An Update on the Pharmacotherapy of Attention-deficit/Hyperactivity Disorder in Adults

Timothy E Wilens; Nicholas R Morrison; Jefferson Prince


Expert Rev Neurother. 2011;11(10):1443-1465. 

In This Article

Abstract and Introduction


Adults with attention-deficit/hyperactivity disorder (ADHD) are more frequently presenting for diagnosis and treatment. Medication is considered to be appropriate among available treatments for ADHD; however, the evidence supporting the use of pharmacotherapeutics for adults with ADHD remains less established. In this article, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. In adults with ADHD, short-term improvements in symptomatology have been documented through the use of stimulants and antidepressants. Studies suggest that methylphenidate and amphetamine maintained an immediate onset of action, whereas the ADHD response to the nonstimulants appeared to be delayed. At a group level, there appears to be some, albeit not entirely consistent, dose-dependent responses to amphetamine and methylphenidate. Generally speaking, variability in diagnostic criteria, dosing parameters and response rates between the various studies was considerable, and most studies were of a relatively short duration. The aggregate literature shows that the stimulants and catecholaminergic nonstimulants investigated had a clinically significant beneficial effect on treating ADHD in adults.


Attention-deficit/hyperactivity disorder (ADHD; use in this article also refers to previous definitions of the disorder) is a prevalent disorder estimated to affect 3–9% of school age children and up to 5% of adults.[1,2] Historically, ADHD was not considered to continue beyond adolescence. However, long-term controlled follow-up studies have demonstrated the persistence of prominent symptoms and/or impairment in approximately 50% of young adults diagnosed with ADHD in childhood.[3–7]

Compared to their non-ADHD peers, adults with ADHD have been reported to have more conflicts in social and marital relations, and underachievement in their careers, economic status and academics despite adequate intellectual abilities.[3–7] A bidirectional over-representation of comorbidity within ADHD has been reported, with adults with ADHD manifesting higher rates of anxiety, mood and substance abuse disorders than non-ADHD adults.[8,9] Conversely, adults with depression, bipolar and substance abuse disorders have been characterized as maintaining high rates of ADHD.[10,11]

Longitudinally derived data in ADHD youth lifespan connote that whereas symptoms of hyperactivity and impulsivity decay over time, the symptoms of inattention persist.[12,13] In support of this, data derived from a large group of adults with ADHD indicate that whereas approximately 50% of adults display clinically significant levels of hyperactive/impulsive symptomatology, 90% display prominent attentional symptomatology.[14,15] More specifically, adults with ADHD evidence a variety of core attentional ADHD symptoms, including poor attention and concentration, easy distractibility, frequent shifting of activities, day dreaming and forgetfulness; followed more distantly by impulsivity, impatience, boredom, fidgeting and intrusiveness.[15] ADHD adults are considered to experience executive function deficits, such as a reduced ability to attend, encode and manipulate information, and difficulties with organization and time management,[16] as well as deficits in emotional regulation.[17]

Attention-deficit/hyperactivity disorder can be diagnosed in adults by carefully querying developmentally appropriate criteria from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV),[18] regarding the childhood onset, persistence and current presence of these symptoms.[19] Adult self-report scales, such as the Adult Self-Report Scale, the Wender–Reimherr scale, Brown Attention-Deficit Disorder scale and Conners' rating scale may assist in diagnosing adults with ADHD.[19] It is important to set clear and realistic treatment goals with the adult and identify specific symptoms and problematic areas of functioning as targets of treatment. To aid in the diagnosis of ADHD in adults, clinicians should use the DSM IV Text Revision criteria and apply them in a developmentally appropriate manner. Clinicians may find it useful to employ self-report scales, including the Wender–Reimherr Adult Attention Deficit Disorder Rating Scale[20] and the Brown Adult ADHD Scale. In order to monitor treatment response, investigator scales exist, including the ADHD Rating Scale and the Conners' adult ADHD rating scale.[19] Additional therapies often compliment the effects of medication. As with children, college students and adults returning to school may benefit from additional educational supports. Coaching and organization training appear to be useful, but remain understudied.[21] Whereas traditional insight-oriented psychotherapies do not appear efficacious for ADHD,[22] cognitive behavioral therapy that is adapted for adults with ADHD has been developed,[23] with recent controlled data suggesting its efficacy in both individual[24] and group settings,[25] when used alone or adjunctly with pharmacotherapy.

Over the course of the past two decades, the database on the safety, tolerability and efficacy of medications to treat adults with ADHD has expanded greatly. To date there are three medication classes specifically US FDA approved for the treatment of ADHD in adults; atomoxetine (ATX), amphetamine (AMP) and methylphenidate (MPH).

Although medication therapy is well studied in treating ADHD in children, the use of pharmacotherapeutic agents for adults with ADHD is evolving.[26,27] In the following sections, we review the literature on the use of medication treatment for ADHD in adults. We focus on the efficacy in shorter-term controlled trials and effectiveness in longer-term trials. We also examine the use of medications in the context of special populations, tolerability, medical screening and monitoring.


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