Treatment Controversies in Adult ADHD.

Abstract

Back to table of contents Previous article Next article Treatment in PsychiatryFull AccessTreatment Controversies in Adult ADHDJames J. McGough, M.D., M.S.James J. McGoughSearch for more papers by this author, M.D., M.S.Published Online:1 Oct 2016https://doi.org/10.1176/appi.ajp.2016.15091207AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail A 32-year-old man is evaluated for a chief complaint of depression with associated marital and work-related difficultiesAfter receiving a negative employment review and incurring his wife’s anger over his poor management of family finances, “Mr. A,” a 32-year-old married salesman, schedules an evaluation for feelings of depression, poor work performance, and increasing marital stress.Mr. A’s primary job responsibilities include identifying potential clients and facilitating interest in his company’s products. Early in his employment, Mr. A completed several large deals that led to significant salary bonuses and high expectations for his future with the company. However, he was unable to maintain this success. Over several months, he became increasingly bored with day-to-day work demands and was often late to meetings, lacked motivation to follow-up with new clients, and was negligent in completing paperwork. Mr. A’s low productivity led to salary decreases with concomitant difficulties meeting financial obligations at home. His wife was furious that they were unable to save money to buy a house and was further irritated after learning that Mr. A repeatedly failed to pay monthly bills.Mr. A’s physician asks him to complete a medical history and other self-report forms prior to his initial appointment. Mr. A reports no relevant personal medical history, but various family members were diagnosed with depression, substance abuse, and learning disabilities. On the Beck Depression Inventory, Mr. A’s score is 18, suggestive of mild clinical depression. On part A of the Adult ADHD Self-Report Scale (1), he endorses five symptoms, indicating a need for further assessment for attention deficit hyperactivity disorder (ADHD).History of Presenting IllnessFor at least 2 years, Mr. A has felt “down” and depressed at work. Related difficulties include low energy, irritability, poor concentration, indecision, and an inability to get things done. Initially, these feelings were limited to work, but, in tandem with increasing marital stress, he became progressively more depressed and irritable at home. He denies appetite changes. Mr. A has long-standing difficulties falling asleep, and he uses marijuana to relax before bedtime several times a week. He remains interested in sex, but his wife’s general hostility had led to a lower frequency of sexual activity. He denies any history of suicidality. On questioning, he insists that his depression is related to work and that both his mood and his marital situation would improve if he could improve his job performance.While discussing the Adult ADHD Self-Report Scale, Mr. A acknowledges lifelong difficulties with being easily distracted and particular problems getting his mind back on task after an interruption. He recalls being considered an intelligent student by his grade school teachers but having increasing academic difficulties in later grades as his schoolwork become more demanding. In response to questioning, Mr. A remembers often being in trouble with his second grade teacher for disrupting class and getting out of his seat frequently. Problems with overactivity and impulsivity diminished in high school, but feelings of internal restlessness and agitation continued. Mr. A endorses long-standing problems with inattention, organization, motivation, forgetfulness, and completing work, which had a negative impact on both his academic performance and his current work performance. At a second assessment interview, Mr. A’s wife describes considerable frustration over his impulsive decision making, organizational difficulties, and forgetfulness.ConceptualizationWhile many adults request ADHD evaluations directly, others commonly request mental health services for other complaints. Given time constraints in initial evaluations, self-report forms completed prior to the first appointment efficiently collect clinical information and help direct clinical inquiry beyond the patient’s chief complaint. Routine ADHD screening is particularly useful given the disorder’s high prevalence and common co-occurrence with other psychiatric conditions.Mr. A suffers from long-standing ADHD symptoms starting in early grade school, a history of related impairments in numerous functional domains, a current number of ADHD symptoms that exceeds the threshold for diagnosis, and several other clinical features, such as poor motivation and time management, that are frequently exhibited by adults with the disorder. Mr. A’s wife confirmed the presence of several symptoms after she joined the evaluation. Mr. A additionally meets criteria for mild depression. With comorbid ADHD and depression, the general recommendation is to direct initial therapy toward the most impairing condition. The presence of other suggested psychiatric conditions, particularly anxiety and substance use disorders, merits further investigation.TreatmentAfter receiving initial psychoeducation about ADHD and related conditions, the recommended treatment options for Mr. A include initial titration of a stimulant to address his ADHD symptoms, initiation of a selective serotonin reuptake inhibitor (SSRI) to treat his depressive symptoms, or use of bupropion monotherapy to address both his ADHD symptoms and his depressive symptoms. In considering these options, Mr. A decides that ADHD is the main cause of his work and marital difficulties, and his preference is to begin stimulant treatment. Mr. A’s physician proposes an initial titration with a once-daily extended-release stimulant approved for adult ADHD. He instructs Mr. A to take low, medium, and high doses of the selected stimulant, each for 5 consecutive days, and to contact him if any untenable side effects emerge. At follow-up 3 weeks later, Mr. A reports no side effects at the low dose, noticeable improvement in attention, distractibility, and work output at the medium dose, and mildly unpleasant restlessness at the high dose. He further reports that the positive effects seemed to wear off about 8 hours after he took the medication. The clinician recommends a 1-month trial at the medium dose, and he adds an immediate-release, short-acting formulation of the same medication for afternoon use, at a dose selected to maintain an ascending pharmacokinetic profile into early evening hours. At follow-up, Mr. A reports consistent reductions in ADHD symptoms and markedly increased work productivity. Both his employer and his wife note positive changes. Given this response, the clinician provides Mr. A with 90-day medication prescriptions and plans for follow-ups every 3 months.Although his ADHD symptoms dramatically improve with medication, Mr. A has ongoing difficulties with organization and time management. He begins cognitive-behavioral group therapy to address these problems, as well as a brief period of marital counseling with his wife. These interventions prove helpful, but after 6 months Mr. A notes persistent low mood, irritability, and sleep disturbance. An SSRI is added to his stimulant regimen to address residual depression.Early conceptualizations of attention deficit hyperactivity disorder (ADHD) viewed it as a developmental delay that was generally outgrown by adolescence (2). Twenty years ago, DSM-IV maintained that most ADHD symptoms attenuated by late adolescence, such that ADHD persisted in only a minority of adults. Ongoing research challenged these assumptions and established that ADHD is a common adult disorder with significant personal and societal consequences (3–6). Studies in genetics and neuroimaging demonstrate the disorder’s biological continuity across the lifespan (7–9). Longitudinally followed cohorts demonstrate symptom persistence with associated impairments in 60%–70% of pediatric cases (10). Current worldwide estimates of the prevalence of adult ADHD range between 4% and 5% (11, 12).In a review examining limitations and controversies surrounding the application of ADHD diagnostic criteria to adults (13), the most salient concerns included 1) reliance on ADHD symptoms derived from field trials in school-age children and failure to examine potential symptoms more developmentally appropriate for adults; 2) a diagnostic threshold of six symptoms derived from the same field trials, which restricted adult diagnosis to individuals with much greater levels of functional impairment compared with same-aged adults than required for children with the diagnosis; 3) insistence on symptom onset with associated impairments before age 7—often difficult to establish retrospectively; and 4) unclear boundaries between ADHD and other common adult conditions, particularly mood and anxiety disorders.Revisions in DSM-5 addressed many of these concerns. Notable changes included decreasing the number of required inattentive or hyperactive/impulsive symptoms from six to five for individuals age 17 or older, increasing the required age at symptom onset from 7 years to 12 years, dropping the requirement for early onset of impairment, and expanding text descriptions of symptom expression and functional difficulties commonly seen in adults. Previous objections to the validity of adult ADHD have largely dissipated.Despite wide acknowledgment that ADHD occurs in adults and a plethora of studies available to guide evidence-based clinical management, only a minority of adults with ADHD receive appropriate therapy. One report estimated that only 10% of adults with ADHD in the United States received treatment during the previous year (12), suggesting that up to 9 million symptomatic adults were not receiving proper care (14). Two broad areas of controversy contribute to this disparity. First, most clinicians fail to diagnose adult ADHD properly, as assessment is confounded both by high rates of psychopathology comorbid with ADHD and by a failure to identify ADHD when it co-occurs with better-recognized disorders. Second, ongoing apprehension about possible malingering, fears that medications, notably psychostimulants, will be abused or misused, and reluctance to prescribe controlled medications for individuals with past or current substance use disorders add to clinician discomfort regarding ADHD diagnosis and treatment.Assessment DifficultiesA major barrier to adult ADHD treatment arises from the failure of treating clinicians to recognize the disorder (15, 16). Between 17% and 22% of psychiatric outpatients suffer from undiagnosed ADHD (17). In a survey, only 8% of primary care practitioners and 28% of psychiatrists described themselves as “extremely confident” in making an adult ADHD diagnosis (18). In primary care settings, the major impediment to proper assessment is a lack of clinical experience, with most physicians having had little, if any, formal ADHD training (19). Among psychiatrists, the greatest obstacle to diagnosis is failure to differentiate ADHD from other conditions (18), likely reflecting the lack of emphasis given to ADHD in general psychiatry residency programs and subsequently by most adult practitioners.The nonspecificity of many ADHD symptoms, along with their high overlap with commonly comorbid conditions, highlights the necessity of an informed and nuanced approach to diagnostic assessment (16, 20). Adults with ADHD have high lifetime rates of additional psychopathology, with estimates of depression, anxiety, and substance use disorders at 38%, 47%, and 15%, respectively (12). Conversely, among adults in treatment for other conditions, undiagnosed ADHD is estimated to occur in 13% of those with mood disorders, 10% of those with anxiety disorders, and 11% of those with substance use disorders (12). Unlike child assessments, which rely heavily on parental and other third-party informants, adult evaluations are primarily based on patient self-report (19). Adults more commonly raise complaints related to perceived depression or anxiety, and clinicians, who are generally more experienced in managing these disorders, focus on problems they are more familiar with in assigning diagnoses (18). Among both general practitioners and psychiatrists, the failure to identify adult ADHD is further confounded by the absence of routine screening, either with self-report questionnaires or as part of the general psychiatric review of symptoms (1, 21).Validated adult ADHD screening tools are widely available and can reveal a need for more detailed diagnostic inquiry (14, 22). Confirmation of the ADHD diagnosis, as well as differentiation from or recognition of other psychiatric disorders, requires a comprehensive diagnostic interview (23, 24). ADHD remains a clinical diagnosis based on history. An adult history suggestive of ADHD should include reports of symptoms occurring continuously from childhood that have led to various impairments over time in multiple life domains. Episodic symptoms, or those with later ages at onset, are more suggestive of other disorders. Concerns have been raised about clinical differentiation of long-standing ADHD versus early dementia in middle-aged adults, as patterns of cognitive dysfunction in both groups share similarities (25). Although additional research is required, it would be expected that a history of long-standing symptoms and related impairments is more consistent with ADHD, while recent onset of progressive memory problems and functional losses suggests incipient dementia.Neuropsychological testing reveals group differences in adults with and without ADHD on measures of executive functioning, working memory, processing speed, and sustained attention (26). However, no specific cognitive profile for ADHD has been established (27). While not useful for making an ADHD diagnosis, such testing can play a role in quantifying levels of impairment to provide a basis for academic and other accommodations (24).A second barrier to appropriate treatment is a persistent concern among clinicians that individuals can easily fake or exaggerate ADHD symptoms (28). Notable reasons for faking ADHD include obtaining controlled prescription medications that may be used for performance enhancement, recreation, or sale; the availability of academic and other accommodations, such as increased time on standardized tests, note-taking services, the option of taking tests or working in preferred quiet areas, and modified coursework or employment responsibilities (29). Several small investigations proposed the inclusion of various cognitive measures during ADHD assessment to assess motivation and likelihood of feigning symptoms (30–32), but these approaches have not been widely implemented. One study found that participants who had been instructed to “fake” ADHD had much higher self-report symptom scores and lower cognitive performance scores than those with known ADHD or nonclinical control subjects (28). This suggests that clinicians should be particularly wary of adults complaining of extreme levels of ADHD symptoms who lack a prior childhood diagnosis and objective corroboration of long-standing ADHD-related difficulties.Treatment ConsiderationsEvidence-based treatments for adult ADHD include medication management and various forms of cognitive-behavioral therapy (CBT) (19, 21, 23, 24). As with children and adolescents, the safety and efficacy of ADHD medications has been demonstrated in numerous randomized placebo-controlled trials, with adult treatment effect sizes (Cohen’s d) ranging from 0.7 to 0.9 for stimulants and 0.4 to 0.6 for atomoxetine (33, 34). Multiple controlled trials have similarly demonstrated the efficacy of CBT, whether administered individually, in groups, or via the Internet (35, 36). While long-term benefits of academic or occupational accommodations have not been systematically examined, they are routinely employed and are felt to be useful anecdotally (37). Other interventions, including ADHD coaching (38), dialectical behavioral therapy (39), and mindfulness-based therapies (40), appear to be helpful to some patients but lack sufficient scientific evidence to support recommendations for routine use.Commonly used medications for adult ADHD are summarized in Table 1 (24, 34). These include both formulations approved by the U.S. Food and Drug Administration (FDA) for ADHD in adults, notably extended-release stimulants and the nonstimulant atomoxetine, and medications approved in children and used off-label in adults, such as the extended-release alpha-2 agonists. Other agents with catecholaminergic activity, such as bupropion, modafinil, and tricyclic antidepressants, have various levels of established efficacy in randomized controlled trials (21) and are preferred by clinicians who are reluctant to prescribe stimulants, but none of these agents has FDA approval as an ADHD medication in any age group. Consensus treatment guidelines, based on experts’ reviews of available evidence, are available for ADHD in children and adolescents (41) as well as in adults (21). These guidelines generally prioritize treatments based on 1) FDA approval, 2) treatment effect sizes, and 3) other literature and clinical trials supporting the efficacy and safety of off-label therapies. For uncomplicated ADHD, absent any contraindications or comorbidity, the general recommendation is to initiate a stimulant trial and to determine optimal medication and dosing, although many clinicians decline to follow this approach because of concerns about malingering and potential drug misuse, as described previously. Broadly, both amphetamine and methylphenidate formulations have large ADHD treatment effects, similar tolerability profiles, and similar patient response rates (42). Some individuals exhibit a preferential response to one stimulant group or the other, which can only be determined with prospective clinical titration. Since individuals both with and without ADHD can experience improved attention and decreased restlessness while taking stimulants (43), medication response is not a basis for diagnosing the disorder.TABLE 1. Commonly Used Medications for Adult ADHDaMedicationEstimated Efficacy (hours)Initial Titration (5–7 days at each dose)Maximum Recommended Total Daily DosebFDA-approved stimulantsDexmethylphenidate, extended release (Focalin XR)8–1210, 15, 20, 25, 30, 35, 40 mg/day40 mgMethylphenidate, extended release (Concerta)8–1218, 36, 54, 72 mg/day108 mgMethylphenidate, biphasic extended release (Metadate CD)6–810, 20, 30, 40, 50, 60 mg/day80 mgMethylphenidate, extended release (Ritalin LA)6–820, 30, 40 mg/day80 mgMixed amphetamine salts, extended release (Adderall XR)8–1210, 20, 30 mg/day40 mgLisdexamfetamine (Vyvanse)8–1230, 50, 70 mg/day70 mgDexmethylphenidate, immediate release (Focalin)4–62.5, 5, 10 mg b.i.d.40 mgMethylphenidate, immediate release (Ritalin)3–45, 10, 15, 20 mg b.i.d. or t.i.d.80 mgMixed amphetamine salts, immediate release (Adderall)4–65, 10, 15, 20 mg b.i.d.40 mgFDA-approved nonstimulantsAtomoxetine (Strattera)2440 mg/day for 7 days, then 80 mg/day100 mgClonidine, extended release (Kapvay)c8–120.1 mg/day at bedtime, then add 0.1 mg each week in a twice daily regimen0.4 mgGuanfacine, extended release (Intuniv)c241 mg/day, then increase 1 mg/day each week4 mgaADHD=attention deficit hyperactivity disorder; FDA=Food and Drug Administration.bMay exceed FDA labeling, based on published studies; includes total of extended- and immediate-release used daily.cNot FDA approved for ADHD treatment in adults, but approved in children.TABLE 1. Commonly Used Medications for Adult ADHDaEnlarge tableInitial stimulant selection is based on numerous factors, including patient preference, insurance coverage, availability, and desired duration of effect (24). Extended-release and prodrug formulations may be preferred for single daily dosing, increased adherence, and decreased risk of abuse and misuse, but some clinicians prefer to titrate initially with short-acting agents. Following a simple approach, clinicians prescribe standard low, medium, and high doses of the selected stimulant for 5–7 consecutive days each and direct patients to note responses and to contact the clinician if problems emerge. Patient feedback reviewed at the follow-up visit provides the basis for selecting an optimal dose that balances symptom relief with tolerability. If the medication proves to be unacceptable, it is recommended that the trial be repeated with a second stimulant selected from the alternative group. Once an effective medication and dose are identified, a second dose or a complementary dose of a short-acting form can be added to achieve the required duration of effect. With appropriate monitoring, total daily doses that slightly exceed FDA labeling are sometimes required to optimize response. After failure of two stimulant trials, or if stimulants are contraindicated, treatment with atomoxetine, also FDA approved for adults, is generally the next step. In adults, an initial dosage of 40 mg/day of atomoxetine for at least a week, followed by an increase to 80 mg/day, minimizes the risk of side effects. Compared with stimulants, response to atomoxetine is more gradual and can take several weeks at full dosing to achieve maximum effects. Once an optimal medication regimen is agreed upon, follow-up visits should be scheduled at least every 3 months to remain compliant with Drug Enforcement Agency regulations for schedule II prescriptions and to promote ongoing treatment adherence. Careful documentation of diagnosis, target symptoms and response, and prescription refills is essential to responsible practice.Although based on limited research performed mostly in youths, available guidelines further inform management of ADHD and co-occurring disorders. Two approaches are described for comorbid anxiety. Stimulant monotherapy can be initiated with an expectation that ADHD symptoms and, in some individuals, anxiety will be sufficiently reduced. If anxiety persists, a selective serotonin reuptake inhibitor (SSRI) can be safely added. Alternatively, atomoxetine monotherapy, shown to reduce both ADHD and anxiety, can be employed, although the medication is not FDA approved for anxiety. With comorbid depression, clinicians must determine which disorder is more impairing. With mild to moderate depression, one option again is to initiate stimulant monotherapy and subsequently add antidepressant treatment for residual mood symptoms. With moderate to severe depression, or when mood symptoms appear to cause greater difficulties, antidepressant monotherapy is the preferred choice, followed with stimulant augmentation if necessary for persistent ADHD symptoms. Some clinicians, in the interest of maintaining monotherapy, choose to treat ADHD and comorbid depression with bupropion, which has demonstrated efficacy for both conditions. This approach requires off-label bupropion use for ADHD. No trials have been conducted to compare bupropion and the combination of a stimulant and an antidepressant for ADHD and comorbid depression. In individuals with bipolar disorder, stimulants have been safely added to lithium or divalproex once euthymia is achieved. While careful monitoring for exacerbations of mania or psychosis is essential, stimulants do not appear to increase the risk of recurrence of bipolar symptoms, provided mood-stabilizing agents are maintained (44).There are particular concerns about treatment of ADHD with co-occurring substance use, and no consensus guidelines are available for this comorbidity (45). Given that recreational drug use, particularly with alcohol and marijuana, is normative among nonclinical adults, there is little justification for denying ADHD treatment to those with intermittent nonimpairing use. With more frequent and clinically meaningful use, concerns arise over potentially harmful drug interactions and potential worsening of underlying substance use difficulties. Both stimulants and atomoxetine have successfully decreased ADHD symptoms even while patients actively used recreational drugs and alcohol (46). Available research suggests that ADHD medications used concurrently with recreational drugs neither worsen nor improve the underlying substance use disorder (47). The decision to provide ADHD pharmacotherapy follows careful assessment of the type, patterns, frequency, and consequences of concurrent substance use. Nonstimulant treatments, including atomoxetine or off-label use of bupropion, provide appealing alternatives when co-occurring substance use is of major concern. With heavy use or dependence, implementation of structured approaches to substance abuse treatment, including evidence-based therapies and medication, if necessary, and maintenance of some period of sobriety are recommended before an attempt at managing ADHD is made (48).Related difficulties pertain to medication diversion and misuse, estimated to occur in 2%–14% of college students (49). Most misuse is motivated by attempts to enhance academic performance, although 30% is recreational, to obtain euphoria. Less commonly, stimulants are misused for weight control. Misuse for academic purposes is highest among white male students attending academically competitive colleges who are in fraternities, are in academic distress, and have past histories of conduct-disordered behaviors and recreational drug, alcohol, and nicotine use (49). No clear guidelines exist for addressing potential misuse. In groups at highest risk, clinicians should preferentially consider extended-release or prodrug stimulants or nonstimulant options. Clinicians should also routinely counsel patients on the need to safeguard medications and obtain commitments that prescriptions will not be diverted to others. Careful record keeping and insistence on regular clinic follow-up visits are likewise essential.ConclusionsAdult ADHD, a common condition causing significant functional difficulties, remains largely undertreated despite the availability of safe and effective evidence-based therapies. Identification and proper diagnosis of individuals with ADHD is enhanced by incorporating routine screening, either with self-report measures or direct questioning, into initial mental health assessments. Concerns about malingering are best addressed with careful history taking and confirmation of symptom-related impairments by third-party sources. Potential misuse of stimulant medications or exacerbation of associated substance use can be minimized by appropriate clinical monitoring and careful documentation of clinical care. Alternatively, nonstimulant options are available when stimulant treatment is clinically contraindicated. Typically, risks associated with ADHD treatment are far outweighed by potential benefits.From the Division of Child and Adolescent Psychiatry, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles.Address correspondence to Dr. McGough ([email protected]).Dr. McGough has received grant or research support from NeuroSigma, NIH, Purdue Pharma, and Shire; he has served as a consultant for Akili Interactive, Merck, and Neurovance and has served on a data safety monitoring board for Sunovion; he receives royalties from Oxford University Press.References1 Faraone SV, Spencer TJ, Montano CB, et al.: Attention-deficit/hyperactivity disorder in adults: a survey of current practice in psychiatry and primary care. Arch Intern Med 2004; 164:1221–1226Crossref, Medline, Google Scholar2 Laufer MW, Denhoff E: Hyperkinetic behavior syndrome in children. J Pediatr 1957; 50:463–474Crossref, Medline, Google Scholar3 Barkley RA, Fischer M, Smallish L, et al.: Young adult outcome of hyperactive children: adaptive functioning in major life activities. J Am Acad Child Adolesc Psychiatry 2006; 45:192–202Crossref, Medline, Google Scholar4 Biederman J, Petty CR, Fried R, et al.: Educational and occupational underattainment in adults with attention-deficit/hyperactivity disorder: a controlled study. J Clin Psychiatry 2008; 69:1217–1222Crossref, Medline, Google Scholar5 Doshi JA, Hodgkins P, Kahle J, et al.: Economic impact of childhood and adult attention-deficit/hyperactivity disorder in the United States. J Am Acad Child Adolesc Psychiatry 2012; 51:990–1002.e2Crossref, Medline, Google Scholar6 Spencer TJ, Faraone SV, Tarko L, et al.: Attention-deficit/hyperactivity disorder and adverse health outcomes in adults. J Nerv Ment Dis 2014; 202:725–731Crossref, Medline, Google Scholar7 Faraone SV: Advances in the genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 2014; 76:599–600Crossref, Medline, Google Scholar8 Franke B, Faraone SV, Asherson P, et al.: The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry 2012; 17:960–987Crossref, Medline, Google Scholar9 Friedman LA, Rapoport JL: Brain development in ADHD. Curr Opin Neurobiol 2015; 30:106–111Crossref, Medline, Google Scholar10 Fischer M, Barkley RA, Smallish L, et al.: Young adult follow-up of hyperactive children: self-reported psychiatric disorders, comorbidity, and the role of childhood conduct problems and teen CD. J Abnorm Child Psychol 2002; 30:463–475Crossref, Medline, Google Scholar11 Fayyad J, De Graaf R, Kessler R, et al.: Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder. Br J Psychiatry 2007; 190:402–409Crossref, Medline, Google Scholar12 Kessler RC, Adler L, Barkley R, et al.: The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163:716–723Link, Google Scholar13 McGough JJ, Barkley RA: Diagn