A 55-Year-Old Man With Attention-Deficit/Hyperactivity Disorder

DR PARKER: Mr L is a 55-year-old father of twin boys who was recently diagnosed as having attention-deficit/hyperactivity disorder (ADHD). He is general manager for a biotechnology company, lives in a suburb of Boston, Mass, and has commercial managed care insurance, which he is concerned may not cover his recent psychological evaluation.

His first memory of difficulties dates to high school. He tended to procrastinate, not allow enough time to do homework, and have difficulty with basic scheduling. His grades were so poor that he initially did not get into college. He eventually completed college and matriculated in a doctoral program at a prestigious university, but he dropped out because of difficulties focusing and managing his time. Mr L attempted to improve the problems through reading self-help books, attending seminars on time management, and receiving counseling, but none of these helped. He also was troubled by his inability to stay with one job for more than 2 or 3 years.

The diagnosis of ADHD became known as Mr L and his wife shared concern about one son's difficulties in school. Mr L's wife read a description of adult ADHD, which seemed to describe her husband, and he agreed. Mr L went through an extensive evaluation that confirmed this diagnosis.

His medical history and family history are unremarkable, although he suspects that his father may have had ADHD. He is an only child. He does not smoke or drink alcohol. His only current medication is methylphenidate hydrochloride (Ritalin), 10 mg 3 times daily.

Mr L stated that the methylphenidate "worked immediately" and has helped him focus and stick with projects. The only adverse effect he noted was periodically feeling a little "speedy." He has not received any other medical treatments, although he is continuing in couples counseling with his wife and participates in a support group for people with ADHD.

My earliest recognition of an attention issue might have been as early as high school. I didn't seem to be performing at the potential that some of my teachers had anticipated. There was a question about, "You seem bright enough, you seem capable of doing the work, but for some reason the work isn't getting done; what is the issue?" It was not an intellectual problem per se. It was more procrastination, scheduling issues, and not allowing enough time to do the homework. Always figuring, "Well, I'll catch up later. I'll find the time. I'll cram." And then finding myself falling behind and getting in a position where I had a difficult time recovering. I also had some indication that perhaps I wasn't really focusing. It haunted me that I was not able to complete the PhD program. It was not related to my capacity to do the work but an inability to focus appropriately to be able to accomplish the required work.

Seeking help with my time management problems is something I have done on my own. I assembled a large self-help library and took many seminars on how to organize your time, and probably had every organizational tool that one can imagine. But I always found that I would be very diligent about using these devices for a 2-week period, then I would gradually slide away from them and return to responding to stimuli and not planning in a rigorous fashion.

My wife and I had been having some marital problems related to this inattention issue. Now that I have had insight into ADHD, and I'm also taking methylphenidate currently, I've noticed some change in my behavior. But my wife has observed enormous change in my behavior. This behavior relates to listening, following through, and being connected and not drifting away in conversations. She had expressed before that I was just not there, I seemed to be in a fog, or I seemed to be self-consumed and unavailable.

Since I've been taking Ritalin, I've noticed a much clearer focus in my ability to stick with a project and complete it. My past work profile would indicate that I'm a great starter but a lousy finisher, and a great starter of too many things, so it's impossible to finish any of them. Now I'm more focused on starting fewer things and finishing them.

I know there's a tendency to want to self-diagnose with something like this because these books are all available, but if patients like me come in and say they have 10 of these 12 characteristics, then I think the primary care physician should listen, because I think the patient probably finds something that clearly rings a bell.

I really didn't suspect ADHD or any specific problem, neurological or otherwise. The patient came to me having seen clinicians elsewhere and said that through contacts with these clinicians and through evaluations of his son, he'd been assigned this diagnosis. So, my initial response was skepticism. I was a little concerned that this problem may be overdiagnosed in some patients and I didn't know anything about the folks he had seen for this. I had no records or reports. He described some of the symptoms to me and they sounded consistent. But I still wanted to know more about the diagnosis, how it was established, and who he was seeing.

Mr L has described difficulty concentrating, difficulty attending to tasks, difficulty following through with one task before establishing other tasks to take on. These were things he had never described to me before and I hadn't asked him about before. The difficulty I have with thinking about this disorder is that it overlaps with what seems to me to be normal. Many adults may have difficulty concentrating or remembering or attending to certain tasks.

I'd like to know how common ADHD is. What types of patients are most likely to have this condition? What distinguishes patients with this disorder from those who have some elements but don't meet criteria for diagnosis? How is a decision made about who to treat and who not to treat and what are the treatment options? What pharmacological agents may be used and what are their risks and benefits for this condition? Are neuropsychological tests helpful? Are there any other ways of monitoring the progress of a patient with this condition?

What are typical patients' perceptions of their problem? How is their life affected in relationships, school, and work? How is ADHD diagnosed? What is the prevalence and does it vary by sex or socioeconomic status? What is the pathophysiology of ADHD? Has the prevalence of ADHD in the United States changed and is there variation across cultures? What is the prognosis for this patient? What are his medical and psychiatric treatment options? Are medications overprescribed?

DR BIEDERMAN: Mr L presents a spectrum of unique challenges. Although the diagnosis and treatment of ADHD in childhood is well established,^{1 - 2} the adult phenotype has been a source of skepticism and controversy. Mr L's complaints of chronic inattention and occupational underachievement are subjective, difficult to quantify, and certainly not life threatening. The diagnostic requirement of onset of symptoms in childhood is not always easy for physicians to corroborate or for patients to clearly remember. Finally, since psychostimulants, the mainstay of treatment for this disorder, are schedule II drugs, their use raises a variety of clinical and medicolegal concerns in the primary care setting.

Attention-deficit/hyperactivity disorder is a major clinical and public health problem in the United States because of its associated morbidity and disability. Its impact on society is enormous in financial cost, stress to families, impact on academic and vocational activities, and negative effects on self-esteem.³ Concern exists regarding the potential overidentification of ADHD in the United States.⁴ Many of the recent concerns raised in the lay press regarding overdiagnosis of this disorder have more to do with rising use of stimulant drugs than with the changing prevalence of the disorder.⁵

Although the exact prevalence of ADHD in adults is not known, considering a prevalence of 5% in childhood⁶ and rates of persistence into adulthood of 10% to 60% of childhood-onset cases,^{7 - 11} approximately 2% of adults may have ADHD. Because the definition of the illness is not standardized worldwide, international prevalence rates are difficult to prove.

Although the disorder is more common in men than women, little doubt remains that ADHD affects both sexes.¹² Recent work has documented that women with ADHD share with their male counterparts prototypical features of the disorder (eg, high rates of school failure and cognitive impairments and high levels of familiality) but tend to be less aggressive and less disruptive than men (J.B., Stephen V. Faraone, PhD, Eric Mick, et al, unpublished data, 1998). This latter characteristic may account for the underidentification and perhaps undertreatment of women with ADHD.

The current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)⁶ definition of ADHD represents the last of various nosological and conceptual definitions of this disorder that have appeared during the last 2 decades. The current definition of ADHD emphasizes inattention and impulsivity-hyperactivity as equally important core features. Depending on which symptoms predominate, 3 subtypes are recognized: a predominately inattentive type, a predominantly hyperactive-impulsive type, and a combined type with features of both inattention and hyperactivity-impulsivity.⁶ Mr L's ADHD falls into the predominantly inattentive type.

Although the underlying neural and pathophysiological substrate of ADHD remains unknown, an emerging neuropsychological and neuroimaging literature suggests that abnormalities in frontal networks or frontostriatal dysfunction are the disorder's underlying neural substrate and catecholamine dysregulation is its underlying pathophysiological substrate.^{13 - 20} Although its origin remains uncertain, data from family (genetic, twin, and adoption) studies, segregation analysis, and association studies linking ADHD to the HD4-7 allele²¹ suggest a genetic origin for some forms of the disorder.^{3 ,22 - 29} However, other origins or influences are also possible, including psychological adversity,^{30 - 31} perinatal insults,³² and perhaps other as-yet-unknown biological and psychosocial causes.

Because adult ADHD is often a self-referred disorder, its validity has been questioned. As Dr M articulates, some practitioners argue that the influence of the media leads many adults to attribute their problems to ADHD. Others note that the clinical manifestations of adult ADHD are compelling and suggest that therapeutic approaches used for child ADHD should be applied. Clearly, Mr L is convinced of his diagnosis.

Spencer and colleagues³³ reviewed 4 sources of data showing that adult ADHD is a valid disorder. Clinical studies of referred adults have found that many adults with a childhood history of ADHD were restless, impulsive, and inattentive as adults. In a systematic study of 84 adults with ADHD, our group³⁴ showed that ADHD was associated with psychosocial disability, psychiatric comorbidity, school failure, and lower socioeconomic status. This pattern of demographic, psychosocial, psychiatric, and cognitive features paralleled findings among children with ADHD and provided further support for the continuity of ADHD from childhood to adulthood. Mr L recalls a school history of inability to concentrate, multiple failures, social disapproval, and demoralization. In some studies, parents of the adults were able to verify the childhood recollections. In addition, adults with ADHD also have clinical features commonly found in childhood ADHD, namely stubbornness, low frustration tolerance, and recurring conflicts in social relationships with peers and authorities. As the case of Mr L illustrates, these features may explain why, despite adequate intellectual abilities, adults with ADHD have deficits in academic and occupational achievement.

Mr L's history is striking in this regard as exemplified by his poor high school and college performance but subsequent admission to a graduate program at an elite university. This puzzling performance is not atypical for ADHD individuals with good intellectual abilities who may either underachieve or function to potential in different settings, contingent on their ability to adequately attend to tasks. Yet, as Mr L's case also illustrates, he was ill prepared to overcome the demands of a rigorous academic program.

As with Mr L, adults with ADHD commonly describe their work difficulties and frequent job changes as stemming from dissatisfaction, easy frustration, boredom, and impulsiveness. Employers of these adults report they have poor levels of work performance, impairment in task completion, lack of independent skills, and poor relationships with supervisors. Although adults with ADHD often have a number of ADHD symptoms that significantly impair their functioning in key areas of their lives, these difficulties are often noticed by others but not by the persons themselves.

Although a valid syndrome need not be familial, the demonstration of familial transmission strengthens the hypothesis that a syndrome is a valid diagnostic entity.³⁵ As a review by Faraone and colleagues²⁶ shows, ADHD is familial, and genetic factors appear to mediate familial transmission. The parents of ADHD children are at high risk for ADHD and vice versa³⁶ ; indeed, one of Mr L's sons has ADHD.

No physical features, laboratory tests, or psychological tests are established as pathognomonic for ADHD. Although minor physical anomalies such as hypertelorism, arched palate, low-set ears, and physical injury may occur at higher rates than in the general population,⁶ none of these characteristics are diagnostic. The diagnosis of ADHD at any age is based on a careful psychiatric history (anamnesis) and psychiatric examination. It is common for the symptoms not to be evident during the interview because they tend to manifest in unstructured situations, such as school or work.

As defined in DSM-IV (Table 1), the diagnosis of adult ADHD is based on (1) the presence in adulthood of behavioral symptoms of inattention, hyperactivity-impulsivity, or both; (2) the symptoms must have an onset by age 7 years and persist into adulthood; (3) association of the symptoms with some degree of distress and impairment; and (4) cross-situational symptoms (occurring in more than 1 setting). In addition to the 3 subtypes described earlier, DSM-IV also recognizes an atypical form of the disorder termed ADHD, not otherwise specified. The DSM-IV category of ADHD "in partial remission" includes adults who had the full syndrome as children and a partial syndrome as adults.

Because of their nature, the symptoms of ADHD in adults can be easily overlooked in clinical practice unless actively elicited with a straightforward approach using the list of symptoms provided in DSM-IV. We have used this approach in clinical trials of adults with ADHD in which the DSM-IV symptoms were converted into a Likert rating scale and used to assess response to various anti-ADHD treatments.^{37 - 39}

In addition to the prototypical symptoms of childhood onset, the anamnesis of adults with ADHD should include questions regarding cognitive difficulties such as a history of academic underachievement, repeating grades, placement in special classes, need for tutoring, and learning disabilities. Although there is no pathognomonic neuropsychological profile of the ADHD patient, cognitive performance measures and school dysfunction data are important supportive clinical data sources for adult ADHD. Although neuropsychological testing can provide relatively objective measures of attention deficits,^{40 - 42} working memory, and organizational abilities, such tests have low sensitivity and low specificity and are not used for the diagnosis.⁴³

Psychiatric comorbidity should be evaluated in adults with ADHD. Like children with ADHD, adults with ADHD often have high lifetime rates of antisocial behavior, anxiety, substance use, and mood disorders.⁴⁴ Because both epidemiological and clinical studies have shown psychiatric comorbidity to be fairly common, clinicians should be wary of attributing one disorder as being secondary to another. For example, it is tempting to attribute the depression of an ADHD patient to a history of social and occupational failure. Yet, family studies suggest that there may be a genetically mediated biological link between the 2 disorders.⁴⁵ To the degree that diagnosis influences treatment, the application of hierarchical diagnostic principles may prematurely limit therapeutic options. Mr L has no signs of psychiatric comorbidity.

Symptoms of inattentiveness, hyperactivity, and impulsivity can be present with other mental disorders, such as mood and psychotic disorders, as well as with other metabolic or neurologic conditions, such as seizures and organic brain syndromes. School difficulties and failure associated with ADHD need to be differentiated from learning disabilities, defined as a significant discrepancy (usually 1.5 SDs) on psychometric testing between cognitive abilities (IQ) and achievement scores on standardized testing. Although these conditions need to be considered in the differential diagnosis of ADHD, they are not mutually exclusive with ADHD and they commonly coexist. By these criteria, Mr L clearly is not learning disabled.

Positive prognostic factors include a circumscribed disorder (ADHD without psychiatric comorbidity), good intellectual abilities, limited learning deficits, history of prior accomplishments, and a supportive environment. Poor prognostic factors include severe mood lability, severe impulsivity, psychiatric comorbidity, substance abuse, limited cognitive abilities, recurrent failure, and demoralization (J.B., Eric Mick, Steven V. Faraone, PhD, unpublished data, 1998).

Like all medical interventions, treatment should be tailored to the particular needs of individual patients. The pharmacotherapy of ADHD, although not curative, can help improve abnormal behaviors and, equally important, the individual's social and family life. Potentially useful psychotherapeutic efforts in the management of ADHD patients include cognitive-behavioral interventions, such as training in self-instruction, self-evaluation, social skills, and anger management.⁴⁶ Patients with both ADHD and learning disabilities may require additional educational support. Because treatment of ADHD is not curative and because ADHD is a chronic disorder, most patients will need long-term intervention. The need for continued pharmacological treatment may be assessed by periodically decreasing or discontinuing treatment. Mr L will likely benefit from and require some form of long-term treatment.

Stimulants. Psychostimulants remain the mainstay of treatment for ADHD.^{47 - 48} Stimulants are sympathomimetic drugs structurally similar to endogenous catecholamines. The most commonly used compounds in this class include methylphenidate hydrochloride (Ritalin), d-amphetamine (Dexedrine), magnesium pemoline (Cylert), and, more recently, mixed salts of a single-entity amphetamine product (Adderall). These drugs are thought to act both in the central nervous system and peripherally by preventing reuptake of catecholamines into presynaptic nerve endings and thus preventing their degradation by monoamine oxidase. Methylphenidate, d-amphetamine, and Adderall are relatively short-acting compounds with an onset of action within 30 to 60 minutes and a peak clinical effect usually seen between 1 and 3 hours after administration. Therefore, multiple daily administrations are required for a consistent daytime response. Slow-release preparations, with a peak clinical effect between 1 and 5 hours, are available for methylphenidate and d-amphetamine and can often allow for a single dose to be administered in the morning that will last for a substantial part of the school or workday. Because the effects of stimulants are neither paradoxical nor specific, they should not be used for diagnosis.⁴⁹

Typically, these compounds have a rapid onset of action so that clinical response will be evident soon after a therapeutic dose has been obtained. Mr L responded quickly and significantly to methylphenidate. Magnesium pemoline is a longer-acting compound generally allowing for 1 or 2 daily doses. Although methylphenidate is by far the most studied stimulant medication, the literature provides little evidence of differential response to the various available stimulants, although individual patients may respond preferentially.^{47 ,50}

Although the efficacy of stimulants in ADHD is most clearly documented in school-aged children,^{48 ,51} an emerging literature reveals that stimulants are also effective in adults.³⁷ The largest response in adults was reported by our group in a recent randomized controlled study of methylphenidate, 1.0 mg/kg daily,³⁷ in patients diagnosed as having childhood-onset Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) ADHD. This double-blind, crossover study found a marked therapeutic response to methylphenidate treatment compared with placebo (78% vs 4%) that appeared to be dose dependent. Response to methylphenidate was independent of sex, psychiatric comorbidity, or family history of psychiatric disorders.

In addition to diminishing motoric overactivity and impulsivity, stimulants can also be effective in patients with ADHD for whom hyperactivity and impulsivity are not significant clinical problems. Stimulants also improve ADHD-associated behaviors, including on-task behavior, academic performance, and social function. These effects appear to be dose dependent and cross-situational, including home, clinic, and school. In adults, occupational and marital dysfunction often improve with stimulant treatment.⁵¹ Mr L eloquently described changes and improvements in his marriage after starting treatment.

Because of their short half-life, the short-acting stimulants (methylphenidate and dextroamphetamine) should be given in divided doses throughout the day, typically 4 hours apart. The suggested total daily dose for methylphenidate ranges from 0.3 mg/kg to 1.0 to 1.5 mg/kg after titration. Amphetamines are approximately twice as potent as methylphenidate, and pemoline is about 3 times less potent. Thus, the typical starting dose for methylphenidate is 10 mg/d; for amphetamines, 5 mg/d; and for pemoline, 37.5 mg/d, with increments in dose every few days thereafter until desired effects occur or adverse effects preclude further increases. The interactions of the stimulants with other prescription and nonprescription medications are generally mild and not usually a source of concern.

Although short-term studies have documented rapid improvement in the core ADHD symptoms, associated functional improvement may lag symptom remission. The ultimate effectiveness of anti-ADHD medication on cognitive and academic performance, social skills, and quality of life remains unknown.⁵²

Commonly reported adverse effects of stimulants are appetite suppression and sleep disturbances, but these are rarely severe in adults. Less commonly, mood and anxiety disturbances and headaches can be associated with stimulant treatment. Although the cardiovascular effects of stimulants have not been fully examined, mild increases in pulse and blood pressure of unclear clinical significance have been observed.⁵³ Mr L described a mild sensation of "raciness," which he attributed to the methylphenidate. A rare stimulant-associated toxic psychosis has been observed, usually in the context of either a rapid dosage increase or very high doses. Administration of magnesium pemoline has been associated with hypersensitivity reactions involving the liver accompanied by elevations in liver function studies (aspartate aminotransferase and alanine aminotransferase) after several months of treatment. Thus, baseline liver function studies and repeat studies are recommended with the administration of this compound.

Antidepressants. After the stimulants, tricyclic antidepressants (TCAs), especially imipramine and desipramine, are the second most-studied compounds in the pharmacotherapy of ADHD.⁵¹ Advantages of TCAs over stimulants include a longer duration of action and greater flexibility in dosing. Disadvantages include the narrow therapeutic margin and their potential lethality in overdoses, as well as other well-known adverse effects. Our group recently reported results of a controlled clinical trial of desipramine in 41 adults with ADHD.³⁶ At an average daily dose of 150 mg (average serum level of 424 nmol/L [113 ng/mL]), desipramine was statistically and clinically more effective than placebo. Fourteen (68%) of the desipramine-treated patients responded compared with none of the placebo-treated patients (P<.001). Moreover, at the end of the study, the average severity of ADHD symptoms in treated patients was reduced to below the level required to meet diagnostic criteria. Importantly, while the full desipramine dose was achieved at week 2, clinical response improved further over the following 4 weeks, indicating a latency of response. Response was independent of dose, serum desipramine level, sex, or lifetime psychiatric comorbidity with anxiety or depressive disorders. Treatment with TCA should be initiated at 25 to 50 mg/d and increased slowly every 4 to 5 days by 20% to 30%, depending on response and adverse effects. Tricyclic antidepressant serum level monitoring is useful to avoid high TCA concentrations associated with adverse cardiovascular effects. Common adverse effects of the TCAs include anticholinergic effects such as dry mouth, blurred vision, and constipation.

In addition to TCAs, bupropion hydrochloride has also been tested in ADHD. Bupropion is a novel aminoketone antidepressant related to the phenylisopropylamines but pharmacologically distinct from available antidepressants.⁵¹ Although bupropion possesses both indirect dopamine and noradrenergic agonist effects, its specific site or mechanism of action remains unknown. In an open study of 19 adults treated with an average of 360 mg of bupropion for 6 to 8 weeks, Wender and Reimherr⁵² reported a moderate-to-marked response in 14 (74%) of the adults with sustained improvement at 1 year noted in 10 subjects. The response of ADHD to bupropion appears to be rapid and sustained. Dosing of bupropion for ADHD is similar to that recommended for depression, with a suggested maximal dose of 450 mg/d in adults, divided into 3 daily doses. Bupropion is associated with a somewhat higher rate of drug-induced seizures (0.4%) relative to other antidepressants, particularly in daily doses higher than 6 mg/kg. However, this risk has been linked to a previous history of seizures and eating disorders, as well as to high dose.

Although several studies suggested the clinical utility of monoamine oxidase inhibitors in the treatment of ADHD,⁴⁶ a major limitation to using monoamine oxidase inhibitors is their well-known adverse effects. Although a single open pediatric study⁵³ suggested that the selective serotonin reuptake inhibitor fluoxetine may have clinical utility in the treatment of ADHD, serotonergic antidepressants appear to have limited effectiveness in the treatment of core symptoms of ADHD. However, these drugs can be most helpful in the management of comorbid mood and anxiety disorders frequently observed in adults with ADHD.⁴⁸ Because Mr L is responding so well to methylphenidate, I see no need to change to antidepressants in his treatment.

Conclusion. Although monotherapy is always preferred, in clinical practice many patients with ADHD require combined treatments. Examples of combined treatment include using an antidepressant plus a stimulant for ADHD and comorbid depression, using clonidine to ameliorate stimulant-induced insomnia, or using lithium plus an anti-ADHD agent to treat ADHD comorbid with bipolar disorder.⁵⁴ Charges for prescription medications prescribed for ADHD are presented in Table 2.

Despite the availability of various agents for managing ADHD, many individuals either do not respond to or are intolerant of the adverse effects of these medications. Severe psychiatric symptoms such as psychosis or mania that emerge during the acute phase of treatment can be problematic, irrespective of the efficacy of the medication for ADHD. These symptoms may require reconsideration of the diagnosis of ADHD and careful reassessment of the presence of comorbid disorders. If reduction of dose or change in preparation (ie, regular vs slow-release stimulants) does not resolve the problem, consideration should be given to alternative treatments. Concurrent nonpharmacological interventions such as behavioral or cognitive therapy may assist with symptom reduction.

Given the high prevalence of childhood ADHD and its known persistence into adulthood, ADHD is a common adult psychiatric disorder. Despite recent media attention and its validity as a serious public health problem, skepticism about this disorder limits its diagnosis and treatment. However, an emerging literature suggests that adult ADHD is a valid and important disorder. Converging evidence from clinical, longitudinal, family-genetic, and treatment studies shows that the diagnosis of ADHD in adults has many of the external correlates and clinical features of the well-documented childhood disorder. Given these data, the lack of recognition of adult ADHD has serious clinical implications. Clinicians who treat children do not often treat their patients when they become adults, and clinicians who treat adults do not often consider adult ADHD. Instead, the symptom picture of an adult with ADHD may be attributed to other causes. Because ADHD symptoms often respond to anti-ADHD treatment, overlooking this diagnosis limits the recovery of many patients. Effective pharmacological treatments for ADHD seem to share noradrenergic and dopaminergic mechanisms of action. Stimulant medications continue to be the first-line drug of choice for uncomplicated ADHD individuals, with TCAs and bupropion the treatment of choice for nonresponders or patients with concurrent psychiatric disorders. Mr L clearly has adult ADHD, which has responded nicely to first-line treatment. If Mr L continues in treatment and works closely with his treating physician, his prognosis is very good.

MR L: That was a very clear description of my situation. One observation Dr Biederman mentioned is the drop-off when the drug leaves the system. I wouldn't call it depression but discouragement. My wife would also mention that the relationship between spouses is greatly affected by this condition. Treatment with Ritalin in our case is not the end of the situation. We have 11 years of history that we're trying to forgive and forget. It's an ongoing process.

DR BIEDERMAN: The way to deal with the drop-off between doses is to anticipate when the symptoms emerge and take the subsequent dose just a little before those symptoms emerge.

DR DELBANCO: How difficult is it to conduct randomized trials of drugs such as Ritalin or tricyclics that have a high side effect profile?

DR BIEDERMAN: That is a shortcoming of all clinical trials. Some of our clinical trials have been crossovers, so the patient serves as his or her own control. Some of the rating scales were not only obtained from the patient but from people around the patient describing improvement. The possibility of side effects can preclude blinding, but not totally, because not everyone has side effects and some drugs have been well tolerated.

AN INTERNIST: Is Ritalin overprescribed?

DR BIEDERMAN: As elegantly reviewed in a recent report on the subject, there is very little evidence to support these claims.⁴

A PSYCHIATRIST: Can you tell us what the nature of ADHD is by comparing it with schizophrenia?

DR BIEDERMAN: I see schizophrenia as a much wider deficit of attention. I see ADHD as localized in the prefrontal cortex, whereas schizophrenia probably represents a more profound deficit that includes prefrontal cortex activity and many other regions as well. Although common circuitry may be affected in both conditions, I see schizophrenia as pervasive and fundamental and ADHD as more localized and limited.

A PSYCHIATRIST: Is it possible that tolerance will develop over time with the long-term use of stimulants? What's your experience over time with long-term use of 30 mg of Ritalin?

DR BIEDERMAN: We need to keep titrating the dose until we control the symptoms very well. Most of my patients are taking a stable dose for years. When you are trying to define the optimal dose for a given patient, you need to periodically escalate the dose until there is a satisfactory response. Once we find a dose that is typically 1 to 1.5 mg/kg in divided doses, most of the patients don't need any adjustment of the dose for a long time.

A PHYSICIAN: What is your opinion about sustained-release Ritalin?

DR BIEDERMAN: Sustained-release Ritalin is a very poor product. The current sustained-release Ritalin has a wax matrix, a very old technology of slow release. It does not work in about 1 of 2 people switched from the immediate release to the slow release and is erratic in its performance. The duration of effect is maybe 1 more hour than the immediate release.

AN INTERNIST: Given the prevalence of the illness, do you think that primary care physicians can initiate therapy for this with stimulants, or should we send them to psychiatrists for evaluation and treatment?

DR BIEDERMAN: I don't think it's necessary if the clinician can endure the frustration of not having an objective test and just be satisfied with a history. However, primary care physicians should be aware that this is not a phenotype that will jump at you. Pediatricians and family doctors, not psychiatrists, treat 90% of children with ADHD. I think we also have to increase practitioners' level of comfort with prescribing controlled substances.

A PSYCHIATRIST: In adults, how do you differentiate between patients with ADHD and mania or hypomania? Many of the symptoms you cite, such as talking a lot, impulsiveness, and short attention span, also fit the criteria for hypomania. If we give hypomanic people stimulants, we may make them worse, yet it's quite surprising that sometimes they are made much better.

DR BIEDERMAN: The distinguishing feature is mood instability in mania or hypomania that is not shared by ADHD. You should not make the diagnosis of mania in the absence of mood instability.

A PSYCHIATRIST: What if there is irritable hypomania?

DR BIEDERMAN: Patients with ADHD come to the office complaining of difficulties attending to task, histories of occupational and educational underachievement like Mr L, even histories of depression, but without any irritability, grandiosity, or inappropriate behavior.