Clinical Supplement

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Joseph Biederman, MD, Allan K. Chrisman, MD, William Dodson, MD, David W. Goodman, MD, James McGough, MD

Moderator: Peter Salgo, MD
Section Editor: David L Ginsburg, MD

 Primary Psychiatry. 2004;11(3):1-10

 

CME accredited monograph of an adapted analysis of a Medical Crossfire© educational initiative

Funding for this supplement has been provided through an unrestricted educational grant by Shire US


Faculty Affiliations and Disclosures

Dr. Biederman is professor of psychiatry and chief of the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts.

Disclosure: Dr. Biederman is on the advisory boards of CellTech, Cephalon, Eli Lilly, Janssen, Johnson & Johnson, McNeil, Novartis, Noven, Pfizer, and Shire; is on the speaker’s bureaus of Cephalon, Eli Lilly, McNeil, Novartis, Pfizer, Shire, and Wyeth; and receives research support from Cephalon, Eli Lilly, Janssen, Neurosearch, Pfizer, and Shire.

Dr. Chrisman is clinical assistant professor of psychiatry and medical director of the Duke ADHD Program at Duke University Medical School in Durham, North Carolina.         

Disclosure: Dr. Chrisman is a consultant to Shire and has served on the speakers’ bureaus of and received honorarium from Eli Lilly, McNeil, Novartis, and Shire.

Dr. Dodson is a psychiatrist in private practice in Denver, Colorado.

Disclosure: Dr. Dodson has been a consultant to Shire and has served on the speaker’s bureaus of Novartis and Shire.

Dr. Goodman is assistant professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine, director of Suburban Psychiatric Associates, LLC, and director of the Adult Attention Deficit Disorder Center of Maryland, all in Baltimore, Maryland.

Disclosure: Dr. Goodman is a consultant to Alza, Eli Lilly, Forest, GlaxoSmithKline, McNeil, and Shire; is on the speaker’s bureaus of Abbott, Alza, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, McNeil, and Shire; receives grants/honoraria from Abbott, Alza, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, McNeil, Shire, and Wyeth; and owns stocks in Bristol-Myers Squibb, Johnson & Johnson, and Pfizer.

Dr. McGough is associate professor of clinical psychiatry in the Division of Child and Adolescent Psychiatry at the David Geffen School of Medicine, University of California, in Los Angeles.

Disclosure: Dr. McGough is a consultant to Cephalon, Eli Lilly, McNeil, Novartis, and Shire; serves on the speaker’s bureaus of Eli Lilly, McNeil, Novartis, and Shire; and has received grant/research support from Boston Life Sciences, Cephalon, Eli Lilly, Janssen, McNeil, NIMH, Novartis, Pfizer, Shire, and Targacept.

Focus Points

Discuss the current diagnostic criteria of attention-deficit/hyperactivity disorder (ADHD) in adults and associated diagnostic challenges.

Review the prevalence, incidence, and socioeconomic impact of adult ADHD.

Discuss comorbid psychiatric conditions often encountered with adult ADHD and their effect on
management.

Compare the currently available pharmacologic agents for the management of adult ADHD.

Abstract

Historically considered a childhood disorder, the recognition of ADHD in adults is increasing among the public and medical community. Follow-up studies have consistently documented the persistence of ADHD into adulthood, yet disagreement over the degree to which ADHD is a chronic disorder continues. Furthermore, the subjectivity of ADHD symptoms in adults, combined with a lack of a “gold standard” to confirm the diagnosis, has had a negative effect on the recognition of this disorder. This is significant given the potential impact of adult ADHD on quality of life. Similar challenges extend into the management of adult ADHD. With medication as first-line treatment, clinicians need to choose the most effective strategy from among the available therapeutic options. The integration of self-management and behavioral approaches into the treatment plan and their effectiveness must be addressed as well. Also complicating the clinical scenario is the high prevalence of comorbid psychiatric conditions in these patients. Distinguishing these disorders from ADHD and identifying the most appropriate algorithms for management remain a challenge.

Joseph Biederman, MD

Clinical Characteristics

For years it was thought that attention-deficit/hyperactivity disorder (ADHD) does not persist into adulthood. However, recent data has clearly documented that ADHD is a prevalent condition affecting ~4% of adults. These adults have high rates of familial history of ADHD; show prominent paths of comorbidity with depression, anxiety, disruptive behavior disorders, and substance abuse; and exhibit dysfunctional symptoms similar to those identified in children with ADHD.1-6 For a diagnosis of ADHD, the disorder must be traced to childhood. This criterion enables the clinician to distinguish ADHD from cognitive problems that may afflict an elderly person.

Among children diagnosed with ADHD, there is a 50% chance that one parent has criteria for the same diagnosis. Often, a parent of a recently diagnosed child with ADHD will express having had the same symptoms in his or her own childhood. Some critics, dubbing this phenomenon “self-diagnosis,” have charged these parents with opportunism, ie, attributing their own failures and dysfunctional behavior to ADHD as a matter of convenience. However, the symptoms in the adult are recognized when the child is diagnosed; they are not influenced by the child’s diagnosis.7

Comorbidity: Age and Gender Differences

More than 70% of adults with ADHD will have at least one comorbid diagnosis, the prevalence of which is significantly different in men and women.2,3,8-12 Approximately 50% of children with ADHD have disruptive behavior disorders, such as conduct and oppositional disorders. These disorders are much more common in males than females and explains why male children are referred more often. These disorders are converted into antisocial personality disorder in adults. Mood and anxiety disorders are prevalent in ~30% to 50% of adults and children with ADHD. While there is a male to female ratio of 10:1 in children, the gender distribution for these disorders becomes more equal in adults, largely because patients at that age are usually self-referred. Learning disabilities are very prevalent in ADHD?patients and much more common in males than females. Finally, the rate of substance abuse in ADHD reaches nearly 50%; although quite prevalent in both genders, particularly in untreated adults, it is more common in males than females.

The rates of comorbid diagnoses quoted from the abovementioned research are lifetime rates. However, lower rates are often observed in the clinic because the comorbidity may not be afflicting the patient at the time of presentation. For example, a patient may have a history of substance abuse, bipolar disorder, or depression, but the symptoms are not currently bothersome whereas the ADHD symptoms are. 

Devising a treatment plan for the adult patient with ADHD?and comorbid disorders requires a careful undertaking. For example, the physician cannot evaluate cognitive dysfunction in the context of bipolar disorder or depression. In addition, some of the medications used for ADHD are depressogenic and should not be used in patients with unstabilized mood disorders. Once a treatment plan is in place to combat ADHD and the comorbidities, improvement can be assessed quickly and effectively using the Clinical Global Impression scale.

Pharmacologic Treatment

There is no treatment modality for core ADHD symptoms that is not pharmacologic. Stimulants remain the mainstay of treatment for both children and adults with ADHD. The extended-release stimulants are prefered because they have a longer duration of action and allow for less frequent dosing schedules. Medium-acting compounds only provide 6 hours of medication, which does not cover the average work or school day. These shorter-acting formulations usually require twice-a-day dosing to provide daylong coverage.

Stimulants are also preffered because of their safety profile. They have a very simple metabolic pathway, which leaves little concern about drug–drug interactions. Stimulants do not effect the cytochrome P450 system and therefore can be safely used with other psychotropics. Methylphenidate and amphetamine stimulants block the dopamine transporter; amphetamines also facilitate exocytosis.

There is little evidence to support the concern that ADHD?patients may use their stimulants recreationally. The uptake and decay of orally administered drugs in the brain are too slow to produce the excitement of addictive drugs such as cocaine. Most addicts are not looking for oral administration; they are looking for drugs to snort, inject, or smoke. Long-acting stimulants, such as mixed amphetamine salts (Adderall XR) and methylphenidate (Concerta), are even less likely to be abused. Furthermore, the adult with untreated ADHD has a phenomenal lifetime risk for substance abuse or dependence, which suggests that psychotropics may be protective against the emergence of subsequent abuse or dependence.

While stimulants remain the mainstay of treatment for children and adults with ADHD, nonstimulants may be appropriate for some patients. For example, stimulants may be anxiogenic in the adult with dysphoria and anxiety; fortunately, there are alternatives for such patients. Nonstimulants block the norepinephrine transporter; this indirectly releases dopamine in the frontal cortex, which enhances dopaminergic neurotransmission. Atomoxetine (Strattera), the only nonstimulant with an indication for adult ADHD, has shown superiority over placebo in several randomized, double-blind, controlled trials in children, adolescents, and adults.13 Atomoxetine tends to have side effects very similar to those of the stimulants, such as insomnia and loss of appetite. There is a small but tangible presence of sexual dysfunction associated with atomoxetine as well. More nonstimulants with different mechanisms of action will likely be available for treatment of ADHD in the future.

Allan K. Chrisman, MD

Transition of Symptoms

The criteria for diagnosis of ADHD were developed for children and are developmentally based. However, as children grow into adults, they take on new responsibilities, their lives get more complicated, and their social roles change. The child with ADHD?may grow into an adult with multiple areas of difficulty leading to underachievement. Yet, because the patient has lived with ADHD for so long, and because the symptoms have changed with each developmental stage, the disorder is often not recognized as ADHD.

ADHD which persists into adulthood is associated with high levels of school failure, poor work history, poor social relationships, impaired self-esteem, and a high incidence of psychiatric morbidity and dysfunction.14 Other, less obvious sequelae of adult ADHD include a higher divorce rate as well as dysfunctional relationships based on impulsiveness and lack of commitment.

Adults with ADHD tend to not seek treatment until their symptoms become unmanageable. Many will often first seek help when confronted with a new work-related challenge. Many patients in the workforce accommodate their ADHD symptoms by finding work that interests them. They may even become so successful that they earn a promotion; for example, from a sales position to an administrative position. However, with the new task may surface the impairment. Another impetus for treatment is the spouse who becomes frustrated with the patient’s behavior. Often, a patient may agree to seek help once the relationship suffers because they are too messy, too disorganized, or never on time.

Diagnosis and Management

In the primary care setting, if a patient presents with symptoms of anxiety or depression that do not respond to an appropriate course of treatment, the clinician must consider the possibility of a missed diagnosis or a coexisting condition. However, physicians do not typically recognize ADHD as a reason for lack of treatment progress. Developing a therapeutic alliance with the patient will help the physician properly determine what comorbid conditions are present and initiate appropriate treatment. Psychoeducation, the ability to talk with patients and help them to create reasonable expectations about treatment progress, back-up strategies, consultations, and other interventions, are critical.

In lieu of well-delineated management guidelines for adult ADHD, practitioners can turn to existing evidence-based guidelines for pediatric patients.15,16 There are principles of ADHD that do apply in the treatment planning for adults. When treating with stimulants, short-acting compounds may be appropriate for those patients who are responsible and reliable, while long-acting agents offer an advantage in patients who have significant dysregulation in lifestyle. In measuring the success of treatment for adult ADHD, valuable insight can be gleaned from reports by significant others and other family members.

Treatment with Stimulants

More than 30 years of experience suggests that stimulants are safe and have very few drug interactions. However, a physical examination is necessary to ensure that the clinician understands the health issues that may be relevant to the prescription choice. When considering prescribing stimulant medications in the adult population, the clinician must screen for other health issues, such as hypertension and the prehypertensive state. Even nonstimulant drugs may increase blood pressure to some extent. In women, dosing adjustments may be required due to fluctuations in estrogen and menopausal state. In pregnant women, prescription of stimulants may require a risk-benefit analysis, although there is no strong
evidence to suggest that these drugs are teratogenic.

Psychotherapy

Patients with a lifetime of functional impairment with ADHD and comorbid illness are often underachievers with poor self-esteem and counterproductive habits. These patients need to be supported and trained in a fashion similar to rehabilitation, to identify and overcome these problems through the adjunctive use of coaching and psychotherapy. However, treatment with psychotherapy must be understood within the context of comorbidity. If the patient’s impairments are due primarily to the comorbidity, such as anxiety or depression, the clinician must make sure that the comorbid disorder is addressed in the appropriate way before treating the ADHD. Thus, the role of nonpharmacologic treatment is often established before selecting a management strategy for ADHD. Because of the extent of the impairment in patients with comorbid illness, nonpharmacologic therapy may include individual, couples, or family therapy.

There are two dimensions to treating ADHD: the core symptoms and the associated features. Psychotherapeutic intervention is much more meaningful with respect to the associated features. Cognitive-behavioral therapies can be used to help educate patients about how to deal with anger, anxiety, and other associated features. Whether ADHD can be treated using only psychotherapeutic applications depends on how much impairment the patient can live with. As shown in the Multimodal Treatment of Children with ADHD (MTA) trial,17 a combination of behavioral therapy and drug therapy confers greater patient satisfaction than drug therapy alone and may allow for a reduction in drug dose.

 

William Dodson, MD

Diagnostic Complications

The clinical picture of the adult with ADHD is different than that of the child with ADHD. However, people do not outgrow ADHD—they outgrow our diagnostic criteria. While active work on defining diagnostic criteria for adult ADHD is needed, it helps to assess symptomatic adults using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)18 criteria. Research has shown that lowering the cutoff to only five of nine DSM-IV symptoms for adults is still pretty accurate. Part of the reason it is difficult to assess adult ADHD is because symptoms can come and go depending on interest level; when people with ADHD are interested in the task they are performing they may have no symptoms. In standard school and work paradigms, however, individuals are expected to apply their abilities to any given situation—a requirement unsuited to those with ADHD. The DSM-IV provides very measurable criteria despite the seemingly inconsistent symptoms in some patients.

Diagnosis is also complicated by the high rates of psychiatric comorbidity in ADHD patients. Tzelepis and colleagues9 assessed adults on the day they were diagnosed with ADHD and found that 42% had another active Axis I condition and 38% had two or more. Virtually all of them had at least one comorbidity. This finding underscores the importance of completing a thorough evaluation for other comorbid diagnoses even after ADHD is confirmed. The finding also explains the increased commonality of ADHD in psychiatry versus primary care: Because ADHD concentrates in those patients with mental health comorbidity, the psychiatrist is going to see far in excess of the estimated 5% prevalence in the general population. One symptom or comorbidity often overlooked in ADHD patients is insomnia. Many ADHD patients report spending 1.5–2 hours/night trying to fall asleep. Many continue to have hyperactive nighttime restlessness after the ADHD diagnosis.

In addition to the complications of comorbidity, diagnosis of ADHD?is often a prolonged process for other reasons. The patient and family must be educated about the disorder. In addition, the necessary development of a rapport between the doctor and patient takes time. In adults in particular, diagnosis of ADHD?is often delayed because they fail to seek help. After the patient has accommodated the disorder for many years, a new challenge may exhaust their ability to compensate. In both sexes, a breaking point in life is the key to seeking help. One of the biggest triggers for males to seek help for ADHD is the birth of a first child. The wife, who may have been organizing her husband’s life and making sure he gets places on time, now has to take care of the baby. The husband is left to deal with his dysfunctions alone.

Treatment with Stimulants

While diagnosis is complicated, treating ADHD is simpler because the medications are effective very quickly. Although the average person may feel more alert after taking stimulants, the change is dramatic and life changing in ADHD patients. The stimulants are widely considered first-line drugs and appear to work better than the second-line drugs. In addition, research has shown a greater effect and immediate response with the stimulants compared to the second-line drugs. The only drawback to stimulants is concern about their status as Schedule II drugs with a potential for abuse or diversion.

ADHD patients are more likely to use long-acting versus short-acting stimulants. By definition, the ADHD patient population is forgetful, disorganized, prone to losing things, and terribly unaware of time. They typically forget to take any medication that lasts only 3–4 hours. In fact, pharmacy data indicates that the average person prescribed an immediate-release stimulant medication fills only 5.42 of 12 prescriptions each year. With an extended-release product, the compliance rate automatically doubles or triples.

While there are several stimulant products, there are only two basic molecules to choose from: methylphenidate and amphetamine. Some physicians will try both a methylphenidate and an amphetamine preparation in each patient. Because optimal response can be achieved within a week in an adult, it takes little time to determine which type of medication the patient prefers. Thus, the second preparation can be tried even if the patient has achieved a response with the first.

Alternative Therapy

Approximately 33% of patients have tried everything they can think of to combat the disorder, before approaching a physician. Another 33% have tried an over-the-counter medication or a remedy advertised on television. The Feingold diet was widely advertised as a method of improving ADHD, but six studies refuted its efficacy. The thing to remember with alternative therapies, is that they usually do not work.

Concerns Specific to Women

Unwanted and unplanned pregnancies are part of the clinical picture of ADHD. There is an eight-fold higher incidence of ADHD among adoptees over the base rate.20 This high incidence has nothing to do with the process of being adopted; rather, it indicates how often people with ADHD have unwanted pregnancies and put their babies—who have a genetic tendency to ADHD—up for adoption. In Drugs in Pregnancy and Lactation19 12,000 stimulant-exposed pregnancies were reviewed and no evidence of teratogenicity with stimulant therapy was found. However, high estrogen states appeared to improve symptoms of ADHD; many women report that while they are pregnant they do not need medication for ADHD. Conversely, with menopause, many women with ADHD begin to suffer symptoms despite being on medication and become concerned that they may have Alzheimer’s disease.

 

David W. Goodman, MD

Diagnosis and Management

While research confirms the existence of adult ADHD, diagnosis is extrapolated from pediatric criteria as it is not yet available for adults. Because ADHD does not begin in adulthood, the clinician should establish a developmental history by interviewing the patient and outside informants when considering an ADHD diagnosis. A symptom checklist from the patient’s parents may confirm an observation of childhood symptoms that persist into adulthood. Evidence of chronic symptoms is necessary for the diagnosis.

One of the less obvious sequelae of adult ADHD includes the “ripple effect” that may result from the young adult driver with untreated ADHD. Such individuals are more likely to get into car accidents, particularly if they are substance abusers. Consequences may include increased insurance rates, loss of license, loss of job, and return to the parents’ home, thereby affecting the entire family.

Because of the high incidence of comorbidity in ADHD, an assessment must be made for each of the other potential psychiatric comorbid conditions, including substance and alcohol abuse. The clinician must then develop a pharmacologic plan that will treat each comorbid diagnosis without worsening the others. Complicating the issue is the potential for symptom overlap among comorbid conditions. For example, impaired cognitive functioning is a symptom of both generalized anxiety disorder and ADHD. In these cases, treating the comorbid conditions first may enable one to determine how much of the cognitive symptoms are a function of ADHD. 

In the absence of guidelines for treating adults with ADHD and concurrent psychiatric disorders, diagnostic prioritization is necessary for treatment. Substance and alcohol abuse is treated first, followed by bipolar disorder, other mood disorders, anxiety disorders, and ADHD. With this method, patients who are addicted to drugs do not receive stimulants until they are completely recovered. Similarly, patients are not treated with stimulants until their mood disorder has stabilized.  

An important measure of response to treatment is the ADHD-RS—a standard 18-item, four-point symptom scale, although adult psychiatrists tend to value the clinical interview for symptoms. In addition, outside informants can be very important for noting improvements. A patient may report that he or she does not notice much of a difference while on medication, but the patient’s significant other will note huge improvement.

Pharmacotherapy: Determining Factors

There is a widespread reluctance to prescribe stimulants for adults because of their status as Schedule II drugs with a potential for abuse or diversion. This stems from inadequate education about adult ADHD among psychiatrists and a long history of primary care physicians (PCPs) being dissuaded from prescribing stimulants. Nonstimulants, such as atomoxetine, offer an opportunity for PCPs to be comfortable writing a prescription for adult ADHD. This is advantageous because the physician will likely offer a stimulant medication once the patient is in treatment and has not responded to a nonstimulant.

A review of six studies of methylphenidate and two studies of pemoline in adults with ADHD found average response rates of 54% for each drug class.21 Controlled studies22,23 and open-label studies24,25 support the efficacy of amphetamines in adult ADHD, with one controlled study22 finding response rates of 70%.

While some physicians prescribe immediate-release stimulant formulations on an as-needed basis, such a strategy may leave patients unmedicated at critical times, eg, while driving a car. The long-acting agents Adderall XR (mixed amphetamine salts) or Concerta (methylphenidate) are generally preffered. Pemoline is useful in adults with a history of substance abuse, and the α2-agonists are effective for sleep disorder, hyperactivity, and fidgetiness when adequate control is not achieved with the stimulant. The antidepressants are useful in patients who also have mood lability, impulsivity, or irritable outbursts.

Psychotherapy

Psychotherapy may be used for the treatment of ADHD, depending on the degree of impairment. Cognitive-behavioral therapy can help patients understand the importance of the medicine and addresses the patient’s self-esteem, thus improving the likelihood of compliance with drug therapy. Unlike medication, psychotherapy does not address the core symptoms of ADHD, which is necessary for optimal response.

Future Research

No teratogenicity research has been performed for most of the medications commonly prescribed for ADHD. Thus, in treating a woman with stimulants, it is important to assess contraception and regularity of menstruation, and stress that she should not become pregnant while on these medications. However, patients are capable of becoming pregnant while on ADHD medications; studies need to be performed to address the issue of possible teratogenicity.

Unfortunately, there is very little literature on the use of stimulants in adults with comorbid medical illnesses or drug interactions. Men in their 40s may have prostate problems or hypertension; women in their 40s may have hypothyroidism. These are problems that typically do not arise in treatment with children, and must be further researched.

 

James McGough, MD

Assessing the Diagnostic Systems

While there are no clearly elucidated guidelines for adult ADHD, data indicate that adult patterns follow those established in children.14 Adults with ADHD reportedly exhibit high rates of antisocial personality, anxiety, mood disorders, depressive disorders, and alcohol and substance abuse disorders.1-6 Data also show that men often have a school-age history of being hyperactive, getting in trouble, or having a discipline problem. Women often do not present with these childhood symptoms but rather with inattentiveness, and feeling “spacey” at 12–15 years of age. Women are less likely than men to exhibit severe conduct disorders in association with ADHD.3,10-12,26

There are two distinct systems of diagnosis: the DSM-IV18 and the Utah criteria27 of Paul H. Wender, MD (interest-based criteria). Both systems have been used to identify adults with neurocognitive, biological, and treatment-response patterns similar to those of children with ADHD. Research28-30 has shown that the DSM-IV criteria are helpful in the identification of adults who have the same patterns of comorbidity and the same source and rates of learning disabilities as children with the disorder. In addition, neuroimaging findings in adults parallel those seen in children, and genetic evidence indicate that biological and clinical data in adults correlate with those in children. However, there are some limitations in using these criteria in adults, as they were tested only in school-aged children. Many of the symptoms, such as excessive running and climbing, do not apply to adults. Moreover, there may be a whole set of symptoms relevant to adults that have yet to be defined and tested. Another diagnostic problem is that one major criterion for diagnosis of ADHD is evidence of the disorder before 7 years of age; many severely impaired adolescents or adults cannot remember what happened yesterday let alone when they were that young. Thus, while the DSM-IV
criteria do work, they do not address the whole picture.

Physicians must remember that response to medication cannot be used as a diagnostic tool. These medicines confer the same effects on everyone; if a patient without ADHD were to take one of these medications, he, too, would be calmer, more focused, and less impulsive.

Psychotherapy and Alternative Medicine

ADHD is a neurodevelopmental disorder that is primarily genetic. The brain of the ADHD patient operates differently than the average person and often results in life experiences that may be addressed through psychotherapy. Understanding the childhood condition is the first step toward treating the adult condition. Some physicians argue that ADHD can be treated using psychotherapeutic applications alone in some patients. However, psychosocial treatments developed for childhood ADHD have repeatedly failed. If the patient has poor social skills, psychosocial intervention may improve his social skills but it will not help his ADHD. There is no evidence on which to base the practice of psychotherapy as a treatment for ADHD. 

In addition, there is no scientific evidence that any alternative or complementary therapy works. Reliance on these ineffective remedies is unfortunate because they prolong the time spent with symptoms. Furthermore, people have died from taking over-the-counter stimulants.

Pharmacotherapy and Stimulants

It is important to identify the patient’s domains of impairment before beginning treatment. The patient who initially reported difficulty with his job but returns and says his work output has tripled, is a treatment success. However, if the impairment is not defined initially, the physician will not know if the patient is exhibiting a response.

For the treatment of ADHD, stimulants are available in 4-hour, 8-hour, and 12-hour formulations. The appropriate treatment plan is dependent on the individual patient’s needs. Short-acting medications may be useful in some cases; for example, a patient may benefit from taking medication in the morning to focus on law studies and letting it wear off in the afternoon when at the gym. 

There are two universes of stimulants: amphetamine and methylphenidate. Methylphenidate works by blocking the dopamine transporter. Amphetamine blocks the dopamine transporter as well, and leads to increased release of catecholamine neurotransmitters. Amphetamine is approximately twice as potent as methylphenidate in terms of dose. Methylphenidate products include Focalin, a 4-hour drug, Metadate CD, an 8-hour compound, and Concerta, an 8–12-hour compound. Amphetamine products include Dexedrine and Adderall, which are 6-hour compounds, and Dexedrine Spansule and Adderall XR, which are 12-hour compounds.

Physicians who choose to prescribe stimulants in drug-abusing patients should get a clear patient history, document the criteria that support the diagnosis, and provide evidence that the decisions are rational. Many physicians do not hesitate to prescribe stimulants in patients with past drug use or in patients actively using marijuana. However, they will not prescribe a stimulant to a patient who is actively using opioids or cocaine. These decisions must be an individual judgment based on the clinician’s clear sense of the patient.

It is important to remember that even the best medicine will work optimally in only ~70% of ADHD patients. When the right stimulant is prescribed, the physician will know when the target dose has been reached. Patients should be taken through the dose range in a systematic way. Optimal dose should be determined by starting in a low range and titrating properly.

 

Question & Answer Forum

Q: Is it possible to develop ADHD?as an adult without ever having experienced it as a child?

Dr. Biederman: It is estimated that ~2% of ADHD patients appear to experience symptoms for the first time during adulthood. While one does not have an acute attack of ADHD at the age of 25, symptoms may first appear at that age in people who had relatively minor childhood symptoms. It appears that for many people the existence of the boundaries of school, obligations, and deadlines provides necessary structure to do well. However, as one grows older the symptoms become more obvious because the person has more responsibility. Things like having a job and a family require multi-tasking and organizing. There is a group of people who have a terrible time functioning in real life once they leave the structured environment of school and their youth. 

Q: How do you differentiate between bipolar disorder and ADHD? And what medications are the most effective in patients with both disorders?

Dr. Goodman: Bipolar disorder is episodic in nature. It is predicated on the subjective mood symptoms coupled with the energy, sleep, and vegetative symptoms. My patients have often said they can tell the difference qualitatively between being happy and being hypomanic, being sad versus being depressed. Cognitive impairments in mood disorders are tied to the mood episodes and they do not occur interepisodically. Thus, if a patient reports that not only has their mood improved interepisodically, but their cognition has not, they likely have both ADHD and bipolar disorder. If the cognitive impairments do not exist when the patient is euthymic, then the cognitive symptoms are a function of the mood disorder, not the ADHD. In patients with both disorders, I usually treat the bipolar disorder first and once they are stable for 2 months, I will treat the ADHD with stimulants. In treating several hundred bipolar ADHD patients, I can recall only two who had mood destabilization with the addition of a stimulant. 

Q: Is there a testing tool for diagnosing adult ADHD?

Dr. McGough: ADHD is a clinical diagnosis, from my view, preferably rooted in the Diagnostic and Statistical Manual of Mental Disorders18 criteria. Everyone wants the holy grail of the objective measure of ADHD diagnosis. Categorically, there is no justification whatsoever to use neuroimaging, electroencephalogram imaging, computerized tests, or psychological testing. None of these things give a diagnosis. The diagnosis is rooted in a clinical assessment alone. 

Q: What is the impact of obesity in dosing, and how does one dose stimulants in adults in general?

Dr. Biederman: If one uses stimulants that are consistent with what is used in children, but is adjusted for weight, one will obtain the same kind of exceptionally good response seen in children. In adult ADHD, it is necessary to use doses that are potent and allow for the optimal effect. We generally use weight as a guide; we start low and titrate to 1–1.5 mg/kg/day of methylphenidate or an equivalent. 

Q: How can biofeedback be applied in the treatment of ADHD?

Dr. Chrisman: Studies show that biofeedback is not effective. The notion that one might gain some state of relaxation does not address the core symptoms and it is not a proven treatment method.

Dr. McGough: It is also an expensive method. One can spend $3,000–$5,000 for completely untested treatment or one can spend a fraction of that using medications that have been proven to be effective. 

Q: Can one lower the dosage of a stimulant by combining it with a nonstimulant?

Dr. Goodman: I do not know of any published research or even a case report using nonstimulants and stimulants. However, it is a common combination. Usefulness of this method depends on what the goal of the treatment is. It makes sense for the patient to be on both medications if they are for two completely different reasons—for example, a stimulant for ADHD and an antidepressant for comorbid disorders. However, some may prescribe a combined regimen of atomoxetine and Adderall XR,?in hopes of achieving a sustained effect over 24 hours with a lower dose of amphetamines. However, I think unnecessary concern about stimulant doses prompt physicians to use this combination. 

Q: What is your experience with atomoxetine in terms of efficacy and tolerability?

Dr. Chrisman: Clinical trials demonstrate that the efficacy is there. Atomoxetine was FDA approved for use in adults with ADHD. This agent may require a complicated titration over time to gain full effectiveness. The dosing guidelines for atomoxetine are still being worked out. There is a suggestion that perhaps the dosing initially suggested by the data may not be the most robust ones to use. In addition, there are side effects of atomoxetine which are very different in adults than in children, although they tend to be mild. They include insomnia, dry mouth, nausea, and other types of side effects that are more similar to those associated with selective serotonin reuptake inhibitors, such as sexual dysfunction. Because the drug is in a postmarketing phase, the dosing question lies with clinicians’ experience, which has been variable. In the initial studies, the dosage went up to 1.8 mg/kg in children and adolescents and 120 mg in adults, but there are suggestions that a higher dosage may be necessary.

Q: How can one identify stimulant abusers who have simply memorized the symptoms of ADHD to get drugs?

Dr. Biederman: There is a common suspicion that every adult complaining of ADHD has done so for the specific purpose of obtaining a prescription for psychostimulants. This is one of the most prejudicious positions that adult clinicians, particularly adults psychiatrists, make. The truth is, there is little evidence to support the concern that stimulants are used inappropriately in ADHD patients. The population of people who seek stimulants for the treatment of ADHD and that of those who use drugs for recreational use, are completely different. Moreover, the long-acting stimulants are extremely unlikely to be abused. Furthermore, adults with untreated ADHD have a significantly increased lifetime risk for substance abuse or dependence. Thus, if a patient has the criteria for diagnosis ADHD, he or she should be treated.

Dr. Dodson: In practical terms, the abuse of ADHD medications is extremely low, while the rate of substance use is 50% in untreated adults. Thus, physicians must remember that the real risk is in not treating the disorder. The typical 1-month prescription for stimulants is not a practical decision made by physicians due to likely abuse; rather, it is dictated by the managed care company that wants the co-payment every month. I am comfortable with prescribing a 3-month prescription for patients who get their medications from companies that allow for such prescriptions through mail order.  

Q: Is there a lot of comorbidity between atypical depression and ADHD? And can atypical depression be treated with stimulants?

Dr. McGough: I tend not to see the atypical depression in patients with ADHD.
 

Dr. Biederman: Atypical depression should be treated with the armamentarium for depression not that for ADHD. That being said, the stimulants are frequently used as augmenters for depressions that have fatigue and cognitive clouding associated with it. 

Q: What key thoughts would you like to leave with the audience?

Dr. Biederman: Clinicians should not take a punitive prejudicial position with patients who present to their office. They should assume that the person complaining of ADHD symptoms is doing so legitimately rather than to obtain psychostimulants for recreational use.

Dr. McGough: Along the same lines, when physicians do not understand the reason for something, like pain or headache, they tend to think it is made up. However, these symptoms are real. ADHD is a real disorder with evidence of genetic and other biological imaging findings. When patients complain that they are hurting, physicians should believe them and initiate treatment.

Dr. Goodman: With these presentations, those who were unfamiliar with ADHD now have more information. Those who were skeptical about ADHD have been informed that there is data to legitimize the disorder. I hope that psychiatrists and primary care physicians alike will put ADHD on their radar screen.

Dr. Chrisman: There are very effective treatments for this disorder. As complex as diagnosis and treatment may sound in the presented discussions, physicians can be very effective in their treatment of ADHD and can greatly improve the lives of their patients.

Dr. Dodson: Physicians should not fear ADHD, rather they should embrace it. The positive thing about treating ADHD?is that the patients get well. Nowhere else in psychiatry can physicians significantly improve the lives of their patients as rapidly as in ADHD. It is a great way to practice.

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