unselected for ADHD, were 28.1%, 29.1%, and 42.1%, respectively. Of the females, 6 (38%) were current smokers, 5 (31%) were ex-smokers, and 5 (31%) had never smoked, as compared with 23.5%, 19.0%, and 57.6%, respectively, in the general population. Quit ratio (percentage of ever-smokers who were ex-smokers) was 29% for ADHD patients, compared with 48.5% in the general population. The discrepancy was accounted for by the males, whose quit ratio was 23%, compared with 51.6% in the general population; the figure for ADHD females (45%) was similar to that in the general population (44.7%). Smokers recalled experiencing a significantly higher number of ADHD symptoms (11.5 ± 1.7) as children than never smokers (9.9 ± 2.3; p < .01) and scored significantly higher on several indices of childhood and adult comorbidity. Our findings suggest that ADHD patients overinclude smokers, and that these smokers find it extremely difficult to quit. For ADHD smokers, smoking may have begun as an attempt to manage deficits in attention and concentration, as suggested by greater childhood symptomatology in these patients.     

Quality of life assessment in adult patients with attention-deficit/hyperactivity disorder treated with atomoxetine

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (or occupational) impairment and dysfunction within the family and society. Despite the existence of research demonstrating the effects of ADHD on certain aspects of life, the clinical trials of treatments for this disorder have focused primarily on efficacy and safety. METHODS: Atomoxetine was approved in the United States in November 2002 for the treatment of ADHD in children, adolescents, and adults. The present study uses data from a clinical trial of atomoxetine in adult patients with ADHD that incorporated a measure of health-related quality of life (the Medical Outcomes Study 36-item short-form health survey [SF-36]) as part of the overall assessment of the success of this relatively new treatment. The primary outcome measure for ADHD symptoms was the Conners Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS) ADHD total symptom score. RESULTS: In agreement with previous studies, adult patients with ADHD treated with atomoxetine at typical doses showed significant amelioration of ADHD symptoms, as measured on the CAARS. At baseline, the measures of overall mental health (one aspect of quality of life) of adult patients with ADHD were below the average level, as measured on the SF-36. Treatment with atomoxetine significantly improved the measures of mental health and ameliorated the ADHD symptoms. In addition, the 2 measures were correlated. CONCLUSIONS: These data suggest that pharmacological intervention with atomoxetine not only ameliorates ADHD symptoms in adult patients but also improves their perceived quality of life.     

Stimulant medication improves recognition memory in children diagnosed with attention-deficit/hyperactivity disorder

The effect of stimulant medication on recognition memory was examined in 18 children with attention-deficit/hyperactivity disorder (ADHD). Recognition memory was assessed using a delayed matching-to-sample task at 6 delays ranging from 1 to 32 s. Each child was tested on 2 separate occasions, once 60 to 90 min after taking stimulant medication and the other at least 18 hr after taking medication. Children performed significantly better on medication than off. Stimulant administration significantly increased accuracy and the number of nickel reinforcers earned. Decreases in observing response latency and correct choice response latency occurred after taking stimulant medication. The results indicate that stimulant medication improved recognition memory for children with ADHD.     

Neurocognitive effects of methylphenidate in adult attention-deficit/hyperactivity disorder

Rationale Features of childhood attention-deficit/hyperactivity disorder (ADHD) often persist into adulthood. It has been shown that adult ADHD is associated with various neurocognitive deficits, including impairments in spatial working memory (SWM) and attention. It is not known whether these deficits are ameliorated by methylphenidate in adult ADHD.Objectives The aim of this study was to evaluate the neurocognitive effects of a single dose of methylphenidate on SWM, visual memory, spatial span and sustained attention in adult ADHD.Methods Twenty-four adult patients, recruited from a specialised clinic for the assessment of adult ADHD, were entered into a double-blind, randomised, placebo-controlled crossover study using a single 30 mg dose of methylphenidate.Results Eighteen patients met DSM-IV criteria for adult ADHD. Methylphenidate resulted in an improvement in SWM performance and sustained attention, together with a speeding in response time, in these patients. Six patients with attentional difficulties, who did not meet a DSM-IV diagnosis of ADHD, showed a different pattern of response to methylphenidate compared to the ADHD group. For the combined group, moderate correlations were shown between childhood ratings of ADHD (both self-reported and informant ratings) and response to methylphenidate on the SWM task.Conclusions Adults with ADHD had a similar neurocognitive response to methylphenidate to that previously reported for childhood ADHD. Our results provide further support for the validity of the ADHD syndrome as defined by DSM-IV and indicate possible neurocognitive substrates for clinical improvement with chronic methylphenidate.     

Bupropion treatment for cocaine abuse and adult attention-deficit/hyperactivity disorder

There are few published studies assessing the efficacy of pharmacologic treatments for attention-deficit hyperactivity disorder (ADHD) among substance abusers seeking treatment. Eleven patients who met DSM-IV diagnostic criteria for cocaine dependence and adult ADHD were entered into a 12-week single-blind trial of divided daily doses of bupropion (BPR). All patients received weekly individual standardized relapse prevention therapy. Treatment compliance and retention were good. Patients reported significant reductions in attention difficulties, hyperactivity and impulsivity. Self-reported cocaine use, cocaine craving, and cocaine positive toxicologies, also decreased significantly. In a previously published trial, 12 patients who met similar diagnostic criteria for adult ADHD and cocaine dependence were entered into a 12-week trial of divided daily doses of sustained-release methylphenidate (MPH). Improvements observed on BPR were similar to, and did not differ from those previously observed with MPH. These preliminary data suggest that BPR may be as effective as sustained-release MPH, when combined with relapse prevention therapy, for cocaine abusers with adult ADHD. However, a future study directly comparing BPR to MPH in a double-blind placebo-controlled trial is needed.     

Treatment modalities among US children diagnosed with attention-deficit hyperactivity disorder: 1995-99

The objective of this study was to determine the prevalence of single and combination treatment modalities among US children aged 5-18 years who were diagnosed with attention-deficit hyperactivity disorder (ADHD). Treatments included: (i) stimulant pharmacotherapy alone; (ii) psychotherapy and/or mental health counselling alone; (ii) a combination; or (iv) no treatment. Data from the US National Ambulatory Medical Care Survey (NAMCS) for the years 1995-99, were used for this analysis. Office-based physician-patient visits documenting a recorded diagnosis of ADHD (ICD-9-CM codes 314.00 or 314.01) were extracted from the NAMCS. Findings are presented for children diagnosed with ADHD with or without comorbid mental illness, for children diagnosed with ADHD without comorbid mental illness, by gender, and by age groups. Over the timeframe 1995-99, an estimated 14 402 090 office-based visits documented a diagnosis of ADHD, with (24%) or without (76%) comorbid mental illness, among children aged 5-18 years. Overall, the most frequent treatment was stimulant medication alone (42.0%). This was followed by the combination treatment of stimulant medication plus psychotherapy and/or mental health counselling (32.1%). Only 10.8% of the children received psychotherapy and/or mental health counselling alone; 15.1% received no treatment beyond the office-based visit. This pattern was consistent for boys and girls; however, a larger proportion of boys (11.7%) were receiving psychotherapy and/or mental health counselling alone than girls (8.2%). More girls (18.7%) were receiving no treatment option compared to boys (13.9%). The percentage of children receiving psychotherapy and/or mental health counselling alone increased with each age group (6.7%, 5-8 years; 11.3%, 9-12 years; 13.6%, 13-18 years), as did the combination treatment of stimulant medication plus psychotherapy and/or mental health counselling (28.2%, 31%, 37.3%, respectively). Only 8.2% of children age 13-18 years were receiving no treatment option compared to 16.9% of children age 9-12 years, and 19.5% of those aged 5-8 years. The reasons for the gender and age group differences discerned in this study require further investigation, as does the reason why 15.1% of children were receiving no treatment beyond the office-based visit.     

Substance abuse in patients with attention-deficit hyperactivity disorder : therapeutic implications

Attention-deficit hyperactivity disorder (ADHD) is a common disorder in children that frequently persists into adulthood. Studies have found that substance use disorders (SUD) are seen more commonly in those with ADHD than the general population. Although treatment with stimulant medications has been shown to be effective for individuals with ADHD, concern about the use of these agents in this population persists. This review article highlights the research in this area with a focus on the treatment of individuals who present with concomitant ADHD and SUD. Although stimulants can be abused, studies have shown that adolescents who are prescribed stimulants for ADHD have lower rates of SUD than those who are not treated with stimulants. It may be particularly difficult to evaluate adults for the diagnosis of ADHD when SUD is a co-morbid factor. Studies show that 20--30% of adults presenting with SUD have concomitant ADHD and approximately 20--40% of adults with ADHD have histories of SUD. Therefore, it is critical to perform careful diagnostic interviews to discern if patients have either or both of these disorders. Many clinical experts suggest that adults with ADHD and active SUD be treated for the SUD until a period of sobriety persists prior to initiation of specific treatment for ADHD. Since individuals with ADHD and active SUD are more likely to have more severe SUD and a worse prognosis, this approach may not serve many patients, as they relapse prior to obtaining ADHD treatment. Therefore, research has been directed towards determining if the treatment of ADHD with stimulant medications can be safe and effective for the individual with active SUD and concomitant ADHD. An initial trial of methylphenidate in a population of adults with active cocaine dependence and ADHD indicates that this is the case. Individuals with ADHD and SUD can present difficult diagnostic and therapeutic challenges. It appears that the most effective treatment option is to create a programme that uses the most effective treatment modalities available, including both behavioural and medical therapies, along with close supervision and monitoring. Newer medical treatment options of long-acting stimulants and non-stimulants (e.g. atomoxetine) offer effective treatment with a lower risk of abuse potential.     

Pharmacological management of attention-deficit hyperactivity disorder

Pharmacotherapy is the most common intervention for attention-deficit hyperactivity disorder (ADHD). Stimulant medications are highly efficacious and are the gold-standard for treating the inattention, impulsivity and excessive motoric activity associated with ADHD. Methylphenidate and amphetamine-based stimulants are now available in longer-acting, once-daily and shorter-acting divided dosing schedules. Several nonstimulant, second-line treatments are now available or under development for the treatment of ADHD in children and adults. This article reviews the support for a variety of pharmacological agents and the issues to be considered when selecting an agent. The authors conclude that there is a need for additional direct comparisons between the longer-acting agents to effectively guide the practicing clinician.     

Pharmacological management of attention-deficit hyperactivity disorder

Pharmacotherapy is the most common intervention for attention-deficit hyperactivity disorder (ADHD). Stimulant medications are highly efficacious and are the gold-standard for treating the inattention, impulsivity and excessive motoric activity associated with ADHD. Methylphenidate and amphetamine-based stimulants are now available in longer-acting, once-daily and shorter-acting divided dosing schedules. Several nonstimulant, second-line treatments are now available or under development for the treatment of ADHD in children and adults. This article reviews the support for a variety of pharmacological agents and the issues to be considered when selecting an agent. The authors conclude that there is a need for additional direct comparisons between the longer-acting agents to effectively guide the practicing clinician.     

Long-acting methylphenidate reduces collision rates of young adult drivers with attention-deficit/hyperactivity disorder

This study investigated whether methylphenidate delivered through a long-acting transdermal system (MTS) would reduce collision rates of young adult drivers with attention-deficit/hyperactivity disorder (ADHD).Seventeen young adults completing the study (mean [SD] age, 20.82 [2.40] years; 14 men and 13 white) met the following inclusion criteria: ADHD diagnoses but not routinely taking ADHD medication, previously responsive to ADHD medication, active drivers with more than 1 collision or citation in the past 2 years, and no significant comorbidities. In this open-labeled, crossover design drivers were randomly assigned either to the no-medication condition for 3 months and then MTS for 3 months or to the reverse sequence. In-car video monitoring of routine driving occurred during these 6 months. At baseline and after each condition, participants completed the Conners Adult ADHD Rating Scale and the Cox Assessment of Risky Driving Scale, and their blood pressure, heart rate, and body weight were monitored.Compared with the no-medication condition, participants in the MTS condition self-reported fewer total ADHD (P < 0.04) and inattentive symptoms (P = 0.014) and a trend for risky driving behaviors (P = 0.059) and had fewer video-recorded collisions (P < 0.005) and other problematic driving events. There were no significant changes in blood pressure, heart rate, or body weight across conditions or any significant skin reactions to the MTS patch.This is the first study demonstrating that long-acting methylphenidate improves activities of daily living among young adults with ADHD. Specifically, methylphenidate improved safety in routine driving while reducing ADHD symptoms with minimal adverse effects.     

Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder

The objective of this study was to compare the efficacy of the alpha-2a agonist guanfacine with that of dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder (ADHD). Seventeen adult outpatients who met DSM-IV criteria for ADHD participated in a double-blind, placebo-controlled, crossover study comparing drug effects on ADHD symptoms. Measures of change included the DSM-IV ADHD Behavior Checklist for Adults and the Copeland Symptom Checklist for Adult Attention Deficit Disorders. Cognitive measures of attention included the Stroop and Controlled Oral Word Association Test using the letters "C," "F," and "L" (COWAT, CFL version). For each trial, the drug was administered daily and titered up to optimal doses of maximum efficacy but with a minimum of side effects, and then data were collected. Both drugs significantly reduced ADHD symptoms on the DSM-IV Adult Behavior Checklist for Adults over placebo (p < 0.05). The Stroop Color subscale showed significant improvement for both drugs (p < 0.05), but the Color-Word measures showed significant improvement for guanfacine only (p < 0.01). The average dose of guanfacine was 1.10 (SD = 0.60), and the most common side effect of guanfacine was fatigue. No subjects discontinued drug trials. This preliminary study indicates that guanfacine may be a well-tolerated treatment option for adult ADHD.     

Drug therapy for adults with attention-deficit hyperactivity disorder

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.     

Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder

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.     

Effects of substance misuse on reward-processing in patients with attention-deficit/hyperactivity disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD. The aim of this study was to examine substance misuse effects on reward-processing in ADHD. Functional MRI data in a Monetary Incentive Delay (MID) task from a multi-site study were compared across ADHD groups with and without substance misuse (ADHD + SM and ADHD-only, respectively) and healthy controls (n = 40/group, 74 males and 46 females, aged 13.7–25.9 years). Substance misuse was defined as misuse of alcohol, nicotine, or drugs. Groups were matched with presence/absence of parental SUD to avoid interference with SUD trait effects. Compared to ADHD-only and controls, ADHD + SM showed hyperactivation in putamen during reward anticipation. Compared to controls, the ADHD groups showed hypoactivation in motor/sensory cortices and hyperactivation in frontal pole and OFC during reward outcome. ADHD + SM also showed hyperactivation in frontal pole during neutral outcome. Moreover, ADHD + SM patients showed higher callous-unemotional (CU) traits that were positively correlated with putamen responses to reward anticipation. Our results show distinct condition-independent neural activation profile for ADHD + SM compared to ADHD-only and controls. Effects of comorbid substance misuse and variability of its prevalence across ADHD studies might have contributed to inconsistencies in ADHD literature. Contrasted with findings for reward-processing in SUD literature, results potentially suggest distinct underlying mechanisms for SUD subgroups with different characteristics, like antisocial/psychopathic traits.Subject terms: Reward, Cognitive neuroscience     

Limits of meta-analysis: methylphenidate in the treatment of adult attention-deficit hyperactivity disorder

Guidelines for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults advocate methylphenidate as first-line treatment. The aim of this study was to review the effectiveness of methylphenidate treatment of adult ADHD and to examine the influence of methods on meta-analytic results. Electronic databases were searched to identify clinical trials comparing methylphenidate with placebo in the treatment of adult ADHD. Studies were summarised with meta-analytic methods. Subgroup analyses were conducted with respect to parallel group versus cross-over trials and self versus observer ratings. The relationship between dosage and effect size was explored by weighted regression analysis. The results were tested for publication bias, and several sensitivity analyses were performed. Findings and methods were compared with a previous meta-analysis. Eighteen studies met the inclusion criteria of which 16 were included in the meta-analysis. The overall effect size (d = 0.42) was significantly different from zero, but was only half the size expected on the basis of a previous meta-analysis. No significant differences could be observed in the subgroup analyses. The regression analysis showed no significant influence of mean daily dose on effect size. These results contradict findings of a previous meta-analysis and challenge guideline recommendations. Methodological issues in meta-analyses are discussed.     

Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder

This article reviews the efficacy of methylphenidate (MPH) for adult attention-deficit/hyperactivity disorder (ADHD). A literature search identified double-blind placebo-controlled MPH treatment studies of ADHD adults. Meta-analysis estimated the pooled effect size for MPH treatment and tested for publication bias. Meta-analysis regression assessed the influence of study design features on medication effects. Six trials met criteria and were included in this meta-analysis. These studies included a total of 140 MPH-treated ADHD adults and 113 placebo-treated ADHD adults. The mean effect size of 0.9 was statistically significant and there was no evidence of publication bias. Larger MPH effect sizes were associated with physician ratings of outcome and use of higher doses. When treatment is optimized to high doses, the effect size for MPH in adults was 1.3. We found strong support for the assertion that MPH is efficacious for treating adult ADHD. Because the degree of efficacy of MPH in treating ADHD adults is similar to what has been reported from meta-analyses of the child and adolescent literature, our work provides further assurance to clinicians that the diagnosis of ADHD can be validly applied in adulthood.     

Animal models of attention-deficit/hyperactivity disorder

Attention-deficit hyperactivity disorder (AD/HD) is a clinically heterogenous disorder including hyperactivity, impulsivity, and inattention. Both psychostimulant and non-psychostimulant drugs such as methylphenidate and atomoxetine, respectively, to modulate catecholeamine neurotransmission are used as current pharmacotherapies for AD/HD. Multiple lines of evidence suggest that genetic factors play major roles in the etiology of AD/HD. meta-Analyses and pooled data analyses have suggested associations between AD/HD and polymorphisms in genes encoding monoamine neurotransmission molecules. There has been considerable research on this disorder using genetic, pharmacological, and neuroimaging approaches, and several animal models of AD/HD such as spontaneously hypertensive rat (SHR), dopamine transporter (DAT) knockout mice, coloboma mutant mouse, and Grin1 mutant mouse have been reported. These animal models are valuable tools for investigating molecular, cellular, and behavioral mechanisms as well as the neural development and circuit mechanisms of AD/HD. Here, we review the recent literature on animal models of AD/HD and discuss their advantages and limitations.     

Pharmacotherapy of attention-deficit hyperactivity disorder in adolescents

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder in children and adolescents, consisting of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. The majority of children with ADHD will continue to experience significant ADHD symptoms as teens. ADHD in adolescents can result in significant functional impairment and poorer quality of life. Children and adolescents with ADHD are at higher risk of developing other psychiatric illnesses such as mood, conduct and substance abuse disorders. Stimulants (amphetamines and methylphenidates) and nonstimulants (atomoxetine, guanfacine extended-release (XR) and clonidine XR) have been found to be effective and are approved by the US FDA for the treatment of ADHD in adolescents in the US. Of the agents approved in the US, only guanfacine XR and clonidine XR are not approved in any other countries. There is growing evidence that treatment of ADHD with stimulants reduces the risk of development of other psychiatric co-morbidities, including substance abuse disorders. To date, all FDA-approved stimulants and nonstimulants that have been adequately studied have been demonstrated to be safe and effective in treating ADHD in both children and adolescents. Therefore, clinical decisions used in selecting pharmacotherapy to treat ADHD in children aged 6-12 years can be applied in the adolescent population.