Timothy E. Wilens

Pharmacotherapy of Attention-Deficit Hyperactivity Disorder across the Life Cycle

OBJECTIVE To evaluate the scope of the available therapeutic armamentarium in attention-deficit hyperactivity disorder (ADHD). METHOD The literature of medication trials in ADHD was systematically reviewed, with attention to issues of psychiatric comorbidity, age, gender, and ethnic background. RESULTS One hundred fifty-five controlled studies of 5,768 children, adolescents, and adults have documented the efficacy of stimulants in an estimated 70% of subjects. The literature clearly documents that stimulants not only improve abnormal behaviors of ADHD, but also self-esteem, cognition, and social and family function. However, response varied in different age groups and with certain comorbid conditions. In addition, there is an impressive body of literature documenting the efficacy of tricyclic antidepressants on ADHD in more than 1,000 subjects. Studies of alternative antidepressants, antipsychotics, antihypertensives, and other compounds were also reviewed. CONCLUSIONS The available literature indicates the important role of psychopharmacological agents in the reduction of the core symptoms of ADHD and associated impairments. More research is needed on alternative pharmacological treatments and to further evaluate established therapeutics beyond school-age Caucasian boys. In addition, more research is needed on the efficacy of treatment for comorbid ADHD, use of combined medications, and the combination of medication and psychosocial treatment.

Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study

BACKGROUND Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder (ADHD) through young adulthood using contemporaneous diagnostic and analytic techniques. METHOD We conducted a case-control, 10-year prospective study of ADHD youth. At baseline, we assessed consecutively referred male, Caucasian children with (n=140) and without (n=120) DSM-III-R ADHD, aged 6-18 years, ascertained from psychiatric and pediatric sources to allow for generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of the ADHD and control children, respectively, were reassessed (mean age 22 years). We created the following categories of psychiatric disorders: Major Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder), Developmental Disorders (elimination, language, and tics disorder), and Substance Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by blinded structured diagnostic interview. RESULTS The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls, with hazard ratios and 95% confidence intervals of 6.1 (3.5-10.7), 2.2 (1.5-3.2), 5.9 (3.9-8.8), 2.5 (1.7-3.6), and 2.0 (1.3-3.0), respectively, for the categories described above. CONCLUSIONS By their young adult years, ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial, addictive, mood and anxiety disorders. These prospective findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies.

Impact of Executive Function Deficits and Attention-Deficit/Hyperactivity Disorder (ADHD) on Academic Outcomes in Children

The association between executive function deficits (EFDs) and functional outcomes were examined among children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were children and adolescents with (n = 259) and without (n = 222) ADHD, as ascertained from pediatric and psychiatric clinics. The authors defined EFD as at least 2 executive function measures impaired. Significantly more children and adolescents with ADHD had EFDs than did control participants. ADHD with EFDs was associated with an increased risk for grade retention and a decrease in academic achievement relative to (a) ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and (d) IQ. No differences were noted in social functioning or psychiatric comorbidity. Children and adolescents with ADHD and EFDs were found to be at high risk for significant impairments in academic functioning. These results support screening children with ADHD for EFDs to prevent academic failure.

Is ADHD a Risk Factor for Psychoactive Substance Use Disorders? Findings From a Four-Year Prospective Follow-up Study

ABSTRACT 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.

Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder.

Objective. To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD). Methods. The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects. Results. Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 [1.8–21.6]). Subjects with ADHD medicated at baseline were at a significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 [0.04–0.6]). For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category. Conclusions. Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth.

Clinical correlates of ADHD in females : Findings from a large group of girls ascertained from pediatric and psychiatric referral sources

OBJECTIVE The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. METHOD Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. RESULTS Compared with female controls, girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. CONCLUSIONS These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females.

Psychiatric Comorbidity and Functioning in Clinically Referred Preschool Children and School-Age Youths With ADHD

OBJECTIVE Although the literature documents that attention-deficit/hyperactivity disorder (ADHD) commonly onsets prior to age 6, little is known about the disorder in preschool children. We evaluated the clinical characteristics, psychiatric comorbidity, and functioning of preschool children and school-age youths with ADHD referred to a pediatric psychiatric clinic for evaluation. METHOD Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed with parents about their children. Family, social, and overall functioning were also assessed at intake. RESULTS We identified 165 children with ADHD aged 4 to 6 years (preschool children) and 381 youths aged 7 to 9 years (school-age) with ADHD. Despite being younger, preschool children had similar rates of comorbid psychopathology compared with school-age youths with ADHD. There was an earlier onset of ADHD and co-occurring psychopathology in the preschool children compared to school-age youths. Both preschool children and school-age youths had substantial impairment in school, social, and overall functioning. CONCLUSIONS The results of this study suggest that despite being significantly younger, clinically referred preschool children with ADHD are reminiscent of school-age youths with ADHD in the quality of ADHD, high rates of comorbid psychopathology, and impaired functioning. Follow-up of these clinically referred preschool children with ADHD to evaluate the stability of their diagnoses, treatment response, and their long-term outcome are necessary.

A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

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.

Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence?

BACKGROUND The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) in adults has been the focus of much clinical and scientific inquiry. In this study we examine the effects of ADHD on the transitions from substance abuse to dependence and between different classes of agents of abuse. METHODS An ADHD sample of 239 consecutively referred adults of both genders with a clinical diagnosis of childhood-onset and persistent DSM-III-R ADHD confirmed by structured interview were compared with 268 non-ADHD healthy adults. RESULTS ADHD was associated with a twofold increased risk for PSUD. ADHD subjects were significantly more likely than comparisons to make the transition from an alcohol use disorder to a drug use disorder (hazard ratio = 3.8) and were significantly more likely to continue to abuse substances following a period of dependence (hazard ratio = 4.9). CONCLUSIONS ADHD is associated with a sequence of PSUD in which early alcohol use disorder increases the risk for subsequent drug use disorder, and early substance dependence increases the risk for subsequent substance abuse. If confirmed such developmental pathways might lead to preventive and early intervention strategies aimed at reducing the risk for PSUD in ADHD subjects.

Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders.

We evaluated the association between attention deficit hyperactivity disorder (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD. We compared 120 referred adults having a clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All diagnoses were obtained using DSM-III-R based structured psychiatric interviews. We used group comparisons of age at onset and Cox proportional hazard models to examine the development of PSUD over time. ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar disorders conferred a significantly increased risk for early onset PSUD independently of ADHD. Psychiatric disorders commonly emerged before the onset of PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD. In addition, comorbidity with conduct and juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non-ADHD individuals. These findings confirm and extend previous findings documenting important associations between PSUD and psychiatric comorbidity including persistent ADHD.