Adult ADHD: A Review of the Clinical Presentation, Challenges, and Treatment Options

Table 1 – Stimulant drug therapy options

Table 2 – Nonstimulant drug therapy options

Premiere Date: October 20, 2015
Expiration Date: April 20, 2017

This activity offers CE credits for:

1. Physicians (CME)
2. Other

ACTIVITY GOAL

To recognize the clinical presentation of adult ADHD as well as the associated challenges of assessment and treatment.

LEARNING OBJECTIVES

At the end of this CE activity, participants should be able to:

• Understand the difficulties associated with making an objective assessment of adult ADHD

• Identify the psychiatric conditions frequently comorbid with adult ADHD

• Distinguish which intervention to use when treating an adult patient with a diagnosis of ADHD

TARGET AUDIENCE

This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

CREDIT INFORMATION

CME Credit (Physicians): This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of CME Outfitters, LLC, and Psychiatric Times. CME Outfitters, LLC, is accredited by the ACCME to provide continuing medical education for physicians.

CME Outfitters designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Jennifer A. Reinhold, PharmD, BCPS, BCPP, has no disclosures to report.

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The inattentive and the hyperactive-impulsive subtypes of ADHD are particularly evident in adults. This inherent heterogeneity complicates the diagnosis and contributes to the lack of uniformly recognized criteria in the adult population. Historically, the diagnostic criteria that were developed based on the traditional childhood presentation have been applied to adult patients. Practitioners have attempted to adapt these criteria to adults in practice, and DSM-5 has also modified some of the qualifiers in order to facilitate the utilization of the criteria in adults. However, the clinical presentation and functional impacts of ADHD in adults vary greatly from their child and adolescent counterparts.

As patients mature and their roles and responsibilities evolve, the functional impairments and symptom presentation evolve in response, thereby presenting a barrier to fulfilling diagnostic criteria. Adults are exposed to a variety of social and professional situations that can provide an opportunity for previously unnoticed symptoms to manifest. Inattentive symptoms may present as difficulty in completing tasks, poor time management, difficulty in sustaining attention in work-related activities, distractibility and forgetfulness, and poor concentration. Occupational performance and professional interpersonal relationships can suffer, and ultimately result in frequent job changes, unemployment, failure to live up to one’s occupational potential, and lower salaries. Moreover, deficits in global performance in the adult patient’s life role, follow-through, and memory can have pervasive effects that extend to those who depend on him or her (eg, children, spouses, employers, friends).

Perhaps the most significant evolution of symptoms occurs in the hyperactivity-impulsivity domain. It is often assumed that these symptoms fade or resolve entirely in adults as they grow older. However, maturation results in a shift in this symptom cluster, and it evolves from behavioral to cognitive-adult patients feel restless as opposed to running around and being disruptive in school. Approximately 90% of adult patients have symptoms of inattention.¹

Challenges in assessing ADHD in adult patients

There are many challenges associated with a diagnosis of ADHD in adults. Objective assessment is difficult because of many factors, including the extensive degree of symptom overlap with other psychiatric diagnoses (eg, psychiatric comorbidities, adaptive compensatory mechanisms, difficulty in assessing functional impact).

Lack of validated diagnostic criteria

The most contemporary multidimensional approach to a relatively objective diagnosis in children and adolescents are DSM-5 criteria, which assess symptoms in all 3 domains. Until the release of DSM-5, there was very little consideration for the assessment of adult patients because DSM criteria had not been validated in the adult population. DSM-5 adapted the previous set of diagnostic criteria to be more accurately applicable to adult symptom presentation. The nomenclature has evolved to reflect more adult-specific situations, such as having difficulty focusing during lectures, avoidance of reviewing lengthy papers, and forgetfulness related to paying bills or keeping appointments.

Revisions that facilitate the application of the criteria to adults are the decrease in the number of required symptoms for adults to fulfill criteria as well as an increase in the age of initial presentation. Previously, adult patients needed to satisfy at least 6 of the 9 inattentive criteria, which is consistent with diagnosis in the pediatric and adolescent population. In DSM-5, adults need to satisfy only 5 of the 9 criteria and children and adolescents still need to satisfy 6 of the 9 inattentive criteria. DSM-IV required that symptoms present before age 7-a challenging retrospective for adult patients who had not previously sought an intervention.

Even with the new criteria, practitioners need to make a retrospective evaluation of the presence of ADHD in childhood in order to establish a diagnosis in adulthood. This was cited as one of the most problematic components of the criteria because many patients could not recall childhood symptoms or they could not produce documentation substantiating a childhood diagnosis. Because ADHD is considered a developmental disorder, the presence of current symptoms as well as a history of previous symptoms (in childhood) needs to be established. Patients with ADHD, however, have impaired short- and long-term memory; therefore, recall bias can affect the accuracy of assessments. The practitioner is faced with the challenge of determining whether this was an established childhood diagnosis, a missed diagnosis in childhood, or a late-onset adult ADHD.

There are a host of validated rating scales for assessing adult patients with suspected ADHD, although each has inherent limitations. The Adult Self-Report Scale (ASRS) is an 18-item screening tool that is based on DSM-IV criteria. Patients rate the items based on the frequency and degree to which they occur. A 6-item version of the ASRS captures abnormalities in the domains related to follow-through, memory, organization, procrastination, restlessness, and hyperactivity.

The Conners Self-Report Scale is a multidimensional assessment scale that both the patient and an observer complete. The long version of this scale has 66 items that assess symptoms consistent with inattention and memory deficits, impulsivity and emotional lability, hyperactivity and restlessness, and problems with self-conceptualization.² Having multiple perspectives is ideal in that the observer can contribute critical data that the patient may be either unaware of or not willing to disclose. One of the most significant limitations of self-report scales is that they are generally not sufficient independently to establish a diagnosis in the absence of more objective data or documentation. A 30-item version of the Conners Adult ADHD Self-Report Scale can also be used.

Psychiatric comorbidity and symptom overlap

Another challenge in the evaluation of adult ADHD is the symptom overlap between ADHD and mood and anxiety disorders. Patients with ADHD tend to have high rates of comorbidity with anxiety, depression, and substance abuse disorders, with prevalence rates that are more than double those observed in patients without ADHD.^3-5 In a 2006 study, 87% of adult patients had at least one psychiatric comorbidity and 56% had two.⁴ Determining whether ADHD is present alone or whether it is comorbid with another psychiatric disorder is critical-a mood or anxiety disorder may be responsible for the ADHD-like symptoms.

Compared with patients who have a depressive disorder, those with ADHD tend to have more occupational or functional impairment, organizational deficits, and impulsivity issues. The distinction between ADHD and bipolar disorder can be especially challenging, since the manic and hypomanic features of bipolar disorder are similar to the hyperactive and impulsive symptoms associated with ADHD. In patients with ADHD, these symptoms tend to be constant, but in bipolar disorder there is a waxing and waning of manic symptoms interrupted with periods of depression. Patients with bipolar disorder tend to be goal-directed and are usually productive, while patients with ADHD are less able to complete tasks.

Substance use disorders are more common in patients with ADHD, and the clinical course of ADHD tends to be more challenging in this patient population. In patients with an opiate or cocaine addiction, the prevalence of ADHD is as high as 35%; and for alcohol-addicted patients, the ADHD prevalence exceeds 70%.^4,6 Alcohol and certain prescription and illicit drugs can produce symptoms that mirror those of ADHD, which may artificially inflate the prevalence of ADHD in patients with an addiction problem and may not be reflective of the true prevalence.

Compensatory mechanisms

Adult patients may develop and depend on compensatory mechanisms in order to overcome some of the functional impairments associated with ADHD.^4,7 Patients who are highly functioning with higher than average IQs tend to develop useful coping mechanisms to overcome symptoms or to hide them from others. Some patients become compulsive list makers or develop a highly structured daily routine in order to complete tasks and to minimize forgetting details or losing belongings.

Also see:

6 Challenges in Assessing ADHD in Adult Patients

They may unknowingly rely on coworkers or family members to an inappropriate extent for reminders or assistance in completing tasks or fulfilling responsibilities. Although compensatory mechanisms are generally therapeutic for the patient, they may cloud the clinical picture particularly in cases where the patient does not self-suspect ADHD but rather a family member or the practitioner suspects ADHD.

Engaging in compensatory mechanisms such as relying significantly on others or forgoing sleep to finish tasks may mask the symptoms of ADHD or suggest that a patient is adequately coping when he or she is not. In any case, the use of appropriate compensatory mechanisms should also be taken into consideration when determining whether drug therapy is indicated. Some patients can manage without a clinically significant functional impact by relying on compensatory mechanisms and are able to avoid drug therapy.

Evidence of significant clinical impact

Among the DSM criteria is an item that evaluates the degree of clinical impact of ADHD symptoms on life domains. For a diagnosis of ADHD, there must be clear evidence of significant clinical impact, which can be especially difficult to objectively assess. Failure to demonstrate significant clinical impact precludes a diagnosis of ADHD even if all other criteria are satisfied. Examples of true clinical impact include disciplinary action at work, risk of job loss, relationship discord, or frequent automobile accidents or accidents in the home.

Underdiagnosis vs overdiagnosis

Given the high degree of psychiatric symptom overlap, the realistic possibility of feigning ADHD symptoms, and a general fear of enabling drug addiction or diversion, the underdiagnosis versus overdiagnosis of ADHD in practice has been called into question. There are no available data to quantify this concern, and therefore no support can be lent to the argument of failure to recognize ADHD or misdiagnosis of ADHD. A psychiatric comorbidity and the point of entry into the health care system (primary care versus a psychiatrist) may influence whether ADHD is overdiagnosed or underdiagnosed. The most frequent point of entry into the health care system and the most common place for ADHD to be evaluated and diagnosed is in the primary care setting, where it may be overdiagnosed. However, when patients are seen by a psychiatrist, it usually is the comorbid psychiatric diagnosis that is treated and not ADHD. Thus, ADHD may be underdiagnosed when patients present to a psychiatrist. Given the assertion that ADHD is overdiagnosed in primary care and underdiagnosed by specialists, the true prevalence of ADHD theoretically lies somewhere in between.^8,9

Prescription drug abuse and drug-seeking behavior

According to the most recent survey by the National Institute on Drug Abuse, adults between the ages of 18 and 25 are statistically the most likely to abuse prescription drugs.¹⁰ Adults between the ages of 18 and 22 are the most likely to abuse stimulant medications, with rates in college students double those in non-college students.¹¹ The majority of adult patients who present with self-suspected ADHD are between the ages of 18 and 24; therefore, the unfortunate but realistic risk of drug seeking must be considered.

A definitive statistic that quantifies the risk and rates of stimulant medication abuse is elusive owing to patient unwillingness to admit abuse or diversion. However, multiple studies have attempted to capture this rate through anonymous surveys and emergency-department visits. Generally stimulants with a rapid onset of effect and shorter half-life are more likely to be abused, since there is a more narrow window between ingesting the drug and realizing the perceived reward. Variability exists within the therapeutic class in terms of abuse potential: rates of abuse of amphetamine salts exceed those of methylphenidate.¹²

Establishing a meaningful comparison of the rates of abuse of stimulant medications compared with prescription drugs for other indications is also challenging. Considering the physiologic consequences of abusing stimulants, opioids, or sedative-hypnotics, it may not be surprising that accidental death due to abuse of a prescription drug is by far the highest for the opioids. Prescription opioid-related accidental deaths were more frequent than cocaine, heroin, and stimulant overdoses combined.¹³

Treatment modalities

Stimulants

Psychostimulants remain the drug class of choice in treating adults and children with ADHD. Most product formulations available are derived from one of two parent molecules: methylphenidate or amphetamine (Table 1). Pharmacologically, the stimulants inhibit the reuptake of dopamine and norepinephrine, thereby increasing concentrations in the presynaptic cleft. Amphetamines also directly stimulate the release of dopamine and norepinephrine. About 14 products are currently available in the US: some of them are immediate-release and others are extended-release formulations. It is generally recommended that drug therapy, particularly in adults, should consist of an extended-release product in order to maximize compliance and minimize the risk of abuse. Stimulant medications mitigate traditional ADHD symptoms and have demonstrated utility in improving interpersonal relationships, self-esteem, and cognition, as well as alleviating symptoms of comorbid anxiety disorders.^14,15 Stimulants are arguably the most effective in resolving ADHD symptoms and comorbid psychopathology; however, because of the risk of adverse effects and abuse potential, these agents may be underprescribed for adult ADHD.¹⁶

Common, transient adverse effects include sleep disturbance, appetite suppression and associated weight loss, agitation, and nervousness. These are typically minimized by taking the drugs with food and using an extended-release formulation. Serious concerns exist regarding cardiotoxicity. Patients can experience palpitations, tachycardia, and elevations in blood pressure. Serious cardiovascular effects include rhythm disturbances and cardiomyopathy, which precludes use in patients who have an existing cardiovascular abnormality.

Nonstimulants

Owing to their less impressive effectiveness compared with stimulants, the nonstimulant medications tend to be prescribed less frequently among all age groups. Generally, practitioners do not initiate drug therapy with a nonstimulant unless the patient has a contraindication to stimulants (cardiac abnormalities, previous or current substance abuse) or is intolerant to or has failed a trial of a stimulant. Currently, the nonstimulant therapeutic class includes atomoxetine, immediate- and extended-release guanfacine, clonidine, and bupropion (Table 2).

Atomoxetine’s efficacy and safety have been demonstrated in adults and children; however, its associated rates of response are less impressive than those of the stimulants. It remains an appropriate option in patients who have contraindications to stimulants or who have a comorbid anxiety disorder, as anecdotal evidence suggests some level of anxiolytic activity.

Bupropion has been evaluated in a small number of studies involving children, adolescents, and adults, in whom its efficacy compared with placebo or with an active stimulant comparator has been established. This is not an approved indication for bupropion in any age group, however. Bupropion may be a therapeutic alternative in adults who have contraindications or are intolerant to stimulant medications, or in patients who have a comorbid depressive illness.

Guanfacine and clonidine are typically reserved for children who also have a hyperactive component. Of the newer extended-release formulations, only extended-release clonidine has an indication for the treatment of adult ADHD.

CASE VIGNETTE

A 42-year-old woman presents to a primary care clinic for an evaluation of her attention issues. Alice’s symptoms became apparent in early grade school, but with extra effort she managed to get good grades throughout elementary school, high school, and college. Lately she has had increasing difficulty in remembering appointments and completing her projects; she has also been losing her belongings, avoiding tasks, getting distracted at meetings, and failing to listen to people when they speak to her. Her direct superior has brought this to her attention and has mentioned possible disciplinary action. Symptoms occur all day, regardless of setting. Her past medical history includes dyslipidemia, anxiety, and gastroesophageal reflux disease. Prescription medications include 20-mg atorvastatin daily, 10-mg escitalopram daily, and 20-mg omeprazole daily. Evaluations for mood and anxiety disorders reveal no additional diagnoses. There is no documented history of or current issues with substance abuse.

Does this patient fulfill DSM-5 diagnostic criteria for ADHD?  Yes. She reports at least 5 symptoms of inattention (remembering appointments, finishing projects, losing belongings, task avoidance, easy distraction, failing to listen to others in conversation). The symptoms (per patient report) began before age 12, occur both at work and at home, and have resulted in functional impairment (evidenced by her supervisor’s threat of disciplinary action). Given her age, it would be difficult to collect collateral supporting information from a teacher or parent, and so the patient report alone will need to be the only account of symptoms. The clinician’s judgment about the validity of these claims will also need to be taken into consideration. If possible, an attempt could be made to discuss these issues with the patient’s husband or work supervisor in order to acquire different perspectives and additional supporting information. Other psychiatric diagnoses and substance abuse issues are ruled out; therefore, the ADHD symptoms are not better explained by another psychiatric disorder.

Is this patient a candidate for a pharmacotherapeutic intervention?  Yes. Current treatment guidelines recommend initiating drug therapy in adults as a first-line treatment.

Is this patient a candidate for non-drug therapy?  Yes, if necessary. There is no treatment guideline that specifically recommends non-drug therapy for adult patients because there is a lack of efficacy data to support it. However, if the patient complains of specific symptoms that may be behavior-mediated (such as time management or procrastination-related symptoms), counseling or other workshop-based interventions may help her to manage these symptoms more effectively and may eventually reduce her dependence on drug therapy for the monotherapy of ADHD.

What pharmacotherapeutic intervention(s) would be most appropriate? Consistent with the domestic guidelines for the management of ADHD in children, the National Institute for Health and Care Excellence guidelines in Europe recommend initiating a stimulant medication as first-line therapy. None of the stimulants are considered superior with regard to safety or efficacy in adults or children. However, a long-acting formulation is generally preferred because of the reduced likelihood of abuse. This patient has no history of substance abuse, but use of longer-acting formulations will minimize any risk.

Longer-acting products tend to have a smoother onset and offset of action compared with immediate-release agents, which produce a noticeable onset in most patients. A longer-acting product will reduce the pill burden and will require less frequent dosing-an advantage for someone who needs coverage throughout the day.

If this patient has a contraindication to stimulants, what is the next most appropriate intervention? Contraindications to stimulants generally include cardiovascular issues such as arrhythmias, uncontrolled hypertension, or concomitant administration of other drugs that can be arrhythmogenic. In the setting of a contraindication, the nonstimulants could be considered. Atomoxetine is generally used first because its efficacy data are more robust than that of clonidine, guanfacine, and bupropion.

If this patient had a comorbid diagnosis of depression or anxiety, how might the treatment plan for ADHD be different? Depending on the severity of symptoms, the practitioner may choose to treat the mood or anxiety disorder first. This depends on which symptoms are most distressing and which are causing the most functional impairment. Improvement in a comorbid mood and/or anxiety disorder may also indirectly improve ADHD symptoms because patients who are euthymic and not anxious may be better equipped to deal with the ADHD symptoms. Assuming that the comorbid diagnosis is depression, a stimulant and an antidepressant could be initiated, but not at the same time in order to gauge which drug resulted in the resolution of which symptoms.

Bupropion might be a possible intervention if a reduction in pill burden is important. Bupropion is not indicated for ADHD, but there is some evidence to support its use. Assuming that the comorbidity is anxiety, the initiation of a stimulant may or may not worsen symptoms. This is highly patient-specific and will depend on whether the anxiety is worsening the ADHD or vice versa. It may be advisable to initiate medication therapy for the anxiety first and once improved or resolved, initiate drug therapy carefully for the ADHD and monitor for worsening of anxious symptoms.

Conclusion

Historically considered a diagnosis of childhood, ADHD persists into adulthood for a vast majority of patients. Secondary to the absence of validated screening tools for adults, the pervasive symptom overlap with other psychiatric illnesses, frequent comorbidity with other psychiatric diagnoses, feigned ADHD, and the risk of drug diversion or abuse, diagnosis in adults has proven to be challenging. However, utilizing the available diagnostic criteria, gathering as much data as possible from as many sources as possible, considering the possible influence of other psychiatric comorbidities, and being diligent in assessing risk of abuse, the diagnosis of ADHD in an adult can be achieved responsibly and with minimal risk.

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Disclosures:

Dr Reinhold is Associate Professor of Clinical Pharmacy in the department of pharmacy practice/pharmacy administration at The Philadelphia College of Pharmacy at the University of the Sciences in Philadelphia.

References:

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. Accessed August 31, 2015.

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13. Calcaterra S, Glanz J, Binswanger IA. National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009. Drug Alcohol Depend. 2013;131:263-270.

14. Upadhyaya HP. Managing attention-deficit/hyperactivity disorder in the presence of substance use disorder. J Clin Psychiatry. 2007;68(suppl 11):23-30.

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16. Greenhill LL, Pliszka S, Dulcan MK, et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry. 2002;41(suppl 2):26S-49S.