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Psychiatric Times
Psychiatric Times Vol 23 No 13
Volume 23
Issue 13

Real-World Office Management of ADHD in Adults

Office management of attention-deficit/hyperactivity disorder (ADHD) differs in many important ways from ADHD management conducted in a research environment. In clinical trials, treatments and eligible patients are selected in advance by committees, patients are randomized to different management strategies, and both clinicians and pa tients are blinded to the treatments.

Office management of attention-deficit/hyperactivity disorder (ADHD) differs in many important ways from ADHD management conducted in a research environment. In clinical trials, treatments and eligible patients are selected in advance by committees, patients are randomized to different management strategies, and both clinicians and patients are blinded to the treatments. In general, one treatment variable is tested at a time. Dosage adjustments are usually made according to the re search protocol rather than according to patient response. Results are aggregated and presented for an "average" patient.

In the real world of psychiatric practice, we see every patient who comes through the door. We use only active treatments, and we persist until we find the best one for a particular patient. Be cause we are dealing with complex hu man beings, who often have other coexisting illnesses, we examine every aspect of their lives to find the best possible combination of therapeutic options. We treat individuals, not averages, and must adjust the treatment to the unique needs and responses of each patient. In this article, I will share what I have learned about optimal office management of adolescents and adults with ADHD.

A FUNCTIONAL DEFINITION
Our understanding of ADHD and its treatment was changed by a 2004 study from the New York University Child Study Center.1 Investigators tested the hypothesis that children with ADHD would experience significant improvements in functioning while taking methylphenidate combined with intense, multidisciplinary psychosocial treatment or with attention control training, compared with methylphenidate alone. In addition, investigators hypothesized that compared with children taking only methylphenidate, more children receiving multidisci plinary treatment plus methylphenidate could have their dose of medication lowered or could even dis continue methylphenidate treatment.

A total of 103 children aged 7 to 9 years who were free of conduct and learning disorders and who were documented responders to short-term methylphenidate treatment were randomized to receive methylphenidate alone; methylhenidate plus an intensive multimodal treatment that included parent training and counseling, social skills training, psychotherapy, and academic assistance; or methyl phenidate plus attention control treatment. During the 2-year course of the study, the investigators were unable to demonstrate that combination treatment was as sociated with superior functioning. Combination treatment did not allow discontinuation of methyl phenidate treatment; the study failed to demonstrate significant benefit from adding an ambitious psy chosocial intervention to the regimen. Significant benefits from methylphenidate persisted for 2 years.1

The findings have led to the relatively new concept that ADHD is not a disorder characterized by deficits of effort, character, willpower, brain ac tivity or size, or integrity. Neither is it caused by poor parenting skills or by diminished executive function, self-control, neurotransmitter levels, or intelligence. A newer, functional definition tries to understand ADHD as a genetically based neurologic disorder characterized by difficulties in engaging on demand in work, school, or per sonal situations. This difficulty in be-ing engaged on demand explains why many patients with ADHD seem to function very well in some situations but are distracted and disorganized in others.

Unfortunately, school and work environments require the ability to engage on demand, and these are the environments in which people with ADHD often perform poorly. This disparity in attentiveness in different situations often leads parents and employers to make a moral judgment that ADHD represents a failure of will, effort, or self-control. Our new understanding that ADHD is a genetically based neurologic disorder challenges this view. It also sheds light on the management strategies that are most likely to help these patients. Because ADHD is a neu rologic condition, we should not expect behavioral techniques to be any more successful as a cornerstone of treatment than they would be in the treatment of a fever, for example.

A DIFFERENT NERVOUS YSTEM
People who do not have ADHD have importance-based nervous systems. That is, the importance of a task helps them engage with it immediately, get access to their abilities, and persist with the task all the way to completion. They see the tasks that require completion, arrange them in order of priority, engage in them, and gain access to the skills they need to complete the tasks. Even when a task is more important to an employer, spouse, teacher, or parent than to the person himself or herself, a person without ADHD still manages to accomplish it.

Adults with ADHD report that they cannot remember a single instance in which the importance of a task all by itself ever helped them accomplish it. To a person with ADHD, importance is nothing but a nag. The helping techniques often offered by teachers or parents are importance-based, not interest-based, and do not work for people with the interest-based nervous systems of persons with ADHD.

Every aspect of performance, mood, and energy in a person with ADHD is determined by his or her momentary sense of 4 things: interest, challenge or competitiveness, novelty, and sometimes a sense of urgency brought on by a deadline or impending disaster. In these circumstances, persons with ADHD can engage and produce huge amounts of high-quality work on dead line-as with the student who com pletes weeks of work the night before an examination or the night before a paper is due. Every person with ADHD can recall a lifetime of experiences in which they are "in the zone" and per form at a high level, only to have it slip away when they lose their sense of in terest, challenge, novelty, or urgency. The clinical challenge is to find multiple ways by which people with ADHD can accomplish the tasks of their lives on demand.

3 STAGES OF OFFICE-BASED TREATMENT
Office-based treatment of adult ADHD includes 3 stages, as shown in Table 1. The first stage includes a thorough assessment of ADHD and all coexisting conditions; aggressive medication management of all the conditions present; and restoration of patient morale. The second stage includes helping pa tients learn to manage an interest-based nervous system and to disregard the importance-based techniques that they have been taught and that they have seen working for people with importance-based nervous systems. The third stage of treatment includes an assessment of the current level of skills necessary for autonomous adult functioning and the acquisition of interest-based skills.

 
 
Stage 1
Thorough assessment of ADHD and all coexisting conditions that impair patient's engagement and mental functioning
Restoration of morale and of hope that things can be different
Aggressive medication response to all conditions found
 
Stage 2
Learning to manage an interest-based nervous system
Unlearning importance-based techniques that will never work
 
Stage 3
Assessment of skills necessary for autonomous adult functioning
Acquisition of interest-based cognitive skills

Stage 1: Assessment, morale, medicationAssessment. First impressions are important. We recommend that psychiatrists who treat adults with ADHD make a special effort to make the office environment welcoming. Many of these patients have what has been termed rejection-sensitive dysphoria. They are excessively sensitive to the mere per ception of rejection, criticism, or ridicule. Many experience what can only be called affective storms as a result. Patients may fail to engage with a practitioner whom they perceive to be analytical, judgmental, and aloof. We encourage our staff to be welcoming and friendly, and we offer soft drinks and snacks in a relaxed and informal setting. These measures send a welcoming signal to patients.

The first step in the treatment of any person with apparent ADHD is a thorough assessment, as outlined in Table 2. In our practice, this may take as long as 3 hours. As many as 70% of patients with ADHD will have another Axis I diagnosis.2 We confirm the ADHD diagnosis while looking for other potential problems, including perceptual problems, learning difficulties, and anxiety.

 
 
Current medications
Contraindications to stimulant use
Heart disease, glaucoma, neurologic conditions/seizures
Conditions that mimic ADHD
Sleep apnea, head injury, petit mal seizures
Academic history (educational testing, if available, special education history)
Work history
Common comorbid conditions in patients with ADHD
Learning disabilities
Substance use disorders
    Mood disorders (unipolar and bipolar)
Anxiety disorders (general anxiety disorder, obsessive-compulsive disorder, panic disorder)
    Sleep disturbances
Oppositional defiant disorder/conduct disorder/antisocial personality disorder
Physical examination
Cardiac workup only when necessary according to history
Baseline blood pressure and heart rate
No screening blood work; scans; computerized continuous performance tests or psychometric testing unless indicated by something in the history (eg, estrogen level in perimenopausal women)

Obtaining a general medical history, along with a list of current medications, is essential. Glaucoma is the only absolute contraindication to stimulant use.

Ask about a female patient's menstrual status. While there has been no formal research concerning this matter, ADHD medications are likely to be less effective when estrogen levels are in the low physiologic range. When large numbers of women stopped taking hormone replacement therapy because of reports of an association with myo cardial infarction and stroke, physicians who treat adults with ADHD received complaints from many of these women that their ADHD medication had be come ineffective; when they resumed taking estrogen, the ADHD drugs began working again.

Particular attention to the cardiovas cular system and especially any fam ily history of early heart disease is essential, because of the presumed risk of cardiac complications with some ADHD medications.3 This perception of increased cardiac risk is being challenged, however. Wilens and colleagues4 have demonstrated that mixed amphetamine salts can be used with safety in adults with preexisting cardiac disease. The details of the cardiac evaluation are shown in Table 3.3

 
 
Congenital or acquired heart disease
Palpitations, chest pain, syncope, postexercise symptoms, murmurs
Family history of premature cardiac disease (age < 30 years)
Other medications (including stimulating over-the-counter medications, such as cold medicines and weight-loss products)
Blood pressure/heart rate: at baseline and each follow-up visit
Adults: cardiac workup only as indicated; no routine or screening electrocardiography, echocardiography, Holter monitoring, or treadmill testing
Suspicion of cardiovascular outflow defect: workup as indicated

It is important to ask about conditions that might mimic or coexist with ADHD, such as petit mal seizures, distraction by obsessions of obsessive-compulsive disorder, bipolar disorder, or head injury. Sleep apnea is a major problem in this regard. We have seen patients with sleep apnea whose daytime behavior bears considerable resem blance to that of people with ADHD. If you suspect sleep apnea, you may need to ask a bed partner whether the patient snores in an apneic pattern.

In a recent study, investigators recorded sleep and assessed behavioral, cognitive, and psychiatric morbidity in 105 children aged 5 to 13 years. Of these, 78 were scheduled for adenotonsillectomy, and 27 were undergoing unrelated surgical care. All assessments were repeated 1 year later in 100 children from the original group. Before surgery, the children who eventually had an adenotonsillectomy were more hyperactive, more inattentive, sleepier, and more likely to meet diagnostic criteria for ADHD, compared with controls.5 One year after surgery, the 2 groups of patients exhibited no significant differences in the same measures. Children who had an adenotonsillectomy showed marked improvements on all measures of hyperactivity, inattentiveness, sleepiness, and ADHD criteria. In contrast, controls showed no improvements.5 The lesson from this and related studies is that sleep quality and duration deserve special attention whe n ever the diagnosis of ADHD is under consideration.

Another condition worth considering is a head injury, which can leave sequelae that include the basic ADHD triad of high distractibility, impulsivity, and agitation. Petit mal seizures can also cause behavior that mimics ADHD-related distractibility. A notable finding that helps distinguish between ADHD and petit mal is that while patients with both conditions may com plete a work assignment, the person with petit mal seizures will remember to turn it in while the person with ADHD commonly forgets to turn it in.

Conditions that are often comorbid with ADHD in adults include Axis I major psychiatric disorders. Learning disabilities, substance abuse, mood disorders, anxiety, sleep disturbances, oppositional-defiant or conduct disorder, and antisocial personality disorder are 2 to 4 times as common in people with ADHD as they are in the general population.

During the evaluation, you may find that you and the patient do not communicate clearly about emotions, and this can make an already long assessment even more arduous. Compared with other people, patients with ADHD have unique ways of describing their internal emotional states.

When a patient describes his mood as depressed, always ask for examples and a description of the events surrounding the depression. What the ADHD patient describes as depression is usu ally clearly tied to a triggering event and matches the nature of the trigger. The mood change is instantaneous. In other words, these are normal reactions in every way except intensity. For patients with ADHD, these emotional reactions are short in duration and can be quickly relieved when the patient is able to participate in some challenging and interesting activity. Rarely do the "downs" of ADHD last more than 5 to 7 days, and usually only a few hours. This is a diagnostic criterion that can be quite useful in distinguishing ADHD from major mood disorders.

Similarly, when patients with ADHD talk about feeling anxious, what they are often describing is the mental and physical agitation that accompanies hyperactivity. What they are calling anxiety is actually the somatic expression of hyperactivity, including a constant feeling of tension and an inability to stay still to read, watch television, or go to sleep.

Morale. We begin working to boost the patient's morale immediately at the first visit. Success in school and work has been elusive for these patients, despite serious efforts on their part. Be aware that these patients are often seriously demoralized and convinced that they are doomed to repeated failure. The messages that they receive from you, your staff, and your office environment should be positive, en couraging, and realistically hopeful about the future.

Ask about family members with ADHD symptoms. If one parent has ADHD, each child has about a 50% risk of having the disorder.6 One of the leading causes of treatment failure in children with ADHD is failure to treat a parent who also has ADHD; if a treatment plan is to be implemented by a parent with untreated ADHD, it has little chance of being followed. Bear in mind that a parent with ADHD faces an extraordinary burden: he must manage his own behavior as well as manage complex behavior modifications and medication schedules in his affected children.

Visits to the patient's home and office make it easier for the clinician to assess the degree to which ADHD interferes with the patient's functioning. Taking digital photos of these areas before treatment and at various points during treatment helps assess the patient's progress. In most cases, patients will not disclose the degree of disorder and disorganization in their work and home lives, which is why a personal visit by the physician or a staff member may be helpful. Remember, too, that patients will be enormously sensitive to your perceptions, so take care to avoid seeming surprised or disapproving of the state of chaos and disorganization in their homes and workspaces.

Medication. Medication choices for patients with ADHD are expanding. In our clinic, we no longer use immediate-release medications because they provide no advantage; they merely give a notoriously forgetful patient population yet another chance to forget. Com pliance with the regimen is increased 2- or 3-fold by the use of sustained- or extended-release formulations. The benefits associated with these formulations are more consistent and sustained than those obtained with im mediate-release medications. They also produce fewer rebound phenomena than immediate-release products. Patient confidentiality and privacy are ex tremely important to this population, and extended-release formulations are the only practical way to get through the school or workday without being observed taking medication. We are optimistic about the role of a skin patch delivery system for methyl phenidate for children with ADHD, and we expect it to improve compliance.

The question about upper dose limits often arises in clinical practice. It is im portant to understand that the upper daily dose limits specified in FDA-approved package inserts for stimulant medications were chosen arbitrarily and have little clinical or research basis. They are based on the highest dosages used in phase 3 FDA trials that are designed only to show that the product is effective and safe. These studies are not designed to provide guidance on optimal clinical practice. The manufacturers set the dosages high enough in these studies to demonstrate effectiveness while minimizing any chance of an adverse effect that would prevent the product being approved by the FDA. Since the FDA will only allow the highest dosage from these studies to be mentioned in package inserts or other communications from the drug company, almost all medications have low maximum doses listed in package inserts and in the Physicians' Desk Reference.

This does not mean that higher dosages cannot be used. FDA guidelines require physicians to use drugs "according to their best knowledge and judgment" and to "be well-informed about the product, to base its use on firm scientific rationale and on sound medical evidence."7 Our advice is to treat the patient in front of you. Docu ment that with each increase in dosage, significant clinical improvements are apparent and that the patient has no clinically significant side effects. Do not stop increasing the dosage at the first sign of improvement. See if continued dosage escalation provides even more improvement.8

We start with the lowest available dosage of the most reliable delivery formulation currently available for either methylphenidate or amphet amine and titrate according to age. For prepubertal patients, the fastest the dosage can be increased is once a week, which allows feedback from teachers and from parents observing at home and during a weekend to be integrated. Older adolescents and adults can often have their medication dose changed every day as long as they see a clear improvement in target symptoms and no side effects other than a mild and transient loss of appetite. The blood pressure and heart rate will show that the patient is not receiving autonomic overstimulation. Once an adult patient is receiving a stable dosage of medication, the dosage generally remains stable for the rest of his life. In up to 5% of adult patients, however, it may be necessary to adjust the dosage after 6 to 9 months of treatment.

Stage 2: Managing an interest-based nervous system
The second stage of management includes instructing the patient on how to work with an interest-based nervous system. An important and difficult task is to help patients relinquish the efforts they have made to work with an importance-based nervous system. Patients often resist this phase of treatment, insisting that there must be some way for them to force themselves to work and succeed the way that others do.

Humor is a powerful tool with these patients, as long as it is not at their expense. We often tell them that persisting with an importance-based strategy is like trying to operate a lawn mower using a manual for a VCR. They require reminders that their brains function differently from those of people without ADHD and that they need to learn to work differently. Teaching these pa tients new techniques is easier than getting them to relinquish the old ones.

Stage 3: Assessment and acquisition of skills
The third stage of treatment begins after about 12 weeks. Patients do not need behavior modification; they need to learn how to access skills they already have that are based on interest, challenge, and novelty. In this phase, it is essential to understand that patients with ADHD do not organize themselves or their activities around time. In our experience, 85% of adults with ADHD do not wear watches. Instead of organizing around time, they organize by deadlines and colors. One strategy that often works for a 5-day work week is to place each day's assignments in different-colored folders, with an admonition that the tasks in the folder for each day must be completed by the end of that work-day. When possible, patients should purchase inexpensive electronic organizers and learn how to use them.

OBSTACLES TO COMPLIANCE
Adherence to the prescribed drug regimen is notoriously poor among patients with ADHD. In a study that included more than 5600 patients taking several different drugs for ADHD, investigators found that half the patients stopped taking the drugs within 3 months of the start of treatment and that by 18 months, 80% of patients had discontinued their medication. Discontinuation rates were the same regardless of the medication that was prescribed. Race, sex, age, and prescription drug coverage status had no bearing on the findings.9 These data confirmed the findings of 2 previous studies. Perwein and associates10 found that 85% of children and 88% of adults were adherent for less than 2 months. Sanchez and colleagues11 demonstrated dropout rates of 50% to 63% in 9549 children with ADHD during a single school year.

Various studies have provided in sight into the factors that lead to poor treatment adherence among patients who receive prescriptions for ADHD medications. Perhaps the most common reason that patients stop taking prescribed medications is that they do not understand the goal of drug treatment. Medication levels the playing field so that patients can begin to learn the skills necessary to live with an interest-based nervous system.

Often, patients-and some physicians-expect a medication to eradicate ADHD symptoms in the same way in which an antibiotic appears to eradicate an infection.9 The treating physician must explain at the outset that ADHD is a chronic disorder that re quires lifelong treatment with medications and the constant honing of important skills. Patients need to know the consequences of discontinuing treatment. How would your patients answer if asked why they take medication for the symptoms of ADHD? How much do they understand?

If patients sense that a physician is not supportive of medication or is un convinced of its benefits, they are less likely to comply with it. In this country, physicians tend to prescribe ADHD medication for use during the school week but not on weekends, in the evenings, or during vacations. Like the physician, the patient soon comes to think of ADHD as strictly a school- or work-related problem; but some of the most damaging consequences of ADHD, such as reckless sexual activity and substance abuse, occur during evenings, weekends, and vacations. An increasing body of clinical data suggests that these consequences of untreated ADHD are mitigated by diligent treatment and compliance.

12

Sometimes, the patient simply is not organized enough to continue getting prescription refills and keeping appointments with the physician. We phone each patient the day before each office visit. Without these calls, our no-show rate is 50%. With reminder calls, we are able to cut unused clinical time to less than 10% by either avoidance of no-shows or rescheduling of appointments. We also send e-mail reminders when appropriate. Similar reminders are necessary to ensure that patients get the required blood tests. All instructions about medication should be provided to the patient in written form.

It takes considerable effort on the part of the clinician to find the best medication, the optimal dosage, the best dosing system, and the most favorable side-effect profile for an individual patient. Much of this effort is in vain without continually checking with the patient to assess compliance. We give every patient a pillbox timer. We always try to enlist a significant other to help monitor the medication regimen.

At each follow-up visit, we ask to see the pill bottle to assess compliance. A patient's awareness that a physician or nurse will be checking his compliance regularly enhances his adherence to the medical regimen. Failure to assess compliance sends a message to these patients that the medication is not im portant. We obtain agreements from patients in advance to participate in occasional random drug screens to check for compliance with the regimen. Our attitude is "trust, but verify."

Patients sometimes point to side effects as the reason for discontinuing medication. As a rule, well-adjusted dos ages of stimulant medications cause few side effects after the first few weeks. When arousal side effects do occur in the course of treatment, they are almost always caused by the patient adding another stimulant medication. Caffeine, which patients may formerly have found beneficial, may now cause unpleasant jitteriness. Smoking produces both diastolic hypertension and rapid heart rates that may be attributed to the ADHD medication. Decongestants such as pseudoephedrine are found in over-the-counter multisymptom cold/sinus/hay fever medication. Systemic corticosteroids cause significant hyperarousal when used concomitantly with any ADHD medication; inhaled and intranasal corticosteroids are usually tolerated well. Prescription and over-the-counter weight loss drugs may also contain stimulants.

MANAGED CARE AND FINANCIAL ISSUES
Can ADHD be treated successfully under managed care plans? That question arises frequently and causes con sid erable anxiety among practitioners. Thorough ADHD evaluations can be enormously time-consuming. The history-taking process is lengthy, and patients tend to loquacity. The review of prior treatment and school records, the neurologic evaluation, assessment for comorbidity, and the need for extensive patient and family education add to the time burden. Useful current procedural terminology-4 codes for these activities are shown in Table 4.

 
 
90887: Consultation with family
96115: Neurobehavioral status examination (Mini-Mental State Examination, computerized continuous performance testing)
99080: Special reports (IEP input, accommodation letters)
99071: Patient education materials
99342: Home visits, moderate
IEP, individualized educational program. monitoring, or treadmill testing

Certain administrative modifications ease the difficulties of treating adults with ADHD. We find it helpful to ob tain all paperwork in advance. We do not schedule appointments until paperwork is completed. Alternatively, some practitioners may ask patients to make an initial deposit of $100; this often enhances patient attendance at the first appointment.

Because a considerable amount of physician and/or staff time has been used or set aside, the fee is charged if the patient cancels or is absent, leaving the clinical time unused. We have found that our no-show rate is quite low after patients have made an investment in advance by completion of paperwork and/or payment of a non refundable deposit.

Financial neglect and impulsiveness are a common consequence of untreated ADHD and should be addressed early on. It is often necessary to require that payments be made at the time of service. We assess an extra charge for carrying a balance on the account. The patient must agree in writing to pay for all late or missed appointments.

Managing time and being punctual is an almost universal impairment in patients with ADHD. It is thus therapeutically, administratively, and financially important to clarify these time and payment issues from the very start of treatment.Remember that medical and drug costs can be a problem for many patients. The type of medication and treatment plan will be affected depending on coverage. None of the medications is cheap, and even working families that do not have insurance may find them financially out of reach. Many of the pharmaceutical companies have come together in the Partnership for Prescription Assistance program at a single Web site (www.pparx.org) to facilitate access to their assistance programs.

As you evaluate the adult patient with ADHD, be aware of the need to evaluate other members of his family. This condition is highly genetically linked. The evaluation may start with the identified patient, but the family will become involved as treatment proceeds. For example, if your patient has children, each has at least a 50% chance of hav ing ADHD. Very likely, this is a family in need of professional assistance. The demands of a child with ADHD may overwhelm any parent, especially one who himself has ADHD. You may also find that the patient has siblings or other relatives who require treatment for ADHD. In our clinic, we treat extended families. At one point, we were treating 40 related people in one family and 60 people in another.

CONCLUSION
I have described the difficulties and pitfalls of treating patients with ADHD, so it may surprise readers to know that I have quite a lot of fun with my pa tients. Where else in medicine would you have an opportunity to begin turning around a patient's life in an afternoon? It is gratifying work. Begin building the emotional bond at the first visit, be sure patients understand the chronic nature of the condition, and give re peated reminders that medication and skill development work hand-in-glove.

Dr Dodson is medical director of the ADHD Treatment Center in Denver. He is a consultant to and on the speakers bureau of Shire Pharmaceuticals and is on the speakers bureau for Novartis Pharmaceuticals. This article is based on a talk given at the U.S. Psychiatric & Mental Health Congress in 2005.

References:

References1. Abikoff H, Hechtman L, Klein RG, et al. Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. J Am Acad Child Adolesc Psychiatry. 2004;43: 802-811.
2. Pliszka SR, Carlson CL, Swanson JM. ADHD With Comorbid Disorders: Clinical Assessment and Management. New York: Guilford Press; 1999.
3. Gutgessell H, Atkins D, Barst R, et al. Cardiovascular monitoring of children and adolescents receiving psychotropic drugs: a statement for healthcare professionals from the Committee on Congenital Cardiac Defects, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 1999;99:979-982.
4. Wilens TE, Zussman RM, Hammerness PG, et al. An open-label study of the tolerability of mixed amphet amine salts in adults with attention deficit-hyperactivity disorder and treated essential hypertension. J Clin Psychiatry. 2006;67:696-702.
5. Chervin RD, Ruzicka DL, Giordani BJ, et al. Sleep-disordered breathing, behavior, and cognition in children before and after adenotonsillectomy. Pediatrics. 2006;117:e769-e778.
6. Biederman J, Faraone SV, Mick E, et al. High risk for attention deficit hyperactivity disorder among children with parents with childhood onset of the disorder: a pilot study. Am J Psychiatry. 1995;152:431-435.
7. Food and Drug Administration. Guidance for institutional review boards and clinical investigator information sheet. 1998 update. “Off-label” and investigational use of marketed drugs, biologics, and medical devices. Available at: http://www.fda.gov/oc/ohrt/irbs/offlabel.html. Accessed July 24, 2006.
8. Gordon M. How to Operate an ADHD Clinic or Subspecialty Practice. Dewitt, NY: GSI Publications; 1995.
9. Capone NM, Mc Donnell T, Buse J, Kochhar A. Persistence with common pharmacologic treatments for ADHD. Poster presented at: the CHADD 2005 Annual International Conference; October 27, 2005; Dallas.
10. Perwein A, Hall J, Swensen A, Swindle R. Stimulant treatment patterns and compliance in children and adults with newly treated attention deficit/hyperactivity disorder. J Managed Care Pharmacy. 2004;10:122-129.
11. Sanchez RJ, Crismon ML, Barner JC, et al. As sess ment of adherence measures with different stimulants among children and adolescents. Pharma co therapy. 2005;25:909-917.
12. Biederman J, Wilens T, Mick E, et al. Pharmacotherapy of attention deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics. 1999;104:e20.

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