The effect of stimulant treatment for ADHD on later substance abuse and the potential for medication misuse, abuse, and diversion

Attention-deficit/hyperactivity disorder (ADHD) is known to be a strong risk factor for substance use disorders (SUD) in adolescence and in adulthood. Research shows that stimulant treatment does not increase the risk of SUD in adolescents or adults with ADHD but rather that stimulant treatments may have a protective effect. However, 2 in 10 youths with ADHD misuse their medication. Recent evidence suggests that slow uptake of medication in the brain allows for effective treatment without patients experiencing the euphoric qualities of immediate-release agents that lead to abuse or diversion. As a result, extended-release products and different formulations, such as lisdexamfetamine dimesylate (LDX), are less likely to be misused and diverted and may have lower abuse potential.     

Effects of ADHD, conduct disorder, and gender on substance use and abuse in adolescence.

OBJECTIVE: The relationships of attention deficit hyperactivity disorder (ADHD), conduct disorder, and gender to substance abuse were studied in a large population-based sample of adolescent twins. METHOD: Structured interviews were administered to 626 pairs of 17-year-old twins (674 girls and 578 boys) and their mothers to generate lifetime psychiatric diagnoses, and computerized measures of current substance use were obtained. Hierarchical logit analyses were performed to assess the independent effects of ADHD, conduct disorder, and gender on current substance use, frequency of substance use, and DSM-III-R diagnoses of substance use disorders. RESULTS: Conduct disorder was found to increase the risk of substance use and abuse in adolescents regardless of gender. In contrast, independent of its association with conduct disorder, an ADHD diagnosis did not significantly increase the risk of substance use problems. CONCLUSIONS: This study found no significant gender differences in the effects of ADHD and conduct disorder on substance use and abuse, although there was some suggestion that girls with ADHD might be at slightly higher risk than boys for substance abuse. In addition, increased risk of substance abuse among adolescents with conduct disorder may be primarily confined to those with persistent conduct disorder.     

A randomized controlled trial of pemoline for attention-deficit/hyperactivity disorder in substance-abusing adolescents

OBJECTIVE: In adolescents with substance use disorder (SUD), comorbid attention-deficit/hyperactivity disorder (ADHD) is associated with greater severity of substance abuse, conduct problems, and worse treatment outcomes. Although many controlled trials have established the efficacy of psychostimulants, including pemoline, for ADHD in children and adolescents, none have been conducted in adolescents with SUD. This randomized, placebo-controlled trial, conducted between 1996 and 2000, evaluated the safety and efficacy of pemoline on substance abuse and conduct problems. METHOD: Sixty-nine adolescents (aged 13-19) with conduct disorder (CD), SUD, and ADHD were recruited from the community and randomly assigned to a 12-week clinical trial of pemoline (n = 35) or placebo (n = 34), titrated over 4 weeks to a single morning dose of 75 to 112.5 mg as tolerated. RESULTS: Pemoline had greater efficacy than placebo for ADHD as determined by significantly more Clinician's Global Impression-Improvement (CGI-I) ratings of 1 (very much improved) or 2 (much improved) at the study endpoint (n = 69; p <.05). There was also greater reduction in ADHD severity on the parent-rated Conners Hyperactivity-Impulsivity scale in pemoline-treated study completers compared to placebo-treated completers (pemoline, n = 17; placebo, n = 16; p <.01), but no difference between groups in the intent-to-treat analysis (n = 68; p <.13). Substance use did not decline in either group, and there was no difference between groups in baseline to study endpoint change in substance use or CD symptoms. Overall, pemoline was well tolerated, demonstrating a good safety profile and no elevation in liver enzyme levels. CONCLUSIONS: Pemoline was efficacious for ADHD but did not have an impact on CD or substance abuse in the absence of specific treatment for SUD.     

Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention-deficit/hyperactivity disorder and mood disorders

OBJECTIVE: Few studies exist on pharmacological interventions for adolescents with substance use disorders (SUD). To this end, we evaluated the response of bupropion hydrochloride sustained release (SR) in SUD adolescents with comorbid psychopathology (both attention-deficit/ hyperactivity disorder (ADHD) and a mood disorder). Methods: Fourteen adolescent outpatients were treated naturalistically and followed openly for 6 months. Adolescents were rated using the Drug Use Screening Inventory--Revised (DUSI-R), ADHD Symptom Checklist, and the Hamilton Rating Scale for Depression (HAM-D). Clinical Global Impression (CGI) Scale scores were obtained for Substance Abuse, ADHD, Anxiety, and Depression. The ratings were completed at baseline, at month 3, and at the 6-month endpoint. Bupropion SR was initiated at 100 mg once-daily and titrated naturalistically to a maximum dose of 400 mg/day. RESULTS: Of the 14 subjects followed, 13 subjects completed 6 months of treatment. At the 6- month endpoint compared to baseline, treatment with bupropion was associated with clinical and significant reductions in DUSI scores (-39%; p < 0.05), ADHD symptom checklist (-43%; p < 0.001), HAM-D (-76%; p < or = 0.001); and reductions in the CGIs for ADHD (p < or = 0.001), depression (p < or = 0.001), and substance abuse (p < 0.05). The mean daily dose of bupropion SR was 315 mg (in divided doses). No significant adverse events were noted during the follow-up period. CONCLUSIONS: These naturalistic data suggest that bupropion is well tolerated and may be an effective medication for the treatment of substance abusing adolescents with comorbid mood disorders and ADHD.     

Attention-deficit/hyperactivity disorder and substance abuse

Recent investigations of possible associations between attention deficit hyperactivity disorder (ADHD) and substance-use disorders are reviewed. ADHD seems to represent a possible risk factor for developing a substance abuse, up to 50% of patients with on continuing ADHD symptoms from childhood were found to develop a substance-use disorder. Based on possible pathophysiological similarities, especially cocaine and nicotine dependence are of focused interest in adolescents and adults with ADHD. The presence of ADHD may influence adolescent and adult substance-use disorders in different ways: earlier age of onset, higher frequency, longer duration of substance abuse and transition from alcohol-abuse to other substance-use disorders. Possible pharmacological and non-pharmacological therapeutic strategies in patients with ADHD and substance abuse are discussed.     

New medication strategies for comorbid substance use and bipolar affective disorders.

Comorbidity of substance abuse disorders (SUD) with bipolar disorders (BPD) is a serious treatment problem. Childhood BPD can be further complicated by comorbidity with attention-deficit/hyperactivity disorder (ADHD) and later SUD during adolescence. The aim of this article is to review the literature on pharmacotherapies for these patients. Developing the ideal pharmacotherapy for BPD and SUD can be informed by the role of gamma-aminobutyric acid (GABA) in the neurobiology of SUD. This ideal pharmacotherapy would have several key characteristics. These characteristics include treating the BPD, relieving withdrawal symptoms, and preventing relapse to SUD. The ideal medication should have low abuse liability, require infrequent dosing, be well tolerated, and have few side effects. A medication approaching this ideal is the GABA enhancer valproate. Adding atypical antipsychotic agents might not improve valproate's efficacy, but combining GABA medications with selective serotonin reuptake inhibitors holds promise for SUD with depression. Pemoline might be the best option for minimizing the risk of SUD complicating comorbid ADHD with BPD.     

When ADHD and substance use disorders intersect: Relationship and treatment implications

There has been increasing interest in the overlap between attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs). In this report, we describe the developmental relationship between ADHD and SUDs. ADHD alone and in combination with co-occurring psychopathology is a risk factor for the development of SUDs in adulthood. Conversely, approximately one fifth of adults with SUDs have ADHD. Pharmacotherapeutic treatment of ADHD in children reduces the risk for later cigarette smoking and SUDs in adulthood. In contrast, medication treatment alone of adults with ADHD and current SUD is inadequate for both ADHD and SUD. Stimulant diversion continues to be of concern, particularly in older adolescents and young adults.     

The abuse potential of medications for attention-deficit/hyperactivity disorder: Recent advances in our understanding

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder that first presents in childhood and can cause impairment in social, emotional, and academic functioning. First-line treatment of ADHD is pharmacotherapy with stimulant medication. However, significant concerns about stimulants include their potential misuse or abuse. This review updates the reader on recent findings on the abuse potential of stimulants used to treat ADHD. Specific points of interest include the prevalence of misuse, risk factors associated with misuse, and implications of misuse on later substance use disorders.     

Electroencephalographic biofeedback for the treatment of attention-deficit hyperactivity disorder in childhood and adolescence

Considerable scientific effort has been directed at developing effective treatments for attention-deficit hyperactivity disorder (ADHD). Among alternative treatment approaches, electroencephalographic (EEG) biofeedback has gained promising empirical support in recent years. Short-term effects were shown to be comparable to those of stimulant medication at the behavioral and neuropsychological level, leading to significant decreases of inattention, hyperactivity and impulsivity. In addition, EEG biofeedback results in concomitant improvement of neurophysiological patterns. EEG biofeedback may already be used within a multimodal setting, providing affected children and adolescents with a means of learning to counterbalance their ADHD symptoms without side effects. However, there is still a strong need for more empirically and methodologically sound evaluation studies.     

The clinical dilemma of using medications in substance-abusing adolescents and adults with attention-deficit/hyperactivity disorder: what does the literature tell us?

OBJECTIVE: Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are increasingly recognized in clinical practice. The role of pharmacological treatment for ADHD in these comorbid individuals remains unclear. METHODS: A systematic review of the medical literature was conducted through PubMed, supplemented with data from scientific presentations, to evaluate the role of medication treatment of ADHD in substance abusing individuals with ADHD. Meta-analysis was used to evaluate the effects of medication therapy on ADHD and SUD outcomes in general, while specifically addressing trial design, trial duration, retention, class of medication, age group, concurrent psychotherapy, and outcome in both SUD and ADHD domains. RESULTS: Four studies in adolescents and five studies in adults with ADHD plus SUD were identified (two controlled and seven open studies; n = 222 subjects). The standard mean difference (SMD) indicated statistically significant improvements in ADHD and SUD that were not maintained when evaluating controlled studies only. Albeit limited by power, trial duration, retention rate, and age group did not influence outcome. No worsening of SUD or drug-drug interactions were observed in any of the studies. The results could not be accounted for by any single study or by publication bias. CONCLUSION: Treating ADHD pharmacologically in individuals with ADHD plus SUD has a moderate impact on ADHD and SUD that is not observed in controlled trials and does not result in worsening of SUD or adverse interactions specific to SUD. Further controlled trials evaluating the effect of novel combinations of psychotherapy and ADHD pharmacotherapy on SUD relapse in these groups are warranted.     

Validity of structured clinical evaluations in adolescents with conduct and substance problems

OBJECTIVE: To determine discriminative and convergent validity for certain structured diagnostic assessments among adolescents with conduct and substance problems. METHOD: Patients were 87 adolescents (both genders) in treatment for conduct and substance problems. Most controls (n = 85; both genders) came from patients' neighborhoods. Assessments included Diagnostic Interview Schedule for Children, Composite International Diagnostic Instrument-Substance Abuse Module, Child Behavior Checklist, and others. Patients' data guided clinical care. RESULTS: Youths' self-reports significantly discriminated patients from controls in DSM-IVconduct and substance use disorders (CD, SUD) and in numerous associated measures. CD and SUD symptoms correlated strongly. However, some patients apparently minimized symptoms. Youths' self-reports did not discriminate patients from controls in attention-deficit/hyperactivity disorder (ADHD) or major depression (MDD). Parent information raised prevalence rates of ADHD and MDD, which then discriminated patients from controls. However, patients and parents usually disagreed on MDD and ADHD diagnoses. CONCLUSIONS: Despite some dissimulation, patients' self-reports of CD and SUD correlated highly and had superb discriminative validity, making them useful for treatment and research. Self-reports of ADHD and MDD, apparently lacking discriminative validity, are less useful. Parent reports improve these discriminations but present additional problems.     

Neurofeedback Treatment of Two Children with Learning,Attention, Mood,Social, and Developmental Deficits

ABSTRACT

Background. Neurofeedback is biofeedback training of EEG activity through an operant conditioning process by which the individual is trained to increase or inhibit the brain's production of electrical activity in specific frequency ranges. Studies have demonstrated efficacy with a variety of disorders, including attention deficit hyperactivity disorder (ADHD), learning problems, and autistic features. This paper describes the application of neurofeedback in a clinical setting with two complex children who manifested multiple diagnoses, including learning disabilities (LD), ADHD, social deficits, mood disorders, and pervasive developmental disorder (PDD). Both boys had adjusted poorly to school, family, and peers.

Methods. Subjects were referred to the author's clinical practice. They received individualized protocols based on their symptoms and functional impairments. They were administered semi-weekly 20-minute sessions of one-channel neurofeedback training for approximately six months. In both cases symptoms were identified and tracked with a parent rating scale and one case, with the Symptom Assessment-45 Questionnaire (SA-45) also.

Results. Each boy improved in all tracked symptoms without adverse effects. One improved on most measures of the SA-45 with no deterioration on any measure. Functional improvements in academic functioning, home behavior, and peer relationships were indicated.

Conclusions. Neurofeedback was a successful treatment for these two multi-symptomatic and diagnosed boys, whose improvements surpassed the gains made with previous therapies. The advantages of neurofeedback include the relative absence of observable adverse effects, the lack of reliance on medication with its possible side effects and noncompliance, and the possibility of long-term gains without continued intervention.     

Desipramine facilitation of cocaine abstinence in an adolescent.

An adolescent who was simultaneously dependent on cocaine and treated for attention-deficit hyperactivity disorder (ADHD) with dexedrine developed symptoms of severe depression followed by suicidal behavior. The patient was treated for cocaine craving, depression, and ADHD with desipramine on an inpatient adolescent unit for substance abusers with comorbid psychiatric disorder. The Minnesota Cocaine Craving Scale was used to monitor the cocaine craving. Issues about the strategies for the treatment of cocaine craving and the stimulant treatment/abuse dilemma are discussed with a special emphasis on comorbidity in adolescent substance abusers. Suicidal behavior related to cocaine abuse and craving and the application of the cocaine abstinence three phase model to an inpatient setting are illuminated.     

Neurofeedback for Adult Attention-Deficit/Hyperactivity Disorder: Investigation of Slow Cortical Potential Neurofeedback—Preliminary Results

Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, impulsivity, and hyperactivity. Compared to ADHD in children, only a few studies have investigated ADHD in an adult population, and even less have investigated new forms of treatment such as neurofeedback. Neurofeedback has been applied effectively in various areas, especially in the treatment of children with ADHD, and symptom improvements were associated with increased amplitude of the contingent negative variation (CNV). This study investigated if any behavioral and electrophysiological changes reflected in the CNV can be observed after 15 sessions of SCP neurofeedback training. Furthermore, a comparison of CNV amplitude in adults with ADHD and a healthy control group was conducted. Continuous 22-channel EEG was acquired from 10 adults who met DSM–IV criteria for ADHD and 8 matched healthy controls. EEG recordings were collected pre/midtreatment and included resting EEG, P300, and CNV tasks as well as ADHD behavioral questionnaires. The adult ADHD group received 15 sessions of SCP training at Cz (referenced to A1, ground A2). The control group only underwent the EEG recording. After 15 sessions of SCP-training a significant improvement in self-ratings of ADHD symptoms was reported. In addition, a trend in increasing CNV mean amplitude was observed after training. A significant difference in baseline CNV between the adult ADHD group and the healthy control group was observed. These results give a promising outlook to the outcome after the completion of 30 sessions of SCP training. The differences in CNV amplitude between the ADHD group and healthy controls are in line with other studies about adult ADHD and CNV. This supports the idea of impaired self-regulation in adult ADHD. The behavioral improvements and increase in CNV after SCP training suggests that SCP training has a positive effect on adult ADHD symptoms and their origin.     

Childhood stimulant treatment and teen depression: is there a relationship?

Recent preclinical data have raised the possibility that prepubertal treatment of attention-deficit/hyperactivity disorder (ADHD) with stimulant medication might increase risk for later depression. The current longitudinal study investigated whether children with ADHD who were treated with stimulant medication displayed heightened levels of adolescent depression. Adolescents diagnosed with ADHD during childhood who had received a minimum of 1 year of treatment with stimulant medication were compared to adolescents with a childhood history of ADHD who were never treated with stimulants and a demographically matched comparison group on self-reports of depressive symptoms and diagnoses of depressive disorders. Both subgroups with childhood ADHD reported significantly higher dimensional ratings of depression and categorical rates of depressive disorders relative to the comparison group (all p<0.05), yet those who were and were not medicated did not differ from one another. Results indicate that, while childhood ADHD increases risk for adolescent depression, stimulant treatment for ADHD neither heightens nor protects against such risk.     

Attention-deficit/hyperactivity disorder and early-onset substance use disorders

In recent years, there has been an increased recognition of the common comorbidity of attention-deficit/ hyperactivity disorder (ADHD) and substance use disorder (SUD) among adolescents and adults. ADHD can be an important factor in the pathogenesis and maintenance of SUD; moreover, retrospective studies suggest that treating ADHD during childhood may prevent the development of SUD. In addition, treatment of ADHD among adults, and possibly adolescents, with SUD can reduce their risk of relapse. Theoretical mechanisms that may explain the relationship between ADHD and SUD are explored in this paper. Current research and recommended clinical practices related to the diagnosis and treatment of ADHD with SUD in adolescents are discussed as well. More research is needed to definitively assess the effectiveness and safety of medications in this population of youths with ADHD and SUD.     

Substance use disorders among adolescents with bipolar spectrum disorders

Objective: We set out to examine the prevalence and correlates of substance use disorders (SUD) in a large sample of adolescents with bipolar disorder (BP). Methods: Subjects were 249 adolescents ages 12 to 17 years old who fulfilled DSM‐IV criteria for bipolar I disorder [(BPI), n = 154], or bipolar II disorder [(BPII), n = 25], or operationalized criteria for BP not otherwise specified [(BP NOS), n = 70], via the Schedule for Affective Disorders and Schizophrenia for School‐Aged Children (K‐SADS). As part of the multi‐site Course and Outcome of Bipolar Youth study, demographic, clinical, and family history variables were measured via intake clinical interview with the subject and a parent/guardian. Results: The lifetime prevalence of SUD among adolescents with BP was 16% (40/249). Results from univariate analyses indicated that subjects with, as compared to without, SUD were significantly less likely to be living with both biological parents, and that there was significantly greater lifetime prevalence of physical abuse, sexual abuse, suicide attempts, conduct disorder, and posttraumatic stress disorder among subjects with SUD. Subjects with SUD reported significantly greater 12‐month prevalence of trouble with police, and females with SUD reported significantly greater 12‐month prevalence of pregnancy and abortion. Significant predictors of SUD in a logistic regression model included living with both biological parents (lower prevalence), conduct disorder and suicide attempts (increased prevalence). In logistic regression analyses controlling for demographic differences and conduct disorder, SUD remained significantly associated with trouble with police, whereas the association of SUD with pregnancy and abortion was reduced to a statistical trend. The prevalence of SUD was not significantly different among child‐ versus adolescent‐onset BP subjects. Conclusions: SUD among adolescents with BP is associated with profound hazards including suicide attempts, trouble with police, and teenage pregnancy and abortion.     

Attention deficit hyperactivity disorder and substance use disorders

Attention deficit hperactivity disorder (ADHD) is highly prevalent among adolescents who have substance use disorder (SUD). Several lines of evidence, although not conclusive, suggest that ADHD might have an independent effect on SUD liability. It is still to be determined, however, whether this association is mediated by conduct disorder. This article reviews ADHD and SUD.     

Applicability of brain wave biofeedback to substance use disorder in adolescents

Neurofeedback treatment for addictions in adults is probably efficacious, and several reported approaches are described with their indications. Neurofeedback is promising as a treatment modality for adolescents, especially those with stimulant abuse and attention and conduct problems. It is attractive as a medication-free, neurophysiologic, and self-actualizing treatment for a substance-based, brain-impaired and self-defeating disorder. More research, beginning with case reporting, is needed to assess use and efficacy in adolescents.