ADHD: What's New?

Two excellent review atricles on attention deficit hypertention disorder (ADHD) follow. The first, by Michael Reiff MD, of the university of Minesota, presents an overview of the assessment and diagnosis of ADHD with clear, straightforward recommendations for the primary care practictioner illustrated with clinical vignettes. The format lends itself to a quick read, but the details are included if you want to drill down.

The second article, by Adelaide Robb, MD, of Children's National Medical Center in Washington, DC, provides a cutting edge review of treatments for ADHD within a developmental model. The tables are concise and the article is loaded with practical advice for decision making and counseling families.

You will find these articles well worth your time if you are a practitioner who evaluates and treats young people or adults with ADHD. These reviews are followed by answers to questions that primary care practitioners frequently ask. References to the answers appear in the review articles.

WHAT'S NEW IN ADHD?

A better understanding of ADHD. Several recent studies reveal more details about the etiopathogenesis of the disorder.^1-3 We are approaching the identification of diagnostic biomarkers that can be used to predict prognosis and to choose treatments more successfully. Neuroimaging studies suggest an anterior and posterior attentional system that may respond preferentially to medications that affect dopamine or norepinephrine.

We are learning that amphetamines, methylphenidate, and atomoxetine work in different ways. This information may explain their differential effects and suggests different treatment targets.

Genetic studies suggest unique genetic profiles that predict subtypes of ADHD and treatment response. However, we do not yet have a diagnostic test or method of choosing treatments that is superior to a careful and thorough interview supplemented by the use of rating scales completed by parents and teachers.

Black box warnings. The huge public attention to the threat of a black box warning for psychosis and cardiac side effects from stimulants made many practitioners cautious about prescribing these agents. Ultimately, however, the severe warning did not seem warranted: revised labeling for amphetamines and methylphenidate compounds will suggest that practitioners consider the cardiovascular effects of prescribing and monitoring these medications--especially in adults. Labels will also warn of the risk that psychotic-like symptoms develop in a small subgroup of people taking stimulant medications.

Bottom line: always take a cardiac history, obtain additional workup if indicated, monitor vital signs, watch for psychotic-like symptoms, and adjust the dosage accordingly.

Atomoxetine. Use of this agent, which increased rapidly over the past few years, has begun to level off and even slightly decrease as practitioners find its place in the armamentarium of ADHD medications. Recent studies suggest that symptom improvement is significantly greater in patients who receive mixed amphetamine salts extended release (MAS XR) than in those who receive atomoxetine on multiple efficacy measures.⁴

However, atomoxetine (Strattera) is still considered a first-line treatment for ADHD. The drug is particularly useful in treatment-naive patients for whom stimulants are not desirable. It is also particularly useful in persons who do not respond to stimulants and for those with adverse effects from stimulants (such as psychotic-like reactions). It may be especially suitable for potential substance abusers, for those with comorbid anxiety, oppositional behavior, or tics (although it can still exacerbate tics), and for those with an autism spectrum disorder who have distractible inattention.

A methylphenidate patch. A new delivery method for methylphenidate (Daytrana) in a 9-hour patch is now approved for those 6 to 12 years old.⁵ This should be helpful to youngsters who have difficulty in swallowing tablets. However, children need to be able to keep the patch on. This delivery system also provides more flexible dosing than oral medication because the patch can be applied for the desired duration.

There is a theoretic concern that allergic sensitization could develop in persons who wear the patch. However, this phenomenon has not been seen and is less likely to occur with the 9-hour dosing than with 12-hour dosing, and with site rotation. When the patch is worn for longer periods, there is a higher rate of insomnia and weight loss. Dr Robb's article (page 14) contains dosing information, which may be lower than the oral dosage.

A drug that regulates wakefulness. Modafinil (Provigil for narcolepsy, Sparlon proposed for ADHD) is a novel nonstimulant agent that is currently approved for the treatment of narcolepsy. It is considered an arousal- or wakefulness-promoting agent.⁶ It regulates wakefulness and has a different mechanism of action than stimulants do.

Modafinil has been shown to significantly diminish symptoms of ADHD--including inattention, impulsivity, and hyperactivity compared with placebo.⁶ It is relatively well tolerated and does not cause rebound effects on discontinuation. However, while modafinil holds promise for certain children with ADHD and avoids some of the side effects of stimulants--including the potential for abuse--it is not yet approved because of concerns about the potential risk of Stevens-Johnson syndrome.

Improving outcome. ADHD is associated with a broad range of undesirable outcomes, including cigarette addiction; substance abuse; accidental injuries; mood and anxiety disorders; and academic, legal, occupational, and relationship problems.⁷ Most studies suggest that the risk of substance abuse increases in untreated ADHD--and that effective treatment decreases the risk of these outcomes.

Potential new treatments (such as nicotine and amphetamine precursors), phenotypic biomarkers for treatment matching, and continued study of longer-acting compounds are exciting areas of research in ADHD.

The following articles bring you up-to-date.

References:

REFERENCES:

1.Spencer TJ, Biederman J, Ciccone PE, et al. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate.

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2. Shaw P, Lerch J, Greenstein D, et al. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention deficit/ hyperactivity disorder.

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2006;63:540-549.
3. Durston S, Fossella JA, Casey BJ, et al. Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls.

MOL Psychiatry,

2005;10:678-685.
4.Wigal SB, McGough JJ, McCracken JT, et al. A laboratory school comparison of mixed amphetamine salts extended release (Adderall XR) and atomoxetine (Strattera) in school-aged children with attention deficit/hyperactivity disorder.

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5.Anderson VR, Scott LJ. Methylphenidate transdermal system in attention-deficit hyperactivity disorder in children.

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6. Turner D. A review of the use of modafinil for attention-deficit hyperactivity disorder.

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7. Biederman J, Monuteaux MC, Mick E, et al. Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study.

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