A Prospective Examination of the Association of Stimulant Medication History and Drug Use Outcomes among Community Samples of ADHD Youths

A continuing debate in the child psychopathology literature is the extent to which pharmacotherapy for children with attention-deficit/hyperactivity disorder (ADHD), in particular stimulant treatment, confers a risk of subsequent drug abuse. If stimulant treatment for ADHD contributes to drug abuse, then the risk versus therapeutic benefits of such treatment is greatly affected. We have prospectively followed an ADHD sample (N = 149; 81% males) for approximately 15 years, beginning at childhood (ages 8 to 10 years) and continuing until the sample has reached young adulthood (ages 22 to 24 years). The sample was originally recruited via an epidemiologically derived community procedure, and all youths were diagnosed with ADHD during childhood. We report on the association of childhood psychostimulant medication and subsequent substance use disorders and tobacco use. The substance use outcomes were based on data collected at three time points when the sample was in late adolescence and young adulthood (age range approximately 18 to 22 years old). We did not find evidence to support that childhood treatment with stimulant medication, including the course of stimulant medication, was associated with any change in risk for adolescent or young adulthood substance use disorders and tobacco use. These results from a community-based sample extend the growing body of literature based on clinically derived samples indicating that stimulant treatment does not create a significant risk for subsequent substance use disorders.     

Challenges and Outcomes of Parallel Care for Patients With Co-Occurring Psychiatric Disorder in Methadone Maintenance Treatment

Objective: Most opioid users seeking treatment in community-based substance abuse treatment programs have at least one co-occurring psychiatric disorder, and the presence of psychiatric comorbidity in this population is associated with increased psychological distress, poorer quality of life, and reduced response to substance abuse treatment. This observational study describes clinical outcomes of referring patients receiving methadone maintenance with at least one co-occurring psychiatric disorder to a community psychiatry program located on the same hospital campus. Methods: Participants (n = 156) were offered priority referrals to a community psychiatry program that included regularly scheduled psychiatrist appointments, individual and group therapy, and enhanced access to psychiatric medications for 1 year. Psychiatric distress was measured with the Symptom Checklist (SCL-90-R), which participants completed monthly. Results: While about 80% of the sample (n = 124) initiated psychiatric care, the average length of treatment was only 128.2 days (SD = 122.8), participants attended only 33% of all scheduled appointments (M = 14.9 sessions, SD = 14.1), and 84% (n = 104) did not complete a full year of care. Of those who did not complete a full year, over half (55%, n = 68) left psychiatric care while still receiving substance abuse treatment. Exploratory negative binomial regression showed that baseline cocaine and alcohol use disorder (p =.002 and.022, respectively) and current employment (p =.034) were associated with worse psychiatric treatment retention. Modest reductions in psychiatric distress over time were observed (SCL-90-R Global Severity Index change score = 2.5; paired t = 3.54, df = 121, p =.001). Conclusions: Referral of patients with co-occurring psychiatric disorders receiving methadone maintenance to a community psychiatry program is often ineffective, even after reducing common barriers to care. Service delivery models designed to improve attendance and retention, such as integrated care models, should be evaluated. This study is part of a larger clinical trial, registered at www.clinicaltrials.gov under #NCT00787735.     

Long-term use of stimulants in children with attention deficit hyperactivity disorder: safety, efficacy, and long-term outcome

The purpose of this review is to summarize existing data on the long-term safety and efficacy of stimulant treatment, and how long-term stimulant treatment of children with attention deficit hyperactivity disorder (ADHD) affects their outcome. Existing controlled studies of children with ADHD treated and untreated with stimulants, as well as long-term prospective follow-up studies, are reviewed. Children with ADHD treated with stimulants for as long as 2 years continue to benefit from the treatment, with improvements observed in ADHD symptoms, comorbid oppositional defiant disorder, and academic and social functioning, with no significant problems of tolerance or adverse effects. Long-term, prospective follow-up studies into adulthood show that stimulant treatment in childhood has slight benefits regarding social skills and self-esteem. Long-term adverse effects from stimulant treatment in childhood regarding adult height or future substance abuse have not been supported by existing studies.     

A Prospective Examination of the Association of Stimulant Medication History and Drug Use Outcomes among Community Samples of ADHD Youths

A continuing debate in the child psychopathology literature is the extent to which pharmacotherapy for children with attention-deficit/hyperactivity disorder (ADHD), in particular stimulant treatment, confers a risk of subsequent drug abuse. If stimulant treatment for ADHD contributes to drug abuse, then the risk versus therapeutic benefits of such treatment is greatly affected. We have prospectively followed an ADHD sample (N = 149; 81% males) for approximately 15 years, beginning at childhood (ages 8 to 10 years) and continuing until the sample has reached young adulthood (ages 22 to 24 years). The sample was originally recruited via an epidemiologically derived community procedure, and all youths were diagnosed with ADHD during childhood. We report on the association of childhood psychostimulant medication and subsequent substance use disorders and tobacco use. The substance use outcomes were based on data collected at three time points when the sample was in late adolescence and young adulthood (age range approximately 18 to 22 years old). We did not find evidence to support that childhood treatment with stimulant medication, including the course of stimulant medication, was associated with any change in risk for adolescent or young adulthood substance use disorders and tobacco use. These results from a community-based sample extend the growing body of literature based on clinically derived samples indicating that stimulant treatment does not create a significant risk for subsequent substance use disorders.     

A treatment algorithm for attention deficit hyperactivity disorder in cocaine‐dependent adults: A one‐year private practice study with long‐acting stimulants,fluoxetine, and bupropion

A subgroup of adults in private treatment for cocaine dependence in remission reported a therapeutic effect from cocaine during the initial phases of cocaine addiction and, also, met DSM‐IV criteria for ADHD. We report evidence that study subjects probably medicated their ADHD symptoms with cocaine and describe a 1‐year treatment algorithm featuring long‐acting stimulants that was effective in the management of their ADHD and cocaine dependence. Nineteen stable patients in full remission from all substance dependence were entered into an open label, prospective, treatment trial for ADHD. The treatment schedule consisted of the progressive introduction—and discontinuation of ineffective medication—of each of several medications in the following order: fluoxetine, bupropion, pemoline, sustained‐release methylphenidate, dextroamphetamine spansules, and methamphetamine gradumets. Treatment of ADHD was successful. Several treatment regimens, especially those including long‐acting stimulants, alone or in combination with other agents, were highly effective. All but 1 of the 19 subjects had a fully effective response for at least 1 full year. Mean UTAH scale scores were 7.4 before any medications were administered and 1.6 at the end of the study. Treatment proved successful in suppressing ADHD symptoms, with minimal cocaine slips or side effects.     

Characteristics of Admissions for Primary Stimulant Dependence During 2001

The production and consumption of synthetic stimulants has been increasing in recent years accompanied by an increase in the number of individuals seeking treatment for synthetic stimulant “abuse.” The misuse of stimulants is occurring at younger ages and primarily in the context of polysubstance use. This article examines the characteristics of admissions entering treatment centers that received some form of public funding in 2001 as compiled in the Treatment Episodes Data Set produced by the Substance Abuse Mental Health Services Administration, Office of Applied Studies. It compares those admissions indicating stimulants as a primary substance of use with those admissions not listing stimulants. Findings indicated that stimulant primary admissions were younger, more frequently Caucasian, and more frequently female than nonstimulant admissions. Additionally, stimulant primary admissions had fewer prior treatment episodes and substance use referrals than the nonstimulant admissions but were more commonly referred by the criminal justice system, raising the concern that adequate screening for stimulant misuse is not occurring in health care settings.     

Psychiatric comorbidities in children with attention deficit hyperactivity disorder: implications for management

Attention deficit hyperactivity disorder (ADHD) is frequently comorbid with a variety of psychiatric disorders. These include oppositional defiant disorder and conduct disorder (CD), as well as affective, anxiety, and tic disorders. ADHD and ADHD with comorbid CD appear to be distinct subtypes; children with ADHD/CD are at higher risk of antisocial personality and substance abuse as adults. Stimulants are often effective treatments for aggressive or antisocial behavior in patients with ADHD, but mood stabilizers or atypical antipsychotics may be used to treat explosive aggressive outbursts. Response to stimulants is not affected by comorbid anxiety, but children with ADHD/anxiety disorder may show greater benefit from psychosocial interventions than those with ADHD alone. The degree of prevalence of major depressive disorder (MDD) and bipolar disorder among children with ADHD is controversial, but a subgroup of severely emotionally labile ADHD children who present serious management issues for the clinician clearly exists. Antidepressants may be used in conjunction with stimulants to treat MDD, while mood stabilizers and atypical antipsychotics are often required to treat manic symptoms or aggression. After resolution of the manic episode, stimulant treatment of the comorbid ADHD may be safely undertaken. Recent research suggests that stimulants can be safely used in children with comorbid ADHD and tic disorders, but the addition of anti-tic agents to stimulants is often necessary. Clinicians who work with patients with ADHD should be prepared to deal with a wide range of emotional and behavioral problems beyond the core symptoms of inattention and impulsivity/hyperactivity.     

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

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

Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats

A recent increase in stimulant treatment of adolescents with attention deficit hyperactivity disorder (ADHD) has been documented. Challenges in treating adolescent ADHD with methylphenidate or dextroamphetamine include compliance with frequent dosing, abuse potential and wear-off or rebound effects. Co-morbid anxiety, occurring in at least 30 percent of ADHD youths, is associated with lower rate of response to stimulants. The effective alternatives, tricyclic antidepressants or pemoline, are each associated with rare but serious toxicity. Bupropion has recently proven effective in controlled trials. Other noradrenergic or dopamine-enhancing agents such as venlafaxine and nicotine show some benefit in open trials. The need for more options in pharmacotherapy of ADHD is evidenced by rapid adoption in clinical practice of alternative and adjunctive medication despite lack of controlled research on efficacy and safety. The indications for long-term stimulant treatment of ADHD present some controversy, and highlight a need for more research on safety and efficacy through the lifespan. Thresholds for diagnosis are much lower with DSM than with ICD, and thresholds for treatment are contentious, given the performance-enhancing effects of stimulants in normal students. The endpoint for treatment is unclear, as stimulants are also effective in adult ADHD. Based on short- and intermediate-term studies to date, stimulant medication is clearly more efficacious than cognitive and behavioral strategies for the symptoms of ADHD. Longer term research is needed to determine whether sustained stimulant therapy will reduce the adverse emotional, behavioral and academic consequences of inattention and impulsivity in adolescents and adults.     

The use of stimulants and atomoxetine in adults with comorbid ADHD and bipolar disorder

Introduction: Attention deficit/hyperactivity disorder (ADHD) persists into adulthood in about 50% of the affected children, with high rates of comorbidity with bipolar disorder (BD). Stimulants and atomoxetine (ATX) are effective treatments for ADHD, but their use in adults with comorbid BD (ADHD-BD) has not been extensively studied and may be problematic.

Areas covered: The aim of the paper is to summarize the available literature regarding the use of these medications in ADHD-BD adult patients. Results of randomized-controlled and open-label trials, case reports, and case series are reviewed. We also reviewed data relative to some specific issues of this comorbidity in adults, especially substance use disorder, malingering, and stimulants misuse.

Expert opinion: ADHD-BD may be associated with more severe symptoms, course, and worst outcome of both conditions. The frequent coexistence with alcohol and substance abuse may further complicate treatment management. Stimulants are the most effective medications for ADHD, but their use may be contraindicated in the presence of a comorbid drug abuse or in patients that simulate or exaggerate ADHD symptoms in order to obtain stimulants for diversion or abuse. ATX may be effective in the treatment of ADHD symptoms in BD patients, with a modestly increased risk of (hypo)manic switches and destabilization of the mood disorder when utilized in association with mood stabilizers. In the majority of the cases, a hierarchical approach is desirable, with mood stabilization preceding the treatment of ADHD symptoms. Although systematic trials on the use of stimulants and ATX in ADHD-BD comorbidity in adulthood are necessary, both treatments should be considered possible options to be carefully evaluated once the patient has been stabilized.     

Efficacy and tolerability of pharmacotherapies for attention-deficit hyperactivity disorder in adults

This review examines the evidence regarding the efficacy and tolerability of long- and short-acting stimulant medications, as well as the non-stimulant medications atomoxetine and bupropion in the treatment of adult attention-deficit hyperactivity disorder (ADHD). Effect sizes in adults appear to be of almost the same magnitude as in school-age children when robust doses are used. There are adequate data demonstrating short-term efficacy and safety of medication in ADHD during adulthood but long-term studies are lacking, particularly in view of concerns regarding cardiovascular adverse events. There is some evidence that stimulant medication can improve driving performance in adults with ADHD. The extent to which medication may improve academic, occupational and social functioning in adults with ADHD is unclear, and future research should investigate these outcomes. Medication treatment of adults with ADHD in sports is controversial. Both stimulant and non-stimulant medications seem to be well tolerated. Monitoring of pulse and blood pressure is recommended with these drugs because of their cardiovascular effects. There have been extremely rare case reports of sudden death in adults and children treated with stimulants and atomoxetine, but it is difficult to clearly establish causality. In view of reports of treatment-related suicide-related behaviour with atomoxetine, it is recommended that adults should be observed for agitation, irritability, suicidal thinking, self-harming or unusual behaviour, particularly in the first months of treatment, or after a change of dose. ADHD in adults continues to remain an under-recognized disorder in many parts of the world and there is a lack of specialist clinics for assessment and treatment of adult ADHD. Studies to date have failed to show efficacy of medications in the treatment of ADHD in the substance misuse population. There is little evidence so far to suggest an increased misuse of stimulants or diversion amongst substance misusers; however, data are insufficient to draw firm conclusions. Further work is necessary to evaluate effective treatments in subgroups such as the substance misuse population, those with multiple co-morbidities and different ADHD subtypes.     

Barriers to Implementation of Treatment Guidelines for ADHD in Adults With Substance Use Disorder

Objective: Attention deficit hyperactivity disorder (ADHD) is common among adult patients with a substance use disorder, yet often goes undetected. This is a qualitative study to explore implementation barriers to a guideline developed in Belgium for the recognition and treatment of ADHD in adult patients with substance use disorder and to gain a better understanding of the strategies to overcome these barriers.

Methods: Focus groups were conducted with caregivers and patients to explore experiences with comorbid substance use disorder and ADHD. The barriers reported in these focus groups became the subject of further study in focus groups with addiction professionals (physicians, psychiatrists, and psychologists) who had tried the guideline and with psychiatrists specializing in addiction but without experience with ADHD.

Results: Our analysis revealed a number of barriers to the implementation of this guideline, including lack of information from the family, pressure from patients and caregivers to make an ADHD diagnosis, and the potential for abuse of ADHD medication. Furthermore, diagnostic instruments for ADHD have not been validated in people with substance use disorder. Although patients with ADHD are usually treated in an outpatient setting, patients with ADHD comorbid with substance use disorder are difficult to identify in an outpatient setting for various reasons. Finally, there is a lack of specific ADHD expertise in substance use treatment organizations.

Conclusions: Despite the availability of an approved guideline for recognizing and treating adult ADHD in patients with a substance use disorder, underdiagnosis and inadequate treatment still persist. As in general substance use treatment, medication only plays a supportive role in the treatment of substance use disorder with comorbid ADHD. An integrated approach and further improvements in the competence of practitioners may help to reduce the resistance to diagnosing ADHD in substance use treatment centers. Practitioners who specialize in addiction medicine and therapists without medical education view the problem from different perspectives and therefore each group needs specific information and training. Targeted interventions need to be developed to keep these patients in treatment.     

A qualitative review of issues arising in the use of psycho­stimulant medications in patients with ADHD and co‑morbid substance use disorders

ABSTRACT

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 ADHD 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 ADHD. 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.     

Impact of Central Nervous System Stimulant Medication Use on Growth in Pediatric Populations with Attention-Deficit/Hyperactivity Disorder: A Review

Central nervous system stimulants are a commonly used first-line treatment option for attention-deficit/hyperactivity disorder (ADHD). Stimulants are generally well tolerated, with anorexia and insomnia the most common adverse effects. However, there are some concerns with long-term use of stimulants, such as potential growth delay. Historically, data regarding this long-term adverse effect have been conflicting. In this article, we review the newer data surrounding the effects of central nervous system stimulants on growth parameters in children with ADHD. We conducted a literature search of the PubMed database; only articles using ADHD criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included to ensure the most up-to-date review of literature. Nine articles were identified for relevance and quality and are discussed in this review, describing clinical observations of height and weight of adolescent or pediatric patients receiving stimulant medications for ADHD therapy. In summary, this review points toward potential associations between duration of treatment and higher doses of stimulants with decreased weight and body mass index. Furthermore, this review demonstrates that evidence is still conflicting regarding the relationship between stimulant use and significant height decreases. Future studies with higher quality of evidence are needed to observe this potential adverse effect of stimulants in children and adolescents.     

The burden of untreated ADHD among adults: the role of stimulant medication

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.     

Safety of stimulant treatment in attention deficit hyperactivity disorder: part II

Importance of the field: Attention deficit hyperactivity disorder (ADHD) is the most common childhood psychiatric disorder and in at least 50% of cases persists into adulthood. Treatment of ADHD with stimulants is one of the oldest and most effective pharmacological treatments in psychiatry. Yet, there continues to be controversy over the safety of stimulant medications in the treatment of ADHD.

Areas covered in this review: This paper is a continuation of an earlier paper that reviewed the safety profile of newer stimulant agents, especially in relation to special populations. This part II reviews, through essentially an organ-system approach, the various clinical concerns that have been raised over the safety of stimulant medications. This includes neuropsychiatric, cardiovascular effects on growth and development, and a number of other less common concerns.

What the reader will gain: A thorough review of safety concerns in stimulants that emphasizes clinical information, case reports, open series or controlled trials relating to stimulant use in the treatment of ADHD.

Take home message: While many safety concerns have been raised in the use of stimulants, the vast majority of treatment complications are either quickly reversible or easily manageable with appropriate clinical care. The negative consequences of untreated ADHD clearly outweigh the risks of the stimulant medicines when used in an appropriate and careful manner.     

Preliminary Support for Multidimensional Treatment Foster Care in Reducing Substance Use in Delinquent Boys

This article describes the disparate research findings regarding the effects of stimulant medication in subsequent substance abuse and dependence. A minimum of 4 to 5% of children in the United States will be diagnosed with ADHD; thus it is important for parents to be informed when making decisions about the use of stimulant medication to treat symptoms. Considering the inconsistencies in the literature, it is still difficult to determine the true effects of stimulant medication on drug abuse and dependence in adulthood.