More than 60 years ago, serendipitous observation revealed thatthe drug d,l-amphetamine reduces the disruptive symptoms ofhyperkinetic children. Today four stimulant medications areavailable for clinical use: methylphenidate (MPH), dextroam-phetamine (DEX), mixed salts of amphetamine (AMP), andpemoline (PEM). They are the most widely prescribed psychotro-pic medications for children, primarily in the treatment of atten-tion-deficit/hyperactivity disorder (ADHD). Long thought of asa childhood disorder, ADHD is now known to persist into ado-lescence and adulthood, and adults are increasingly being treatedwith stimulants for this condition. Stimulants are also indicatedfor the treatment of narcolepsy, based on controlled studies.

This practice parameter will (1) review the literature perti-nent to the clinical use of stimulants; (2) describe indicationsand contraindications for stimulant treatment, with an empha-sis on judicious use; (3) describe the initiation and dosing of thevarious stimulant agents; (4) describe the side effects encoun-

tered in stimulant treatment; (5) discuss long-term mainte-nance using stimulant agents; and (6) discuss the combinationof stimulants and other psychotropic agents in the treatment ofcomorbid conditions.

EXECUTIVE SUMMARY

The treatment of patients with stimulant medications requiresthe consideration of many factors that cannot be fully conveyedin the brief executive summary. The reader is encouraged toreview the entire practice parameter. Each recommendation inthe Executive Summary is identified as falling into one of the fol-lowing categories of endorsement, indicated by an abbreviationin brackets following the statement. These categories indicate thedegree of importance or certainty of each recommendation.

“Minimal Standards” [MS] are recommendations that arebased on substantial empirical evidence (such as well-controlled,double-blind trials) or overwhelming clinical consensus.Minimal standards are expected to apply more than 95% of thetime, i.e., in almost all cases. When the practitioner does not fol-low this standard in a particular case, the medical record shouldindicate the reason.

“Clinical Guidelines” [CG] are recommendations that arebased on limited empirical evidence (such as open trials, casestudies) and/or strong clinical consensus. Clinical guidelinesapply approximately 75% of the time. These practices shouldalways be considered by the clinician, but there are exceptionsto their application.

“Options” [OP] are practices that are acceptable but notrequired. There may be insufficient empirical evidence to sup-port recommending these practices as minimal standards orclinical guidelines. In some cases they may be appropriate, butin other cases they should be avoided. If possible, the practiceparameter will explain the pros and cons of these options.

“Not endorsed” [NE] refers to practices that are known tobe ineffective or contraindicated.

Accepted June 18, 2001.This parameter was developed by Laurence L. Greenhill, M.D., principal author,

Steven Pliszka, M.D., Mina K. Dulcan, M.D., and the Work Group on QualityIssues: William Bernet, M.D., Chair, Valerie Arnold, M.D., Joseph Beitchman,M.D., R. Scott Benson, M.D., Oscar Bukstein, M.D., Joan Kinlan, M.D., JonMcClellan, M.D., David Rue, M.D., Jon A. Shaw, M.D., and Saundra Stock,M.D. AACAP staff: Kristin Kroeger. Comments were solicited from expert consul-tants, including L. Eugene Arnold, M.D., Joseph Biederman, M.D., Louise G.Cohen, Pharm.D., Greg Fritz, M.D., and F. Xavier Castellanos, M.D. In addition,the authors acknowledge the many academy members for their written and verbalfeedback.

The summary and full text of the Practice Parameter for the Use of StimulantMedications in the Treatment of Children, Adolescents, and Adults are availableto AACAP members on the World Wide Web (www.aacap.org) and will appearin a supplement to this Journal. This parameter was made available to the entireAACAP membership for review in September 2000 and was approved by theAACAP Council on June 4, 2001.

Reprint requests to the AACAP Communications Department, 3615Wisconsin Avenue, N.W., Washington, DC 20016.

0890-8567/01/4011–1352�2001 by the American Academy of Child andAdolescent Psychiatry.

A A C A P O F F I C I A L A C T I O N

Summary of the Practice Parameter for the Use ofStimulant Medications in the Treatment of Children,

Adolescents, and Adults

ABSTRACT

This practice parameter describes treatment with stimulant medication. It uses an evidence-based medicine approach

derived from a detailed literature review and expert consultation. Stimulant medications in clinical use include methylpheni-

date, dextroamphetamine, mixed salts of amphetamine, and pemoline.They carry U.S. Food and Drug Administration indi-

cations for the treatment of attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2001, 40(11):

1352–1355. Key Words: stimulants, attention-deficit/hyperactivity disorder, methylphenidate, amphetamine, pemoline.

1352 J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 40 :11 , NOVEMBER 2001

BRIEF HISTORY

Stimulants are among the most effective psychotropic med-ications in clinical use today. Their effects on disruptive behaviorwere discovered in 1937, when these drugs proved to increasecompliance, improve academic performance, and reduce motoractivity in hyperkinetic children. Studies of the short-term ben-efits of stimulants on the symptoms of ADHD constitute thelargest body of treatment literature on any childhood-onset psy-chiatric disorder. By 1996 there were 161 randomized controlledtrials (RCTs) published, encompassing 5 preschool, 150 school-age, 7 adolescent, and 9 adult studies. Improvement occurred in65% to 75% of the 5,899 patients randomized to stimulantsversus only 5% to 30% of those assigned to placebo for MPH(n = 133 trials), DEX (n = 22 trials), and PEM (n = 6 trials).Over the past two decades, there has been a steady increase in thediagnosis of ADHD and the use of stimulants, particularly inthe United States. Because stimulant medications can be abused,the rapid increase in stimulant use has raised concerns about therisks of diversion and abuse. In part because of these concerns,their use to treat children remains controversial, particularly inthe lay media and Internet. As always, practitioners should exer-cise care in making an accurate diagnosis.

PSYCHOPHARMACOLOGICAL EFFECTSOF STIMULANTS

Short-term trials have reported improvements in the mostsalient and impairing behavioral symptoms of ADHD. Exceptfor PEM, the immediate-release preparations of the major stim-ulants have a brief duration of action, providing clinical benefitsfor 3 to 5 hours after oral dosing. Thus multiple doses duringthe day are required to maintain improvement. In the class-room, stimulants decrease interrupting, fidgetiness, and finger-tapping and increase on-task behavior. At home, stimulantsimprove parent–child interactions, on-task behaviors, andcompliance. In social settings, stimulants improve peer nomina-tion rankings of social standing and increase attention duringsports activities. Stimulants decrease response variability andimpulsive responding on laboratory cognitive tasks, increase theaccuracy of performance, and improve short-term memory,reaction time, math computation, problem-solving in games,and sustained attention. Time-response studies show a differen-tial impact across symptom domains, with behavior affectedmore than attention. Stimulants continue to ameliorate thesymptoms of ADHD in the presence of other comorbid Axis Idisorders and may even show positive benefit on the comorbiddisorder (such as conduct disorder and anxiety disorder).

Until recently, the benefits of stimulant treatment have beendemonstrated only in short-duration trials, most lasting less than12 weeks. To address this issue, prospective, longer-durationRCTs—lasting 12 to 24 months—have been conducted. MPHdoses up to 50 mg/day were used in these long-duration studies.

The largest of these studies, the NIMH Collaborative MultisiteMultimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA study), showed that stim-ulants (either by themselves or in combination with behavioraltreatments) lead to stable improvements in ADHD symptoms aslong as the drug continues to be taken.

Though there are only a few RCTs documenting their efficacy,stimulants have proven effective in the treatment of narcolepsy.

INDICATIONS

A clinician determines that a patient (child, adolescent, oradult) has a condition indicated for the use of stimulant med-ications [MS].

Psychiatric evaluation should include a detailed history (psy-chiatric and medical) of the patient, collateral information fromparents or significant others, documentation of target symp-toms, and a mental status examination. It is helpful to gatherinformation from at least two adult sources—preferably fromdifferent settings in a child’s life (e.g., home or school)—aboutthe child’s symptoms. The following conditions may be thefocus of stimulant use.

ADHD. The clinician should document that the patient hasthe DSM-IV or ICD-10 diagnosis of ADHD. There is noempirically proven threshold of ADHD symptoms that can beused to predict treatment response to stimulant medication.Fortunately, the ratio of benefit to side effects is very favorablefor MPH, DEX, and AMP. The severity of the symptoms andthe resulting impairment in the patient’s academic or occupa-tional, social, and family functioning should be assessed. Onlythose patients with moderate to severe impairment in two dif-ferent settings should be considered for stimulant treatment. Achild with ADHD, predominately inattentive type, with severeacademic problems at school and during homework may beconsidered for stimulant treatment, even if his or her peer rela-tionships and family functioning are not otherwise affected.Teacher ratings of ADHD symptoms, using a validated andage- and sex-normed instrument, should be obtained at base-line and after treatment with stimulants [CG]. To qualify fortreatment, the child should be living with a responsible adultwho can administer the medication; the school should alsoprovide personnel for supervising in-school doses. In additionto stimulants, consider other effective modalities, such as par-ent training, psychoeducation, and others, as described in theAcademy’s practice parameters for ADHD (AmericanAcademy of Child and Adolescent Psychiatry, 1997).

ADHD With Comorbid Conduct Disorder. Only those patientswith symptoms that cause moderate to severe impairment in atleast two different settings should be considered for stimulanttreatment. If the patient is an adolescent, the clinician should becertain that he or she is not using nonprescribed stimulants [CG].

Narcolepsy. The patient with narcolepsy suffers from excessivesleepiness with recurrent sleep attacks and cataplexy (brief epi-

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sodes of bilateral weakness typical of the rapid eye movementphase of sleep, even though the individual is awake). Onlyamphetamines are Food and Drug Administration (FDA)-approved for this indication [CG].

Apathy due to a General Medical Condition. Individuals whohave suffered a brain injury due to a cerebral vascular accident,trauma, human immunodeficiency virus, or a degenerative neu-rological illness often exhibit apathy or symptoms of inatten-tion and impulsivity similar to ADHD. If the illness or traumaoccurred after age 7, they would not meet criteria for ADHD.Clinical experience and small controlled trials suggest that stim-ulants are helpful in reducing such behaviors in these patients[OP]. Doses of the stimulants are typically lower than thoseused in the treatment of ADHD.

Adjuvant Medical Uses of Stimulants. Some severely medicallyill patients develop severe psychomotor retardation secondaryto the illness itself, the sedative effects of pain medication, ortoxic effects of the agents used to treat the primary illness (e.g.,chemotherapy for cancer). Case reports suggest that low dosesof stimulants may enable these patients to be more alert andhave a higher energy level and better appetite [OP].

Treatment-Refractory Depression. Stimulants, particularlyMPH, have been used to augment the effects of tricyclicantidepressants [OP]. Doses are usually lower than those usedto treat ADHD.

CONTRAINDICATIONS

Contraindications to the use of stimulants in clinical practiceinclude previous sensitivity to stimulant medications, glau-coma, symptomatic cardiovascular disease, hyperthyroidism,and hypertension. These medications must be used with greatcare if there is a history of drug abuse. They are contraindicatedin patients with a history of illicit use or abuse of stimulants,unless the patient is being treated in a controlled setting or canbe supervised closely [NE]. If a member of the household has ahistory of use or abuse of stimulants, steps should be taken tomake certain that the medications prescribed are not abused.Concomitant use of a monoamine oxidase inhibitor is contra-indicated [NE]. Stimulants should not be administered to apatient with an active psychotic disorder [NE].

The FDA-approved package inserts add other contraindica-tions, including motor tics, marked anxiety, and a family historyor diagnosis of Tourette’s disorder. However, the recent clinicaltrial literature reveals that these conditions may not be worsenedby stimulant treatment. Because the package insert mentionsthat MPH lowers the seizure threshold, it is best to initiate MPHafter the seizure disorder is under control with anticonvulsants.There are published studies showing that patients with epilepsywho are taking anticonvulsants do not show a change in theirseizure frequency when MPH is added. The package insertwarns against starting MPH in children under the age of 6,although there are now eight published reports that MPH is

effective in this age range. On the other hand, the package insertsfor PEM, DEX, and mixed salts of AMP allow their use in chil-dren down to age 3, even though there are no published con-trolled studies of these drugs in preschool children.

USE OF STIMULANTS

Using stimulant medication in treating patients with ADHDor ADHD plus conduct disorder requires careful documenta-tion of prior treatments, selection of the order of stimulants tobe used, using the recommended starting dose of each stimu-lant, deciding on both a minimum and maximum dose, using aconsistent titration schedule, deciding on a method of assessingdrug response, managing treatment-related side effects, andproviding a schedule for the monitoring of long-term med-ication maintenance [CG].

Documentation of Prior Treatment. Documentation of ade-quate assessment, previous psychosocial treatments, and pre-vious psychotropic medication treatments should be doneprior to initiating stimulant treatment [MS]. Information col-lected should include the name of the medication, dosage,duration of the trial, response and side effects, and estimationof compliance. Other useful information may include specialschool placements and psychosocial treatments includingbehavioral modification, parent training, and daily report card.

Obtain a Baseline Blood Pressure, Pulse, Height, and Weightin the Context of a Physical Examination. All children shouldhave a routine physical examination prior to starting stimu-lant medications. This examination should assess vital signs,including blood pressure, pulse, height, and weight. This willhelp discover adolescents and younger children who may havemalignant hypertension and adults who have essential hyper-tension and/or cardiac arrhythmias. Children should havetheir vital signs checked annually during their routine physicalexamination. Adults who are taking stimulants should haveblood pressure and pulse checked on a quarterly basis by thetreating physician or by the primary care physician.

Selecting the Order of Stimulants to be Used. The first stimu-lant used may be MPH, AMP, or DEX, depending on clinicianand patient preference. However, on average, the problematiceffects on appetite and sleep are greater with AMP or DEX,consistent with their longer excretion half-lives. PEM is notrecommended by this parameter because, although it is effec-tive, it may lead to hepatic failure.

Using the Recommended Starting Dose of Each Stimulant.The starting doses of stimulants are 5 mg for MPH and 2.5mg for DEX/AMP, generally given in the morning after break-fast and at around noon after lunch.

Deciding on Both a Minimum and Maximum Dose. For chil-dren and adolescents, minimum effective doses should beused to initiate therapy. A minimum starting dose is either 5mg of MPH or 2.5 mg of AMP in children and adolescents,given in the form of an immediate-release tablet. These doses

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should be started on a twice- or three-times daily basis becauseof their very short duration of action. The maximum totaldaily doses are calculated by adding together all doses takenduring a given day. The Physician’s Desk Reference (PDR) statesthat the maximum total daily dose is 60 mg for MPH and 40mg for amphetamines. Children weighing less than 25 kg gen-erally should not receive single doses greater than 15 mg ofMPH or 10 mg of DEX/AMP. The consensus from practice isthat doses may go higher than the PDR-recommended upperlimits on rare occasions. Experts often limit the upper range toa total daily dose of 40 mg of AMP, or 25 mg for a single doseof MPH, when MPH is given in multiple doses throughoutthe day. If the top recommended dose does not help, more isnot necessarily better. A change in drug or environmental orpsychosocial intervention may be required.

Using a Consistent Titration Schedule. If symptom control isnot achieved, the dose generally should be increased in weeklyincrements of 5 to 10 mg per dose for MPH or 2.5 to 5 mg forDEX/AMP [CG]. Alternatively, the physician may elect to use afixed-dose titration trial, similar to that found in the MTA study,where a full set of different doses is switched on a weekly basis.At the end of such a trial, the parent and physician can meet todecide which dose worked best for the child. The advantage ofsuch a full dose trial is that a child is less likely to miss a high dosethat might yield additional improvement [OP].

Deciding on a Method of Assessing Drug Response. Follow-upassessment should include evaluation of target symptoms ofADHD, asked regularly of the parent and of a teacher [CG].These clinical assessments may be supplemented by the use ofparent and teacher rating scales. It is important to obtain self-ratings from adolescents and from adults.

Managing Treatment-Related Side Effects. Side effects shouldbe systematically assessed by asking specific questions topatients and to parents about known side effects, such asinsomnia, anorexia, headaches, social withdrawal, tics, andweight loss [CG]. Weighing the patient at each visit providesan objective measure of loss of appetite.

Providing a Schedule for Initial Titration and Monitoring [CG].During initial titration and during later drug dose adjustments,contact can be maintained on a weekly basis by telephone [CG].The titration phase of stimulant initiation, which covers theperiod of dose adjustment, often requires 2 to 4 weeks.

Providing a Schedule for Monitoring the Drug MaintenancePhase. Afterward, patients can be followed regularly forlengthy periods on the same dose; they are said to be in amaintenance phase. Follow-up appointments should be made

at least monthly until the patient’s symptoms have been sta-bilized [MS]. Changes in the frequency of physician visitsshould be governed by robustness of drug response, adherenceof the family and patient to a drug regimen, concern aboutside effects, and need for psychoeducation and/or psycho-social intervention. More frequent appointments should bemade if there are side effects, significant impairment fromcomorbid psychiatric disorders, or problems in adherence totaking the stimulants. The response and severity of thepatient’s symptoms determine the frequency of appointments.Optional treatment components include the collection ofteacher reports prior to or at each visit, provision of readingmaterials, and discontinuation trials.

COMPLICATIONS AND SIDE EFFECTS

Almost all stimulant-related side effects reported for childrenand adolescents with ADHD are rare and short-lived and areresponsive to dose or timing adjustments. Mild side effects arecommon, and serious side effects are rare and short-lived if themedication is reduced in dose or discontinued. Severe move-ment disorders, obsessive-compulsive ruminations, andpsychotic symptoms are very rare and disappear when the med-ication is stopped. Recently, it has been determined that patientstaking PEM experience hepatic failure 17 times more frequentlythan the spontaneous rate; this rare but serious side effect is amajor complication of PEM use. In placebo-controlled studiesof stimulants, parents report only seven side effects occurringmore often on stimulant than on placebo: delay of sleep onset,reduced appetite, weight loss, tics, stomach ache, headache, andjitteriness. Careful lowering of the dose or changing the timingof the dose administration may alleviate the side effect [CG].When insomnia or appetite loss occurs but the stimulant ishighly beneficial in reducing the target symptoms, a variety ofadjunctive tactics are available to ameliorate the side effects.Staring, daydreaming, irritability, anxiety, and nail-biting maytypically decrease with increasing dose, representing preexistingsymptoms rather than side effects.

REFERENCES

American Academy of Child and Adolescent Psychiatry (in press), Practiceparameter for the use of stimulant medications in the treatment of chil-dren, adolescents, and adults. J Am Acad Child Adolesc Psychiatry

American Academy of Child and Adolescent Psychiatry (1997), Practiceparameters for the assessment and treatment of children, adolescents, andadults with attention-deficit/hyperactivity disorder. J Am Acad ChildAdolesc Psychiatry 36(suppl):85S–121S