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57th Annual Conference of the Canadian Psychiatric Association

Montreal, Quebec / November 15-17, 2007

Up to 60% of patients with a diagnosis of attention-deficit hyperactivity disorder (ADHD) will continue to experience symptoms as adults. According to the US National Comorbidity Survey (NCS) of 3199 adults, some 4.4% of the adult population has ADHD (Kessler et al. Am J Psychiatry 2006;163:716-23). Predictors of the disorder’s persistence into the adult years include family history of ADHD, psychosocial adversity and comorbidity, according to Dr. Timothy Bilkey, Adjunct Professor of Psychiatry, University of Western Ontario, London, and Director, Bilkey ADHD Clinic, Barrie. “If you have all three factors, you have a sevenfold chance of ADHD persistence across the timeline,” he observed.

The Company It Keeps

In adults, ADHD tends to coexist with other psychiatric conditions, stated Dr. Roger McIntyre, Associate Professor of Psychiatry and Pharmacology, University of Toronto, Ontario, and Head, Mood Disorders Psychopharmacology Unit, University Health Network. He commented that patients with treated mood disorders may fail to return to an adequately functional status—for example, exhibiting absenteeism or presenteeism, remaining unemployed or on disability pension—because of persistent disturbances in attention, cognition and executive function. Current evidence suggests ADHD may be an explanation for this situation. “Most of the patients we see in clinical practice have comorbid conditions and often, it seems a patient not responding adequately to an antidepressant or mood stabilizer has a covert medical or psychiatric condition that we miss. It draws our attention to the need to refine what is the underlying diagnosis.”

The NCS emphasized the substantial overlap between mood disorders and ADHD in adult patients. Among patients who were diagnosed with a mood disorder, ADHD was more common than in the healthy population, with a prevalence of 13.1% (Figure 1). More specifically, ADHD prevalence was 9.4% in patients with depression, 22.6% in patients with chronic dysthymia, 21.2% in those with bipolar disorder and 11.9% in individuals with generalized anxiety disorder (GAD). “If you had an anxiety-related disorder as part of a mood disorder, you were also more likely to meet criteria for ADHD... These are companions,” Dr. McIntyre remarked. Very small numbers of these individuals (1.7% of those with depression, 2.5% of those with bipolar disorder and 2.7% of those with GAD) were receiving treatment for ADHD in addition to their primary disorder.

Patients with disorders of substance use and impulse control were also more likely than healthy respondents to have ADHD. Similarly, the prevalence of substance use disorder among patients with ADHD was 15.2%, nearly triple the 5.6% reported in those without ADHD.

Although these data from a population survey are striking, even more telling are figures from a clinical database of 500 patients with bipolar disorder. In this group, the rate of ADHD was 13%. Patients with comorbid ADHD had disease onset five years earlier on average than those without. They also had a more severe and chronic disease course (Simon et al. J Clin Psychopharmacol 2004;24(5):512-20). A further report on 1000 patients examined the link between bipolar disorder phenotypes and ADHD. Those described as having a mixed state characterized by depression with hypomanic symptoms such as irritability and racing/crowded thoughts had a nearly 60% rate of ADHD. In those with depression but with minimal manic symptoms, the rate was about 25%. “This resonates with my clinical experience,” Dr. McIntyre remarked.

Figure 1. Cormorbidity of ADHD and Other DSM-IV Disorders

Making a Diagnosis of Adult ADHD

According to the current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the diagnosis of ADHD requires at least six symptoms of hyperactivity, impulsivity or inattention. They must have been present before the age of 7 and for at least six months. The patient must exhibit impairment in at least two of social, academic or occupational functioning.

Because the symptoms metamorphose over time, adults have often “outgrown” the DSM-IV description, Dr. Bilkey cautioned. While childhood onset is still necessary for a diagnosis, the age of onset can be extended up to about age 13 to account for latency or inadequate history. A collateral history and a review of school records, if available, may be helpful. The Adult ADHD Self-Report Scale (ASRS) Screener (Kessler et al. Psychol Med 2005;35(2):245-56) (Table 1) is a useful brief screening questionnaire. Individuals with at least four positive scores on significant items (dark boxes) are likely to have ADHD.

About 70% of children with ADHD have a combined phenotype. In contrast, more than half of adult patients can be categorized as primarily inattentive, because the symptoms of inattention are more persistent and/or prominent than hyperactivity or impulsivity. Common complaints include rapid boredom with and inability to initiate and sustain tedious tasks, deficient time management or sense of time, procrastination, poor organization and planning, distractibility and forgetfulness. Complaints that connote hyperactivity or impulsivity include rapid development and explosive expression of anger or frustration, impulsive comments or decisions, trouble sustaining friendships or other interpersonal relationships, failure in or dropping out of post-secondary education, frequent job changes or loss of employment, restlessness, substance abuse/dependence and self-selection for act
ble 1. ASRS Screener

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The effects of adult ADHD may be covert, noted Dr. Bilkey. He explained that patients have often developed comprehensive compensatory or coping measures, such as dependence on family support and reliance on memory aids such as electronic agendas and sticky notes. In some cases, the diagnosis may only be made when a young adult heads off to university, where the intellectual demands, requirements for time management, paper organization and a regular sleep/wake cycle, and an overall increased demand on executive functioning become overwhelming. Questions about the patient’s daily life should capture symptom frequency, the degree of impairment, challenge and compensatory burden. The clinician should record examples of impairment, such as the number of work tasks left undone, amount of time spent looking for lost items, etc. Other causes of the symptoms, including mood and substance use disorders, should be ruled out.

The ADHD Burden

Untreated ADHD is highly morbid and costly, Dr. Bilkey commented. Together, the characteristic symptoms may handicap the patient in numerous areas of daily life. He described ADHD-related academic impairment as “a catastrophe,” given statistics showing that only 20% of affected patients attend college and that of those, only one in four graduates. Patients often say they are demoralized because they are underachieving in their employment, but many leave their jobs because of contextual boredom. In a recent report, nearly half of 500 adults with ADHD were unemployed, compared with 27% of unaffected controls (J Clin Psychiatry 2006;67(4):524-40). In the NCS, the annual national cost of adult ADHD in the US workplace was calculated as $19 billion, resulting from 47 million days of absenteeism and 75 million days of presenteeism (J Occup Environ Med 2005;47(6):565-72).

The symptoms of the disorder also impair social and intimate relationships. The divorce rate is two to three times higher than average in patients with ADHD. Management of household duties, dealing with children, maintenance of a healthy lifestyle and safe operation of a vehicle all present possible challenges. In some cases, adult ADHD may actually lower life expectancy, Dr. Bilkey remarked—for example, if impulsive behaviour leads to car accidents, substance abuse or sexually transmitted disease.

Treatment Aimed at Improving Function

Psychostimulant medication for ADHD in children is one of the most effective treatment regimens in medicine, Dr. Bilkey stated. In adults, a multimodal approach with pharmacologic therapy is ideal. “The cornerstone, because it’s a neurobiological disorder, is medication. But there is an evidence base for cognitive therapy and a significant emphasis on treating comorbid conditions.” If the patient has another disorder along with ADHD, it is necessary to prioritize and treat the most severe—typically, the mood disorder—first.

To date, very few randomized, placebo-controlled studies on the treatment of patients with comorbid mood disorders and ADHD have been conducted. In one trial observing children with bipolar disorder and ADHD, the addition of mixed amphetamine salts to divalproex produced better outcome measures for both disorders (Scheffer et al. Am J Psychiatry 2005;162(1):58-64). Given the lack of study evidence, clinicians may be reluctant to prescribe a stimulant for fear of destabilizing a patient with bipolar disorder. “What I would say we are learning is that the notion that psychostimulants are all bad is probably incorrect,” Dr. McIntyre commented. Many psychiatrists have initiated a stimulant in an individual with major depression. “I think that speaks to the point that there’s a gap between what we’re doing and what the evidence base is,” he indicated.

The aim of therapy of ADHD, as with mood disorders, is remission. In ADHD, remission can be measured by functional improvement, a reduction in compensatory burden, and “a new developmental trajectory—figuring out what they want to do with themselves once you sufficiently treat their condition,” Dr. Bilkey indicated. Standardized outcome instruments such as the 18-point ASRS questionnaire can be used to evaluate progress. Many of the existing ADHD therapies are now approved for use in adults, he stated.

Studies have demonstrated the positive impact compared with placebo of long-acting formulations of mixed amphetamine salts and oros methylphenidate (at present, only the former is indicated for adults in Canada). In a recent open-label study of treatment with mixed amphetamine salts (Goodman et al. CNS Spectr 2005;10(12 suppl 20):26-34), patients reported improvement in symptoms, function and quality of life within 10 weeks, Dr. Bilkey noted.

Patients do not always respond in the same way to individual stimulants, so it is appropriate to try a second long-acting agent in the case of initial inadequate response. Because they are effective over several hours, these agents offer more convenient dosing than short-acting psychostimulants; and none is subject to abuse. Their side effects include minor increases in blood pressure and heart rate, which should be addressed as required. Dry mouth may occur but is seldom a source of complaints.

Another option in adult ADHD is atomoxetine, although titration must be very slow and the time to response is several weeks longer for this agent than for the psychostimulants. This compound may be used in combination in patients who do not respond adequately to a psychostimulant alone. It may be appropriate for individuals who have tics, anxiety or an active addiction, Dr. Bilkey suggested. Atomoxetine is less appropriate for patients with comorbid bipolar disorder, as it may activate mania. Its side effects also include blood pressure and heart rate increase as well as nausea and fatigue. A baseline liver assessment is required due to rare reports of chemical hepatitis.

Long-acting bupropion, a nonstimulant, may be appropriate for patients with comorbid mood disorder or nicotine dependence. It may also be used in combination with stimulants.

Additional Approaches

There is an increasing evidence base for psychotherapeutic approaches in addition to medication in adult ADHD, Dr. Bilkey continued. He cited a multisession cognitive therapy program developed at the Massachusetts General Hospital (Mastering Your Adult ADHD, Oxford University Press, 2005), where patients are instructed in adaptive thinking, organization and planning, and reducing distractibility. A small study has shown that patients who followed this program had significantly reduced symptom severity compared with those receiving pharmacologic treatment alone. Other nondrug modalities that may be of assistance in adult ADHD include coaching and mentoring.