Special Medical Reports

NIH Issues Consensus Statement on Attention-Deficit/Hyperactivity Disorder
Verna L. Rose

The National Institutes of Health (NIH) has issued a draft consensus development conference statement on the diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD). The conference that culminated in the draft statement was convened by the NIH to address the following questions about ADHD:

• What is the scientific evidence to support ADHD as a disorder?
• What is the impact of ADHD on individuals, families and society?
• What are the effective treatments for ADHD?
• What are the risks of the use of stimulant medication and other treatments?
• What are the existing diagnostic and treatment practices, and what are the barriers to appropriate identification, evaluation and intervention?
• What are the directions for future research?

The two- and one-half-day conference brought together experts in the field of relevant medical research and health care as well as representatives from the public. After listening to presentations and audience discussion at the conference, the panel, chaired by David J. Kupfer, M.D., Western Psychiatric Institute and Clinic, University of Pittsburgh, Pa., developed the statement.

The consensus statement can be found on the NIH Web site at http://odp.od.nih.gov/consensus/. The document can also be obtained from the NIH Consensus Program Information Center, P.O. Box 2577, Kensington, MD 20891; telephone: 888-644-2667.

ADHD is noted in the report to be the most commonly diagnosed behavioral disorder in childhood and represents a major public health problem. It is estimated that it affects 3 to 5 percent of all school-age children.

The report emphasizes that the impact of ADHD on the individuals with this disorder, their families and society is great. Children with ADHD cannot sit still and pay attention in class, and the negative consequences of such behavior have far-reaching and long-term consequences. The families of these children experience increased levels of parental frustration, marital discord and divorce. In addition, the medical care of these children is very expensive. Many children who have ADHD consume a large share of resources and attention from the health care system, criminal justice system, schools and other social service agencies. Decisions that have to be made in the care of these children often are made even more difficult by the conflicting reports in the media as to the benefits and adverse effects of treatments.

ADHD often does not present as an isolated disorder, and the panel believes that coexisting conditions may act as confounders in any research studies, which may explain why there are so many inconsistencies in research findings. The panel concluded that ADHD is a valid diagnosis and defines a cluster of maladjustive characteristics.

A wide variety of treatments have been used for children with ADHD, including various psychotropic medications, psychosocial treatment, dietary management, herbal and homeopathic treatments, biofeedback medication and perceptual stimulation/training. Research on these treatment strategies has centered primarily on medications and psychosocial interventions. Most of the clinical trials have been short term (only about three months). Overall, these studies have been positive for the use of stimulants and psychosocial treatments for ADHD. However, no information is available on the long-term outcome of these treatments. Combined medication and behavioral treatment may help social skills, and parents and teachers judged this treatment favorably.

Methylphenidate, dextroamphetamine and pemoline have been shown in trials to improve the core symptoms of ADHD, according to the report. However, stimulant treatments do not normalize the entire range of behavioral problems. Several short-term studies of antidepressants show that desipramine produces improvements over placebo in parent and teacher ratings of ADHD symptoms. Results from studies of imipramine are inconsistent. Data from the studies of other psychotropic medications are not extensive enough to allow for conclusions.

Conclusions

The following conclusions of the panel have been excerpted from the consensus statement:

• Children with ADHD usually have pronounced difficulties and impairments resulting from the disorder across multiple settings. They also can experience long-term adverse effects on later academic, psychosocial and psychiatric outcomes.
• Despite progress in the assessment, diagnosis and treatment of ADHD, this disorder and its treatment remain controversial in many public and private sectors. The major controversy regarding ADHD continues to be the use of psychostimulants for both short- and long-term treatment.
• Although a consistent diagnostic test for ADHD does not exist, evidence supporting the validity of the disorder can be found. Further research will need to be conducted with respect to the dimensional aspect of ADHD, as well as the coexisting conditions present in both childhood and adult ADHD. An important research need is the investigation of standardized age- and gender-specific diagnostic criteria.
• The impact of ADHD on individuals, families, schools and society is profound and necessitates immediate attention because a considerable share of resources from the health care system and various social service agencies is currently devoted to ADHD. Resource allocations based on better cost data leading to integrated care models need to be developed.
• Effective treatments for ADHD have been evaluated primarily for the short term (only three months). These studies have included randomized clinical trials that have established the efficacy of stimulants and behavioral treatments for positive effects on the defining symptoms of ADHD and associated aggressiveness. Lack of consistent improvement beyond the core symptoms leads to the need for treatment strategies that use combined approaches. Currently, there is a paucity of data providing information on long-term treatment beyond 14 months. Although trials combining drugs and behavioral modalities are under way, conclusive recommendations concerning treatment for the long term cannot be made easily.
• The risks of treatment, particularly the use of stimulant medication, are of considerable interest. Substantial evidence exists of wide variations in the use of psychostimulants across communities and among physicians, suggesting no consensus among practitioners regarding which patients should be treated with psychostimulants. As measured by attention/activity indexes, patients with varying levels and types of problems may benefit from stimulant therapy. However, there is no evidence regarding the appropriate ADHD diagnostic threshold above which the benefits of psychostimulant therapy outweigh the risks.
• Existing diagnostic and treatment practices, in combination with the potential risks associated with medication, point to the need for improved awareness by the health service sector concerning an appropriate assessment, treatment and follow-up. A more consistent set of diagnostic procedures and practice guide is of utmost importance. Current barriers to evaluation and intervention exist across the health and education sectors. The cost barriers and lack of coverage preventing the appropriate diagnosis and treatment of ADHD and the lack of integration with special educational services represent considerable long-term cost for society. The lack of information and education about accessibility and affordabilty of services must be addressed.
• After years of clinical research and experience with ADHD, knowledge about the cause or causes of ADHD remains speculative. Consequently, there are no strategies for the prevention of ADHD.

Future Research

The panel believes that more research is needed to better define ADHD. Studies should focus on cognitive development and cognitive processing in ADHD. Brain imaging studies should be conducted before the initiation of medication, and individuals who have ADHD should be followed through young adulthood and into middle age. The impact of ADHD should also be determined. Additional studies are needed to develop a systematized treatment strategy. Greater attention should also be given to developing integrated programs for diagnosis and treatment.

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Neurologic Group Develops Recommendations for Management of Epilepsy
Sharon Scott Morey

Recommendations for the medical management of epilepsy have been developed by a group of 40 neurologists. The recommendations, published in the November 1998 issue of Neurology, come from a symposium convened at the 1998 annual meeting of the Southern Clinical Neurological Society. The report states that the recommendations are based on a review of the literature as well as actual clinical practice.

The recommendations are divided into sections that cover epilepsy in children and adolescents, adults, women and elderly persons. The following report summarizes the recommendations.

Epilepsy in Children and Adolescents

The recommendations state that a child with an initial single seizure should undergo evaluation to determine whether the seizure represents an epilepsy syndrome. A single seizure does not, however, signify the need for treatment. More intensive evaluation is required in children who have recurrent, unprovoked seizures. Among the studies that should be included in the evaluation are an electroencephalogram and imaging studies of the brain. According to the recommendations, high-resolution magnetic resonance imaging (MRI) is the preferred imaging study. If MRI is not available, computed tomography would be acceptable.

General treatment principles include initiation of therapy with one drug and the use of patient-specific factors to guide therapy. The expected duration of therapy depends on the epilepsy syndrome, the child's response to therapy and the child's age at the time of onset of seizures. In the section on epilepsy in children and adolescents, the recommendations describe the management approach for different types of seizure disorders in this group.

• Idiopathic Benign Partial Seizures. The recommendations state that the symptoms should guide the selection of treatment and, in some children, drug therapy may not be necessary. If drug therapy is required, drug selection can be based on the safety and side effect profile. The recommendations state that almost all antiepileptic drugs effectively control partial seizures. The recommendations note that carbamazepine is one drug of choice for this type of seizure disorder. The newer antiepileptic agent gabapentin may also be another drug of choice because of its safety and low side effect profile. Barbiturates and benzodiazepines should not be used as first-line therapy.
• Symptomatic Partial Epilepsy. Intensive evaluation, including assessment for early surgical intervention, is recommended for children with symptomatic partial epilepsy. The recommendations mention the antiepileptic agent gabapentin as a drug with a favorable side effect profile. According to the recommendations, many of the newer antiepileptic agents that are not yet approved for use in children may be tried in patients who are refractory to first-line treatment with standard agents.
• Generalized Absence Epilepsy. While ethosuximide and valproate are most often used to control generalized absence epilepsy, the recommendations state that some of the newer antiepileptic agents may be an option if absence epilepsy is refractory to standard treatment or if the patient cannot tolerate standard therapy.
• Simple Febrile Seizures. Clinical evaluation is recommended in children who have simple febrile seizures, but treatment is not usually required. The recommendations note that a diagnostic evaluation is indicated if complex febrile seizures have occurred.
• Status Epilepticus. According to the recommendations, the risk of seizure recurrence is increased in children who initially present with seizures in the form of status epilepticus. The findings on the clinical evaluation dictate whether long-term therapy is required.

Epilepsy in Adults

The recommendations state that a thorough, detailed history and an electroencephalogram are the two most important aspects in the evaluation of an adult who presents with the onset of seizures. High-resolution MRI is recommended; the report states that computed tomography, which may have been performed during emergency evaluation of an adult presenting with a seizure, is not a substitute for an MRI of the brain.

According to the recommendations, phenytoin and valproate may offer the best control for the different forms of primary generalized epilepsy. Ethosuximide or valproate are considered appropriate for nonconvulsive absence syndromes. The report notes that the newer agents lamotrigine, topiramate and felbamate are effective in controlling primary generalized epilepsy and can be used if standard agents fail.

With respect to partial seizures, the recommendations note that phenytoin and carbamazepine are considered first-line agents.

• Managing Poor Response. If the initial drug fails to control seizures, that agent should be discontinued and another antiepileptic agent tried. According to the recommendations, the patient should be reevaluated if monotherapy with two different agents fails to control the seizures. High-resolution MRI should be performed and electroencephalograms obtained again to exclude the development of a new disorder.

The report states that no clear recommendations can be made about the use of multidrug therapy in general or about which combinations of drugs might be helpful.

Epilepsy in Women

The recommendations discuss the importance of counseling women with epilepsy about pregnancy, family planning and lactation. Antiepileptic agents that induce the cytochrome P450 enzyme system pose an increased risk of contraceptive failure with hormonal agents.

Issues to discuss in prepregnancy counseling include the importance of seizure control and drug compliance, the need for folic acid supplementation, the risks of fetal loss and adverse fetal outcome, the need for prenatal diagnostic testing and the implications of child-care responsibilities on the seizure disorder. For example, sleep deprivation from taking care of an infant may have an effect on seizure control.

Desirable Qualities for Consideration When Prescribing Antiepileptic Drugs in Elderly Patients Desirable quality Gabapentin Lamotrigine Phenytoin Carbamazepine Valproate Phenobarbital Topiramate Tiagabine Once-daily doses ?X X X Low cost X X X Efficacy X X X X X X X X Few or no side effects X X Few or no drug interactions X X X Low protein binding X X X X X Linear pharmacokinetics X X X X X X Little or no allergic potential X X X X Parenteral formulation X X Reprinted with permission from Consensus statements: medical management of epilepsy. Neurol 1998;51:S39-S43.

Epilepsy in Elderly Persons

According to the recommendations, a key aspect in the management of epilepsy in elderly persons is the decision of whether to treat the first-onset seizure or wait for recurrence. The report notes that the risk of recurrence after an initial seizure is approximately twice as high in older patients as in younger patients.

The recommendations describe a number of factors that would make an antiepileptic agent ideal for an elderly patient: These factors include once- or twice-daily doses; low cost; minimal or no side effects and no potential for major organ toxicity; few or no drug interactions; low protein binding; linear pharmacokinetics; little or no potential for allergic or other idiosyncratic reactions; and the availability of the drug in a parenteral formulation (see the accompanying table).

The recommendations note that certain qualities may be more important in some patients. For example, the qualities of gabapentin may make it a first-line drug for an elderly patient who has organ dysfunction or who is receiving other drug therapy. However, the cost of gabapentin and its dosing of three times daily may make it less attractive as a drug for a healthy elderly patient. According to the recommendations, antiepileptic agents that can be administered parenterally are the drugs of choice for acutely ill, frail individuals. In patients with dementia, the potential for cognitive side effects may be an important consideration.

The recommendations note that there have been no controlled clinical trials of the efficacy and safety of antiepileptic drugs in elderly patients. A Veterans Affairs study comparing gabapentin, lamotrigine and carbamazepine in this age group is currently under way.

Copyright © 1999 by the American Academy of Family Physicians.
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