Serving Substance Abuse Professionals Since 1993

Last Update: 23.03.10

C O R K O N L I N E

powerpoint presentations
CORK database search
resource materials
bibliographies
clinical tools
user services
newsletters
about cork
home

CORK Bibliography: Attention Deficit/Hyperactivity Disorder

89 citations. June 2005 to present

Prepared: March 2010

Adler L; Wilens T; Zhang SY; Durell T; Walker D; Schuh L et al. Retrospective safety analysis of atomoxetine in adult ADHD patients with or without comorbid alcohol abuse and dependence. American Journal on Addictions 18(5): 393-401, 2009. (41 refs.)

This post hoc analysis compared the safety of atomoxetine treatment of ADHD in adults with or without comorbid alcohol abuse/dependence. Study completion rates in patients receiving atomoxetine were comparable between heavy drinkers (60.9%) and patients with no alcohol-use disorder (71.0%) but lower in nonheavy drinkers (35.7%); however, there was no significant difference in discontinuation rates due to adverse events or lack of efficacy among these groups. Alcohol-use disorder patients, especially heavy drinkers, generally experienced the greatest frequency of treatment-emergent adverse events in both the atomoxetine and placebo groups. Vital signs and measures of hepatic function were not significantly different among the 3 drinking status groups taking atomoxetine.

Advokat CD; Guidry D; Martino L. Licit and illicit use of medications for Attention-Deficit Hyperactivity Disorder in undergraduate college students. Journal of American College Health 56(6): 601-606, 2008. (22 refs.)

Objective: The authors studied the relationship between a diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD), grade point average (GPA), and licit and illicit drug use. Participants and Methods: They obtained survey data from a convenience sample of undergraduates in a large southern public university. Results: Among 1,550 respondents, 163 (10.5%) reported an ADHD diagnosis (ADHD Group). Of those without an ADHD diagnosis, 591 (43%) reported using prescription stimulants illicitly (No ADHD, Illicit Use group), and 794 (57%) reported not using prescription drugs illicitly (No ADHD, No Illicit Use group). The GPA of the ADHD group was significantly lower than the GPA of the other 2 groups. The ADHD group and the No ADHD, Illicit Use group reported significantly greater use of all other drugs than did the No ADHD, No Illicit Use group. Conclusions: Drug use was associated with a lower GPA in ADHD-diagnosed students than in students without ADHD.

Aharonovich, E.; Garawi, F.; Bisaga, A.; Brooks, D.; Raby, WN; Rubin, E. et al. Concurrent cannabis use during treatment for comorbid ADHD and cocaine dependence: Effects on outcome. American Journal of Drug and Alcohol Abuse 32(4): 629-635, 2006. (10 refs.)

Cannabis is the most widely used illicit substance in the United States with especially high prevalence of use among those with psychiatric disorders. Few studies have examined the relationship between concurrent cannabis use and treatment outcome among patients receiving treatment for comorbid substance abuse and psychiatric disorders. This study investigated the effects of cannabis use on treatment retention and abstinence from cocaine among cocaine dependent patients with Attention Deficit Hyperactivity Disorder (ADHD). Cocaine dependent patients diagnosed with current ADHD (DSM-IV, N = 92) aged 25 to 51 participated in a randomized clinical trial of methylphenidate for treatment of ADHD and cocaine dependence in an outpatient setting. The majority of patients (69%) used cannabis during treatment. Results suggest that moderate/intermittent cannabis users had greater retention rates compared to abstainers and consistent users (p = .02). This study is the first to examine concurrent cannabis use in cocaine dependent patients diagnosed with ADHD.

Altink ME; Slaats-Willemse DIE; Rommelse NNJ; Buschgens CJM; Fliers EA; Arias-Vasquez A et al. Effects of maternal and paternal smoking on attentional control in children with and without ADHD. European Child and Adolescent Psychiatry 18(8): 465-475, 2009. (56 refs.)

Maternal smoking during pregnancy is a risk factor for attention-deficit/hyperactivity disorder (ADHD), but data on its adverse effects on cognitive functioning are sparse and inconsistent. Since the effect of maternal smoking during pregnancy may be due to correlated genetic risk factors rather than being a pure environmental effect, we examined the effect of prenatal exposure to smoking on attentional control, taking into account the effects of both maternal and paternal smoking, and examined whether these effects were genetically mediated by parental genotypes. We further examined whether the effect of prenatal exposure to smoking on attentional control interacted with genotypes of the child. Participants were 79 children with ADHD, ascertained for the International Multi-centre ADHD Gene project (IMAGE), and 105 normal controls. Attentional control was assessed by a visual continuous performance task. Three genetic risk factors for ADHD (DRD4 7-repeat allele of the exon 3 variable number of tandem repeats (VNTR), DAT1 10/10 genotype of the VNTR located in the 3' untranslated region, and the DAT1 6/6 genotype of the intron 8 VNTR) were included in the analyses. Paternal smoking had a negative effect on attentional control in children with ADHD and this effect appeared to be mediated by genetic risk factors. The prenatal smoking effect did not interact with genotypes of the child. Maternal smoking had no main effect on attentional control, which may be due to lower smoking rates. This study suggests that the effects of paternal smoking on attentional control in children with ADHD should be considered a proxy for ADHD and/or smoking risk genes. Future studies should examine if the results can be generalized to other cognitive domains.

Arias AJ; Gelernter J; Chan G; Weiss RD; Brady KT; Farrer L; Kranzler HR. Correlates of co-occurring ADHD in drug-dependent subjects: Prevalence and features of substance dependence and psychiatric disorders. Addictive Behaviors 33(9): 1199-1207, 2008. (37 refs.)

We examined the prevalence and course of psychiatric and substance dependence (SD) disorders in subjects with SD and attention deficit hyperactivity disorder (ADHD). Method: We interviewed 1761 adults with a lifetime diagnosis of cocaine and/or opioid dependence using the Semi-Structured Assessment for Drug Dependence and Alcoholism. Generalized linear regression with generalized estimating equation analysis was used to examine the associations between a lifetime diagnosis of ADHD and indicators of clinical course, and to identify unique correlates of ADHD. Results: Lifetime ADHD prevalence in the SD sample was 5.22% (vs. 0.85% in a group of individuals without SD). ADHD was associated with an earlier age of first substance use, more SD and psychiatric diagnoses, a greater likelihood of attempted suicide, and more hospitalizations. After controlling for conduct disorder, there were unique effects of ADHD on age of first substance use and number of SD diagnoses. Conclusion: In subjects with cocaine or opioid dependence, ADHD is associated with greater SD and psychiatric comorbidity and a more severe course of illness.

Baker A; Velleman R. Clinical Handbook of Co-existing Mental Health and Drug and Alcohol Problems. London: Routledge, 2007

Co-occurring mental health and drug and/or alcohol problems are frequently seen in primary care and clinical settings. However, health professionals rarely receive training in how to detect, assess and formulate interventions for co-existing problems and few clinical guidelines exist. This Handbook endeavors to fill this void. It defines best practices. Among the topics addressed are the components of a cognitive behavioural framework; consultation-liaison services, training and supervision; individual, group and family interventions; as well as working with rural isolated populations. The psychiatric conditions that are addressed include anxiety, depression, schizophrenia, bipolar disorder and learning difficulties.

Barnow S; Schuckit M; Smith T; Spitzer C; Freyberger HJ. Attention problems among children with a positive family history of alcohol abuse or dependence and controls: Prevalence and course for the period from preteen to early teen years. European Addiction Research 13(1): 1-5, 2007. (59 refs.)

This longitudinal study investigated the scope and course of attention problems over a period of time from preteen (ages 7-12 years) to early teen years (ages 13-17 years). We compared symptoms in subjects with and without a family history (FH) of alcohol abuse or dependence from among families without evidence of antisocial personality disorder. Evaluations of attention problems for the offspring were based on the Child Behavior Checklist and a validated semistructured interview carried out with the mother. The findings indicate no higher risk for attention problems and attention-deficit hyperactivity disorder (ADHD)-like symptoms in the children of families with an alcohol use disorder. Regarding the course of problems, the ADHD symptom count tended to decrease over time, especially for children without a FH of alcohol abuse or dependence. Further research will be needed to determine whether results can be replicated with families from different social strata and including subjects with the antisocial personality disorder.

Biederman J Petty CR Wilens TE Fraire MG Purcell CA Mick E et al. Familial risk analyses of attention deficit hyperactivity disorder and substance use disorders. American Journal of Psychiatry 165(1): 107-115, 2008. (37 refs.)

Objective: A robust and bidirectional comorbidity between attention deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (alcohol or drug abuse or dependence) has been consistently reported in the extant literature. Method: First-degree relatives from a large group of pediatrically and psychiatrically referred boys with (112 probands, 385 relatives) and without (105 probands, 358 relatives) ADHD were comprehensively assessed by blind raters with structured diagnostic interviews, Familial risk analysis examined the risks in first-degree relatives for ADHD, psychoactive substance use disorder, alcohol dependence, and drug dependence after stratifying probands by the presence and absence of these disorders. Results: ADHD in the proband was consistently associated with a significant risk for ADHD in relatives. Drug dependence in probands increased the risk for drug dependence in relatives irrespective of ADHD status, whereas alcohol dependence in relatives was predicted only by ADHD probands with comorbid alcohol dependence. in addition, ADHD in the proband predicted drug dependence in relatives, and drug dependence in comparison probands increased the risk for ADHD in relatives. Both alcohol dependence and drug dependence bred true in families without evidence for a common risk between these disorders. Conclusions: Patterns of familial risk analysis suggest that the association between ADHD and drug dependence is most consistent with the hypothesis of variable expressivity of a common risk between these disorders, whereas the association between ADHD and alcohol dependence is most consistent with the hypothesis of independent transmission of these disorders. Findings also suggest specificity for the transmission of alcohol and drug dependence.

Biederman J; Monuteaux MC; Faraone SV; Mick E. Parsing the associations between prenatal exposure to nicotine and offspring psychopathology in a nonreferred sample. Journal of Adolescent Health 45(2): 142-148, 2009. (35 refs.)

Purpose: Several studies have suggested an association between maternal smoking during pregnancy and both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in the offspring of women who smoke during pregnancy. However, it is unclear whether one or both of the documented links are spurious, given the considerable comorbidity between these disorders. The main aim of this study was to disentangle the association between maternal smoking during pregnancy with psychopathological outcomes, adjusting for possible confounders. Methods: Two large, identically designed, longitudinal, case-control family studies of male and female probands with and without ADHD were combined. We used data from the nonreferred siblings of the probands from both studies (n = 536). All subjects were blindly assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of exposure to maternal smoking during pregnancy. Results: Among all siblings, maternal smoking during pregnancy was significantly associated with ADHD, independent of CD and other covariates. In contrast, maternal smoking during pregnancy was a risk factor for CD only in siblings of control probands, after adjusting for covariates. Conclusions: These results support the hypothesis that maternal smoking during pregnancy is a risk factor for both ADHD and CD, independently of each other. However, the risk for CD appears to be conditional on family risk status.

Biederman J; Spencer TJ; Wilens TE; Prince JB; Faraone SV. Treatment of ADHD with stimulant medications: Response to Nissen perspective in The New England Journal of Medicine. (editorial). Journal of the American Academy of Child and Adolescent Psychiatry 45(10): 1147-1150, 2006

This editorial is a response to an article in the New England Journal of Medicine (SE Nissen, ADHD drugs and cardiovascular risk, 354(14): 1445-1448, 2006) written by a consultant to the Food and Drug and Administration (FDA) Committee that recommended a "black-box" warning describing the cardiovascular risks associated with stimulant drugs used to treat attention deficit-hyperactivity disorder (ADHD).

Brook JS; Duan T; Zhang CS; Cohen PR; Brook DW. The association between attention deficit hyperactivity disorder in adolescence and smoking in adulthood. American Journal on Addictions 17(1): 54-59, 2008. (35 refs.)

This longitudinal study examined the interrelationships between early and/or middle adolescent attention deficit hyperactivity disorder (ADHD), middle adolescent conduct disorder (CD), and later adult smoking behavior. This is a prospective longitudinal study. Data were collected via structured interviews of representative families in the northeastern United States (N=641). The mean ages of the offspring were as follows: 14 years (T2, 1983), 17 years (T3, 1985 - 1986), and 32 years (T6, 2002). The dependent variable was the participants' daily cigarette smoking in their early thirties. Logistic regression analyses indicated that the relationship between ADHD and daily smoking behavior was mediated by CD with control on gender, age, SES, and adolescent smoking. CD had a direct effect on daily smoking in adulthood. Our findings suggest that ADHD is related to CD, which in turn is associated with daily smoking. Therefore, interventions with ADHD adolescents who have ADHD at an early age might lead to some reduction in later smoking provided that the intervention has a positive effect on CD. For those adolescents who never had ADHD, our findings suggest that prevention or treatment aimed at reducing CD may be most successful in reducing daily smoking later in adulthood.

Brooks DJ; Vosburg SK; Evans SM; Levin FR. Assessment of cognitive functioning of methadone-maintenance patients: Impact of adult ADHD and current cocaine dependence. Journal of Addictive Diseases 25(4): 15-25, 2006. (48 refs.)

The purpose of this study was to determine if methadone-maintained patients (MMP) with cocaine dependence (CD) and/or adult Attention Deficit Hyperactivity Disorder (ADHD) exhibited compounded cognitive dysfunction associated with their poly-substance use and/or co-morbid psychiatric diagnoses. The sample consisted of 79 MNIP (59% male, 51 % Caucasian), maintained on methadone doses ranging from 40-130 mg/day, who were placed into one of four diagnostic categories: (1) a control group (no ADHD, no CD) (n = 24), (2) CD alone (n = 18),(3) ADHD alone (n = 18), and (4) ADHD + CD (n = 19). The California Computerized Assessment Package (CalCAP((R))) was administered to assess cognitive functioning requiring focused and sustained attention in a standardized fashion. There were no group differences on Simple Reaction tasks. Compared to the control group, the ADHD + CD group was slower and less accurate on 33% of the Choice Reaction (CR) tasks. Specifically, individuals in the ADHD + CD group and the ADHD alone group performed significantly worse on tasks measuring attention and psychomotor responding. These tasks are associated with broader cognitive skills in working memory, language discrimination and flexibility of cognitive sets that may have implications for treatment outcome. Diagnostic services capable of identifying cognitive deficits among MMP with ADHD and/or CD are needed to maximize the likelihood of treatment success and to serve as ail indicator for the efficacy of therapeutic approaches.

Clarke AR; Barry RJ; McCarthy R; Selikowitz M; Johnstone SJ. Effects of stimulant medications on the EEG of girls with Attention-Deficit/Hyperactivity Disorder. Clinical Neurophysiology 118(12): 2700-2708, 2007. (56 refs.)

Objective: Stimulant medications are the most commonly used treatments for Attention-Deficit/Hyperactivity Disorder (AD/HD) in North America and Australia, although it is still not entirely known how these medications work. This study investigated the effects of stimulant medications on the EEG of girls with AD/HD. Methods: An initial EEG was recorded during an eyes-closed resting condition. Data from 19 electrode sites were Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. The data were then averaged into 9 regions and an analysis of both global and regional differences was performed. Subjects were placed on a six-month trial of a stimulant and a second EEG was recorded at the end of the trial. Results: The unmedicated girls had significantly greater total power, absolute delta and theta, more relative theta especially in the frontal regions, and reduced frontal relative delta and beta activity compared with controls. Medication resulted in normalisation of theta power, but after medication, increased relative beta was also apparent in the AD/HD group. Conclusions: These results indicate that stimulant medications result in a normalisation of slow wave activity in the EEG. In line with published research on the effects of arousal on the EEG, these results suggest that stimulant medications may have their therapeutic effect by improving the EEG substrate of processing deficits in these children. However, this requires further testing during active processing tasks. Significance: This is the first study to investigate the effect of stimulant medications on the EEG of girls with AD/HD.

Covey L; Manubay J; Jiang HP; Nortick M; Palumbo D. Smoking cessation and inattention or hyperactivity/impulsivity: A post hoc analysis. Nicotine & Tobacco Research 10(12): 1717-1725, 2008. (59 refs.)

Tobacco use is more prevalent and smoking cessation less likely among persons with attention deficit hyperactivity disorder (ADHD) than the general population. Evidence that tobacco use and nicotine hold divergent relationships with inattention and hyperactivity/impulsivity, the core symptoms of ADHD, prompted this post hoc investigation of abstinence patterns by type of ADHD symptoms. Subjects were 583 adult smokers treated openly with bupropion and nicotine patch during the initial 8-week phase of a maintenance treatment study. Using the ADHD Current Symptom Scale, clinically significant ADHD symptom subtypes, i.e., predominantly inattention (ADHD-inattention) and predominantly hyperactivity/impulsivity with or without inattention (ADHD-hyperactivity/impulsivity with or without inattention), were identified. The study outcome was abstinence status, verified by expired carbon monoxide 8 parts per million, at five clinic visits from Week 1 through the end of treatment at Week 8. The distribution by ADHD symptom status was: No ADHD=540; ADHD-inattention=20; ADHD-hyperactivity/impulsivity with/without inattention=23. The study groups did not differ on demographic or smoking variables. The frequency of past major depression was highest with ADHD-inattention and the frequency of past alcohol dependence was highest with ADHD-hyperactivity/impulsivity with/without inattention. Compared to smokers with no ADHD, smokers of both ADHD subtypes combined showed lower abstinence rates throughout the study (OR=0.54, 95% CI=0.32-0.99). Disaggregation by symptom subtype and separate comparisons against smokers with no ADHD showed that lower odds of quitting occurred mainly with ADHD-hyperactivity/impulsivity with/without inattention (OR=0.40, 95% CI=0.19-0.82), not with ADHD-inattention (OR=0.74, 95% CI=0.36-1.51). Combined bupropion and nicotine patch treatment appears to be helpful for smokers with inattention but not smokers with hyperactivity/inattention symptoms. The reasons for this divergent treatment response warrant further investigation.

Crocker N; Vaurio L; Riley EP; Mattson SN. Comparison of adaptive behavior in children with heavy prenatal alcohol exposure or attention-deficit/hyperactivity disorder. Alcoholism: Clinical and Experimental Research 33(11): 2015-2023, 2009. (41 refs.)

Background: Adaptive behavior, the ability to respond successfully to everyday demands, may be especially sensitive to the effects of heavy prenatal alcohol exposure. Similar adaptive dysfunction is common in other developmental disorders including attention-deficit/hyperactivity disorder (ADHD). ADHD is frequently present in alcohol-exposed children and this overlap in clinical presentation makes identification of alcohol-exposed children difficult. Direct comparison of children with prenatal alcohol exposure and ADHD may yield distinct patterns of cognitive and behavioral performance and add to growing knowledge of the neuropsychological and behavioral profile of prenatal alcohol exposure. Therefore, the aim of the current study was to compare adaptive behavior in children with histories of heavy prenatal alcohol exposure (ALC), nonexposed children with ADHD (ADHD), and typically developing controls (CON). Methods: Sixty-five children (ALC = 22, ADHD = 23, CON = 20) were selected from a larger ongoing study of the behavioral teratogenicity of alcohol. Alcohol-exposed and control participants were selected to match the ADHD subjects on age, sex, socioeconomic status, and race/ethnicity. Caregivers were administered the Vineland Adaptive Behavior Scales, a semi-structured interview, and were asked to rate their child's behavior on 3 domains of adaptive function. Data were analyzed using regression techniques. Results: Relative to controls, children in both the ALC and ADHD groups showed adaptive behavior deficits on all 3 domains and children in the ALC group were significantly more impaired than the ADHD group on the daily living skills domain. Within the ALC group, socialization standard scores were lower at older ages. This negative relationship between age and standard scores in the ALC group was also observed on the communication domain, a finding not previously reported. Conclusions: This study suggests that both children with prenatal alcohol exposure and children with ADHD show impairments in adaptive function relative to controls, but that the pattern of impairment differs between these clinical groups. Adaptive ability in children with prenatal alcohol exposure is characterized by an arrest in development, as evidenced by a lack of improvement with age in socialization and communication scores. In contrast, children with ADHD exhibit a developmental delay in adaptive ability as their scores continued to improve with age, albeit not to the level of control children. Continued research focused on elucidating the patterns of deficits that exist in alcohol-exposed children ultimately will lead to improved differential diagnosis and effective interventions.

Cumyn L; French L; Hechtman L. Comorbidity in adults with attention-deficit hyperactivity disorder. (review). Canadian Journal of Psychiatry 54(10): 673-683, 2009. (35 refs.)

Objective: To examine the prevalence of comorbid Axis I (current and lifetime) and II disorders in adult men and women with attention-deficit hyperactivity disorder (ADHD). Method: Adult patients (n = 447; 266 men, 181 women) received comprehensive assessments for ADHD and Axis I and II disorders. Adults were aged between 17 and 74 years. Among the patients diagnosed with ADHD (n = 335), there were those with ADHD inattentive subtype (ADHD-I) (n = 199), hyperactive-impulsive subtype (ADHD-H) (n = 24), or combined ADHD subtype (ADHD-C) (n = 112). Chi-square and logistic regression analyses were performed to examine associations between adults with and without ADHD on Axis I and II disorders. Results: Adults with ADHD, compared with those without ADHD, had higher rates of Axis I (46.9% and 27.31%) and Axis II (50.7% and 38.2%) disorders. Adults with ADHD-C were more likely to have mood disorder, anxiety, conduct disorder, and substance use disorder as well as obsessive-compulsive personality disorder, passive-aggressive personality disorder, depressive personality disorder, narcissistic personality disorder, and borderline personality disorder (BPD). Men with ADHD were more likely to have antisocial personality disorder and had higher rates of current drug abuse than women with ADHD. Women with ADHD had higher rates of past and current panic disorder, and past anorexia and bulimia. Women with ADHD were more likely to have BPD than men with ADHD. Conclusions: Adults with ADHD have very high rates of comorbid Axis I and II disorders, with differences found between men and women on certain comorbid disorders.

DeSantis AD; Hane AC. "Adderall is definitely not a drug": Justifications for the illegal use of ADHD stimulants. Substance Use & Misuse 45(1/2): 31-46, 2010. (25 refs.)

In-depth interviews were conducted in 2007 with 175 undergraduate students (94 males, 81 females, 13 non-Caucasian) at a large, public southeastern research university located in an urban area in the United States. Our primary goal was to identify how these students conceive of Attention Deficit Hyperactivity Disorder (ADHD) stimulants and their illegal use. We discovered that these students frame stimulant use as both physically harmless and morally acceptable. Specifically, these students justify their drug use through the use of four recurring pro-stimulant arguments: 1) comparison-and-contrast, 2) all-things-in-moderation, 3) self-medicating, and 4) minimization arguments. We discuss limitations to the study and conclude by suggesting five strategies for prevention researchers that would directly target these four arguments.

Doig J; McLennan JD; Ben Gibbard W. Medication effects on symptoms of attention-deficit/hyperactivity disorder in children with fetal alcohol spectrum disorder. Journal of Child and Adolescent Psychopharmacology 18(4): 365-371, 2008. (32 refs.)

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

Faraone SV; Biederman J; Wilens TE; Adamson J. A naturalistic study of the effects of pharmacotherapy on substance use disorders among ADHD adults. Psychological Medicine 37(12): 1743-1752, 2007. (33 refs.)

Background. Studies of adults with attention deficit hyperactivity disorder (ADHD) show an elevated prevalence of substance use disorders (SUDs) and the substance abuse literature shows that ADHD is elevated in substance users. Some researchers postulate that stimulant treatment of ADHD increases the risk for SUD in ADHD patients but follow-up studies suggest treatment protects patients from subsequent SUDS. This report uses retrospective data to assess the impact of prior ADHD pharmacotherapy on SUDS in 206 ADHD adults (n = 79 late-onset ADHD, n = 127 full ADHD) grouped by lifetime history of ADHD treatment (no treatment, past treatment, current and past treatment). Method. Structured Clinical Interview for DSM-IV (SCID) data were used to establish abuse and dependence, and Drug Use Screening Inventory (DUSI) responses were used to establish prevalence of use, preference for cigarettes, alcohol and drugs of abuse, complications from use, and motivation for use (get high, change mood, sleep better). Results. No differences were found in the prevalence of cigarette smoking, alcohol or drug abuse or dependence, as well as no significant differences in 1-month prevalence of any use or use more than 20 times. No differences were found in complications of drug or alcohol use across groups. Subjects with current treatment rated getting high as a motivating factor significantly more frequently than subjects in the past treatment group; this result lost significance when we included ADHD diagnostic category. Conclusions. Our results are consistent across substances and ADHD diagnoses, and support the hypothesis that pharmacotherapy does not cause subsequent SUDS.

Faraone SV; Wilens TE; Petty C; Antshel K; Spencer T; Biederman J. Substance use among ADHD adults: Implications of late onset and subthreshold diagnoses. American Journal on Addictions 16(Supplement 1): 24-34, 2007. (42 refs.)

Diagnosing ADHD in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age seven or if the number of symptoms does not achieve the DSM threshold for diagnosis. These diagnostic issues are an even larger concern for clinicians faced with adults with substance use disorders (SUD). The present study compared four groups of adults: full ADHD subjects who met all DSM-IV criteria for childhood onset ADHD, late onset ADHD subjects who met all criteria except the age at onset criterion, subthreshold ADHD subjects who did not meet full symptom criteria, and non-ADHD subjects who did not meet any of the above criteria. Diagnoses were by the Structured Clinical Interview for DSM-IV, and the Drug Use Severity Index (DUSI) was used for self-report of substance use. Cigarette and marijuana use was significantly greater in all ADHD groups relative to non-ADHD controls. Although usage rates of other drugs failed to reach significance, the ADHD groups were more likely to have used each drug (except alcohol) compared with the non-ADHD group. The late onset and full ADHD groups were more likely to have endorsed ever having a problem due to use of cigarettes, alcohol, or marijuana and reported more trouble resisting use of drugs or alcohol. The full ADHD group was more likely than the other groups to have reported "getting high" as their reason for using their preferred drug. Adults with ADHD have elevated rates of substance use and related impairment. Data about late onset ADHD provides further support for the idea that the DSM-IV age at onset criterion is too stringent. In contrast, subthreshold ADHD seems to be a milder form of the disorder, or perhaps a heterogeneous group of true ADHD cases and false positives.

Fergusson DM; Boden JM. Cannabis use and adult ADHD symptoms. Drug and Alcohol Dependence 95(1/2): 90-96, 2008. (37 refs.)

Background: The present study examined the associations between cannabis use in adolescence and young adulthood and self-reported adult attention deficil/hyperactivity disorder (ADHD) symptoms in adulthood. Methods: A 25-year prospective longitudinal study of the health, development, and adjustment of a birth cohort of 1265 New Zealand children. Measures included assessments of adolescent and young adult cannabis use and ADHD symptoms at age 25, measures of childhood socioeconomic disadvantage, family adversity, childhood and early adolescent behavioural adjustment and cognitive ability, and adolescent and young adult other drug use. Results: Cannabis use by age 25 was significantly (p <.0001) associated with increasing self-reported adult ADHD symptoms at age 25. Adjustment of the association for potentially confounding factors from childhood and early adolescence reduced the magnitude of the association, but it remained statistically significant (p<.0001). However, control for the mediating effects of other drug use in adolescence and early adulthood reduced the association between cannabis use and adult ADHD symptoms to statistical non-significance (p >.20). Conclusions: The current study suggested that the association between cannabis use and adult ADHD symptoms was mediated by other substance use that was associated with cannabis use. The results suggest that cannabis use leads to other drug use, which in turn leads to increased ADHD symptoms. However, it should be noted that the potential influence of such factors as genetic predispositions may still be unaccounted for.

Fuemmeler BF; Kollins SH; McClernon FJ. Attention deficit hyperactivity disorder symptoms predict nicotine dependence and progression to regular smoking from adolescence to young adulthood. Journal of Pediatric Psychology 32(10): 1203-1213, 2007. (36 refs.)

Objective To examine the association between retrospectively reported attention deficit hyperactivity disorder (ADHD) symptoms and progression to smoking and the association with nicotine dependence. Methods Study sample consisted of a nationally representative cohort of U. S. adolescents (n = 13,494). Logistic regression was used to examine ADHD symptoms from both the inattentive (IN) and hyperactive-impulsive (HI) domains and smoking trajectories. Linear regression was used to examine nicotine dependence. Results HI symptoms were associated with progression from nonsmoking to regular smoking (OR = 1.14, 95% CI = 1.07-1.21), and with progression from experimentation to regular smoking (OR = 1.16, 95% CI = 1.08-1.26). In and HI symptoms were associated with nicotine dependence among current smokers (IN: beta = 0.17, SE = 0.03, p< 0.0001; HI: beta = 0.10, SE = 0.04., p<. 001). Conclusions These results have important implications for the development of prevention and treatment modalities.

Galera C; Bouvard MP; Messiah A; Fombonne E. Hyperactivity-inattention symptoms in childhood and substance use in adolescence: The youth gazel cohort. Drug and Alcohol Dependence 94(1/3): 30-37, 2008. (60 refs.)

Background: This study addresses in both genders the relationship between childhood Hyperactivity-inattention symptoms and subsequent adolescent substance use, while controlling for psychiatric comorbidity, temperament and environmental risk factors. Methods: 916 subjects (421 males, 495 females) aged 7-18 were recruited from the general population and surveyed in 1991 and 1999. Child psychopathology and substance use patterns were evaluated through parent and adolescent self-reports. Multivariate modeling was performed to assess the effects of childhood Hyperactivity-inattention symptoms and other risk factors on adolescent substance use. Results: In males, Hyperactivity-inattention symptoms alone accounted for the risk of subsequent regular cannabis smoking (OR = 3.14, p=0.03) and subsequent lifetime use of other drugs including stimulants, opiates, inhalants and sedatives (OR = 2.72, p = 0.02). In females, Hyperactivity-inattention symptoms did not independently increase the liability to later substance use. In males, the temperament trait activity was a significant predictor of subsequent regular cannabis smoking (OR = 2.32, p = 0.04). Conclusions: This survey points to a possible specific link between Hyperactivity-inattention symptoms and subsequent cannabis use and experimentation of harder drugs in males.

Gehricke JG; Hong N; Whalen CK; Steinhoff K; Wigal TL. Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder. Psychology of Addictive Behaviors 23(4): 644-655, 2009. (82 refs.)

The aim of the study was to test the self-medication hypothesis by examining the effects of nicotine in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder (ADHD). Fifty-two adults with ADHD (25 abstinent smokers and 27 nonsmokers) participated in a double-blind placebo controlled study with one nicotine patch condition and one placebo patch condition in counterbalanced order. Each condition continued for two consecutive days in which patches were administered each morning. The effects of nicotine on ADHD symptoms, moods, and side effects were assessed with electronic diaries. Cardiovascular activity was recorded with ambulatory blood pressure monitors and physical activity was monitored with actigraphs. Nicotine reduced reports of ADHD symptoms by 8% and negative moods by 9%, independent of smoking status. In addition, nicotine increased cardiovascular activity during the first 3 to 6 hours after nicotine patch administration. The results support the self-medication hypothesis for nicotine in adults with ADHD and suggest that smoking cessation and prevention efforts for individuals with ADHD will need to address both the symptom reducing and mood enhancing effects of nicotine.

Goksoyr PK; Nottestad JA. The burden of untreated ADHD among adults: The role of stimulant medication. Addictive Behaviors 33(2): 342-346, 2008. (9 refs.)

The present study investigated to what degree medication with stimulants for children with ADHD will reduce comorbid complications in adulthood. Two groups (N=17 and N=74) were defined retrospectively using data from archives at the Expert team for ADHD for Middle and Northern Norway. The groups were compared on the "Index of Burden", an index constructed on the basis of data from five variables: alcohol abuse, substance abuse, criminality, the Global Severity Index of SCL-90 and the "Functioning and quality of life" questionnaire. Results showed that treatment with stimulants in childhood/youth contribute to increased social and psychological functioning in adult age.

Gray KM; Upadhyaya HP. Tobacco smoking in individuals with attention-deficit hyperactivity disorder epidemiology and pharmacological approaches to cessation. CNS Drugs 23(8): 661-668, 2009. (69 refs.)

The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and nicotine dependence is common. Individuals with ADHD are more likely to initiate smoking and become dependent on nicotine than their non-ADHD counterparts, and recent evidence suggests that they may have more difficulty quitting smoking. Little is known about how to best approach treating these co-morbidities to optimize clinical outcome. Clinicians treating individuals with either ADHD or nicotine dependence should be aware of their common co-occurrence and the need to address both in treatment. This review of ADHD and nicotine dependence provides an overview of relevant epidemiology, bidirectional interactions and implications for pharmacological and adjunctive psychosocial treatment. Incorporating the current evidence base and their clinical experience, the authors propose a stepwise approach to treating patients with co-morbid ADHD and nicotine dependence. Given the potential for ADHD symptoms to interfere with smoking cessation success, the first priority is to stabilize ADHD. The first-line pharmacological approach should be a long-acting psychostimulant. Upon ADHD stabilization, motivational techniques should be used to encourage readiness for a smoking cessation attempt. In the context of behavioural cessation Interventions sensitive to the patient's needs and developmental stage, pharmacological intervention targeting smoking cessation may be initiated. The authors recommend varenicline as a first-line agent, given Its superior effect size among available medication treatments. Symptoms of ADHD, as well as nicotine withdrawal and craving symptoms, should be monitored closely during the cessation attempt, and adjustments to therapy should be considered if warranted. The authors conclude that, while current treatments may potentially be effective for co-morbid ADHD and nicotine dependence, further research is needed to parse the complex associations between these disorders and prospectively study combined treatments.

Greenbaum RL; Stevens SA; Nash K; Koren G; Rovet J. Social cognitive and emotion processing abilities of children with fetal alcohol spectrum disorders: A comparison with attention deficit hyperactivity disorder. (review). Alcoholism: Clinical and Experimental Research 33(10): 1656-1670, 2009. (110 refs.)

Background: Although children with Fetal Alcohol Spectrum Disorders (FASDs) are at high risk of attention deficit hyperactivity disorder (ADHD), direct comparisons show distinct cognitive phenotypes in the 2 diagnoses. However, these groups have not been directly compared for social problems or social cognition, nor has social cognition been directly examined in FASDs. Objectives: To compare FASDs and ADHD groups on social cognition tasks and determine whether deficient social cognition and emotion processing predict behavioral problems and social skills. Methods: Studied were 33 children with FASDs, 30 with ADHD, and 34 normal controls (NC). All received tasks of social cognition and emotion processing. Parents and teachers rated children on measures of completed questionnaires assessing child's behavioral problems and social skills using the Child Behavior Checklist, Teacher Report Form, and Social Skills Rating Scale. Children received 3 subtests from the Saltzman-Benaiah and Lalonde (2007) Theory of Mind Task as a measure of social cognition and 4 subtests from the Minnesota Test of Affective Processing (Lai et al., 1991) to assess emotion processing. Results : Parents and teachers reported more behavior problems and poorer social skills in children in FASD and ADHD than NC groups. FASDs demonstrated significantly weaker social cognition and facial emotion processing ability than ADHD and NC groups. Regression analyses identified social cognition as a significant predictor of behavior problems and emotion processing as a significant predictor of social skills. Conclusions: Children with FASDs show a distinct behavioral profile from children with ADHD. Difficulties in social cognition and emotion processing in children with FASDs may contribute to their high incidence of social behavioral problems.

Han DH; Lee YS; Na C; Ahn JY; Chung US; Daniels MA et al. The effect of methylphenidate on Internet video game play in children with attention-deficit/hyperactivity disorder. Comprehensive Psychiatry 50(3): 251-256, 2009. (48 refs.)

Objective: A number of studies about attention-deficit/hyperactivity disorder (ADHD) and Internet video game play have examined the prefrontal cortex and dopaminergic system. Stimulants such as methylphenidate (MPH), given to treat ADHD, and video game play have been found to increase synaptic dopamine. We hypothesized that MPH treatment would reduce internet use in subjects with co-occurring ADHD and Internet video game addictions. Methods: Sixty-two children (52 males and 10 females), drug-naive, diagnosed with ADHD, and Internet video game players, participated in this study. At the beginning of the study and after 8 weeks of treatment with Concerta (OROS methylphenidate HCl, Seoul, Korea). participants were assessed with Young's Internet Addiction scale, Korean version (YIAS-K), Korean DuPaul's ADHD Rating Scale, and the Visual Continuous Performance Test. Their Internet usuage time was also recorded. Results: After 8 weeks of treatment, the YIAS-K scores and Internet Usage times were significantly reduced. The changes in the YIAS-K scores between the baseline and 8-week assessments were positively Correlated with the Changes in total and inattention scores from the Korean DUPaul's ADHD Rating Scale, as well as omission errors from the Visual Continuous Performance Test. There was also a significant difference in the number of omission errors among non-Internet-addicted, mildly Internet addicted, and severely Internet addicted participants. Discussion: We suggest that video game playing might be a means of self-medication for children with ADHD. In addition, we cautiously suggest that MPH might be evaluated as a potential treatment of Internet addiction.

Hazell P. Does the treatment of mental disorders in childhood lead to a healthier adulthood? (editorial). Current Opinion in Psychiatry 20(4): 315-318, 2007. (28 refs.)

Purpose of review To review mechanisms by which intervention for childhood mental disorders may exert an influence on mental health and wellbeing in adulthood, the challenges to demonstrating long-term benefit of harm from such intervention,existing evidence of long-term benefit, and strategies for improving the long-term benefit of treatment. Recent findings Intervention may improve long-term outcome through the promotion of protective interpersonal relationships, by enhancing scholastic and later occupational functioning, by arresting the progression of disorder, and by improving general health. Challenges to demonstrating benefits of harms in the long term include variability in the natural course of childhood mental disorders, heterotypic outcomes, and the influence of other variables over time on long-term functioning. Examples of demonstrated benefit include the lowering of risk for substance abuse seen with psychostimulant treatment for attention-devicit/hyperactivity disorder, improved outcomes for autism since the introduction of early interventions to address language impairment, and reduced mortality in anorexia nervosa. Summary There are feasible enduring benefits of treatment for childhood mental disorders. Treatment of complex problems may have a greater long-term impact than in conditions that follow a benign natural course. Success requires more assertive approaches to treatment than are traditionally employed by child and adolescent mental health services.

Herpertz-Dahlmann B. Long-term effects of methylphenidate on neural networks associated with executive attention in children with ADHD: Results from a longitudinal functional MRI study. Journal of the American Academy of Child and Adolescent Psychiatry 46(12): 1633-1641, 2007. (46 refs.)

Objective: Little is known about the long-term effects of stimulants on the functional organization of the developing brain. Nonacute effects of stimulants on neural activity related to three aspects of attention (alerting, reorienting, and executive control) were examined in children with attention-deficit/hyperactivity disorder (ADHD) using a longitudinal functional magnetic resonance imaging approach. Method: Nine boys with ADHD were scanned while drug naive (t1) and after 1 year of methylphenidate treatment (t2). Eleven matched controls were also investigated twice. ADHD children stopped medication 1 week before t2. Results: Although all of the children showed stable alerting and reorienting performance from t1 to t2, normal controls significantly improved their executive control performance at t2, whereas children with ADHD did not. Neurally, controls showed a larger increase in neural activity from t1 to t2 in regions critical to task performance (i.e., in the temporoparietal junction during reorienting of attention and in the anterior cingulate cortex during executive control) compared to the patient group. However, only children with ADHD showed a decrease in neural activity in the insula and putamen during reorienting, indicating a reduction in compensatory brain activation over time. Conclusions: These data suggest that 1 year of MPH treatment may be beneficial, albeit insufficient, to show enduring normalization of neural correlates of attention.

Huizink AC; van Lier PAC; Crijnen AAM. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking. European Addiction Research 15(1): 1-9, 2009. (54 refs.)

Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized controlled intervention trial, we examined whether intervention-induced reductions in ADHD symptoms at age 9 mediated the reduced risk of tobacco use onset among these children at age 10 or 11 years. A sample of 477 first-grade boys and girls were randomly assigned to the Good Behavior Game intervention (n = 263), a 2-year (grades 2 and 3) universal classroom-based intervention aimed at reducing disruptive behavior problems, or to a control condition (n = 214). ADHD symptoms were assessed through teacher ratings. Early onset of tobacco use was assessed through self-report. Results: The intervention-induced reductions in ADHD symptoms fully mediated the distal effect of intervention on reductions in early-onset smoking. Conclusions: Our results showed that programs that target ADHD symptoms may protect children from early-onset smoking as well. Further research is needed to examine pathways from ADHD symptoms to tobacco use.

Jester JM; Nigg JT; Buu A; Puttler LI; Glass JM; Heitzeg MM et al. Trajectories of childhood aggression and inattention/hyperactivity: Differential effects on substance abuse in adolescence. Journal of the American Academy of Child and Adolescent Psychiatry 47(10): 1158-1165, 2008. (53 refs.)

Objective: Aggression and hyperactivity/inattention each are linked to risk of alcohol use disorder (AUD), but their unique contributions remain ambiguous. The present study disaggregated these two domains developmentally and examined the relation between childhood behavior trajectories and adolescent substance use. Method: A total of 335 children of alcoholic and nonalcoholic fathers were studied prospectively. Parallel process latent trajectory class analysis was developed with behavioral ratings by parents and teachers of aggression and inattention/hyperactivity across ages 7 to 16. Membership in the four latent classes was used as a predictor for problem adolescence alcohol use and substance onset. Results: Youths in the four latent trajectory classes differed in number of alcohol problems at age 16: healthy class (39% of sample, mean 2.1 alcohol-related problems), inattentive/hyperactive but not aggressive (33%; mean 2.7 problems), aggressive but not inattentive/hyperactive (4%, mean 5.0 problems), and comorbid (24%; mean 4.0 problems). Survival analysis revealed that the aggressive, comorbid, and inattentive/hyperactive classes had significantly earlier onsets of drinking, drunkenness, and marijuana use than the healthy class. Illicit drug use was also significantly increased in the comorbid, aggressive, and inattentive/hyperactive classes compared to the healthy class. Conclusions: Three levels of behavioral risk of substance abuse exist, the highest having trajectories of increased aggressive and inattentive/hyperactive problems throughout childhood, the next involving only an increased inattentive/hyperactive behavioral trajectory, and the lowest involving those with neither type of problem. Children with both inattention/hyperactivity and aggression have the greatest need for childhood intervention to prevent substance abuse in adolescence.

Kalil KLS; Bau CHD; Grevet EH; Sousa NO; Garcia CR; Victor MM et al. Smoking is associated with lower performance in WAIS-R Block Design scores in adults with ADHD. Nicotine & Tobacco Research 10(4): 683-688, 2008. (44 refs.)

Adults with attention-deficit/hyperactivity disorder (ADHD) are predisposed to smoking, but the neuropsychological correlates of this association have not been elucidated so far. The present study evaluates possible associations between cognitive performance and smoking and other comorbidities in adults with ADHD. Two hundred and sixty-four (264) patients were evaluated in the adult ADHD outpatient clinic of the Hospital de Clinicas de Porto Alegre. The diagnoses were based on the DSM-IV criteria and interviews were performed with the Portuguese version of K-SADS-E for ADHD and oppositional-defiant disorder. Axis I psychiatric comorbidities were evaluated with the SCID-IV and the cognitive performance with the Vocabulary and Block Design subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). The evaluation of the influence of the WAIS-R scores on each dependent variable was performed with logistic regression analyses. Lower scores in the Block Design subtest of WAIS-R were associated with smoking and the presence of anxiety disorder. These results suggest that a subgroup of ADHD patients with lower Block Design subtest scores may be at increased risk of smoking as a cognitive enhancement. Our findings also confirmed the previously suggested association between anxiety and lower Block Design scores.

Kaloyanides KB; McCabe SE; Cranford JA; Teter CJ. Prevalence of illicit use and abuse of prescription stimulants, alcohol, and other drugs among college students: Relationship with age at initiation of prescription stimulants. Pharmacotherapy 27(5): 666-674, 2007. (20 refs.)

Study Objective. To examine associations between age at initiation of prescription stimulants and illicit use and abuse of prescription stimulants, alcohol, and other drugs among college students in the United States. Design. Web-based survey of college students. Setting. A large (full-time undergraduate population > 20,000) university. Intervention. A Web-based survey was sent to a random sample of 5389 undergraduate college students plus an additional 1530 undergraduate college students of various ethnic backgrounds over a 2-month period. Measurements and Main Results. Alcohol abuse was assessed by including a modified version of the Cut Down, Annoyance, Guilt, Eye-opener (CAGE) instrument. Drug use-related problems were assessed with a slightly modified version of the Drug Abuse Screening Test, short form (DAST-10). The final sample consisted of 4580 undergraduate students (66% response rate). For the analyses, five subgroups were created based on age at initiation of prescription stimulant use: no prescription stimulant use, grades kindergarten (K)-4, grades 5-8, grades 9-12, and college. Undergraduate students to whom stimulants were prescribed in grades K-4 reported similar rates of alcohol and other drug use compared with that of the group that had no prescription stimulant use. For example, students who started prescription stimulants in grades K-4 were no more likely to report coingestion of alcohol and illicit prescription stimulants (odds ratio [OR] 1.4, 95% confidence interval [CI] 0.2-11.5, NS] than the group that had no prescription stimulant use. However, undergraduate students whose prescription stimulant use began in college had significantly higher rates of alcohol and other drug use. For example, students who started a prescription stimulant in college were almost 4 times as likely (OR 3.7, 95% CI 1.9-7.1, p < 0.001) to report at least three positive indicators of drug abuse on the DAST-10 compared with the group that had no prescription stimulant use. Conclusions. In concordance with results of previous research, these results indicate that initiation of prescription stimulants during childhood is not associated with increased future use of alcohol and other drugs.

Kim J-W; Park CS; Hwang J-W; Shin M-S; Hong K-E; Cho S-C et al. Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder. Alcohol and Alcoholism 41(4): 407-411, 2006. (49 refs.)

Aims: To examine the clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder (ADHD). Methods: The present study included 85 male alcoholics who were diagnosed as having DSM-IV alcohol dependence. A total of 28 (32.9%) alcoholics were diagnosed as having DSM-IV ADHD with ongoing symptoms in adulthood. For the evaluation of their psychiatric conditions, the alcohol dependence scale (ADS), Beck depression inventory (BDI), Beck anxiety inventory (BAI), Barratt impulsiveness scale (BIS), brief anger-aggression questionnaire (BAQ), overt aggression scale (OAS), codependence test, and obsessive compulsive drinking scale (OCDS) were administered. The genotype frequencies of the dopamine type 2 receptor gene (DRD2), aldehyde dehydrogenase type 2 gene (ALDH2), functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR), and catechol-O-methyltransferase gene (COMT) polymorphisms were examined. Results: Compared with alcoholics without ADHD, the mean ages for the onset of pathological drinking and alcohol withdrawal hallucinations were significantly earlier in alcoholics with ADHD. There was also a significant difference in the history of antisocial behaviour between the two groups. Compared with alcoholics without ADHD, the mean scores of the ADS, BDI, BAI, OAS, and OCDS were significantly higher in alcoholics with ADHD. With regard to the codependence test results, the mean scores of the interpersonal problem, low self-esteem and anxiety/fear subscales, and the mean total score of the codependence test were significantly higher in alcoholics with ADHD when compared with those without ADHD. There were no significant differences in the genotype frequencies of the DRD2, ALDH2, 5-HTTLPR, and COMT polymorphisms between alcoholics with and without ADHD. Conclusions: The results of this study suggest that the comorbidity of alcohol dependence and ADHD in this Korean sample forms a distinct clinical phenotype that shows an increased severity of alcohol-related symptoms and behavioural/emotional problems and that ADHD is associated with an increased risk for the early onset of alcohol dependence in Korean male alcoholics.

Knight M. Stimulant-drug therapy for attention-deficit disorder (with or without hyperactivity) and sudden cardiac death. (editorial). Pediatrics 119(1): 154-155, 2007. (6 refs.)

Knop J; Penick EC; Nickel EJ; Mortensen EL; Sullivan MA; Murtaza S et al. Childhood ADHD and Conduct Disorder as independent predictors of male alcohol dependence at age 40. Journal of Studies on Alcohol and Drugs 70(2): 169-177, 2009. (54 refs.)

Objective: The Danish Longitudinal Study on Alcoholism was designed to identify antecedent predictors of adult male alcoholism. The influence of premorbid behaviors consistent with childhood conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD) on the development of alcohol misuse was examined. Method: Subjects were selected from a Danish birth cohort (9,125), which included 223 soils of alcoholic fathers (high risk) and 106 matched soils of nonalcoholic fathers (low risk). These subjects have been Studied systematically over the past 40 years. They were evaluated in their teens (n = 238), later as adults at age 30 (n = 241), and more recently at age 40 (n = 202). At 19-year/20-year follow-ups, an ADHD scale was derived from teacher ratings and a CD scale was derived from a social worker interview. At 30-year and 40-year follow-tips, a psychiatrist used structured interviews and criteria from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, to quantify lifetime alcoholism severity and to diagnose alcohol-use disorder. Of file original subjects, 110 had complete data for the two childhood measures and the adult alcoholism outcomes. Results: In this smaller subsample, paternal risk did not predict adult alcohol dependence. Subjects who were above a median split on both the ADHD and the CD scales were more than six times more likely to develop alcohol dependence than subjects who scored below the median on both. Although the two childhood measures were correlated, a multiple regression showed that each independently predicted a measure of lifetime alcoholism severity. Conclusions: ADHD comorbid with CD was the strongest predictor of later alcohol dependence.

Knopik VS; Jacob T; Haber JR; Swenson LP; Howell DN. Paternal alcoholism and offspring ADHD problems: A children of twins design. Twin Research and Human Genetics 12(1): 53-62, 2009. (55 refs.)

Objective: A recent Children-of-Female-Twin design suggests that the association between maternal alcohol use disorder and offspring ADHD is due to a combination of genetic and environmental factors, such as prenatal nicotine exposure. We present here a complementary analysis using a Children-of-Male-Twin design examining the association between paternal alcoholism and offspring attention deficit hyperactivity problems (ADHP). Methods: Children-of-twins design: offspring were classified into 4 groups of varying genetic and environmental risk based on father and co-twin's alcohol dependence status. Results: Univariate results are suggestive of a genetic association between paternal alcohol dependence and broadly defined offspring ADHP. Specifically, offspring of male twins with a history of DSM-III-R alcohol dependence, as well as offspring of non-alcohol dependent monozygotic twins whose co-twin was alcohol dependent, were significantly more likely to exhibit ADHP than control offspring. However, multivariate models show maternal variables independently predicting increased risk for offspring ADHP and significantly decreased support for a genetic mechanism of parent-to-child transmission. Conclusions: In support of earlier work, maternal variables (i.e., maternal ADHD and prenatal exposure) were strongly associated with child ADHP; however, the role of paternal alcohol dependence influences was not definitive. While genetic transmission may be important, the association between paternal alcohol dependence and child ADHP is more likely to be indirect and a result of several pathways.

Kollins S. Subjective effects of methylphenidate. IN: Earleywine M, ed. Mind-Altering Drugs: The Science of Subjective Experience. New York: Oxford University Press, 2005. pp. 275-304. (121 refs.)

Methylphenidate (Ritalin) is among the most widely prescribed psychoactive agents. This chapter review sthe the reseach and theory on the subjective effects. It begins with a review of the history of the use of methylphenidate, and recent trends of use. It then examines the type of information about the subjective effects that can provide insights into abuse potential for abuse, and reviews human subject studies. It also examines the subjective effects of those with Attention Deficit/Hyperactivity Disorder. The chapter concludes with an overview of potential mechanisms that may account for the subjective effects and the basis for differences between those with ADHD and controls.

Kollins SH. A qualitative review of issues arising in the use of psychostimulant medications in patients with ADHD and co-morbid substance use disorders. (review). Current Medical Research and Opinion 24(5): 1345-1357, 2008. (94 refs.)

Objective: This review addresses the relationship between attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs), with an emphasis on factors that determine the potential for psychostimulant abuse. Strategies for identification and treatment of patients with ADHD who are at risk for, or have, co-morbid SUD are also addressed. Research design and methods: The article was based on a qualitative review of current literature addressing co-morbid AND and SUD. Discussion: Adolescent and adult patients with ADHD are at increased risk for SUD, as well as a number of other psychiatric disorders. Psychostimulant agents like methylphenidate (MPH) and mixed amphetamine salts (MAS) are effective first-line pharmacotherapies for ADHD; however, they are Schedule II controlled substances with a potential for abuse. Evidence suggests that treatment of ADHD during childhood with stimulant agents may reduce the risk of developing SUD later on. Factors associated with the highest risk of SUD in patients with ADHD include co-morbid antisocial personality disorder, bipolar disorder, an eating disorder, severe ADHD and/or antisocial behavior symptoms, and dropping out of school. Treatment initiation during adolescence or young adulthood also has been linked to increased risk of polydrug use and non-medical stimulant use, a pattern of behavior consistent with a risk of SUD development. Treatment plans for patients with ADHD and co-morbid SUD should include behavioral interventions, careful monitoring, and when appropriate, pharmacotherapy. When oral formulations of psychostimulants are used at recommended doses and frequencies, they are unlikely to yield effects consistent with abuse potential in patients with AND. Long-acting stimulant formulations and non-stimulants, like atomoxetine or bupropion, have a lower potential for abuse, and provide several safe and effective treatment options for the development of a comprehensive management plan for patients with co-morbid ADHD and SUD. Conclusions: The present review is neither exhaustive nor systematic. Moreover, the reviewed studies vary widely with regards to methodology and patient populations. In light of these limitations, several conclusions are still warranted. Patients with ADHD are at increased risk for SUD. Under certain conditions, psychostimulants may be a pharmacologic option in the treatment of patients with co-morbid ADHD and SUD. However, clinicians should be mindful of the risks and benefits of this treatment approach in a high-risk population and should also bear in mind the labeling guidelines when working with this co-morbidity.

Kollins SH. Abuse liability of medications used to treat attention-deficit/hyperactivity disorder (ADHD). American Journal on Addictions 16(Supplement 1): 35-44, 2007. (58 refs.)

The use of psychostimulants to treat attention-deficit/hyperactivity disorder (ADHD) has been controversial for a number of reasons. In an effort to clarify the extent to which the psychostimulant methylphenidate has abuse potential, the existing published evidence has been reviewed and is summarized here, with an emphasis on delineating a number of related but independent issues that are often confused. The existing evidence reviewed is pertinent to three questions: Does stimulant drug use increase the risk for substance abuse later in life? Do ADHD medications have the potential for abuse? and What is the distinction between drug abuse and misuse/diversion with respect to ADHD medication?

Kollins SH; English J; Robinson R; Hallyburton M; Chrisman AK. Reinforcing and subjective effects of methylphenidate in adults with and without attention deficit hyperactivity disorder (ADHD). Psychopharmacology 204(1): 73-83, 2009. (51 refs.)

There has been controversy over the abuse potential of methylphenidate (MPH) in the context of treatment for attention deficit hyperactivity disorder (ADHD). The objective of this study was to compare the reinforcing and subjective effects of oral MPH in adults with and without ADHD. Following screening, 33 adults (n = 16 with ADHD; n = 17 free from psychiatric diagnoses) completed four pairs of experimental sessions, each of which included a sampling session and a self-administration session. During sampling sessions, subjects received in randomized order 0 (placebo), 20, 40, and 60 mg MPH. During self-administration sessions, subjects completed a progressive ratio (PR) task to earn portions of the dose received on the corresponding sampling session. Subjective effects were recorded throughout all sessions. The main outcome measure for the study was the number of ratios completed on the PR task. Secondary measures included peak subjective effects and area-under-the-curve values for subjective effects. Compared to the control group, the ADHD group completed more ratios on the PR task. Both groups showed robust effects of methylphenidate on subjective endpoints. Main effects of group were noted on subjective effects involving concentration and arousal. Compared to placebo, MPH produced reinforcing effects only for the ADHD group and not for the control group. Increases in stimulant-related subjective effects in non-ADHD subjects were not associated with drug reinforcement.

Kollins SH; Garrett ME; McClernon FJ; Lachiewicz AM; Morrissey-Kane E; FitzGerald D et al. Effects of postnatal parental smoking on parent and teacher ratings of ADHD and oppositional symptoms. Journal of Nervous and Mental Disease 197(6): 442-449, 2009. (65 refs.)

To assess the effects of postnatal parental smoking on subsequent parent and teacher ratings of DSM-IV attention deficit hyperactivity disorder (ADHD) symptoms and oppositional behaviors in children diagnosed with ADHD and their siblings. Children between 5 and 12 years of age with ADHD and their siblings were included. DSM-IV ADHD symptom subscales (Inattentive and hyperactive-impulsive), and oppositionality subscale scores from Conners' Rating Scales were predicted on the basis of parental smoking status in the first 7 years after birth using Generalized Estimating Equations controlling for a range of relevant covariates. Postnatal parental smoking was associated with both parent and teacher ratings of ADHD symptoms and oppositional behavior. After controlling for a number of covariates, several of these relationships were still significant. The risk of maternal smoking for the development of ADHD symptoms does not end during pregnancy. Research on the mechanisms underlying the observed associations is needed.

Kollins SH; McClernon FJ; Epstein JN. Effects of smoking abstinence on reaction time variability in smokers with and without ADHD: An ex-Gaussian analysis. Drug and Alcohol Dependence 100(1-2): 169-172, 2009. (16 refs.)

Smoking abstinence differentially affects cognitive functioning in smokers with ADHD, compared to non-ADHD smokers. Alternative approaches for analyzing reaction time data from these tasks may further elucidate important group differences. Adults smoking >= 15 cigarettes with (n = 12) or Without (n = 14) a diagnosis of ADHD completed a continuous performance task (CPT) during two sessions under two separate laboratory conditions-a 'Satiated' condition wherein participants smoked up to and during the session; and an 'Abstinent' condition, in which participants were abstinent overnight and during the session. Reaction time (RT) distributions from the CPT were modeled to fit an ex-Gaussian distribution. The indicator of central tendency for RT from the normal component of the RT distribution (mu) showed a main effect of Group (ADHD < Control) and a Group x Session interaction (ADHD group RTs decreased when abstinent). RT standard deviation for the normal component of the distribution (sigma) showed no effects. The ex-Gaussian parameter taLl, which describes the mean and standard deviation of the non-normal component of the distribution, showed significant effects of session (Abstinent > Satiated), Group x Session interaction (ADHD increased significantly under Abstinent condition compared to Control), and a trend toward a main effect of Group (ADHD > Control). Alternative approaches to analyzing RT data provide a more detailed description of the effects of smoking abstinence in ADHD and non-ADHD smokers and results differ from analyses using more traditional approaches. These findings have implications for understanding the neuropsychopharmacology of nicotine and nicotine withdrawal.

Levin FR; Adamson JJ; Antshel KM; Biederman J; Faraone SV; Kollins SH. ADHD and substance abuse update. (editorial). American Journal on Addictions 16(Supplement 1): 1-4, 2007. (0 refs.)

Levin FR; Bisaga A; Raby W; Aharonovich E; Rubin E; Mariani J et al. Effects of major depressive disorder and attention-deficit/hyperactivity disorder on the outcome of treatment for cocaine dependence. Journal of Substance Abuse Treatment 34(1): 80-89, 2008. (56 refs.)

Co-occurring psychiatric disorders have been associated with poor prognosis among substance-dependent patients, but few studies have examined this association among patients with cocaine dependence (CD). We compared baseline characteristics and treatment outcome between cocaine-dependent patients with major depressive disorder (MDD; n = 66), those with attention-deficit/hyperactivity disorder (ADHD; n = 53), and those with CD without comorbid disorders (CD alone; n = 48) who had been randomized to the placebo arms of clinical trials with venlafaxine, methylphenidate, and gabapentin, respectively. The three groups differed significantly in racial makeup, with more Caucasians and Hispanics among patients With MDD and those with ADHD but more African Americans among those with CD alone. The groups did not differ significantly in treatment retention, with retention rates ranging from 42% to 47%; neither did they differ in the rates of achieving 2 consecutive weeks of urinalysis-confirmed abstinence, with rates ranging from 40% to 50%. Using logistic regression for repeated measures with general estimating equations, modeling the likelihood of a cocaine-positive week over time in treatment, we found the diagnostic group to interact with the baseline level of cocaine use and time. Among cocaine-dependent patients who achieved abstinence at baseline, those with MDD and those with ADHD had better outcome over time as compared with patients with CD alone. However, among patients with cocaine-positive urine specimens at baseline, those with MDD and those with ADHD were associated with poor outcome as compared with patients with CD alone. The findings suggest that diagnosis and treatment of co-occurring disorders such as depression and ADHD may be important components of treatment planning for CD and that the baseline level of cocaine use should be included as a covariate in studies evaluating the impact of such treatment.

Levin FR; Evans SM; Brooks DJ; Garawi F. Treatment of cocaine dependent treatment seekers with adult ADHD: Double-blind comparison of methylphenidate and placebo. Drug and Alcohol Dependence 87(1): 20-29, 2007. (56 refs.)

The purpose of this double-blind 14-week trial was to compare the efficacy of sustained-release methylphenidate (MPH) to placebo (PBO) in treating adult attention deficit hyperactivity disorder (ADHD) symptoms in current cocaine dependent (CD) treatment seekers. The randomized sample consisted of 106 participants who were predominately male (83%) and 60% Caucasian, 14% Hispanic, 20% African-American and 6% other. All participants met DSM-IV criteria for ADHD and CD. There were no significant demographic differences between the two treatment groups. All participants received weekly individual cognitive behavioral therapy. There was no difference in retention rate based on treatment group (p = .91). The majority of the PBO group and the MPH group reported > 30% improvement in their ADHD symptoms (55% versus 47%), with no significant difference between the two groups (p = .44). Using a combined outcome measure (> 30% reduction in ADHD symptoms and CGI < 3), the response rates were similar for both groups (28% PBO versus 30% MPH; p = .83). Longitudinal analyses of the urine toxicology data using generalized estimating equations, revealed a decrease in the probability of cocaine positive urine samples during the trial for the MPH group compared to the PBO group (p = .001). Further analysis suggested that for the MPH group, ADHD treatment responders, based on a semi structured clinical interview, were more likely to have a reduction in cocaine use compared to the non-ADHD responders. Although sustained-release MPH did not show superiority over PBO in treating ADHD symptoms, this trial provides some evidence that improvement in ADHD symptoms (clinician rated) among those patients receiving MPH, but not placebo, was associated with a reduction in cocaine use.

Looby A. Childhood attention deficit hyperactivity disorder and the development of substance use disorders: Valid concern or exaggeration? Addictive Behaviors 33(3): 451-463, 2008. (59 refs.)

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder associated with many behavioral problems in adolescence and adulthood. In particular, researchers have identified comorbid substance use disorders in many adolescents and young adults who were diagnosed with ADHD as children. Conflicting reports exist regarding the developmental risk for substance use problems and disorders in these individuals. This paper reviews the recent literature evaluating the relationship between childhood ADHD and substance use. Research suggests that in the absence of conduct disorder, ADHD carries only a moderate risk for subsequent substance use. Degree of risk appears to be related to specific drugs of abuse and particular ADHD symptoms. Additionally, whether stimulant treatment of ADHD symptoms predisposes children to later substance use is an important concern. Currently, little evidence exists to support this notion and most research suggests that stimulant treatment serves as a protective factor for substance use. ADHD is an important precursor to subsequent disorders in children and further research is necessary to diminish the risk for substance use in this population.

Luty J; Arokiadass SMR; Sarkhel A; Easow JM; Desai R; Moorti OP et al. Validation of self-report instruments to assess attention deficit hyperactivity disorder symptoms in adults attending community drug and alcohol services. Journal of Addiction Medicine 3(3): 151-154, 2009. (33 refs.)

Background: Symptoms of attention deficit disorder of predominantly inattentive, predominantly hyperactive-impulsive subtype, or combined (hereafter referred to as ADHD), may persist into adulthood, although the diagnosis in adults remains controversial. The study aimed to validate self-report instruments for assessment of adult ADHD in a sample of treatment-seeking adults attending community drug and alcohol teams. Methods: Adult patients attending 3 National Health Service (NHS) community drug and alcohol learns in England completed several self-report instruments for assessment of adult ADHD symptoms, and a diagnosis of adult ADHD was determined using Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria with an interview with both the patient and an informant. Results: One hundred seven subjects completed the project. Thirty-nine percent of subjects had an undisputed diagnosis of adult ADHD. The most accurate self-report instrument for diagnosis of adult ADHD was the Connors Adult ADHD Rating Scale Self-report Long version-a cutoff of 91 of 198 gave a sensitivity of 97% and specificity of 83%. Analysis of the WHO Adult ADHD Self-report Screener confirmed the optimal recommended cutoff as 12 of 13 giving 89% sensitivity and 83% specificity for adult ADHD against diagnostic interview. Although the Wender Utah adult ADHD scale is designed to retrospectively assess symptoms of ADHD in childhood it gave a sensitivity of 88% and specificity of 70% for diagnosis of ADHD in adults. Conclusion: The symptoms of ADHD in adults can be reliably assessed by self-report instruments.

Luty J; Sarkhel A; O'Gara C; Umoh O. Prevalence of childhood attention deficit hyperactivity disorder in opiate-dependent adults. International Journal of Psychiatry in Clinical Practice 11(2): 157-162, 2007. (43 refs.)

Background. There is a clear association between childhood attention deficit hyperactivity disorder and substance use disorders in adulthood. Symptoms of attention deficit disorder may also persist into adulthood. The study aimed to determine the prevalence of childhood ADHD in a sample of treatment seeking opiate-dependent adults. Methods. Treatment-seeking opiate-dependent subjects completed the Utah adult ADHD screening test and the self-report early delinquency scale. Results. A total of 15% were "likely'' and 49 were "highly likely'' to have suffered ADHD in childhood. The averages scores for the delinquency scales were over 6 times those reported from population norms. Conclusion. Symptoms of childhood ADHD is common in adults with opiate dependence. The residual symptoms in adults should be investigated as may be amenable to newer treatments for adult attention deficit disorder.

Mann N; Bitsios P. Modafinil treatment of amphetamine abuse in adult ADHD. Journal of Psychopharmacology 23(4): 468-471, 2009

Substance abuse is a frequent co-morbid condition of adult attention deficit hyperactivity disorder (ADHD). Treatment with conventional psychostimulants in adult ADHD with co-morbid stimulant abuse may be problematic. In this study, we report the case of a patient with adult ADHD with co-morbid amphetamine abuse who was treated successfully with the non-stimulant alertness-promoting drug modafinil. The drug resolved both the inattention/hyperactivity symptoms as well as the amphetamine abuse. Modafinil may be a suitable candidate treatment for adults with ADHD and stimulant abuse.

Mariani JJ; Levin FR. Treatment strategies for co-occurring ADHD and substance use disorders. (review). American Journal on Addictions 16(Supplement 1): 45-56, 2007. (106 refs.)

Attention-deficit hyperactivity disorder (ADHD) is a common co-occurring mental disorder among patients with substance use disorders (SUD). Clinicians must be cognizant of the complicated nature of diagnosis and treatment of ADHD when comorbid with SUD. Pharmacotherapy remains the mainstay of treatment for ADHD, although complementary psychotherapeutic approaches have been developed. Psychostimulant medications are the most commonly used medications to treat ADHD, but many clinicians are reluctant to prescribe stimulants to patients with SUD. Recommendations for treatment planning and clinical management for patients with co-occurring ADHD and SUD are discussed.

Marshal MP; Molina BSG; Pelham WE; Cheong J. Attention-deficit hyperactivity disorder moderates the life stress pathway to alcohol problems in children of alcoholics. Alcoholism: Clinical and Experimental Research 31(4): 564-574, 2007. (69 refs.)

Background: Parent alcoholism is a well-established risk factor for the development of pathological alcohol involvement in youth, and life stress is considered to be one of the central mechanisms of the parent alcoholism effect; however, little is known about the moderators of the life stress pathway. Attention-deficit hyperactivity disorder (ADHD) has also been shown to predict pathological alcohol involvement, however, little is known about whether or not ADHD interacts with parent alcoholism to increase offspring risk. The goals of this study were to examine stressful life events as mediators of the relationship between parent alcoholism and adolescent pathological alcohol involvement, and to examine whether or not this mediated pathway was stronger for adolescents with ADHD than for adolescents without ADHD. Method: Participants were 142 adolescents with a childhood ADHD diagnosis (probands) and 100 demographically matched control adolescents without childhood ADHD. Probands, controls, and at least 1 parent were interviewed about drinking behavior; probands and controls were interviewed about negative life events. Results: A moderated mediation paradigm was used to test the hypotheses using ordinary least squares regression. Results showed that the relationships between parent alcoholism and 2 of the stress variables ("family" stress and "peer" stress) were significant for probands only, and that stress in the probands mediated the parent alcoholism effect on offspring alcohol involvement. Conclusions: These results provide preliminary support for the hypothesis that offspring characteristics might moderate the life stress pathway to alcoholism, and indicate that ADHD may serve to facilitate the transmission of pathological alcohol use from parent to child.

Mayes R; Rafalovich A. Suffer the restless children: The evolution of ADHD and paediatric stimulant use, 1900-80. History of Psychiatry 18(4): 435-457, 2007. (78 refs.)

This article traces the historical evolution of Attention Deficit/Hyperactivity Disorder (ADHD) and the controversial use of stimulants as a treatment for children diagnosed with the disorder in North America. While the children in question have exhibited similar behaviour over the last century, the diagnostic labels used to identify them have changed due largely to cultural, medical and scientific changes and discoveries. For decades, children's treatment with psychotropic drugs was sufficiently controversial that pharmaceutical companies would not finance research in the area. The only substantial source of research funding for paediatric psychopharmacology in the USA from the 1950s to the 1970s was the National Institute of Mental Health (NIMH). In 1970, the first in a long-running series of controversies erupted over children's treatment with stimulants.

McCarthy S; Cranswick N; Potts L; Taylor E; Wong ICK. Mortality associated with Attention-Deficit Hyperactivity Disorder (ADHD) drug treatment a retrospective cohort study of children, adolescents and young adults using the general practice research database. Drug Safety 32(11): 1089-1096, 2009. (37 refs.)

Background: Following reports of sudden death in patients taking medication to treat attention-deficit hyperactivity disorder (ADHD), this study aimed to identify cases of death in patients prescribed stimulants and atomoxetine and to determine any association between these and sudden death. Method: The UK General Practice Research Database (GPRD) was used to identify patients aged 2-21 years from I January 1993 to 30 June 2006 with a prescription for methylphenidate, dexamfetamine or atomoxetine. Patients were followed from the date of first prescription until whichever came first: date of death, transferred-out date, age >21 years or end of the study period. Results: From a cohort of 18 637 patient-years, seven patients died. Cause of death was obtained for six of the patients. None were deemed to be cases of sudden death. Compared with a general population rate of sudden death in the literature, the worst-case scenario of one case of sudden death gave an incident rate ratio of 1.63 (95% CI 0.04, 9.71). Although it was not the primary Outcome of the study, following reports of suicide in the cohort the standardized mortality ratio (SMR) of suicide was calculated. Due to differences in the definition of suicide used for children and adults, patients were categorized into two age groups: 11-14 years and 15-21 years. The SMR for suicide for patients aged 11-14 years was 161.91 (95% CI 19.61, 584.88). The SMR for suicide for patients aged 15-21 years was 1.84 (95% CI 0.05, 10.25). Conclusion: This study demonstrated no increase in the risk of sudden death associated with stimulants or atomoxetine. However, an increased risk of suicide was seen. Although we cannot exclude that the medications may contribute to the increased risk of suicide, there are other factors such as depression and antisocial behaviour that frequently co-exist with ADHD, which can also predispose to teenage suicide. Clinicians should identify patients at increased risk of cardiovascular events and identify those patients at increased risk of suicide, particularly males with co-morbid conditions, and monitor them appropriately.

McClernon FJ; Fuemmeler BF; Kollins SH; Kail ME; Ashley-Koch AE. Interactions between genotype and retrospective ADHD symptoms predict lifetime smoking risk in a sample of young adults. Nicotine & Tobacco Research 10(1): 117-127, 2008. (83 refs.)

Attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with an increased risk of smoking, and genetic studies have identified similar candidate genes associated with both ADHD and smoking phenotypes. This paper addresses the question of whether ADHD symptoms interact with candidate gene variation to predict smoking risk. Participants were a subsample of individuals from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset from Add Health of 1,900 unrelated individuals with genotype data. Multiple logistic regression was used to examine relationships between self-reported ADHD symptoms, genotype, and lifetime history of regular smoking. Polymorphisms in the DRD2 gene and, among females, the MAOA gene interacted with retrospective reports of ADHD symptoms in contributing to risk for smoking. Trends were observed for interactions between the DRD4 gene and, among males, the MAOA gene and ADHD symptoms to predict smoking risk. No main effect for any of these polymorphisms was observed. We observed neither main effects nor interactions with CYP2A6, DAT, and SLC6A4 genes. These findings suggest that genotypes associated with catecholamine neurotransmission interact with ADHD symptoms to contribute to smoking risk.

McClernon FJ; Kollins SH. ADHD and smoking: From genes to brain to behavior. Annals of the New York Academy of Sciences 1141(Addiction Reviews 2008): 131-147, 2008. (137 refs.)

Attention-deficit/hyperactivity disorder (ADHD) and tobacco smoking are among the most common and costly psychiatric and behavioral problems. The rates of co-occurrence of these two common problems are larger than expected by chance. Despite progress in identifying the neural and genetic substrates of each, the mechanisms underlying the high rates of comorbidity between ADHD and smoking remain largely unknown. We propose that ADHD and smoking involve dysregulation of dopaminergic and nicotinic-acetylcholinergic circuits and that these aberrations are likely to arise, at least in part, from genetic variations. This review describes an integrative model of the ADHD-smoking comorbidity, with an emphasis on shared neuropharmacological mechanisms. We first describe the prevalence of smoking among ADHD patients. We then describe how ADHD influences stages of smoking behavior e.g., initiation, maintenance, and relapse). We review common potential genetic substrates of ADHD and smoking, focusing on genes that regulate monoaminergic neurotransmission. We review the behavioral and neuropharmacological bases of smoking and ADHD, focusing on the modulatory roles of nicotine on attention and behavioral control. Finally, we discuss the implications of this model for prevention and clinical outcomes.

McClernon FJ; Kollins SH; Lutz AM; Fitzgerald DP; Murray DW; Redman C; Rose JE. Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: Results of a preliminary study. Psychopharmacology 197(1): 95-105, 2008. (65 refs.)

Rationale: Individuals with attention deficit hyperactivity disorder (ADHD) smoke at higher rates than the general population; however, little is known about the mechanisms underlying this comorbidity. Objective: This study evaluated the effects of overnight abstinence on withdrawal symptoms and cognitive performance in adult smokers with and without ADHD. Materials and methods: Individuals smoking >= 15 cigarettes per day were recruited from the community and underwent an evaluation to establish a diagnosis of ADHD (n=12) or not (n=14). Withdrawal symptoms, mood, craving, cognitive performance, and smoking cue reactivity were measured during two laboratory sessions-in a 'Satiated' condition participants smoked up to and during the session while in an 'Abstinent' condition, participants were required to be smoking abstinent overnight and remain abstinent during the session. Results The effects of abstinence on ADHD and non-ADHD smokers did not differ for withdrawal symptom severity, mood, craving or cue reactivity. Significant Group x Condition interactions were observed for measures of attention and response inhibition on the Conners' CPT. For reaction time (RT) variability and errors of commission, the ADHD group exhibited greater decrements in performance after overnight abstinence compared to the non-ADHD group. The effects of abstinence on other cognitive measures (e.g., rapid visual information processing task, cued Go/No-Go task) did not differ between the two groups. Conclusion: This preliminary study is the first to systematically evaluate the effects of acute smoking abstinence in adult smokers diagnosed with ADHD. Individuals with the disorder may smoke at higher rates due to greater worsening of attention and response inhibition after abstinence.

Monuteaux MC; Faraone SV; Hammerness P; Wilens TE; Fraire M; Biederman J. The familial association between cigarette smoking and ADHD: A study of clinically referred girls with and without ADHD, and their families. Nicotine & Tobacco Research 10(10): 1549-1558, 2008. (60 refs.)

Attention-deficit/hyperactivity disorder (ADHD) is a strong risk factor for smoking. Since both ADHD and smoking are familial disorders, one way to further our understanding of this association is to examine the familial relationship between them. Our aim was to evaluate the familial association between ADHD and smoking in families ascertained from girls with and without ADHD. Subjects were derived from a longitudinal case-control family study of girls with (n=140) and without (n=122) ADHD ascertained from pediatric and psychiatric clinics, and their biological first-degree relatives. Diagnoses of ADHD and smoking (i.e., full or subthreshold nicotine dependence) were made with structured psychiatric interviews. We stratified the relatives into four groups based on probands' ADHD and smoking status: (1) relatives of controls without smoking (probands n=100, relatives n=317), (2) relatives of controls with smoking (probands n=22, relatives n=71), (3) relatives of ADHD girls without smoking (probands n=100, relatives n=320), and (4) relatives of ADHD girls with smoking (probands n=39, relatives n=133). We compared the rates of ADHD and smoking across the four relative groups using survival analysis. ADHD in the proband increased the risk for ADHD in the relatives irrespective of probands' smoking and smoking in the proband increased the risk for smoking in the relatives irrespective of probands' ADHD status. Furthermore, we found statistically significant evidence for cosegregation of smoking and ADHD, suggesting that the two disorders are transmitted together through families more often than expected by chance. These findings support the hypothesis that the combination of ADHD and smoking comprises an etiologically distinct familial subtype of ADHD in girls.

Monuteaux MC; Wilens TE; Biederman J. Does social class predict substance problems in young adults with ADHD? American Journal on Addictions 16(5): 403-409, 2007. (44 refs.)

The relationship between social class and substance use problems is unclear. We aimed to clarify this association in a sample of young adult males with and without attention deficit/hyperactivity disorder ( ADHD). We included 69 ADHD and 78 control subjects. Substance use problems were measured with the Drug Use Screening Inventory -Revised ( DUSI). Among ADHD subjects, we found a U-shaped association, with elevated risk for substance-related problems at both ends of the SES spectrum. No significant association was found in controls. These findings indicate that substance use risk in ADHD subjects is especially vulnerable to social class.

Morrow CE; Accornero VH; Xue LH; Manjunath S; Culbertson JL; Anthony JC et al. Estimated risk of developing selected DSM-IV disorders among 5-year-old children with prenatal cocaine exposure. Journal of Child and Family Studies 18(3): 356-364, 2009. (49 refs.)

We estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n = 476) with prenatal drug exposures documented by maternal interview, urine and meconium assays. Study participants included 400 African-American children from the birth cohort, 208 cocaine-exposed (CE) and 192 non-cocaine-exposed (NCE), who attended a 5-year follow-up assessment and whose caregiver completed the Computerized Diagnostic Interview Schedule for Children. Under a generalized linear model (logistic link), Fisher's exact methods were used to estimate the PCE-associated relative risk (RR) of these disorders. Our results indicated a modest but statistically robust elevation of ADHD risk associated with increasing levels of PCE (p < 0.05). Binary comparison of CE versus NCE children indicated no PCE-associated RR. Estimated cumulative incidence proportions among CE children were 2.9% for ADHD (vs 3.1% NCE); 1.4% for SAD (vs 1.6% NCE); and 4.3% for ODD (vs 6.8% NCE). Our findings suggest evidence of increased risk of ADHD (but not ODD or SAD) in relation to an increasing gradient of PCE during gestation.

Neuman RJ; Lobos E; Reich W; Henderson CA; Sun LW; Todd RD. Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype. Biological Psychiatry 61(12): 1320-1328, 2007. (63 refs.)

Background: In utero exposure to smoking and alcohol are common risk factors that have been associated with attention-deficit/hyperactivity disorder (ADHD) in human beings and animal models. Furthermore, molecular studies have focused on the association between ADHD and DNA polymorphisms in dopamine pathway-related genes. We examined the joint effects of genetic and prenatal substance exposures on DSM-IV and population-defined subtypes of ADHD. Methods: Logistic regression was used to assess the relationship between ADHD subtypes, DAT1 and DRD4 polymorphisms, and prenatal substance exposures in a birth-record sample of male and female twin pairs, aged 7-19 years. Results: Interactions between prenatal exposure to smoking and variations in the DAT1 and DRD4 loci were observed in children with either the DSM-IV or population-defined ADHD combined subtypes. The odds of a diagnosis of DSM-IV combined subtype was 2.9 times greater in twins who had inherited the DAT1 440 allele and who were exposed, than in unexposed twins without the risk allele. The OR was 2.6 in the population-defined subtype. Odds ratios for the DRD4 seven-repeat allele were 3.0 (2.8) in the population-defined (DSM-IV) combined ADHD subtypes. The OR for exposed children with both alleles was 9.0 (95% confidence interval = 2.0-41.5) for the population-defined combined subtypes. Conclusions: Results indicate that smoking during pregnancy is associated with specific subtypes of ADHD in genetically susceptible children.

Obel C; Linnet KM; Henriksen TB; Rodriguez A; Jarvelin MR; Kotimaa A et al. Smoking during pregnancy and hyperactivity-inattention in the offspring-comparing results from three Nordic cohorts. International Journal of Epidemiology 38(3): 698-705, 2009. (32 refs.)

Background: Prenatal exposure to smoking has been associated with Attention Deficit Hyperactivity Disorder (ADHD) in a number of epidemiological studies. However, mothers with the ADHD phenotype may 'treat' their problem by smoking and therefore be more likely to smoke even in a society where smoking is not acceptable. This will cause genetic confounding if ADHD has a heritable component, especially in populations with low prevalence rates of smoking since this reason for smoking is expected to be proportionally more frequent in a population with few 'normal' smokers. We compared the association in cohorts with different smoking frequencies. Methods A total of 20 936 women with singleton pregnancies were identified within three population-based pregnancy cohorts in Northern Finland (1985-1986) and in Denmark (1984-1987 and 1989-1991). We collected self-reported data on their pre-pregnancy and pregnancy smoking habits and followed the children to school age where teachers and parents rated hyperactivity and inattention symptoms. Results: Children, whose mothers smoked during pregnancy, had an increased prevalence of a high hyperactivity-inattention score compared with children of nonsmokers in each of the cohorts after adjustment for confounders but we found no statistical significant difference between the associations across the cohorts. Conclusion: The estimated association was not strongest in the population with the fewest smokers which does not support the hypothesis that the association is entirely due to genetic confounding.

Office of Applied Studies, Substance Abuse and Mental Health Administration. The New DAWN Report. Issue 29 (rev. August 2009). Rockville MD: Substance Abuse and Mental Health Administration, 2009. (10 refs.)

For 2004, according to the Drug Abuse Warning Network (DAWN) about 106 million ED visits occurred in short-term, general, non-Federal hospitals in the United States in 2004. DAWN estimates that about 2.5 million of these ED visits were drug related. The ADHD drugs examined in this report were implicated in less than 1 percent of those drug-related visits. Methylphenidate was involved in an estimated 5,148 ED visits, and amphetamine-dextroamphetamine was involved in an estimated 5,119 ED visits. A total of 10,146 ED visits involved one of these two drugs. (A few visits involved both drugs, so the total is slightly less than the sum of the drug-specific estimates.) In 2004, an estimated 10,146 drug-related emergency department (ED) visits involved methylphenidate or amphetamine-dextroamphetamine, two medications used to treat attention-deficit/hyperactivity disorder (ADHD). The most frequent reason for these ED visits was nonmedical use (47%), followed by adverse reactions (35%), accidental ingestions (11%), and suicide attempts (7%). The rate of ED visits for adverse reactions to these two ADHD drugs for patients aged 12 to 17 years was double that for patients aged 18 to 24 years (3.3 and 1.6 visits per 100,000 population, respectively), while rates for nonmedical use were similar (5.3 and 5.5, respectively). Two thirds (66%) of the ED visits for nonmedical use of these two drugs involved other substances-such as alcohol, illicit drugs, or pharmaceuticals.

Public Domain

Ohlmeier MD; Peters K; Kordon A; Seifert J; Wildt BT; Wiese B et al. Nicotine and alcohol dependence in patients with comorbid attention-deficit/hyperactivity disorder (ADHD). Alcohol and Alcoholism 42(6): 539-543, 2007. (38 refs.)

Aims: Several studies have shown that attention-deficit/hyperactivity disorder (ADHD) represents a significant risk factor for the onset and development of an addiction. Thirty-five per cent of adult ADHD patients are known to be addicted to alcohol. Many ADHD patients also have an increased nicotine consumption, which typically, leads to an improvement of attention, ability to concentrate and control of impulses. There may be pathophysiological connections here. On the other hand, it can also be assumed that there is a high prevalence of addicted patients with undiagnosed ADHD. Methods: Ninety-one adult alcohol-dependent patients were examined for ADHD in this study, using the Wender Utah Rating Scale (WURS-k), Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptom check-list for ADHD and the Conners Adult ADHD Rating Scales (CAARS, Long Version). The patients were divided into diagnostic sub-groups according to DSM-IV (inattentive type, impulsive type, combined type). Nicotine consumption was investigated using the Fagerstrm Test of Nicotine Dependence (FTND) and then graded as minimal, average or high nicotine dependence. Results: There were 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the patients addicted to alcohol, who showed evidence of ADHD in childhood. With the help of CAARS, it could be demonstrated that 33.3% of the patients who fulfilled the diagnostic criteria of ADHD, according to DSM-IV, had persisting ADHD in adulthood. The FTND showed a statistically significant difference in nicotine dependence between alcohol-dependent patients with and without ADHD in childhood. Patients numbering 76.2% with ADHD, demonstrated an average to high level of nicotine dependence compared to 45.7% of those patients without ADHD. Furthermore, the number of patients not addicted to nicotine (19%) was significantly lower than among those without ADHD (36.6%) (P = 0.029). Conclusions: The results of this investigation reveal that a large number of ADHD patients suffer from alcohol dependence, and an even greater number from excessive nicotine dependence. The outcome indicates that there are most likely pathophysiological connections with alcohol and nicotine dependence, and that this substance abuse is probably a form of self-medication. The results clearly underline the great importance of early and adequate diagnosis and therapy of ADHD, in order to prevent exacerbation of addictive illness.

Ohlmeier MD; Peters K; Wildt BTT; Zedler M; Ziegenbein M; Wiese B et al. Comorbidity of alcohol and substance dependence with attention-deficit/hyperactivity disorder (ADHD). Alcohol and Alcoholism 43(3): 300-304, 2008. (37 refs.)

Aims: Attention-deficit/hyperactivity disorder (ADHD) is of great clinical importance not only because of its high prevalence but also due to the frequent comorbid illnesses that are connected with this disorder. Several studies were able to demonstrate that ADHD constitutes a significant risk factor for the exacerbation of habit-forming illnesses, i.e. addictions. Methods: We conducted a study on 152 adult patients with alcohol dependence (n = 91) or multiple substance addiction (n = 61) to determine whether or not these patients were affected by ADHD. For retrospective assessment of childhood ADHD, the WURS-k was used as well as the DSM-IV symptom checklist for ADHD. The CAARS was used to assess the persisting symptoms of ADHD in adults. Results: 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the alcohol-dependent patients showed evidence of retrospective ADHD affliction in childhood. With the help of CAARS, ADHD was proved to be persistent in 33.3% of the adult patients. In the group of substance-addicted patients 50.8% (WURS-k) and 54.1% (DSM-IV) presented with diagnostic criteria for ADHD in childhood and 65.5% (CAARS) showed evidence of ADHD persisting in adulthood. Conclusions: These results reveal that habit-forming illnesses can be associated with a high comorbidity with ADHD, expressed in the form of alcohol abuse and also in consumption of illegal drugs. The results underline the great importance of early and adequate diagnostics and therapy of ADHD for the prevention of habit-forming illnesses.

Pinkhardt EH; Kassubek I; Brummer D; Koelch M; Ludolph AC; Fegert JM et al. Intensified testing for attention-deficit hyperactivity disorder (ADHD) in girls should reduce depression and smoking in adult females and the prevalence of ADHD in the longterm. Medical Hypotheses 72(4): 409-412, 2009. (58 refs.)

Attention-deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in youth. About a third to one-half of the affected subjects continue to have symptoms in adulthood. Remarkably, the prevalence numbers published for adult females are higher than for girls. The differences in the epidemiological data between the age groups clearly point to underdiagnosed ADHD in girls, Major depression, the most frequent psychiatric condition worldwide in adulthood, is twice is common in female as in male adults, Anxiety and depression are also among the most common comorbidities in adults with ADHD. Therefore, an undiagnosed ADHD may often underlie the psychopathology in depressive women. Another possibly associated phenomenon is the increased frequency of smoking in adult females. Since nicotine indirectly enhances the intrasynaptic dopamine level which presumably is too low both in ADHD and in depression, smoking might be used as a self-medication in women with untreated ADHD and consecutive depression. Furthermore, smoking during pregnancy is a major risk factor for ADHD in the offspring, so the vicious circle is complete. Depression in mothers of children with ADHD is associated with a higher rate of comorbidity in the children. Improved screening for ADHD in girls and treatment in childhood might thus reduce the rate of depression and smoking in adult females. We hypothesize that earlier identification and interventions might not only improve the lives of millions of girls and women but might also reduce the prevalence rates in future generations or at least moderate the deviant behaviour in this highly heritable disorder in which the development and severity of symptoms and the functional impairment depend to a high degree on epigenetic factors.

Poulin C. From attention-deficit/hyperactivity disorder to medical stimulant use to the diversion of prescribed stimulants to non-medical stimulant use: Connecting the dots. Addiction 102(5): 740-751, 2007. (40 refs.)

Aims To describe the connections among the likelihood of attention deficit/hyperactivity disorder (ADHD), medical and non-medical methylphenidate and amphetamine use and the diversion of prescribed methylphenidate in the general adolescent population. Design Cross-sectional self-reported anonymous data from the 2002 Student Drug Use Survey in the Atlantic Provinces. Setting: The Atlantic provinces of Canada. Participants: A total of 12,990 students participated. Measurements The outcomes were a positive ADHD screening test, medical and non-medical use of methylphenidate, medical and non-medical use of amphetamine and the giving and selling of methylphenidate medication by students with a prescription. The Ontario Child Health Study Hyperactivity Scale was used to screen for ADHD. Findings The prevalence of a positive ADHD screening test was 6% with no significant gender difference. The prevalence of medical and non-medical methylphenidate use and medical and non-medical amphetamine use was 2.0%, 6.6%, 1.2% and 8.7%, respectively. A positive ADHD screening test was independently predictive of these four patterns of use. About 26% of students with prescribed methylphenidate gave or sold some of their medication. Students in a class where at least one student had given or sold some of their prescribed pills had a 1.52-fold increased risk of non-medical methylphenidate use than their counterparts in classes where no giving or selling had taken place. Conclusions: Connections were demonstrated at the population level between ADHD, medical methylphenidate use, the diversion of prescribed methylphenidate and the non-medical use of methylphenidate. The appropriate assessment and management of ADHD are essential to minimize both the risk of diversion and of substance use associated with unrecognized or untreated ADHD.

Powers RL; Marks DJ; Miller CJ; Newcorn JH; Halperin JM. Stimulant treatment in children with attention-deficit/hyperactivity disorder moderates adolescent academic outcome. Journal of Child and Adolescent Psychopharmacology 18(5): 449-459, 2008. (60 refs.)

Treatment with psychostimulant medication has been shown to improve scholastic functioning in children with attention-deficit/hyperactivity disorder (ADHD). However, the extent to which long-term academic gains are apparent in those having received such treatment remains elusive. This study examined prospectively the relationship of childhood stimulant treatment to academic functioning during adolescence. Children (n = 169) were initially recruited and diagnosed with ADHD when they were 7-11 years old. A subsample of those with childhood ADHD (n = 90) was reevaluated on average 9.13 (SD = 1.5) years later. Probands who did and did not receive treatment with stimulant medication were compared to each other and to a never-ADHD comparison group (n = 80) on three subtests from the Wechsler Individual Achievement Test-II (WIAT-II), as well as high school grade point average (GPA) and number of retentions in school as derived from school records. Analyses of covariance controlling for severity of childhood ADHD symptoms indicated that probands treated with psychostimulant medication achieved better academic outcomes, as measured by WIAT-II subtests and high school GPA, than those not treated with psychostimulants (p < .05). However, treated probands did not fare as well as the never-ADHD comparison group. Psychostimulant treatment for children with ADHD may benefit long-term adolescent academic performance, although the extent of improvement is likely to vary as a function of multiple factors.

Realmuto GM; Winters KC; August GJ; Lee S; Fahnhorst T; Botzet A. Drug use and psychosocial functioning of a community-derived sample of adolescents with childhood ADHD. Journal of Child & Adolescent Substance Abuse 18(2): 172-192, 2009. (44 refs.)

We describe the late adolescent psychosocial outcomes from a relatively large, community-identified sample of children with ADHD who have been assessed longitudinally from childhood through late adolescence. A range of outcomes were compared between ADHD (n=119) and normal control (n=93) groups, as well as ADHD subgroups that varied as a function of the course of externalizing predominantly ODD problems (persisters, desisters, escalaters, and resisters). ADHD youths that did not show externalizing problems during childhood (ADHD resisters) were associated with drug use outcomes generally comparable to the normal non-affected controls. All other ADHD groups with externalizing problems (ADHD persisters, ADHD escalaters, and ADHD desisters) consistently revealed worse drug use outcomes compared to controls/ADHD resisters. However, ADHD youths with or without externalizing problems showed worse outcomes compared to the control group on the non-drug, psychosocial functioning variables. The study highlights that ADHD with coexisting disruptiveness, whether the disruptiveness persists or remits before adolescence, is associated with an increased risk for drug involvement and that ADHD, regardless of the comorbid pattern, confers a poorer level of psychosocial functioning.

Ribeiro SN; Jennen-Steinmetz C; MH; Becker K. Nicotine and alcohol use in adolescent psychiatric inpatients: Associations with diagnoses, psychosocial factors, gender and age. Nordic Journal of Psychiatry 62(4): 315-321, 2008. (49 refs.)

The aim of the survey was to describe the proportion of smokers and alcohol users in a group of children and adolescents admitted to a German department of child and adolescent psychiatry and psychotherapy. In addition, the proportion of smokers in this group of patients was compared with the proportion in the general population of the same age. The sample was composed of all children and adolescent inpatients (n = 432, 8-17 years old meeting inclusion criteria) admitted to a German department of child and adolescent psychiatry between May 2001 and June 2003. A shortened adaptation of the questionnaire on legal and illegal drug use, developed by the Swiss Professional Service for Alcohol Problems, Lausanne, was used. Initiation, frequency and quantity of drug use, and parental substance use were assessed. The results showed an association between conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD) and an early initiation of nicotine and alcohol use. Girls and boys with CD and ADHD were significantly more likely to be involved in higher levels of nicotine use compared with the general population. Parental nicotine use was associated with smoking in girls, while maternal nicotine use was associated with smoking in boys. Furthermore, regular alcohol use in both girls and boys was associated with nicotine use. To conclude, early initiation and elevated rates of nicotine and alcohol use are a particular risk for adolescents with CD and ADHD.

Rodriguez A; Miettunen J; Henriksen TB; Olsen J; Obel C; Taanila A et al. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: Evidence from three prospective pregnancy cohorts. International Journal of Obesity 32(3): 550-557, 2008. (44 refs.)

Objectives: We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring. Design: Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD. Methods: Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as 'severe' and two as 'present' (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to children's ADHD core symptoms. Results: Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women. Conclusions: We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.

Roy A. The relationships between attention-deficit/hyperactive disorder (ADHD), conduct disorder (CD) and problematic drug use. Drugs: Education, Prevention and Policy 15(1): 55-75, 2008. (76 refs.)

This paper presents a comprehensive review of the literature examining the relationships between attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD) and problematic drug use. The review considers the main debates around the structure and aetiology of ADHD and the main theoretical frameworks offered to explain the relationships between ADHD, CD and problematic drug use. ADHD is one of the most commonly diagnosed psychiatric disorders of childhood and one of the most researched. However, many people who meet the diagnostic criteria for ADHD also meet the criteria for other disorders such as CD. Most studies suggest that it is CD, not ADHD, that is the most relevant factor in predicting the development of problematic drug use. However, some evidence suggests that those with coexisting ADHD and CD may be at the highest risk. The paper concludes that ADHD is less important than CD in predicting problematic drug use.

Schubert SJ; Hansen S; Dyer KR; Rapley M. 'ADHD patient' or 'illicit drug user'? Managing medico-moral membership categories in drug dependence services. Discourse & Society 20(4): 499-516, 2009. (71 refs.)

Amphetamine-dependent patients seeking treatment are diagnosed with ADHD at a significantly higher rate than members of the general population. To study this relationship as it is constructed in everyday life, we draw on membership categorization analysis to examine how individuals account for their candidate memberships in two social categories - 'illicit amphetamine user' and 'ADHD patient'. We analyse interviews with four drug-dependent individuals, diagnosed with adult ADHD, undergoing detoxification treatment in Perth, Western Australia. Participants formulated their problematic behaviour via membership in the morally neutral category 'ADHD patient' and methodically constructed symptoms as predicates of this category, despite the availability of the equally valid alternative category 'illicit amphetamine user'. The category 'ADHD patient' is shown to be functional: it absolves drug users from responsibility for troublesome conduct, and provides continued access to amphetamines as 'medication'. In such cases, the diagnosis of ADHD arguably affords the conditions of possibility for an iatrogenic disorder in that the prescription of ATS medication provides for a morally and legally sanctioned form of drug dependence.

Schuckit MA; Smith TL; Pierson J; Trim R; Danko GP. Externalizing disorders in the offspring from the San Diego Prospective study of alcoholism. Journal of Psychiatric Research 42(8): 644-652, 2008. (72 refs.)

Object: Conduct disorder (CD) and attention deficit hyperactivity disorder (ADHD) may be more prevalent in relatives of alcoholics and may predict alcohol and drug problems, but not all studies agree. This paper evaluates these questions in well-educated families of alcoholics and controls. Methods: Data from 165, 14-25-year-old offspring in the San Diego Prospective Study were used to create Group 1 (n = 17) with CD or ADHD and Group 2 (n = 148) with no such diagnoses. Correlations and hierarchical logistic regressions evaluated characteristics associated with these disorders, comparing the impact of CD and ADHD. Results: The rates of CD (6.1%) and of ADHD (4.8%) were not strikingly elevated, and did not relate to the family history of alcohol or drug use disorders. Group 1 offspring were more likely to have divorced parents, a relative with bipolar disorder, a higher intake of alcohol and illicit substances, and associated problems.

Setlik J; Bond GR; Ho M. Adolescent prescription ADHD medication abuse is rising along with prescriptions for these medications. Pediatrics 124(3): 875-880, 2009. (37 refs.)

OBJECTIVE: We sought to better understand the trend for prescription attention-deficit/hyperactivity disorder (ADHD) medication abuse by teenagers. METHODS: We queried the American Association of Poison Control Center's National Poison Data System for the years of 1998-2005 for all cases involving people aged 13 to 19 years, for which the reason was intentional abuse or intentional misuse and the substance was a prescription medication used for ADHD treatment. For trend comparison, we sought data on the total number of exposures. In addition, we used teen and preteen ADHD medication sales data from IMS Health's National Disease and Therapeutic Index database to compare poison center call trends with likely availability. RESULTS: Calls related to teenaged victims of prescription ADHD medication abuse rose 76%, which is faster than calls for victims of substance abuse generally and teen substance abuse. The annual rate of total and teen exposures was unchanged. Over the 8 years, estimated prescriptions for teenagers and preteenagers increased 133% for amphetamine products, 52% for methylphenidate products, and 80% for both together. Reports of exposure to methylphenidate fell from 78% to 30%, whereas methylphenidate as a percentage of ADHD prescriptions decreased from 66% to 56%. Substance-related abuse calls per million adolescent prescriptions rose 140%. CONCLUSIONS: The sharp increase, out of proportion to other poison center calls, suggests a rising problem with teen ADHD stimulant medication abuse. Case severity increased over time. Sales data of ADHD medications suggest that the use and call-volume increase reflects availability, but the increase disproportionately involves amphetamines.

Szobot CM; Rohde LA; Bukstein O; Molina BSG; Martins C; Ruaro P et al. Is attention-deficit/hyperactivity disorder associated with illicit substance use disorders in male adolescents? A community-based case-control study. Addiction 102(7): 1122-1130, 2007. (58 refs.)

Aims: This study aims at evaluating the association between attention-deficit/hyperactivity disorder (ADHD) and illicit substance use disorders (SUD) (marijuana, cocaine and inhalants), controlling for the association with conduct disorder (CD), in a community-based sample of adolescents. Design Case-control, community-based study. Setting A delimited geographical area in the South of Brazil, served by four public health clinics. Participants: A total of 968 male adolescents (15-20 years of age) were screened for SUD in their households. Of the subjects who were screened positive, we selected 61 cases with illicit SUD. For each case we selected, from the group which was screened negative, three controls without illicit or alcohol SUD, matched by age and proximity with the case's household. Measurements: The screening instrument was the Alcohol Smoking and Substance Screening Test (ASSIST). SUD diagnoses were assessed by the drug section of the Mini International Neuropsychiatry Interview (MINI). Other psychiatric diagnoses were based on semistructured (Schedule for Affective Disorders and Schizophrenia for School-Age Children-epidemiological version; MINI) and clinical interviews. Findings Adolescents with ADHD presented a significantly higher odds ratio (OR) for illicit SUD than youths without ADHD, even after adjusting for potential confounders (CD, ethnicity, religion and estimated IQ) (OR = 9.12; 95% CI = 2.84 -29.31, P < 0.01). Conclusions: Our results suggest an association between ADHD and illicit SUD in Brazilian adolescents that is not mediated by CD. These findings are potentially important from a prevention perspective because treatments are available for ADHD.

Thapar A; Rice F; Hay D; Boivin J; Langley K; van den Bree M et al. Prenatal smoking might not cause attention-deficit/hyperactivity disorder: Evidence from a novel design. Biological Psychiatry 66(8): 722-727, 2009. (29 refs.)

Background: It is widely considered that exposure to maternal cigarette smoking in pregnancy has risk effects on offspring attention-deficit/hyperactivity disorder (ADHD). This view is supported by consistent observations of association. It is, however, impossible to be certain of adequate control for confounding factors with observational designs. We use a novel "natural experiment" design that separates prenatal environmental from alternative inherited effects. Methods: The design is based on offspring conceived with Assisted Reproductive Technologies recruited from 20 fertility clinics in the United Kingdom and United States who were: 1) genetically unrelated, and 2) related to the woman who underwent the pregnancy. If maternal smoking in pregnancy has true risk effects, association will be observed with ADHD regardless of whether mother and offspring are related or unrelated. Data were obtained from 815 families of children ages 4 years-11 years with parent questionnaires and antenatal records. Birth weight was used as a comparison outcome. The key outcome considered was child ADHD symptoms. Results: Association between smoking in pregnancy and lower birth weight was found in unrelated and related mother-offspring pairs, consistent with a true risk effect. However, for ADHD symptoms, the magnitude of association was significantly higher in the related pairs (beta=.102, p<.02) than in the unrelated pairs (beta=-.052, p>.10), suggesting inherited effects. Conclusions: Our findings highlight the need to test causal hypotheses with genetically sensitive designs. Inherited confounds are not necessarily removed by statistical controls. The previously observed association between maternal smoking in pregnancy and ADHD might represent an inherited effect.

Thompson J; Thompson JR. Acute myocardial infarction related to methylphenidate for adult attention deficit disorder. Journal of Emergency Medicine 38(1): 18-21, 2010. (17 refs.)

Adult Attention Deficit Disorder is increasingly diagnosed and treated. Psychostimulant medications, such as methylphenidate, are commonly prescribed for this condition, but the long-term safety of such medications in an adult population is unknown at present. Because these medications are closely related to amphetamines, it is expected that toxic side effects would be similar. We present the case of a 27-year-old man who suffered an acute myocardial infarction due to coronary vasospasm related to use of methylphenidate complicated by concomitant use of pseudoephedrine.

Upadhyaya HP; Carpenter MJ. Is attention deficit hyperactivity disorder (ADHD) symptom severity associated with tobacco use? American Journal on Addictions 17(3): 195-198, 2008. (17 refs.)

Several studies report a strong link between ADHD and tobacco use; however, the nature of this relationship is not entirely clear. We examined the relationship between attention deficit hyperactivity disorder (ADHD) symptoms and tobacco use within a sample of college students. Although tobacco use was the main focus, we also examined alcohol and marijuana use. We examined the association between the number of ADHD symptoms endorsed (severity), and tobacco, alcohol, and marijuana use in a convenience sample of 334 college students in the southeastern United States. Survey data were based on the annual Core Alcohol and Drug Survey for substance use, and the Current Symptom Scale (CSS) for ADHD, conduct disorder (CD), and antisocial personality disorder (ASPD) symptoms. Among ever users of a substance, the number (severity) of current ADHD symptoms, including inattentive and hyperactive symptoms, were significantly associated with the frequency of tobacco and marijuana use in the past month and past year, as well as to the frequency of alcohol use in the past month. The results suggest that the number of ADHD symptoms is proportionally associated with tobacco, alcohol, and marijuana use.

West SL; Mulsow M; Arredondo R. An examination of the psychometric properties of the attention deficit scales for adults with outpatient substance abusers. American Journal of Drug and Alcohol Abuse 33(5): 755-764, 2007. (26 refs.)

A growing body of research has established a high co-morbidity in the rates of attention deficit/hyperactivity disorder (ADHD) and substance abuse. The co-occurrence of these two conditions and the negative impact of untreated ADHD on the course and treatment of substance abuse highlights the need for ADHD assessment in individuals seeking substance abuse treatment. In this article, we investigated the clinical utility of the Attention Deficit Scales for Adults (ADSA) in a sample of substance abusers in an outpatient treatment program by assessing its sensitivity, specificity, positive and negative predictive values, and likelihood ratios at two potential cut-off levels ( 161 and 181) using a DSM-IV based ADHD diagnosis as the criterion. The ADSA had strong reliability (Cronbach's alpha.93; Guttman split-half.92) and correlated well with DSM-IV diagnostic criteria. Sensitivity and specificity of the device were relatively strong at both cut-off levels, as were the positive and negative predictive values.

Wilens TE Adamson J Sgambati S Whitley J Santry A Monuteaux MC et al. Do individuals with ADHD self-medicate with cigarettes and substances of abuse? Results from a controlled family study of ADHD. American Journal on Addictions 16(Supplement 1): 14-23, 2007. (63 refs.)

Studies report increased rates of cigarette and substance use in youths with Attention-Deficit/Hyperactivity Disorder (ADHD), though the mechanism of risk remains unclear. The present study tests the hypothesis that ADHD individuals "self-medicate" with cigarettes and substances of abuse. As part of five- and ten-year case-control longitudinal family studies of ADHD, responses to the Drug Use Screening Inventory (DUSI) were examined for evidence of self-medication. DUSI data from 90 ADHD probands and 96 control probands were obtained. Thirty-six percent of subjects reported self-medication, 25% used to get high, and 39% had unknown motivation. No significant differences were found between ADHD and controls in motivation. ADHD symptoms did not differ between self-medicators and subjects using to get high. DUSI problem scores were higher in ADHD (versus controls), those using to get high (versus self-medicators), and subjects using alcohol (versus other substances). More than one-third of adolescents and young adults endorsed using cigarettes and substances for self medication. Studies clarifying the role of self-medication in substance use disorders are necessary.

Wilens TE; Adamson J; Monuteaux MC; Faraone SV; Schillinger M; Westerberg D et al. Effect of prior stimulant treatment for attention-deficit/hyperactivity disorder on subsequent risk for cigarette smoking and alcohol and drug use disorders in adolescents. Archives of Pediatrics & Adolescent Medicine 162(10): 916-921, 2008. (39 refs.)

Objective: To examine the effects of early stimulant treatment on subsequent risk for cigarette smoking and substance use disorders (SUDs) in adolescents with attentiondeficit/hyperactivity disorder (ADHD). Design: Case-controlled, prospective, 5-year follow-up study. Setting: Massachusetts General Hospital, Boston. Participants: Adolescents with and without ADHD from psychiatric and pediatric sources. Blinded interviewers determined all diagnoses using structured interviews. Intervention: Naturalistic treatment exposure with psychostimulants for ADHD. Main Outcome Measures: We modeled time to onset of SUDs and smoking as a function of stimulant treatment. Results: We ascertained 114 subjects with ADHD (mean age at follow-up, 16.2 years) having complete medication and SUD data; 94 of the subjects were treated with stimulants. There were no differences in SUD risk factors between naturalistically treated and untreated groups other than family history of ADHD. We found no increased risks for cigarette smoking or SUDs associated with stimulant therapy. We found significant protective effects of stimulant treatment on the development of any SUD (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.13-0.60; chi(2)(113) = 10.57, P =. 001) and cigarette smoking(HR, 0.28; 95% CI, 0.14-0.60; chi(2)(111) = 10.05, P=. 001) that were maintained when controlling for conduct disorder. We found no effects of time to onset or duration of stimulant therapy on subsequent SUDs or cigarette smoking in subjects with ADHD. Conclusion: Stimulant therapy does not increase but rather reduces the risk for cigarette smoking and SUDs in adolescents with ADHD.

Wilens TE; Adler LA; Adams J; Sgambati S; Rotrosen J; Sawtelle R et al. Misuse and diversion of stimulants prescribed for ADHD: A systematic review of the literature. (review). Journal of the American Academy of Child and Adolescent Psychiatry 47(1): 21-31, 2008. (56 refs.)

Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in adolescent and young adult populations. The purpose of this systematic review of the literature is to evaluate the extent and characteristics of stimulant misuse and diversion in attention-cleficit/hyperactivity disorder (ADHD) and non-ADHD individuals. Method: We conducted a systematic review of the literature of available studies looking at misuse and diversion of prescription ADHD medications using misuse, diversion, stimulants, illicit use, and ADHD medications as key words for the search. Results: We identified 21 studies representing 113,104 subjects. The studies reported rates of past year nonprescribed stimulant use to range from 5% to 9% in grade school and high school-age children and 5% to 35% in college-age individuals. Lifetime rates of diversion ranged from 16% to 29% of students with stimulant prescriptions asked to give, sell, or trade their medications. Recent work suggests that whites, members of fraternities and sororities, individuals with lower grade point averages, use of immediate-release compared to extended-release preparations, and individuals who report ADHD symptoms are at highest risk for misusing and diverting stimulants. Reported reasons for use, misuse, and diversion of stimulants include to concentrate, improve alertness, "get high," or to experiment. Conclusions: The literature suggests that individuals both with and without ADHD misuse stimulant medications. Recent work has begun to document the context, motivation, and demographic profile of those most at risk for using, misusing, and diverting stimulants. The literature highlights the need to carefully monitor high-risk individuals for the use of nonprescribed stimulants and educate individuals with ADHD as to the pitfalls of the misuse and diversion of the stimulants.

Wilens TE; Adler LA; Weiss MD; Michelson D; Ramsey JL; Moore RJ et al. Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders. Drug and Alcohol Dependence 96(1-2): 145-154, 2008. (68 refs.)

Objective: Adults with attention-deficit/hyperactivity disorder (ADHD) have higher rates of alcohol and drug use disorders than adults without ADHD. The study aim was to determine if atomoxetine was superior to placebo in improving ADHD and alcohol use in recently abstinent adults with ADHD and comorbid alcohol use disorder. Methods: Adults with DSM-IV diagnoses of ADHD and alcohol abuse and/or dependence were abstinent from alcohol at least 4 days (maximum 30 days) before study randomization. Participants received atomoxetine (25-100mg daily) or placebo for 12 weeks. ADHD symptoms were assessed using ADHD Investigator Symptom Rating Scale (AISRS) total score. Time-to-relapse to heavy alcohol use was analyzed using a 2-sided log-rank test based on Kaplan-Meier estimates and cumulative heavy drinking events over time were evaluated post hoc with recurrent-event analysis. Results: Subjects received atomoxetine (n = 72) or placebo (n = 75) and 80 subjects completed the 12-week double-blind period (n = 32 and 48, respectively). ADHD symptoms were significantly improved in the atomoxetine cohort compared to placebo (AISRS total score mean [S.D.], atomoxetine: -13.63 [11.35], P < .001; placebo: -8.31 [11.44], P < .001, difference: P = .007; effect size = 0.48). No significant differences between treatment groups occurred in time-to-relapse of heavy drinking (P = .93). However, cumulative heavy drinking days were reduced 26% in atomoxetine-treated subjects versus placebo (event ratio = 0.74, P =.023). There were no serious adverse events or specific drug-drug reactions related to current alcohol use. Conclusions: This 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder demonstrates clinically significant ADHD improvement, and inconsistent effects on drinking behavior.

Wilens TE; Vitulano M; Upadhyaya H; Adamson J; Sawtelle R; Utzinger L et al. Cigarette smoking associated with attention deficit hyperactivity disorder. Journal of Pediatrics 153(3): 414-419, 2008. (31 refs.)

Objective: To evaluate the association between attention deficit hyperactivity (ADHD) and severity of physical dependence on nicotine in a controlled study of adolescents and young adults with ADHD. Study design In controlled longitudinal family studies of ADHD, we examined self-reports on the modified Fagerstrom Tolerance Questionnaire (mFTQ) for degrees of physical dependence on nicotine. Results: We obtained mFTQ data from 80 ADHD probands and 86 control probands (mean age, 19.2 years). The smokers with ADHD had significantly higher scores on the mFTQ, indicative of more severe physical dependence on nicotine. Similarly, in current smokers, a positive linear relationship was found between mFTQ score and both inattentive and hyperactive ADHD symptoms. Environmental factors, such as current parental smoking, peer smoking, and living with a smoker, all increased the risk for smoking in those with ADHD compared with controls. Conclusion: Male and female smokers with ADHD manifest more severe physical dependence on smoking compared with controls. Important environmental factors appear to add to the risk of smoking associated with ADHD.

Willoughby MT; Kollins SH; McClernon FJ. Association between smoking and retrospectively reported attention-deficit/hyperactivity disorder symptoms in a large sample of new mothers. Nicotine & Tobacco Research 11(3): 313-322, 2009. (32 refs.)

This study investigated the association between retrospectively reported attention-deficit/hyperactivity disorder (ADHD) symptoms experienced during childhood and five cigarette smoking-related outcomes in adulthood. A large sample (N = 1,117) of new mothers participating in an ongoing longitudinal study completed retrospective reports of their childhood ADHD symptomatology, as well as concurrent and retrospective reports of their smoking behavior. Linear regression models tested the association between ADHD symptomatology and smoking outcomes. Childhood ADHD symptomatology was predictive of the number of cigarettes smoked per day currently and during pregnancy, as well as the age at onset of smoking. We found nonlinear associations between hyperactive-impulsive symptoms and the number of cigarettes smoked per day in pregnancy, as well as between inattentive symptoms and the number of cigarettes smoked per day currently. Women who retrospectively reported intermediate levels of ADHD symptoms during their childhood reported smoking more cigarettes per day than women who reported low or high levels of ADHD symptoms during childhood. We also found multiplicative relationship between inattentive and hyperactive-impulsive symptoms, such that inattentive symptoms were predictive of an earlier age at smoking onset only when hyperactive-impulsive symptoms were low; moreover, the magnitude of this association was stronger for Black relative to White women. These findings demonstrate the importance of considering differential effects of ADHD symptoms and smoking outcomes as a function of sex and race. They also represent a potentially indirect means through which women who have even a moderate childhood history of ADHD symptomatology may create a set of circumstances that compromise the health and well-being of their own children.

Wilson JJ. ADHD and substance use disorders: Developmental aspects and the impact of stimulant treatment. American Journal on Addictionssss 16(Supplement 1): 5-13, 2007. (74 refs.)

Adolescents and adults with substance use disorders often demonstrate symptoms of inattention, impulsivity, and hyperactivity. These core symptoms of ADHD may contribute to the development of substance use disorders by promoting antisocial behavior and substance use; conversely, substance use itself can adversely affect these symptoms. Common deficits in self-regulatory processes could underlie the developmental progression of these disorders, deficits further worsened by ongoing substance use. Some investigators have questioned whether stimulant treatment itself could promote substance abuse, while others have argued that such treatment reduces substance abuse. With an increased awareness of the phenomenon of adult ADHD and its relevance to substance-abusing persons, there is an increased awareness of the potential benefit of ADHD treatment on substance abuse treatment outcome. Consideration of an individual's developmental relationship between attention deficit/hyperactivity symptoms and substance use can inform treatment planning among patients seeking substance abuse treatment.

Winterstein AG; Gerhard T; Shuster J; Johnson M; Zito JM; Saidi A. Cardiac safety of central nervous system stimulants in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 120(6): E1494-E1501, 2007. (33 refs.)

OBJECTIVES. Case reports have raised concerns about the risk of cardiac events associated with central nervous system stimulants for the treatment of attention-deficit/hyperactivity disorder. PATIENTS AND METHODS. This was a retrospective cohort study that used 10 years ( July 1994 to June 2004) of Florida Medicaid claims data cross-linked to Vital Statistics Death Registry data. The cohort was composed of all youth 3 to 20 years old who were newly diagnosed with attention-deficit/hyperactivity disorder. Each month of follow-up was classified according to stimulant claims ( methylphenidate, amphetamines, and pemoline) as current use ( active stimulant claim), former use ( time after periods of current use), or nonuse ( time preceding the first stimulant claim, including follow-up of youth who were never exposed to stimulants). The study's end points were ( 1) cardiac death, ( 2) first hospital admission for cardiac causes or ( 3) first emergency department visit for cardiac causes. Risks were compared with time-dependent Cox regression analysis adjusting for various cardiac risk factors. RESULTS. During 124 932 person-years of observation ( n = 55 383), 73 youth died, 5 because of cardiac causes. No cardiac death occurred during 42 612 person-years of stimulant use. Hospital admissions for cardiac cause occurred for 27 children ( 8 during stimulant use, 11 during 35 671 person-years of former use, and 8 during 46 649 person-years of nonuse); and 1091 children visited the emergency department for cardiac causes ( 8.7 per 1000 person-years). Current stimulant use was associated with a 20% increase in the hazard for emergency department visits when compared with nonuse. No increased risk was found for periods of former use when compared with nonuse. CONCLUSIONS. Incidence rates of cardiac events requiring hospitalization were small and similar to national background rates. Stimulants were associated with an increase in cardiac emergency department visits. More evidence is needed that addresses the long-term risk/benefit of the various treatment options and the effect of other cardiac risk factors and comedications.