There are several important issues regarding the manner in which medications are tested prior to their release and monitored after approval that must be appreciated in considering issues related to cardiovascular safety of medication treatments for attention-deficit/hyperactivity disorder (ADHD) in adults. First, patients treated in clinical trials are not necessarily representative of those seen in practice settings, as specific inclusion/exclusion criteria in studies limit a variety of psychiatric, medical, and social factors that could potentially introduce confounds related to the collection and/or interpretation of efficacy, tolerability, and safety data. However, many of these factors are present in patients treated in clinical practice. In addition, the manner in which medications are administered in clinical trials does not necessarily replicate the way they are used in the community. Often, there are differences in titration schemes and dosing options. Also, in clinical trials, drugs are rarely studied in combination, although they are often used in this manner in practice settings. Further, Phase III clinical trials (at least in psychiatry) often do not enroll a large enough sample to evaluate infrequently occurring adverse events. Rather, the predominance of information regarding rare side effects is derived from voluntary reports made after a drug comes to market—and therefore likely under-reports the phenomenon. Finally, information regarding drug safety that comes to practitioners in the form of medication warnings or advisories may reflect concerns that extend beyond the strict interpretation of clinical trials data. These and other issues represent major obstacles in attempting to fully understand issues related to safety and tolerability of medication in “real world” settings.

In discussions of diversion and misuse of medications in adult attention-deficit/hyperactivity disorder (ADHD), the word “misuse” is intentionally used. Abuse of a medication refers to excessive use of a drug to achieve a “high,” which may result in addiction to the medication and which causes dysfunction in a patient's life. However, misuse refers to usage of a medication without a prescription or for reasons other than that which it was prescribed. Diversion refers to the diverting of legally prescribed medication into illegal use by other than the patient. Sahakian and Morein-Zamir recently discussed the use of cognitive-enhancing drugs by individuals with a variety of disorders as well as off-label and non-prescription use by the general public. In addition to inappropriate use of medications, patients with ADHD often turn to other substances that are detrimental to their health, such as nicotine.

When performing a diagnostic evaluation for an adult patient with possible adult attention-deficit/hyperactivity disorder (ADHD), clinicians must pay particular attention to possible mimics. ADHD mimics are conditions responsible for the symptoms or impairments that superficially resemble, and may be confused with ADHD. These mimics may produce symptoms and impairments similar to those seen in adults with ADHD, but differ in etiology, course, or response to treatment of ADHD. When evaluating someone for ADHD, clinicians should first rule out the possibility of medical, psychiatric, and social mimics of ADHD.