Subsequent Substance Use Disorders Research Articles

How life events may confer vulnerability to addiction: the role of epigenetics.

Substance use disorder (SUD) represents a large and growing global health problem. Despite the strong addictive potency of drugs of abuse, only a minority of those exposed develop SUDs. While certain life experiences (e.g., childhood trauma) may increase subsequent vulnerability to SUDs, mechanisms underlying these effects are not yet well understood. Given the chronic and relapsing nature of SUDs, and the length of time that can elapse between prior life events and subsequent drug exposure, changes in SUD vulnerability almost certainly involve long-term epigenetic dysregulation. To validate this idea, functional effects of specific epigenetic modifications in brain regions mediating reinforcement learning (e.g., nucleus accumbens, prefrontal cortex) have been investigated in a variety of animal models of SUDs. In addition, the effects of epigenetic modifications produced by prior life experiences on subsequent SUD vulnerability have been studied, but mostly in a correlational manner. Here, we review how epigenetic mechanisms impact SUD-related behavior in animal models and summarize our understanding of the relationships among life experiences, epigenetic regulation, and future vulnerability to SUDs. Despite variations in study design, epigenetic modifications that most consistently affect SUD-related behavior are those that produce predominantly unidirectional effects on gene regulation, such as DNA methylation and histone phosphorylation. Evidence explicitly linking environmentally induced epigenetic modifications to subsequent SUD-related behavior is surprisingly sparse. We conclude by offering several directions for future research to begin to address this critical research gap.

Attention deficit hyperactivity and oppositional defiant disorder symptoms in adolescence and risk of substance use disorders-A general population-based birth cohort study.

Externalizing symptoms are associated with risk of future substance use disorder (SUD). Few longitudinal studies exist using general population-based samples which assess the spectrum of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms. We aimed to study the associations between adolescent ADHD symptoms and subsequent SUD and additionally examine whether the risk of SUD is influenced by comorbid oppositional defiant disorder (ODD) symptoms. The Northern Finland Birth Cohort 1986 was linked to nationwide health care register data for incident SUD diagnoses until age 33 years (n = 6278, 49.5% male). ADHD/ODD-case status at age 16 years was defined using parent-rated ADHD indicated by Strengths and Weaknesses of ADHD symptoms and Normal Behaviors (SWAN) questionnaire with 95% percentile cut-off. To assess the impact of ODD comorbidity on SUD risk, participants were categorized into four groups based on their ADHD/ODD case status. Cox-regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to study associations between adolescent ADHD/ODD case statuses and subsequent SUD. In all, 552 participants (8.8%) presented with ADHD case status at the age of 16 years, and 154/6278 (2.5%) were diagnosed with SUD during the follow-up. ADHD case status was associated with SUD during the follow-up (HR = 3.84, 95% CI 2.69-5.50). After adjustments for sex, family structure, and parental psychiatric disorder and early substance use the association with ADHD case status and SUD remained statistically significant (HR = 2.60, 95% CI 1.70-3.98). The risk of SUD remained elevated in individuals with ADHD case status irrespective of ODD symptoms. ADHD in adolescence was associated with incident SUD in those with and without symptoms of ODD. The association of ADHD and SUD persisted even after adjustment for a wide range of potential confounds. This emphasizes the need to identify preventative strategies for adolescents with ADHD so as to improve health outcomes.

Sex differences in addiction-relevant behavioral outcomes in rodents following early life stress

In humans, exposure to early life stress (ELS) is an established risk factor for the development of substance use disorders (SUDs) during later life. Similarly, rodents exposed to ELS involving disrupted mother-infant interactions, such as maternal separation (MS) or adverse caregiving due to scarcity-adversity induced by limited bedding and nesting (LBN) conditions, also exhibit long-term alterations in alcohol and drug consumption. In both humans and rodents, there is a range of addiction-related behaviors that are associated with drug use and even predictive of subsequent SUDs. In rodents, these include increased anxiety-like behavior, impulsivity, and novelty-seeking, altered alcohol and drug intake patterns, as well as disrupted reward-related processes involving consummatory and social behaviors. Importantly, the expression of these behaviors often varies throughout the lifespan. Moreover, preclinical studies suggest that sex differences play a role in how exposure to ELS impacts reward and addiction-related phenotypes as well as underlying brain reward circuitry. Here, addiction-relevant behavioral outcomes and mesolimbic dopamine (DA) dysfunction resulting from ELS in the form of MS and LBN are discussed with a focus on age- and sex-dependent effects. Overall, these findings suggest that ELS may increase susceptibility for later life drug use and SUDs by interfering with the normal maturation of reward-related brain and behavioral function.

Cumulative exposure to traumatic events and craving among women in residential treatment for substance use disorder: The role of emotion dysregulation and mindfulness disposition.

Strong evidence links exposure to traumatic life events with subsequent substance use disorders (SUD). Compared to men, women in SUD treatment are more likely to have a history of trauma, characterized in part by emotion dysregulation known to negatively influence treatment outcomes. Existing research has been conducted with predominantly male and non-Hispanic White samples, with an emphasis on adverse childhood experiences. Little is known about how exposure to cumulative traumatic events across the lifespan affects emotion dysregulation and how this may influence craving, particularly among racial and ethnic minoritized women with SUD. Mindfulness disposition may serve as a protective factor that could buffer the impact of trauma exposure and emotion dysregulation on substance use craving among underrepresented minoritized women with SUD. This study examined the association between cumulative exposure to traumatic events, emotion dysregulation, and mindfulness disposition on substance use craving in a sample of predominantly Hispanic and non-Hispanic Black women in residential treatment for SUD. Cross-sectional data were analyzed for a baseline sample of 241 women (56.96% Hispanic, 20.7% non-Hispanic White, 20.7% non-Hispanic Black; age: M = 32.11) entering a SUD residential treatment facility who agreed to participate in a parent randomized controlled trial. Findings indicated that greater cumulative exposure to traumatic events and emotion dysregulation were associated with higher levels of craving. Cumulative traumatic event exposure was indirectly associated with higher craving via lower levels in the mindfulness dimension of acting with awareness. Interaction effects also revealed greater exposure to traumatic events was associated with higher levels of craving among women with low and average (but not high) levels of mindfulness disposition. These findings provide insight into the potential benefits of targeting emotion regulation and mindfulness-building strategies such as acting with awareness in interventions among racial-ethnically diverse women with SUD. These strategies may be particularly beneficial among those that have experienced extensive histories of trauma exposure. Overall, knowledge gained from the present study can be particularly valuable towards informing treatment models in minoritized groups that currently experience disparities in treatment utilization and outcomes.

Substance use disorder among adolescents before and during the COVID-19 pandemic in Uganda: Retrospective findings from a psychiatric ward registry.

It has been reported that the COVID-19 pandemic has predisposed adolescents to risky behaviors such as substance use and subsequent substance use disorder (SUD). However, it is unknown how the pandemic has changed the prevalence of SUD among adolescents in Uganda. We aimed to determine the prevalence of SUD and associated factors among adolescents in southwestern Uganda. Retrospectively, psychiatry ward records from November 2018 to July 2021 were collected from the largest tertiary hospital in southwestern Uganda. A total of 441 adolescent records were included in the analysis, with a mean age was 17±1.88 years, and the majority were males (50.34%). The overall prevalence of SUD was 7.26% (5.90% and 9.80% before and during the pandemic). Despite a little rise in SUD (3.9% increment) during the COVID-19 pandemic, there was no statistical difference compared to before the pandemic. The likelihood of being diagnosed with SUD was more among older adolescents at any period. In addition, having a diagnosis of bipolar mood disorder reduced the likelihood of SUD during the pandemic. This study indicated no statistical change in the diagnosis of SUD among adolescents before and during the COVID-19 pandemic. As older-male adolescents (17 to 19 years) were at higher risk of SUD, there is a need for early intervention for this group.

Risks versus consequences of adolescent and young adult substance use: A focus on executive control.

This review examines the role of executive control processes in the liability for substance misuse and whether substance use, once initiated, leads to subsequent decrements as proposed by neurotoxicity models of substance use disorder (SUD). As indicated by a number of recent meta-analyses, executive control processes, which include working memory, cognitive flexibility and numerous aspects of attentional, behavioral and emotional control, are impaired in the context of active SUD. Longitudinal studies of behaviorally disinhibited children, individuals with familial risks for SUD, and twins within whom genetic versus environmental influences on behavior can be modeled robustly indicate that relatively poor control is a vulnerability factor for early substance use initiation, binge patterns of use, and subsequent SUD. Evidence of further declines in executive control, once substance use is initiated, is mixed, although a growing number of neuroimaging studies indicate that frontostriatal, frontolimbic, and frontocerebellar systems are altered as a consequence of use. Together these patterns suggest strategies for identifying children and adolescents at high risk for SUD, avenues through which substance-related neurotoxicities can be more reliably detected, and the need to structure prevention efforts in a manner that is developmentally appropriate and perhaps personalized to individual vulnerabilities.

A systematic review of research on adolescent solitary alcohol and marijuana use in the United States.

Alcohol use and marijuana use tend to be social activities among adolescents. Some youth use alcohol or marijuana while alone. This article provides a framework for examining the risk factors for and consequences of solitary alcohol and marijuana use, grounded in a motivational model that emphasizes coping with negative emotions, and provides the first systematic review of research on solitary alcohol and marijuana use among middle school- and high school-aged adolescents in the United States. PubMed, PsycINFO and Web of Science were searched. Articles were included if they mention solitary alcohol or marijuana (or illicit drug) use among adolescents aged 12-18years. Studies on non-human animals, college students, non-English language publications and articles exclusively about solitary tobacco or inhalant use were excluded. Overall, 22 articles were selected. Prevalence of adolescent solitary alcohol and marijuana use was relatively high (e.g. 14% life-time solitary drinking in the general adolescent population), particularly in high-risk subgroups (e.g. 38.8% life-time solitary drinking in a sample of youth recruited from clinical and community settings). Risk factors for solitary alcohol and marijuana use include earlier onset and heavier use, coping motives, negative emotions and positive expectancies about use. Solitary alcohol and marijuana use are prospectively associated with later substance use disorder (SUD) symptoms, diminished academic performance and perceived health. Approximately 1 in 7 adolescents in the US appear to have engaged in solitary alcohol and marijuana use at some point. It is positively associated with extent of drinking and marijuana use, cop;ing motives, negative emotions, and positive expectancies, as well as subsequent SUD symptoms and poor academic and health-related outcomes.

A prospective study of nonmedical use of prescription opioids during adolescence and subsequent substance use disorder symptoms in early midlife

BackgroundThis longitudinal study assesses characteristics associated with adolescents’ nonmedical use of prescription opioids (NMUPO) including: frequency, co-ingestion, motives, specific opioid type; sequence of initiation of medical use of prescription opioids and NMUPO in relationship to subsequent substance use disorder (SUD) symptoms. MethodsTwenty-one independent national cohorts of U.S. high school seniors (n = 8,373) were surveyed and followed 17 years from adolescence to age 35. ResultsThe majority of adolescents who engaged in NMUPO reported occasional/frequent NMUPO, non-pain relief motives for NMUPO, simultaneous co-ingestion involving NMUPO and other drugs, opioid analgesics with high misuse potential, and multiple types of opioid analgesics. Adolescents who reported NMUPO for pain relief, NMUPO involving opioid analgesics with high misuse potential, or multiple prescription opioids had significantly greater odds of SUD symptoms at age 35, relative to those who had no history of NMUPO during adolescence. In addition, medical use of prescription opioids after initiating NMUPO (or NMUPO only) during adolescence was associated with significantly greater odds of subsequent SUD symptoms at age 35 relative to those who reported the medical use of prescription opioids only or had no medical use or NMUPO during adolescence. ConclusionsThis is the first U.S. national prospective study to examine the relationships between adolescents’ NMUPO characteristics and later SUD symptoms in early midlife. Several characteristics (frequency, co-ingestion, motives, opioid type, and medical/NMUPO initiation history) were identified that could be used to screen and detect high-risk youth for indicated interventions to reduce prescription opioid misuse and SUDs.

The power of negative mood in predicting posttraumatic stress disorder and alcohol abuse comorbidity.

Individuals with posttraumatic stress disorder (PTSD) show a high risk of developing substance use disorders (SUD). Many studies have shown that PTSD often precedes SUD, and some studies have been able to identify factors that might predict which individuals might develop subsequent SUD. Attempts to treat PTSD and SUD comorbidity have proven difficult, but new methods for simultaneous treatment have shown promise for treating PTSD. The ability to identify factors that predict PTSD/SUD comorbidity and the advent of new combined treatment methods warrant investigation of how differences in specific types of PTSD symptoms individuals experience might predict who will go on to develop SUD symptoms and thus benefit from new combined treatments. In this study, we analyzed which clusters of PTSD symptoms predicted whether individuals with PTSD met criteria for alcohol use disorder. Analyses revealed that frequency and intensity of negative alterations in cognition and mood predicted SUD, but re-experiencing symptoms, hyperarousal, and avoidance did not. Our results indicate that those who experience negative alterations in cognition and mood may be at increased risk of developing SUD, and that we may be able to predict which individuals in clinical settings will be strong candidates for new combined PTSD/SUD treatments. Further considerations for our results and for future directions are also discussed. (PsycINFO Database Record

Self-medication with alcohol or drugs for mood and anxiety disorders: A narrative review of the epidemiological literature.

BackgroundThe comorbidity of mood and anxiety disorders (MD and AD) with substance use disorders (SUD) is common. One explanation for this comorbidity is the self‐medication hypothesis, which posits that individuals with MD or AD use substances to cope with the difficult symptoms associated with the disorder. Over time, self‐medication (SM) can develop into an independent SUD. This narrative review will present the prevalence and correlates of SM with alcohol and/or drugs for MD and AD and the relationship between SM and subsequent SUD using both cross‐sectional and longitudinal epidemiological data.MethodsScopus and PsycINFO were searched from January 1997 to April 2018 to identify original research articles that examined the prevalence and correlates of SM and the temporal relationship between MD/AD and SUD in the general population (n = 22).ResultsThe prevalence of SM with alcohol and/or drugs among those with MD or AD ranged from 21.9% to 24.1%. Male sex, younger age, being separated, divorced or widowed, and being Caucasian were characteristics associated with higher proportions of respondents endorsing SM with alcohol/drugs for MD and AD. Longitudinal data supports the temporal onset of primary MD/AD and secondary SUD among those who self‐report SM.ConclusionProviding and promoting alternate coping strategies for those with MD/AD may reduce SM, the development of SUD, and the comorbidity of MD/AD with SUD. The concurrent treatment of MD/AD and substance use is the current “gold standard” model of care, and the results of this review support its use.

Marital Status as a Partial Mediator of the Associations Between Young Adult Substance Use and Subsequent Substance Use Disorder: Application of Causal Inference Methods

Young adult substance use is linked with the risk of substance use disorders (SUDs) later in adulthood. Marriage may be part of this pathway because of both selection effects (early substance use reducing marriage) and socialization effects (marriage reducing later substance use and disorder). We examine whether marital status mediates the association between young adult substance use and subsequent SUDs, using causal mediation methods to strengthen inferences. Using panel data from high school seniors in 1990-1998, we examined whether the effects of two exposures (level of alcohol/marijuana use at age 19/20) on the outcomes (alcohol use disorder [AUD]/ marijuana use disorder [MUD], nondisordered use, or abstinence at age 35) were mediated by marital status at age 29/30. Propensity score weights adjusted for potential confounding regarding both the exposures and the mediator. Moderate and heavy alcohol/marijuana use at age 19/20 were associated with higher odds of AUD/MUD and lower odds of abstinence, each relative to nondisordered use, at age 35. The association between heavy alcohol use at age 19/20 and subsequent AUD was partially mediated by being unmarried at age 29/30; the associations between moderate and heavy marijuana use at age 19/20 and subsequent marijuana abstinence were partially mediated by being unmarried at age 29/30. Both selection and socialization effects related to marriage explain the perpetuation of substance use behaviors across adulthood. Selection effects on marriage seem to occur at different thresholds for young adult alcohol and marijuana use.

Sleep disturbance as a predictor of time to drug and alcohol use treatment in primary care

BackgroundSleep Disturbances (SDs) are a symptom common to mental health disorders (MHD) and substance use disorders (SUD). We aimed to identify the value of SD as a predictor for subsequent treatment of illicit drug and alcohol use disorders (SUDs) in primary care and relative to the predictive value of mental health disorders (MHDs). MethodsWe used electronic health records data from ambulatory primary care in a safety net Boston area healthcare system from 2013 to 2015 (n = 83,920). SUD (separated into illicit drug use disorder and alcohol use disorder) and MHD were identified through ICD-9 codes and medical record documentation. We estimated Cox proportional hazard models to examine the risk of SUD across four comparison groups (SD only, SD and MHD, MHD only, and neither SD nor MHD). ResultsCompared to patients with no sleep or MHD, patients with SD had a greater risk for subsequent SUD treatment. Approximately one-fifth of patients with SD were treated for an illicit drug use disorder and approximately 12% were treated for alcohol use disorder. Risk for SUD treatment, estimated at over 30% by the end of the study, was greatest for patients with a MHD, either alone or comorbid with SD. Risk was greater for older patients and men, and lower for minority patients. ConclusionsSD and MHD, individually and comorbid, significantly predict subsequent treatment of illicit drug and alcohol use disorder in primary care. Screening and evaluation for SD should be a routine practice in primary care to help with identifying potential SUD risk.

Orbitofrontal Cortex Volume and Effortful Control as Prospective Risk Factors for Substance Use Disorder in Adolescence

Background: Orbitofrontal cortex (OFC) dysfunction has been proposed to increase the risk for developing a substance use disorder (SUD) during adolescence. In this study, we suggest that a reduction in OFC volumes might underlie temperament-based risk factors for SUD, and examined whether smaller OFC volumes during early adolescence could predict later development of SUD. Methods and Materials: Adolescents (n = 107; 58 male, 49 female) underwent structural MRI and completed a self-report measure of temperamental effortful control at age 12. At 3 subsequent assessments (aged 15, 16, and 18) SUD was assessed via a semi-structured clinical interview. By the third assessment, 24 participants (22.4%) had received a lifetime diagnosis of SUD. Results: Smaller volumes of the left OFC, right OFC, and left medial subregions predicted lifetime history of SUD by age 18. Volumes of the left OFC and left lateral subregions were positively correlated with effortful control, and left OFC volumes mediated the relationship between effortful control and SUD. Conclusions: Smaller volumes of the OFC and low effortful control during adolescence appear to be associated phenotypes that increase the risk of subsequent SUD. Further studies examining the temporal sequence of these risk factors are needed to fully understand this relationship.

Does psychostimulant treatment in children with ADHD increase later risk of substance use disorder?

Psychostimulants are the first choice medication in children with attention-deficit/hyperactivity disorder (ADHD). Despite the proven high efficacy of psychostimulants, at least in the short term, for ADHD core symptoms, concerns continue to be raised on their adverse effects, including putative increased risk of substance use disorders (SUDs). A recent multicentre, case-control, longitudinal, prospective, European study by Groenman and colleagues found that treatment with psychostimulants in children with ADHD lowered the risk of SUDs in adolescence. However, this finding is at odds with other recent evidence concluding that ADHD children with and without medication treatment history did not significantly differ on any subsequent SUDs rates. In the present paper, we discuss the study by Groenman and colleagues in view of its methodological strengths and limitations, and we suggest possible implications for day-to-day clinical practice.

Effectiveness of a Feedback-Based Brief Intervention to Reduce Alcohol Use in Community Substance Use Disorders Treatment

Feedback brief interventions for alcohol use problems have been highly effective with undergraduate populations. However, there has been little research on the effectiveness of administering feedback alone to community treatment populations. The goal of this study was to assess the effectiveness of a feedback brief intervention in a community treatment setting with patients characterized largely by dependence on alcohol and drugs, ethnic diversity, and low socioeconomic status. It was hypothesized that pretreatment brief individualized feedback would reduce alcohol consumption and increase participation in subsequent substance use disorder (SUD) treatment. Participants were recruited from a public hospital's SUD clinic. After the intake but prior to entry into the treatment as usual, 121 participants were randomized to receive personalized feedback or a condition without feedback. Eighty-seven participants completed post-intervention follow-up interviews and were included in the final analyses. Repeated-measures ANOVAs and MANCOVAs were used to examine variables obtained from the Addiction Severity Index of drinking quantity and frequency, and motivation for treatment. Results indicated that personalized feedback delivered no benefit beyond that of pretreatment assessment procedures (phone screening and intake interview) alone. Intervention conditions did not differ on other outcomes at follow-up, including days of heavy drinking, motivation for treatment, or drug use frequency. Therefore, feedback-based brief interventions may be not helpful in reducing the drinking frequency and intensity of individuals presenting to community-based substance use treatment.

Onset of alcohol or substance use disorders following treatment for adolescent depression.

This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD). For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in the Treatment for Adolescents with Depression Study (TADS; TADS Team, 2004) and who had no prior diagnoses of AUD or SUD. TADS initial treatments were cognitive behavior therapy (CBT), fluoxetine alone (FLX), the combination of CBT and FLX (COMB), or clinical management with pill placebo (PBO). We used both the original TADS treatment response rating and a more restrictive symptom count rating. During follow-up, diagnostic interviews were completed at 6- or 12-month intervals to assess onset of AUD or SUD as well as MDD recovery and recurrence. Achieving a positive response to MDD treatment was unrelated to subsequent AUD but predicted a lower rate of subsequent SUD, regardless of the measure of positive response (11.65% vs. 24.72%, or 10.0% vs. 24.5%, respectively). Type of initial MDD treatment was not related to either outcome. Prior to depression treatment, greater involvement with alcohol or drugs predicted later AUD or SUD, as did older age (for AUD) and more comorbid disorders (for SUD). Among those with recurrent MDD and AUD, AUD preceded MDD recurrence in 24 of 25 cases. Effective short-term adolescent depression treatment significantly reduces the rate of subsequent SUD but not AUD. Alcohol or drug use should be assessed prior to adolescent MDD treatment and monitored even after MDD recovery.

Posttraumatic stress disorder and substance use disorder in adolescent bipolar disorder

Anxiety disorders such as posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are increasingly recognized as comorbid disorders in children with bipolar disorder (BPD). This study explores the relationship between BPD, PTSD, and SUD in a cohort of BPD and non-BPD adolescents. We studied 105 adolescents with BPD and 98 non-mood-disordered adolescent controls. Psychiatric assessments were made using the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiologic Version (KSADS-E), or Structured Clinical Interview for DSM-IV (SCID) if 18 years or older. SUD was assessed by KSADS Substance Use module for subjects under 18 years, or SCID module for SUD if age 18 or older. Nine (8%) BPD subjects endorsed PTSD and nine (8%) BPD subjects endorsed subthreshold PTSD compared to one (1%) control subject endorsing full PTSD and two (2%) controls endorsing subthreshold PTSD. Within BPD subjects endorsing PTSD, seven (39%) met criteria for SUD. Significantly more SUD was reported with full PTSD than with subthreshold PTSD (chi(2) = 5.58, p = 0.02) or no PTSD (chi(2) = 6.45, p = 0.01). Within SUD, the order of onset was BPD, PTSD, and SUD in three cases, while in two cases the order was PTSD, BPD, SUD. The remaining two cases experienced coincident onset of BPD and SUD, which then led to trauma, after which they developed PTSD and worsening SUD. An increased rate of PTSD was found in adolescents with BPD. Subjects with both PTSD and BPD developed significantly more subsequent SUD, with BPD, PTSD, then SUD being the most common order of onset. Follow-up studies need to be conducted to elucidate the course and causal relationship of BPD, PTSD and SUD.

Effect of Prior Stimulant Treatment for Attention-Deficit/Hyperactivity Disorder on Subsequent Risk for Cigarette Smoking and Alcohol and Drug Use Disorders in Adolescents

To examine the effects of early stimulant treatment on subsequent risk for cigarette smoking and substance use disorders (SUDs) in adolescents with attention-deficit/hyperactivity disorder (ADHD). Case-controlled, prospective, 5-year follow-up study. Massachusetts General Hospital, Boston. 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. We modeled time to onset of SUDs and smoking as a function of stimulant treatment. 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. Stimulant therapy does not increase but rather reduces the risk for cigarette smoking and SUDs in adolescents with ADHD.

Substance Use Disorders in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Review the association between attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) in children and adolescents. Discuss treatment implications and the role of the primary care physician in the management of this comorbidity. Articles published from 1991 to 2007 were identified through a MEDLINE search using the search terms attention-deficit/hyperactivity disorder and substance use disorder. Publications cited include reviews of substance use disorders in children and adolescents with ADHD, manuals of diagnostic tests, and 69 studies of substance use disorders in children and adolescents with ADHD. No non-English-language publications were identified. Recent reports identify SUD in a high proportion of respondents with ADHD and ADHD in a high proportion of respondents with many types of SUD. Factors that appear to increase the risk for SUD include comorbid psychiatric disorders, particularly conduct disorder. Pharmacotherapy for ADHD appears not to increase the risk for subsequent SUD. Guidelines for the evaluation and treatment of patients with comorbid ADHD and SUD are outlined. Psycho-stimulants carry the risk for misuse by both patients and family members through diversion. Although nonstimulants such as atomoxetine have low abuse potential, they appear to be less efficacious than stimulants. Formulations that have the potential to lower the abuse liability of stimulants are being developed. These include a transdermal form of methylphenidate that has been shown to be efficacious in the treatment of ADHD and a prodrug stimulant, lisdexamfetamine, recently approved for the treatment of ADHD. Clinical data indicate that lisdexamfetamine is efficacious, and significantly lower likability scores were seen with lisdexamfetamine than with equivalent oral doses of d-amphetamine sulfate. Pharmacotherapy may reduce the risk for SUD in patients with ADHD. Psycho-stimulants remain the first-line therapy for the core symptoms of ADHD. New formulations of pharmacologic agents with a reduced potential for abuse are being developed.

Impact of Substance Use Disorder on ADHD and Its Treatment

Attention deficit/hyperactivity disorder (ADHD) is associated with a high rate of psychiatric comorbidity. Substance use disorder (SUD) is common, affecting 1 in 5 adults with ADHD. Adolescents with ADHD are twice as likely to become cigarette smokers as those without ADHD, and cigarette smoking is a significant risk factor for the development of subsequent SUD in adulthood. Patients with SUD and ADHD have been shown to have lower retention in SUD treatment programs, lower rates of SUD remission, and longer courses of SUD. SUD also complicates the diagnosis of adult ADHD. Fortunately, pharmacologic treatment of ADHD does not appear to increase the risk for development of SUD in ADHD patients.