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.     

Therapeutic challenges of attention-deficit hyperactivity disorder with substance use disorders

Attention-deficit hyperactivity disorder (ADHD), a common neuropsychiatric disorder of childhood, adolescence and adulthood, is frequently comorbid with substance use disorders (SUDs) in both adolescents and adults. This paper will provide an overview of the relationship between ADHD and SUDs and discuss the primary areas of therapeutic challenge in the treatment of individuals with comorbid ADHD and SUDs, including the diagnosis of ADHD in populations with SUDs, selecting appropriate agents for use and prevention of abuse and/or diversion of the therapeutic pharmacological agents used in ADHD treatment. The authors will also provide a discussion on the future of research and treatment in this area and key issues for clinicians.     

Examining the association between attention deficit hyperactivity disorder and substance use disorders: A familial risk analysis

ObjectiveThe main aim of this study was to use familial risk analysis to examine the association between attention deficit hyperactivity disorder (ADHD) and substance use disorders (SUDs) attending to sex effects and the specificity of alcohol and drug use disorder risks.MethodsSubjects were derived from two longitudinal case-control family studies of probands aged 6–17 years with and without DSM-III-R ADHD of both sexes and their first degree relatives followed from childhood onto young adult years. Cox proportional hazard models were used to estimate rates of ADHD and SUDs (any SUD, alcohol dependence, and drug dependence). Logistic regression was used to test both co-segregation and assortative mating.ResultsOur sample included 404 probands (ADHD: 112 boys and 96 girls; Control: 105 boys and 91 girls) and their 1336 relatives. SUDs in probands increased the risk for SUDs in relatives irrespective of ADHD status. The risk for dependence to drug or alcohol in relatives was non-specific. There was evidence that even in the absence of a SUD in the proband, ADHD by itself increased the risk of SUDs in relatives. Proband sex did not moderate the familial relationship between ADHD and SUDs. There was evidence of co-segregation between ADHD and SUD.ConclusionsFindings indicate that various independent pathways are involved in the transmission of SUD in ADHD and that these risks were not moderated by proband sex. ADHD children and siblings should benefit from preventive and early intervention strategies to decrease their elevated risk for developing a SUD.     

Towards Precision Addiction Treatment: New Findings in Co-morbid Substance Use and Attention-Deficit Hyperactivity Disorders

Attention-deficit hyperactivity disorder (ADHD) and substance use disorders (SUDs) may have common etiologies. ADHD is more prevalent in patients with substance use disorders, and this pattern is consistent across different substances of abuse. Individuals with SUDs and ADHD exhibit significant variations in their clinical presentations. The developmental trajectory of ADHD to SUDs is complex: ADHD symptoms appear first in some patients but not in others. Many patients present with a heterogeneous collection of psychiatric and substance use co-morbidities, and these symptoms change over time. ADHD symptom severity is also highly variable, and more severe ADHD symptoms worsen co-morbid SUDs and complicate treatment. New longitudinal studies with innovative methods in high-risk populations and in community-based samples may clarify issues related to patient-treatment matching. When closely monitored, psychostimulant and other adjunct medications can be safely used to treat ADHD in this population, and such treatment may also improve outcome of SUDs. In particular, emerging evidence suggests individual-level tailoring (“precision medicine”) approaches may represent a key pathway to improve clinical outcome.     

Molecular imaging genetics of methylphenidate response in ADHD and substance use comorbidity

Purpose: Attention‐deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. The goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs. Methods: Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc^99m]TRODAT‐1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype. Results: The combination of both DRD4 7‐repeat allele (7R) and homozygosity for the DAT1 10‐repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P ≤ 0.02; R² from 0.50 to 0.56). Conclusions: In patients with ADHD/SUDs, combined DRD4 7R and DAT1 10/10 could index MPH reduced DAT occupancy. This might be important for clinical trials, in terms of better understanding individual variability in treatment response. Synapse 2011. © 2010 Wiley‐Liss, Inc.     

The International ADHD in Substance Use Disorders Prevalence (IASP) study: background,methods and study population

Attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized comorbid condition in subjects with substance use disorders (SUDs). This paper describes the methods and study population of the International ADHD in Substance Use Disorders Prevalence (IASP) study. Objectives of the IASP are to determine the prevalence of ADHD in adult treatment seeking patients with SUD in different countries and SUD populations, determine the reliability and validity of the Adult ADHD Self‐report Scale V 1.1 (ASRS) as ADHD screening instrument in SUD populations, investigate the comorbidity profile of SUD patients with and without ADHD, compare risk factors and protective factors in SUD patients with and without a comorbid diagnosis of ADHD, and increase our knowledge about the relationship between ADHD and the onset and course of SUD. In this cross‐sectional, multi‐centre two stage study, subjects were screened for ADHD with the ASRS, diagnosed with the Conner's Adult ADHD Diagnostic Interview for DSM‐IV (CAADID), and evaluated for SUD, major depression, bipolar disorder, anti social personality disorder and borderline personality disorder. Three thousand five hundred and fifty‐eight subjects from 10 countries were included. Of these 40.9% screened positive for ADHD. This is the largest international study on this population evaluating ADHD and comorbid disorders. Copyright © 2013 John Wiley & Sons, Ltd.     

The Massachusetts General Hospital studies of gender influences on attention-deficit/hyperactivity disorder in youth and relatives.

With the single exception of SUDs, no statistically significant gender-by ADHD interactions were identified in the multiple, outcomes evaluated. These results suggest that with the exception of SUDs, ADHD expresses itself similarly in boys and girls relative to comparison subjects of the same gender, indicating that ADHD-associated impairments are correlates of ADHD in both genders. Gender differences, such as the higher prevalence of symptoms of inattention and lower rates of comorbidity with disruptive behavior disorders, major depression, and learning disability, were identified among the ADHD subjects. Because these differences were caused by the main effects of gender rather than effect modification of ADHD by gender, these findings indicate that girls were at the same relative risk for these adverse outcomes as boys, but that female gender resulted in a different clinical presentation than that affecting boys.The single statistically significant gender-by-ADHD interaction identified was the association between ADHD and SUDs (alcohol or drug abuse or dependence). ADHD in females was a more serious risk factor for SUDsthan it was in males was an unanticipated and surprising finding. In light of ongoing concerns regarding ADHD as a putative risk factor of SUDs [12],this finding may indicate that girls are particularly at risk in early adolescence. Considering that the age of onset of ADHD and SUDs are separated by at least a decade [13.14], this finding would support targeting of substance abuse prevention programs to girls with ADHD.Furthermore, results show that although the combined type of ADHDwas the predominant type in both genders, girls with ADHD were twice as likely as boys with ADHD to manifest the predominantly inattentive type of the disorder. Because symptoms of inattention are more covert than those of hyperactivity and impulsivity, their higher prevalence in girls with ADHDrelative to boys also may explain partially the markedly higher male-to-female ratios in referred versus nonreferred samples of children withADHD.This work also showed that the pattern of transmission of ADHD and comorbid disorders is not influenced by the proband's gender. This is true for the type of disorder transmitted and the degree of risk to relatives. The finding of no interactions between proband ADHD diagnosis and pro-band gender clearly rejects the idea that gender differences in comorbid disorders can be attributed to genes or other familial causes. Prior work had shown this to be true for the diagnosis of ADHD in relatives [15-20].Thus, gender and ADHD appear to be independent risk factors for comorbid psychopathology and for the familial transmission of comorbid psychopathology.In summary, these results suggest that gender was a limited effect modifier of ADHD as a risk factor for ADHD-associated dysfunction in referred children and adolescents. Gender, however, did impact the clinical presentation of the disorder. This was largely because girls with ADHDwere less likely than boys to have comorbid disruptive behavior problems and higher prevalence of symptoms of inattention. Because these features could result in gender-based referral bias unfavorable to girls, more work is needed in referred and nonreferred samples of youth with ADHD to more fully assess this issue. These results also showed similar patterns in the familial transmission of comorbid disorders in families of boys and girls with ADHD. Thus, although ADHD is associated with the familial trans-mission of comorbid disorders, the pattern of transmission is not influenced by the proband's gender. These similar patterns provide further evidence for the idea that, when ADHD is diagnosed in girls it corresponds to the same disorder diagnosed in boys.     

Treatment of substance use disorders in schizophrenia: A unifying neurobiological mechanism?

Substance use disorders (SUDs) are highly prevalent and are associated with poor outcomes among individuals with schizophrenia. Integrating treatments for both disorders improves outcomes. Numerous individual pharmacologic and psychosocial treatments have shown effectiveness at reducing substance use in individuals with a primary diagnosis of schizophrenia and co-occurring substance use disorders. Of these treatments, medications such as certain atypical antipsychotics and naltrexone, and psychosocial treatments such as contingency management, seem to be particularly promising. The development and evaluation of psychopharmacologic and psychosocial treatments for SUDs in schizophrenia would benefit from a better understanding of the neurobiological mechanisms underlying the effectiveness of such treatments. Several theories have been put forth to explain the heightened risk for SUDs in schizophrenia. Of these, brain reward circuitry dysfunction, hypothesized to be etiologically important in SUDs, may be an especially salient target for treatments aimed at the reduction of substance use in patients with schizophrenia. We review current pharmacologic and psychosocial treatments for SUDs in schizophrenia, and theoretical mechanisms underlying the increased risk for SUDs in this population. We propose that effective treatments may in part work through the modulation of brain reward circuitry dysfunction.     

Substance use disorders in an obsessive compulsive disorder clinical sample

The prevalence and clinical correlates of substance use disorders (SUDs) were examined in a clinical sample of Obsessive Compulsive Disorder (OCD). As part of their intake interview into an observational study of the course of OCD, 323 participants completed a battery of standardized measures. Twenty-seven percent of the sample met lifetime criteria for a SUD. 70% of participants with comorbid SUDs reported that OCD preceded SUD onset by at least one year. Younger age at OCD onset and presence of Borderline Personality Disorder (BPD) were each associated with increased risk of alcohol use disorders but only BPD was associated with increased risk of drug use disorders. SUDs affect more than one-quarter of individuals who seek treatment for OCD. Individuals with a juvenile-onset of OCD or comorbid BPD may be especially vulnerable to SUDs. Further research is needed to identify risk factors for SUDs and to better understand their impact on OCD course.     

Impact of ADHD and its treatment on substance abuse in adults

Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance abuse in adults. Additional psychiatric comorbidity increases this risk. ADHD is associated with different characteristics of substance abuse: substance abuse transitions more rapidly to dependence, and lasts longer in adults with ADHD than those without ADHD. Self-medication may be a factor in the high rate of substance abuse in adults with ADHD. While previous concerns arose whether stimulant therapy would increase the ultimate risk for substance abuse, recent studies have indicated that pharmacologic treatment appears to reduce the risk of substance abuse in individuals with ADHD. When treating adults with ADHD and substance abuse, clinicians should assess the relative severity of the substance abuse, the symptoms of ADHD, and any other comorbid disorders. Generally, stabilizing or addressing the substance abuse should be the first priority when treating an adult with substance abuse and ADHD. Treatment for adults with ADHD and substance abuse should include a combination of addiction treatment/psychotherapy and pharmacotherapy. The clinician should begin pharmacotherapy with medications that have little likelihood of diversion or low liability, such as bupropion and atomoxetine, and, if necessary, progress to the stimulants. Careful monitoring of patients during treatment is necessary to ensure compliance with the treatment plan.     

Seizure risk in patients with attention-deficit-hyperactivity disorder treated with atomoxetine

The comorbidity of seizures, epilepsy, and attention-deficit-hyperactivity disorder (ADHD) prompted the examination of whether atomoxetine use for ADHD is associated with an increased risk of seizures. Seizures and seizure-related symptoms were reviewed from two independent Eli Lilly and Company databases: the atomoxetine clinical trials database and the atomoxetine postmarketing spontaneous adverse event database. Review of clinical trial data indicated that the crude incidence rates of seizure adverse events were between 0.1 and 0.2%, and were not significantly different between atomoxetine, placebo, and methylphenidate. Only 2% of the postmarketing spontaneous reports of seizure events were classified as having no clear contributing or confounding factors, and the reporting rate (8 per 100 000 patients exposed) was within the expected range of population-based incidence. Although children with ADHD are increasingly recognized as being at an elevated risk for seizures, treatment of ADHD symptoms with atomoxetine does not appear to elevate this risk further. The shared vulnerability between ADHD and seizure activity should be taken into account when making treatment decisions for populations of children with epilepsy and children with ADHD.     

Outcome of patients with dual diagnosis in secondary psychiatric care

Background: Dual diagnosis (DD) is a common co-morbidity of mental illness and substance use disorder (SUD) and patients with DD are prone to complications. Better knowledge on the outcome, mortality and management of patients with DD in usual secondary psychiatric care would help to inform improved treatment strategies in the future. Aims: To explore the functional outcome and mortality of patients with DD receiving psychiatric treatment. To assess the recognition of substance use disorders (SUDs) in terms of diagnosis, and the associations of clinically diagnosed SUDs with treatment-related variables. Methods: The sample of 330 patients was collected by screening all currently treated patients with the Alcohol Use Disorders Identification Test (AUDIT) and a question about other substances used. The inclusion criteria were AUDIT?>7 and/or reported use of other substances during the preceding 12 months. The Global Assessment of Functioning scale was used to assess functional outcomes during a 2-year follow-up. Information concerning treatment and patient characteristics was collected retrospectively. Results: Level of functioning remained stable among all study patients during follow-up. The mortality rate was not increased. Effective medication use was associated with improved functional outcomes. SUDs were underdiagnosed. A clinically diagnosed SUD seemed to have an impact on the regularity of appointments and the doses of prescribed medications. Conclusions: Given our results suggesting a stable level of functioning, patients with DD appear to be well managed within secondary psychiatric care. Attention should be paid to more precise diagnostics of SUDs and to effective use of medication.     

The effect of comorbid substance use disorders on treatment outcome for anxiety disorders

This study examined the impact of concurrent substance use disorders (SUDs) on outcomes for psychotherapy targeting anxiety disorders. Study 1 (N=484) sought to determine the prevalence of SUDs in a sample referred to a community anxiety disorders clinic, as well as the impact of comorbid SUDs on outcomes for a subsample (n=200) completing cognitive behavior therapy (CBT). Around one-quarter (22-29%) of patients with one or two anxiety disorders met criteria for at least one SUD, but this rate was substantially higher (46%) for patients with three anxiety disorders. Concurrent SUDs were associated with higher levels of anxiety but not depression or stress, compared to those without a SUD. However, concurrent SUDs did not moderate treatment outcomes. Study 2 (N=103) focused on the impact of alcohol use on diagnosis-specific symptom measures and generic measures of distress and disability, following a course of CBT for panic disorder or social phobia. Pre-treatment alcohol use did not predict changes in panic symptoms, performance anxiety, distress, or disability, but it did predict changes in social interaction anxiety. Problem drinking per se did not have any predictive utility in terms of treatment outcome. These findings suggest that clinicians treating patients for a primary anxiety disorder and concurrent SUD can be relatively optimistic about treatment outcomes.     

Substance use disorders in bipolar disorder: An update

Substance use disorders (SUDs) commonly co-occur during the course of bipolar type I disorder, and they can negatively affect illness outcome. This paper reviews recent research examining SUDs in bipolar disorder. These studies confirmed the high prevalence rate of SUDs but found that they are less common in younger patients (< age 17 years). Two new longitudinal studies suggest that a co-occurring SUD worsens the prognosis of bipolar disorder and leads to more affective symptoms and suicide attempts. Two new studies have examined the treatment of bipolar patients with a comorbid SUD. These studies suggest that valproate (as an adjunct to lithium) and aripiprazole may be useful in the treatment of the affective symptoms of bipolar patients with a comorbid SUD and may also help with the treatment of the SUD.     

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.     

Prevalence of psychopathology in bipolar high-risk offspring and siblings: a meta-analysis

This meta-analysis aimed to update existing data on the comparison of prevalence rates of psychopathology primarily among offspring with at least one parent with bipolar disorder (BD) and offspring of parents without psychiatric illness. Seventeen studies were derived from a systematic search of PsychInfo, Medline, Scopus and Embase. Inclusion criteria were use of a control offspring group, standardized diagnostic procedures and reporting of clear frequency data. Risk of psychopathology was estimated by aggregating frequency data from selected studies. Compared to control offspring, high-risk BD offspring are nine times more likely to have a bipolar-type disorder, almost two and a half times more likely to develop a non-BD affective disorder and over two times more likely to develop at least one anxiety disorder. High-risk offspring also showed a significant increased risk of other non-mood psychopathology such as attention deficit hyperactivity disorder (ADHD), any type of behavioral disorder and substance use disorder (SUDs). Risk of developing a broad range of affective and non-affective psychopathology is significantly higher in high-risk BD offspring. Identifying clinical presentations of this genetically high-risk cohort is important in establishing appropriate preventative treatment.     

Diagnostic controversies in adult attention deficit hyperactivity disorder

OBJECTIVE: While it is increasingly recognized that attention deficit hyperactivity disorder (ADHD) persists into adulthood, there is no consensus on diagnostic criteria for adult ADHD. In this article the authors describe and contrast competing approaches for diagnosis of adult ADHD used in clinical and research practice. METHOD: The authors review the Wender Utah criteria, DSM criteria, and laboratory assessment strategies for adult ADHD. Advantages and disadvantages of each approach are described, and recommendations are made as a basis for clinical assessment and future research. RESULTS: Both the Wender Utah criteria and DSM-based approaches identify significantly impaired ADHD adults with neurocognitive, biological, and treatment response patterns similar to pediatric ADHD patients. The Wender Utah criteria established the need for retrospective childhood diagnosis and recognize developmental differences in adult symptom expression. The Wender Utah criteria fail to identify patients with predominantly inattentive symptoms, exclude some patients with significant comorbid psychopathology, and diverge significantly from the DSM conception of ADHD. The DSM criteria have never been validated in adults, do not include developmentally appropriate symptoms and thresholds for adults, and fail to identify some significantly impaired adults who are likely to benefit from treatment. There are insufficient scientific data to justify use of laboratory assessment measures, including neuropsychological tests and brain imaging, in diagnosing adult ADHD. CONCLUSIONS: Adult ADHD remains a clinical diagnosis. Clinicians should be flexible in application of the current ADHD criteria to adults. Additional research is required to validate adult diagnostic criteria.     

Psychosis in a cocaine-dependent patient with ADHD during treatment with methylphenidate

Objective

The objective was to report a case of experienced psychosis during the treatment with methylphenidate (MPH) in a cocaine-dependent adult treated for attention-deficit/hyperactivity disorder (ADHD) with comorbid cocaine dependence.

Conclusion

ADHD is a frequent comorbidity in substance use disorder (SUD) patients. MPH may be effective in treating ADHD symptoms in SUD patients, thus preventing possible adverse outcomes. Cocaine-induced psychosis may be a risk factor for development of psychosis in the presence of a concurrent treatment with MPH.     

National Institutes of Health Consensus Development Conference Statement: diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is a commonly diagnosed behavioral disorder of childhood that represents a costly major public health problem. Despite progress, ADHD and its treatment have remained controversial, especially the use of psychostimulants for both short- and long-term treatment. Although an independent diagnostic test for ADHD does not exist, there is evidence supporting the validity of the disorder. Studies (primarily short-term, approximately 3 months), including randomized clinical trials, have established the efficacy of stimulants and psychosocial treatments for alleviating the symptoms of ADHD and associated aggressiveness and have indicated that stimulants are more effective than psychosocial therapies in treating these symptoms. Because of the lack of consistent improvement beyond the core symptoms and the paucity of long-term studies (beyond 14 months), there is a need for longer-term studies with drugs and behavioral modalities and their combination. Although trials are under way, conclusive recommendations concerning treatment for the long term cannot be made at present. There are wide variations in the use of psychostimulants across communities and physicians, suggesting no consensus regarding which ADHD patients should be treated with psychostimulants, and thus the need for improved assessment, treatment, and follow-up. Furthermore, the lack of insurance coverage, preventing the appropriate diagnosis and treatment of ADHD, and the lack of integration with educational services are substantial barriers and represent considerable long-term costs for society. Finally, after years of clinical research and experience with ADHD, knowledge about the cause or causes of ADHD remain largely speculative. Consequently, there are no documented strategies for the prevention of ADHD.     

Substance use disorders among older adults: A review of randomized controlled pharmacotherapy trials

Substance use disorders (SUDs) are a growing problem among older adults. Acamprosate, disulfiram, and naltrexone are United States Food and Drug Administration (referred to as FDA) approved for the treatment of alcohol use disorder, and buprenorphine is approved for the treatment of opiate use disorder among adults. However, the data on the use of these medications for the treatment of SUDs among older adults are unclear from randomized controlled trials (referred to as RCTs). A review of the literature indicates that there are only two RCTs that evaluated the use of pharmacologic agents for SUDs among older adults (≥ 50 years). One trial evaluated the use of naltrexone when compared to placebo for the treatment of alcohol use disorder among individuals, 50-70 years in age. The other trial evaluated the use of naltrexone or placebo as adjuncts with sertraline in the treatment of alcohol use disorder among individuals older than 55 years in age. Both trials indicated that the use of naltrexone reduced the rates of relapse among older adults with alcohol use disorder. However, we did not identify any RCTs that studied the use of buprenorphine, acamprosate, or disulfiram for SUDs among older adults. Based on available evidence, it would be safe to conclude that limited data indicate some efficacy for naltrexone in the treatment of alcohol use disorder among older adults. However, data from controlled trials on the use of other medications that are FDA approved for the treatment of SUDs among younger adults are nonexistent among older adults with SUDs.