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Attention Deficit Hyperactivity Disorder: Treatment & Medication

Author: Susan Louisa Montauk, MD, Medical Director, The Affinity Center, Cincinnati; Professor, Departments of Family Medicine and Public Health Science, University of Cincinnati College of Medicine
Coauthor(s): Christine A Mayhall, PhD, Clinical Psychologist, The Affinity Center
Contributor Information and Disclosures

Updated: Feb 27, 2009

Treatment

Medical Care

The 2 major components in the medical care of children with attention deficit hyperactivity disorder (ADHD), previously termed attention deficit disorder (ADD), are behavioral and pharmaceutical therapies. The pharmaceutical component is covered in Medication. In addition, the eMedicine article on adult Attention-Deficit/Hyperactivity Disorder provides extensive tables about the nonstimulant medications.

Most components of behavioral care take place outside of the primary care provider's office. Common components are briefly described below to assist in referral and consultation. Not all components are necessary for every child.

• School or education interventions
  • The age of the child at initial diagnosis and the severity of the symptoms of ADHD (ADD) likely affect the extent to which the child benefits from working with education specialists.
  • Consultants initially involved with diagnosis and evaluation can also be important in promoting the development of study skills.
  • Teachers have an important function. Their periodic feedback about the child's school performance through the use of standardized scales, narrative descriptions, and telephone follow-up is generally an indispensable component of ongoing care.
  • Implementation of academic accommodations and adaptations is often necessary
• Psychotherapeutics
  • For adolescents, ADHD (ADD) coaching, participating in a support group, or both can help normalize the disorder and assist them in obtaining well-focused peer feedback and general information.
  • Counselors such as psychologists, behavioral developmental pediatricians, clinical social workers, and advanced practice nurses who are well familiarized with ADHD (ADD) can be invaluable to affected children and their families.
  • Behavioral modification and family therapy are usually necessary for optimal care.
  • Refer parent(s) for evaluation of ADHD (ADD), if suspected.
  • Coexisting conditions must be addressed as part of therapy.

Consultations

The timing of consultations depends on the practitioner's degree of knowledge and experience with the evaluation and treatment of ADHD (ADD). Several possible scenarios are described below.

• No consultation is necessary: In this scenario, the patient is well known and perhaps has a family member with ADHD (ADD) but no coexistent conditions. The patient has a clear history consistent with ADHD (ADD) without coexistent conditions.
• Referral to an ADHD (ADD) specialist, clinic, and/or a psychiatrist or a behavioral developmental pediatrician
  • The patient may or may not be well known and may have a family member with ADHD (ADD) but no coexistent conditions whose condition. However, the clinician feels the patient must be questioned further about ADHD or coexistent conditions.
  • The patient may or may not be well known and may have no family history of ADHD (ADD) but has a concerning family history of a mood or anxiety disorder.
  • The patient may or may not be well known and perhaps has other family members with ADHD (ADD) whose condition is stabilized by medications without problems with coexistent conditions; however, ADHD (ADD) cannot be diagnosed and/or coexistent conditions cannot be ruled out with confidence.
• A brief consultation with or referral to an ADHD (ADD) specialist or a psychiatrist or behavioral developmental pediatrician: In this scenario, the patient may or may not be well known to the practitioner, and the condition has been stabilized by medications without problems with identified coexistent conditions. However, the medication either no longer works or has started to cause adverse effects, and the medication cannot be adjusted with confidence.
• Referral as soon as possible to a specialist or specialty clinic for drug rehabilitation: In this scenario, a patient is being evaluated and is not taking psychostimulants or is being re-evaluated for current psychostimulants and chemical abuse is noted. If the patient is taking psychostimulants and if the medications are being taken properly, a consultation call to decide whether the stimulants should be continued may be more appropriate than simply stopping them.

Diet

No special diet clearly affects ADHD (ADD). Until this situation changes, a healthy diet with minimal, if any, caffeine should be emphasized. Note that, in children, caffeine is often consumed in the form of chocolate candy, chocolate milk, or "energy" drinks.

Activity

No evidence-based studies have been conducted to elucidate the potential role of physical activity in children with ADHD (ADD). However, anecdotal clinical reports commonly attest to improvements in focus and sleep quality associated with regular physical activity and exercise. In addition, regular physical activity is important in patients with some of the common coexistent conditions (eg, depression, anxiety) and helps improve concentration. Therefore, physical activity is often an important component of therapy.

Medication

The 2 major components in the medical care of children with attention deficit hyperactivity disorder (ADHD), previously termed attention deficit disorder (ADD), are behavioral and pharmaceutical therapies. The behavioral component is covered in the Treatment section above. In addition, the eMedicine article on adult Attention-Deficit/Hyperactivity Disorder provides extensive tables about the nonstimulant medications.

Pediatric dosing of stimulant medications

Dosing of stimulant medications vary among ADHD (ADD) centers throughout the medical community in the United States. The table below is derived from the stimulant trial protocol of The Affinity Center, Inc, a center for the evaluation and treatment of ADHD (ADD) and mood disorders in Cincinnati, Ohio.

Pediatric Dosing of Stimulant Medications

Open table in new window

Note.—In general, when the terms methylphenidate, Dexedrine, and Ritalin are used without abbreviations for extended-release preparations (eg, continuous release [CR], SR, osmotic-release oral system [OROS]), a short-acting, IR preparation is implied.

^* Maximum pediatric dose suggested by the US Food and Drug Administration (FDA). Although some children benefit greatly from doses greater than these, benefit from use of either the lowest and highest ends of the dose range is uncommon.

†The methylphenidate patch contains a different total methylphenidate dose than the name implies because it is designed to last 12 hours (eg, 10-mg patch [patch size 12.5 cm²] delivers about 10 mg over 9 h [estimated delivery rate is 1.1 mg/h for this particular patch]). Delivery rate varies depending on patch size.

‡Many patients describe their experience with methylphenidate SR preparations as erratic and uncomfortable.

Dose conversions

Conversions for psychostimulants are always approximations, especially when one is converting between stimulants, such as methylphenidate and dextroamphetamine. Different forms of the same drug have slightly different pharmacokinetics, and patients often have different responses to them. FDA-recommended conversions between short-acting and long-acting (LA) preparations of the same drug are based on attempts to match serum-concentration curves and not clinical-performance curves.

In clinical practice, ratios for converting among medications vary by ADHD (ADD) manifestations, adverse effects, comorbidities, and the patients' metabolism. Common approximations are described below. Individual patients vary; therefore, close follow-up, and possibly titration, is initially necessary.

For methylphenidate LA, CD, or ER preparations, convert by using a ratio of 2:1 with immediate-release methylphenidate. For example, Ritalin 10 mg q4h is converted to Ritalin LA 20 mg q8h. For a few patients, effects last only 5-6 hours with the LA preparations, although effects last 3.5-4 hours with the IR form. However, a short effect from one 8-hour preparation does not always mean another 8-hour preparation has the same problem.

For XR mixed amphetamine salts (MAS), convert using a ratio of 2:1 with IR MAS. The half-life of MAS widely varies among individuals. Some patients do better with a lower second dose and, thus, may benefit from an IR and XR morning combination.

Dexedrine Spansule seems to have the greatest interpatient variance when converting the IR form to the CR form. The IR-to-CR ratio for equivalent clinical effects appears to vary from 1:1 to about 1:1.5; however, this conversion has not been well studied. For example, Dextrostat 10 mg q4h is converted to Dexedrine CR 10-15 mg q8h.

Methylphenidate OROS tablets are converted in an 18:5 ratio with methylphenidate. For example, Ritalin 10 mg q4h is converted to Concerta 36 mg. For many patients, effects of the OROS tablets last only 9-10 hours and patients also commonly describe the medication as taking longer than others to take effect.

Methylphenidate OROS tablets are converted in an 18:10 ratio with methylphenidate LA, CD, or ER. For example, Ritalin LA 10 mg q8h is converted to Concerta 18 mg.

Methylphenidate transdermal patch is converted in a 1:1 ratio with methylphenidate IR and a 1:2 ratio with the LA preparations, although the FDA suggests starting with the lowest dose patch and working up.

Lisdexamfetamine dosing conversion may be compared with dextroamphetamine immediate-release (Dexedrine IR). The prescribing information describes a dose of lisdexamfetamine dimesylate 100 mg as equivalent to d-amphetamine sulfate immediate-release 40 mg.

Categories of medications

Psychostimulants are effective in patients with ADHD (ADD). In addition, they have been available for many decades, allowing for a strong appreciation of their lack of major adverse effects when used at therapeutic doses.

Atomoxetine (Strattera), a nonstimulant selective norepinephrine reuptake inhibitor (SNRI), has been effective in many people with ADHD (ADD). This relatively new medication has the advantages of qd-to-bid dosing and unscheduled status with the Drug Enforcement Agency (DEA). However, cases of reversible hepatic failure have been directly attributed to atomoxetine, and an evaluation of other long-term adverse effects has been limited to data from a few years.

Patients may significantly benefit more from stimulants than from atomoxetine, but some may have untenable adverse effects with any stimulant product or dose. In the experience of numerous subspecialists, these patients may benefit from a combination of atomoxetine and a stimulant. For many patients, atomoxetine appears to augment the clinical effects of the stimulant, allowing for clinical efficacy with a low dose and decreasing the likelihood of adverse effects.

Antidepressants and alpha-agonists have an important role in some individuals with ADHD (ADD). Most have well-known adverse-effect profiles. Antidepressants and alpha-agonists can cause cardiac adverse effects, and this possibly must be kept in mind.

Modafinil (Provigil), a medication used to treat excessive daytime sleepiness, improves core symptoms in many children with ADHD (ADD). In early studies in children, common adverse affects occurring at rates higher than those of placebo were insomnia (24%) and anorexia (14%).

In August 2006, Cephalon, the manufacturer of modafinil (Sparlon), received a nonapprovable letter from the FDA for the treatment of ADHD (ADD). Cephalon has decided that it will not pursue further development of Sparlon for ADHD (ADD). Modafinil is still available as Provigil, which does have FDA approval to improve wakefulness for adults with narcolepsy, sleep apnea, or shift-work sleep disorders. Many ADHD (ADD) specialists continue to use modafinil in selected patients without problems. To view information from a media briefing describing the FDA decision, see Cephalon Media Briefing.

Transcripts of the FDA Psychopharmacologic Drugs Advisory Committee minutes that describe the rashes observed in clinical trials with modafinil are available. For more information see FDA Psychopharmacologic Drugs Advisory Committee minutes from March 23, 2006 that discuss modafinil for ADHD.

Central alpha agonists

Central alpha agonists can be helpful in treating hyperactivity, tics, or delayed sleep onset. They have a long history of pediatric use for this indication. Rare cases of sudden death had been reported several years ago in a few children who were given clonidine with concurrent methylphenidate. Reports also described fatal ventricular fibrillation in patients in whom treatment with clonidine was abruptly stopped rather than slowly tapered, as is appropriate. Details of these cases do not substantiate a cause-and-effect association, only concurrence. 

The FDA has not stated that these drugs should not be simultaneously used. Nevertheless, a prudent approach is to avoid using these drugs together in any patient with a first-degree relative who died from a sudden cardiac cause without first getting an ECG. Obtaining an ECG in any patient who may benefit from this combination but who has a history of arrhythmia is also prudent. Most experts continue to use clonidine with any of the stimulants when clinically indicated.

Guanfacine (Tenex)

Stimulates alpha2-adrenoreceptors in brainstem, activating an inhibitory neuron, which reduces sympathetic outflow. Result is decreased vasomotor tone and HR.

Clonidine (Catapres)

Stimulates alpha2-adrenoreceptors in brainstem, activating an inhibitory neuron, which reduces sympathetic outflow. Result is decreased vasomotor tone and HR.

Selective norepinephrine reuptake inhibitors (SNRIs)

These are nonstimulant ADHD (ADD) medications generally used as adjuncts to stimulants.

Atomoxetine (Strattera)

SNRI that inhibits presynaptic norepinephrine transporter. Also appears to indirectly stimulant dopamine activity in frontal lobes. Many anecdotal reports state that, when stimulants are not well-tolerated at a dose necessary for efficacy (eg, because of anxiety) and atomoxetine is not efficacious enough alone, the combination of atomoxetine and low dose (tolerable) stimulants is often very effective.
About 5-10% of patients are poor metabolizers of the drug and have increased drug exposure, peak serum levels, and half-lives. If intolerable but benign adverse effects are present at FDA-recommended doses, but not at lower dose, efficacy may be observed at the lower dose; therefore consider a low-dose trial. Usually clinically effective qd despite 5-h half-life (24 h in poor metabolizers); unknown if serum levels are correlated with efficacy.

Antidepressants

Many patients have reported clinically significant improvement with the use of some antidepressants. Although antidepressants are beneficial when added to a stimulant or SNRI in certain clinical situations, a psychostimulant or SNRI is still the medication of choice for most persons with ADHD (ADD) because of its safety profile and superior efficacy.

Imipramine (Tofranil)

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron.

Bupropion (Wellbutrin)

Inhibits neuronal dopamine reuptake. Weak blocker of serotonin and norepinephrine reuptake.

Desipramine (Norpramin)

May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase and downregulation of beta-adrenergic and serotonin receptors. Adjust dose to response and serum level.

Psychostimulants

Psychostimulants stimulate the areas of decreased activation to a higher state of arousal. The spectrums of therapeutic efficacy and adverse effects of all the FDA-scheduled category II psychostimulants for ADHD (ADD) are similar. For any individual, therapeutic efficacy may vary greatly among drugs, preparations, or formulations (generic vs brand name).

The most common adverse effects include anorexia, sleep disturbances, mild anxiety, and rebound (eg, post-therapeutic agitation, anger, lethargy). Most individuals who take psychostimulants for ADHD (ADD) develop tolerance for the adverse effects within a few weeks. Although adverse-effect profiles, akin to therapeutic profiles, are similar for all psychostimulants, patients have their own positive and negative responses, which vary among the drugs.

Individuals with certain current or latent coexistent psychiatric disorders (eg, psychosis, bipolar disorder, some disorders of anxiety or depression) are particularly vulnerable to the adverse effects of stimulants if they do not receive concurrent medication, psychological counseling, or both for the coexistent condition.

The following contains FDA-approved dosing information and FDA-stated contraindications. Of note, many experts question the FDA's maximums for most stimulant medications (see the Table above for ranges). Experts also question several comorbidities thought to be contraindications because evidence suggests that tics may be as likely to improve with stimulants as worsen with them. Furthermore, blood pressure improves in some individuals with hypertension receiving stimulants, whereas others simply need a slight increase in their dose of antihypertensive. Finally, although the FDA lists glaucoma as a contraindication, the specific concern is only narrow-angle glaucoma.

Dextroamphetamine (Dexedrine, Dexedrine Spansules, Dextrostat)

Increases amount of circulating dopamine and norepinephrine in cerebral cortex by blocking reuptake of norepinephrine or dopamine from synapse. Short-acting brands fairly similar in cost; generic is 50-60% less expensive. Dexedrine available as 5-mg scored tab. Dextrostat available as 5-mg or 10-mg scored tab. Dexedrine Spansules (CR) available as 5-mg, 10-mg, or 15-mg Spansules.

Methylphenidate (Concerta, Methylin, Metadate, Ritalin)

Stimulates cerebral cortex and subcortical structures. Generic and branded-generic (Methylin and Metadate regular or ER) formulations 50-60% less expensive than Ritalin. LA preparations more expensive than short-acting preparations. Concerta (LA) tends to be more expensive than other preparations; 1 cap of Concerta, similar to other stimulants, costs the same whatever dose.

Although clinical difference between generic drug and branded-generics or Ritalin has not been verified, many patients have enough variability among preparations that they are willing to pay the difference. Many experts observed enough variability that they do not prescribe plain generic products unless patient (or insurance) insists. FDA allows for 20% variability in certain parameters between generics and brands and determines equivalence solely by pharmacokinetics and not data from clinical studies.

Dextroamphetamine and amphetamine mixture (Adderall)

Produce CNS and respiratory stimulation. CNS effect may occur in cerebral cortex and reticular activating system. May have direct effect on alpha-receptor and beta-receptor sites in peripheral system and release stores of norepinephrine in adrenergic nerve terminals. Mixture contains various salts of amphetamine and dextroamphetamine. Available as 5-mg, 7.5-mg, 10-mg, 12.5-mg, 15-mg, 20-mg, or 30-mg scored IR tabs and 10-mg, 20-mg, and 30-mg XR caps.

Dexmethylphenidate (Focalin, Focalin XR)

Contains pharmacologically active d -enantiomer of racemic methylphenidate. Blocks norepinephrine and dopamine reuptake into presynaptic neuron and increases release of these monamines into extraneuronal space.

Methylphenidate transdermal patch (Daytrana)

CNS stimulant. Therapeutic action for ADHD (ADD) not known but thought to block norepinephrine and dopamine reuptake into presynaptic neuron and to increase release of these monoamines into extraneuronal space. Racemic mixture composed of the d -enantiomer and l -enantiomer. The d -enantiomer is more pharmacologically active than the l -enantiomer. Transdermal administration exhibits minimal first-pass effect compared with PO administration; consequently, lower dose of transdermal methylphenidate (on mg/kg basis) compared with PO dose of methylphenidate may still produce higher d -methylphenidate level.
Available in 4 dosage strengths. Different-sized patches contain different amounts of methylphenidate and deliver different amounts over 9-h dose period. Respective patch sizes, methylphenidate content per patch, and dose delivered over 9 h are 12.5, 18.75, 25, and 37.5 cm²; 27.5, 41.3, 55, and 82.5 mg; and 10, 15, 20, and 30 mg. Onset of desired effect occurs approximately 2 h after application and persists 3-4 h after removal.

Lisdexamfetamine (Vyvanse)

Inactive prodrug of dextroamphetamine. Elicits CNS stimulant activity. Blocks norepinephrine and dopamine reuptake in presynaptic neurons and increases release of these monoamines in extraneuronal space. Indicated for ADHD in children aged 6 y or older and adults.

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