BMJ 2001;323:1232-1235 ( 24 November )

Clinical review

Evidence based paediatrics

Evidence based management of attention deficit hyperactivity disorder

This is the last in a series of five articles

James P Guevara, assistant professor of paediatrics a, Martin T Stein, professor of paediatrics b. 

a Division of General Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA, b Division of Primary Care and Adolescent Medicine, University of California, San Diego, La Jolla, CA 92037, USA

Correspondence to: V A Moyer Virginia.A.Moyer{at}uth.tmc.edu


    THE CASE
Top
THE CASE
Background
Database queries
General approach to searching...
Critical review of the...
Applying the evidence
References

Your first patient of the morning is brought in by his parents for evaluation of school problems. He has always been described as "on the go." When he was 4 years old, a preschool teacher expressed concern that his activity level at times limited play with other children. Now, in the middle of second grade, he is underachieving and not keeping up with either reading or mathematics. His teacher reports that he fidgets constantly and cannot keep his hands off other children. Friendships are limited and not sustained. His teacher suggested that his paediatrician should be asked whether he has attention deficit hyperactivity disorder.


Summary points

Some 7% of children of school age have attention deficit hyperactivity disorder, and boys are affected three times as often as girls
Between 18% and 35% of affected children have an additional psychiatric disorder
ADHD-specific ratings scales are useful in the diagnostic evaluation
Stimulants, and perhaps tricyclic antidepressants, are effective treatments for attention deficit hyperactivity disorder in children
Symptoms diminish over time, but in up to half of affected children the disorder is still present in adolescence or young adulthood




    Background
Top
THE CASE
Background
Database queries
General approach to searching...
Critical review of the...
Applying the evidence
References

Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders in children.1 Its hallmarks are hyperactivity, impulsiveness, and inattention beyond the norm for a child's age (box).2

The disorder is frequently diagnosed in children with behavioural problems or in those who underachieve at school.3 Although the diagnosis is reliable if made by a standardised approach, concerns about the validity of the disorder often arise.4 At present there is no biological marker that clearly identifies affected children. Furthermore, it is unclear whether the disorder is unique or merely one end of the continuum of age appropriate behaviour. 5 6

You wonder how frequently academic difficulties or disruptive behaviours in a child are due to attention deficit disorder or to another psychiatric disorder; what tests will be helpful to diagnose the disorder; what treatments are effective; and what is the prognosis. For your patient, these questions need to be answered before you can decide on the best course of action.


    Database queries
Top
THE CASE
Background
Database queries
General approach to searching...
Critical review of the...
Applying the evidence
References

You wish to use an evidence based approach, so you frame your questions to maximise the yield from searching, and you look first for high quality systematic reviews and evidence based guidelines to answer your questions. You specify in each case the population, the event or exposure, the intervention, and the outcome, and identify the question type---whether it seeks evidence of a prevalence or risk in a baseline population, a prognosis, or the value of therapy.


Diagnostic criteria for ADHD

A. Either (1) or (2):

(1) Six (or more) of the following symptoms of inattention have persisted for at least six months to a degree that is maladaptive and inconsistent with developmental level:

Inattention:

(a) Often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities

(b) Often has difficulty sustaining attention in tasks or play activities

(c) Often does not seem to listen when spoken to directly

(d) Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behaviour or failure to understand instructions)

(e) Often has difficulty organising tasks and activities

(f) Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework)

(g) Often loses things necessary for tasks or activities (for example, toys, school assignments, pencils, books, or tools)

(h) Is often easily distracted by extraneous stimuli

(i) Is often forgetful in daily activities

(2) Six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for at least six months to a degree that is maladaptive and inconsistent with developmental level:

Hyperactivity:

(a) Often fidgets with hands or feet or squirms in seat

(b) Often leaves seat in classroom or in other situations in which remaining seated is expected

(c) Often runs about or climbs excessively in situations it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness)

(d) Often has difficulty playing or engaging in leisure activities quietly

(e) Is often "on the go" or often acts as if "driven by a motor"

(f) Often talks excessively

Impulsivity:

(g) Often blurts out answers before questions have been completed

(h) Often has difficulty awaiting turn

(i) Often interrupts or intrudes on others (for example, butts into conversations or games)

B. Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age 7 years

C. Some impairment from the symptoms is present in two or more settings (for example, at school (or work) and at home)

D. There must be clear evidence of clinically significant impairment in social, academic, or occupational functioning

E. The symptoms do not occur exclusively during the course of pervasive developmental disorder, schizophrenia, or other psychotic disorder and are not better accounted for by another mental disorder (for example, mood disorder, anxiety disorder, dissociative disorder, or a personality disorder)

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition2

(1) In children of school age (population), what is the likelihood of ADHD (outcome)? [baseline risk]

(2) In children of school age (population) with ADHD (exposure), what is the likelihood of additional psychiatric disorders (outcome)? [baseline risk]

(3) In children of school age (population) suspected of having ADHD (exposure), what is the value of behavioural rating scales and other tests (intervention) in the diagnosis (outcome)? [diagnostic test]

(4) In children of school age (population) with ADHD (exposure), what effect do stimulant medications, other psychotropic medications, or behavioural treatments (intervention) have on ADHD behaviours (outcome)? [therapy]

(5) In children of school age (population) with ADHD (exposure), what is the long term risk of persistent symptoms, delinquency, school failure, or substance abuse (outcome)? [prognosis]


    General approach to searching for evidence
Top
THE CASE
Background
Database queries
General approach to searching...
Critical review of the...
Applying the evidence
References

You first look for high quality evidence in the Cochrane Library.7 Your search of the Cochrane databases using the search term "attention deficit disorder" yields no relevant reviews, but from the "other sources of information" you find three recent systematic reviews of attention deficit hyperactivity disorder. One is published by the Canadian Coordinating Office for Health Technology Assessment in Ottawa,8 and two more are published by the Agency for Health Care Research and Quality in the United States. 9 10 From other databases available in your library (MedLine, CINAHL, HealthSTAR, Embase, PsycINFO), using the search terms "attention deficit disorder and hyperactivity and child," you find three other recent systematic reviews which are available in print. The first review may help with your question on treatment, but its review of diagnostic tests and prognosis is too cursory.1 The second review is a qualitative synthesis of psychosocial interventions,11 and the third is qualitative synthesis of drug therapy and prognosis.12 Two of these reviews refer to a large scale randomised clinical trial, the multimodal treatment study of children with attention deficit hyperactivity disorder. You type that name at the search screen using the textword format, which allows you to search for articles using free test as opposed to MESH terms, and locate the study.13 For completeness, you also search the Centre for Evidence-Based Mental Health (www.psychiatry.ox.ac.uk/cebmh), which has an online journal with evidence based reviews of publications on mental health disorders. You search the journal using the term "attention deficit hyperactivity disorder", finding one publication on treatment and one on prognosis. 14 15


    Critical review of the evidence
Top
THE CASE
Background
Database queries
General approach to searching...
Critical review of the...
Applying the evidence
References

Baseline risk for ADHD
The systematic review by Green et al examined the prevalence of attention deficit hyperactivity disorder.10 The authors undertook a comprehensive search using multiple electronic databases, hand searches of reference lists of articles and a clinical guideline on the disorder, and requests for additional citations from members of the American Academy of Pediatrics. The review was limited to children aged 6-12 years from non-referred samples in communities and schools. No scoring system was used to grade study quality.

Ten of the 14 articles included in this review were published between 1982 and 1996 and used unscreened populations of children of school age. Prevalences ranged from 4.2% to 26.0%. Pooled prevalence estimates from a random effects model were 6.8% using DSM-III criteria, and 10.3% using DSM-IIIR criteria. A single study using DSM-IV criteria reported a prevalence of 6.8%. The prevalence was three times higher for boys (9.2% v 3.0%) than for girls, but it did not vary with age.

Baseline risk for comorbidity in ADHD
The same review included a section on prevalence of comorbidity in the disorder.10 Prevalence data were reported for oppositional defiant disorder, conduct disorder, depressive disorder, anxiety disorder, and learning disabilities. The results were aggregated across age and sex categories. No combined estimate of all psychiatric disorders was given.

The review included five studies. Pooled estimates of prevalence from a random effects model, were 35.2% for oppositional defiant disorder, 25.7% for conduct disorder, 18.2% for depressive disorders, and 25.8% for anxiety disorders. A single study reported a 12% prevalence of learning disabilities. Over 28% of children had multiple disorders.

Diagnosis of ADHD
The review10 contained a section on diagnostic testing for attention deficit hyperactivity disorder, which examined seven studies of rating scales, four studies of broadband checklists, 12 studies of continuous performance tests, nine studies of central nervous system imaging, and eight studies of electroencephalography. The results from studies were reported as effect sizes, which represent the number of standard deviations that separate the populations with and without ADHD.16 Effect sizes were converted into sensitivity and specificity, although the method for doing this was not clear.

Checklists specific for attention deficit hypersensitivity disorder discriminate adequately between children with and without it. The combined effect size for all checklists specific for ADHD was 2.9 (95% confidence interval 2.2% to 3.5%). This was translated into a sensitivity and specificity of 94% or a likelihood ratio of over 15. The Conners ADHD index and DSM-IV symptoms scales (both teacher and parent versions) performed best, while Barkley's school situations questionnaire performed worst. Reliability may be limited, because effect sizes for each checklist were calculated from single studies.

Broadband checklists and continuous performance tests did not seem to discriminate sufficiently between children with and without the disorder. The likelihood ratio for broadband checklists was 4, while for continuous performance tests it was below 3. Imaging studies of the central nervous system and electroencephalographic studies were of little help in evaluation because their findings were inconsistent.

Management of ADHD
To assess the effectiveness of stimulant drugs, you examine the systematic review by Miller et al.8 The authors undertook a comprehensive search of multiple electronic databases, hand searches of reference lists of review articles and book chapters, and requests to drug manufacturers to identify trials. Inclusion criteria stipulated that trials be randomised, published after 1981, include children with the disorder, and measure outcomes using behavioural rating scales. A scale was used to judge study quality.

The authors identified 18 randomised controlled trials that used behavioural rating scales as the outcome. With the use of a random effects model, methylphenidate, dextroamphetamine, and pemoline were all more effective on teachers' assessments of behaviour than placebo. One additional trial, found on the Centre for Evidence-Based Mental Health website, reported that stimulants over a period of 15 months were superior to placebo on ratings of disruptive behaviour and on a scale of intelligence.14 However, the study enrolled children from a referral population, and a significantly greater number of patients withdrew from the placebo group than from the treatment group, which may have biased results in favour of treatment.

To evaluate the relative effectiveness of stimulants and tricyclic antidepressants, you examine the systematic review by Jadad et al.9 The authors undertook a comprehensive search of electronic databases from 1966, a search of the Cochrane Library, hand searches of the bibliography of eligible articles, and searches of their personal files. Trials were included if they were published in peer reviewed journals, evaluated a treatment for ADHD, and were randomised controlled trials. The authors used a quality score to evaluate for bias. Owing to significant dissimilarity between studies, results were not pooled. Eighteen studies compared only stimulant drugs, and in these methylphenidate, dextroamphetamine, and pemoline were found to be generally equivalent. Nine studies compared the effectiveness of tricyclic antidepressants with placebo: five of six studies of desipramine showed a benefit over placebo on ratings of behaviour, while one of three studies of imipramine reported a similar benefit. Four studies compared stimulants with tricyclic antidepressants but with inconsistent results.

Psychosocial treatments used for attention deficit hyperactivity disorder include cognitive behavioural, behaviour modification, and intensive contingency management.17 Pelham et al systematically reviewed the evidence for their effectiveness.11 The authors undertook a literature search and included articles that met the requirements of the Task Force on the Promotion and Dissemination of Psychological Procedures. However, these requirements were not specified. Few details were given of the search strategy, inclusion criteria, or details of included studies, so you wonder whether important studies were overlooked or excluded. Fifty eight articles were selected. The data were not pooled but were examined qualitatively. The results indicated that cognitive behavioural treatments do not improve the behaviour or academic performance of children with attention deficit hyperactivity disorder. However, treatments by behaviour modification or contingency management consistently showed a benefit on behaviour in all relevant studies.

Combined treatments consist of use of a drug and psychosocial intervention. The systematic review by Miller et al reviewed the effectiveness of combined treatments on ratings of behaviour8 and identified three studies that met the inclusion criteria. The results from a random effects model indicated that combined treatments did not differ significantly from medication alone. Jadad et al also reviewed the effectiveness of combination treatments.9 The results were similar to those obtained by Miller et al, and four of five studies showed little difference between combined treatments and stimulants alone.
 
(Credit: FORMAT)

To assess the long term effect of combined therapy, you examine the MTA (multimodal treatment of ADHD) trial.13 This trial randomised 579 children aged 7-9 years to one of four treatment arms over 14 months: monthly management of drug treatment with supportive care; intensive behavioural treatment; a drug plus supportive care and intensive behavioural treatment; and usual community care. There was excellent follow up and results were analysed on an intention to treat basis, but you are concerned that the strict drug titration regimen may not be feasible for your patient. The results showed that combined and drug only treatments were better than behavioural treatments and community care in reducing attention deficit hyperactivity disorder and oppositional-aggressive symptoms. Combined treatments and treatments with a drug alone did not differ in their effects on symptoms, but combined treatments had modest benefits over treatment with a drug alone on internalising symptoms such as anxiety disorders, social skills, consumer satisfaction, and possibly academic achievement.

Prognosis of ADHD
The review by Elia et al, which included nine studies that prospectively followed cohorts of children with ADHD until adolescence or early adulthood, may answer your question about prognosis.12 Because the search strategy and inclusion criteria were not stated, again you wonder whether important studies were overlooked or excluded. Baseline characteristics of the children in the studies were not stated, so you are unsure whether the results are applicable to your patient. The data were reported qualitatively. The results indicated that symptoms of attention deficit hyperactivity disorder abated over time, but 22%-85% of adolescents and 4%-50% of adults who had the disorder in childhood continued to meet the criteria for its diagnosis. The proportion of those with conduct disorder diminished in adolescence, while the proportion with substance misuse did not.

To determine the risk of academic failure among children with ADHD, you examine the cohort study you found on the Centre for Evidence-Based Mental Health web site.12 This study followed a birth cohort of 1265 children from an urban region of New Zealand until age 18 years. No formal diagnoses of attention deficit hyperactivity disorders were made, but the children were divided at age 8 years into five groups with increasing attention difficulties, based on a behavioural rating scale. Children in the highest group of attention difficulties showed the highest proportion of school failures (60%) by age 18.


    Applying the evidence
Top
THE CASE
Background
Database queries
General approach to searching...
Critical review of the...
Applying the evidence
References

You confirm the diagnosis of attention deficit hyperactivity disorder by using the DSM-IV diagnostic criteria and the Conners parent and teachers rating scales. You inform the parents of the potential risk of additional psychiatric disorders and persistence of symptoms into adolescence. You prescribe a stimulant drug and arrange review.

    Footnotes

Series editor: Virginia A Moyer

   Competing interests: None declared.

Evidence Based Pediatrics and Child Health can be purchased through the BMJ Bookshop (www.bmjbookshop.com); further information and updates for the book are available on www.evidbasedpediatrics.com


    References
Top
THE CASE
Background
Database queries
General approach to searching...
Critical review of the...
Applying the evidence
References

1. Goldman L, Genel M, Bezman R, Slanetz P. Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents. JAMA 1998; 279: 1100-1107[Abstract/Free Full Text].
2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994.
3. Mulhern S, Dworkin P, Bernstein B. Do parental concerns predict a diagnosis of attention-deficit hyperactivity disorder? J Dev Behav Pediatr 1994; 15: 348-352[Medline].
4. American Academy of Child and Adolescent Psychiatry. Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1997; 36(suppl 10): 85S-121S[CrossRef][Medline].
5. Diagnosis and treatment of attention deficit hyperactivity disorder (ADHD). NIH Consens Statement 1998 Nov 16-18:16(2):1-37.
6. Carey W. Problems in diagnosing attention and activity. Pediatrics 1999; 103: 664-666[Free Full Text].
7. The Cochrane Collaboration. The Cochrane Library of Systematic Reviews. (http: //updateusa.com/clibpw.clib.htm)
8. Miller A, Lee S, Raina P, Klasses A, Zupancic J, Olsen L. A review of therapies for attention-deficit/hyperactivity disorder. Ottawa: Canadian Coordinating Office for Health Technology Assessment, 1998.
9. Jadad A, Boyle M, Cunningham C, Kim M, Shachar R. The treatment of attention-deficit/hyperactivity disorder. Evidence report/technology assessment: Number 11. AHCPR Publication No. 99-E017, Rockville, MD: Agency for Health Care Policy and Research (in press).
10. Green M, Wong M, Atkins D, Taylor J, Feinleib M. Diagnosis of attention-deficit/hyperactivity disorder. Rockville, MD: Agency for Health Care Policy and Research, 1999. (Technical review No 3. AHCPR Publication No 99-0050.)
11. Pelham W, Wheeler T, Chronis A. Empirically supported psychosocial treatments for attention deficit hyperactivity disorder. J Clin Child Psychol 1998; 27: 190-205[CrossRef][Medline].
12. Elia J, Ambrosini P, Rapoport J. Treatment of attention-deficit-hyperactivity disorder. N Engl J Med 1999; 340: 780-788[Free Full Text].
13. MTA Cooperative Group. 14-month randomized clinical trial of treatment strategies for attention deficit hyperactivity disorder. Arch Gen Psychiatry 1999; 56: 1073-1086[Abstract/Free Full Text].
14. Gillberg C, Melander H, Von Knorring A, Janols L, Therlund G, Hagglof B, et al. Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry 1997; 54: 857-864[Abstract].
15. Fergusson D, Lynskey M, Horwood L. Attentional difficulties in middle childhood and psychosocial outcomes in young adulthood. J Child Psychol Psychiatry 1997; 38: 633-644[Medline].
16. Petitti D. Meta-analysis, decision analysis, and cost-effectiveness analysis: methods for quantitative synthesis in medicine. In: New York: Oxford University Press, 1994.
17. Parrish J. Child behavior management. In: Levine M, Carey W, Crocker A, eds. Developmental-behavioral pediatrics. 3rd ed. Philadelphia: WB Saunders, 1999.

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Rapid Responses:

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'Unproven' status of ADHD
George Halasz
bmj.com, 25 Nov 2001 [Full text]
Real or imagined?
A P J Lake
bmj.com, 27 Nov 2001 [Full text]
A naive use of evidence
David Coghill
bmj.com, 27 Nov 2001 [Full text]
Re: 'Unproven' status of ADHD
Enid Neil
bmj.com, 27 Nov 2001 [Full text]
Shouldn't management include a full assessment?
Steven Adlard
bmj.com, 28 Nov 2001 [Full text]
Evidence based malpractice ?
Alexander Vischer
bmj.com, 1 Dec 2001 [Full text]
Example of medical imperialism not evidence based practice
Sami Timimi
bmj.com, 3 Dec 2001 [Full text]
ADHD and evidence based management conclusions
John Barry D Wright, et al.
bmj.com, 6 Dec 2001 [Full text]
ADHD is not a disease
Andrew Firestone
bmj.com, 17 Dec 2001 [Full text]
Lessons from this correspondence
Trisha Greenhalgh, et al.
bmj.com, 10 Jan 2002 [Full text]
Re: Lessons from this correspondence
Brian Morgan
bmj.com, 12 Jan 2002 [Full text]

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