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Guest Editorial
Imaging Brain Chemistry and Function in Neuropsychiatric Disorders
Peter C Williamson

In Review
In vivo Magnetic Resonance Spectroscopy and Its Application to Neuropsychiatric Disorders
Jeffrey A Stanley

Studies of Altered Social Cognition in Neuropsychiatric Disorders Using Functional Neuroimaging
Cheryl L Grady, Michelle L Keightley


Review Papers
Attention-Deficit Hyperactivity Disorder: Critical Appraisal of Extended Treatment Studies

Russell Schachar, Alejandro R Jadad, Mary Gauld, Michael Boyle, Lynda Booker, Anne Snider, Marie Kim, Charles Cunningham


Clinical Implications of a Link Between Fetal Alcohol Spectrum Disorder and Attention-Deficit Hyperactivity Disorder
Kieran D O'Malley, Jo Nanson


Original Research
Prescription Medication Use Among an Aboriginal Population Accessing Addiction Treatment

Dennis Wardman, Nadia Khan, Nady el-Guebaly


The Impact of Latitude on the Prevalence of Seasonal Depression
Anthony J Levitt, Michael H Boyle


Preliminary Assessment of Intrahemispheric QEEG Measures in Bipolar Mood Disorders
OJ Oluboka, SL Stewart, V Sharma, D Mazmanian, E Persad


Brief Communciation
Hepatic Adverse Reactions Associated With Nefazodone
Donna E Stewart


Book Reviews
(PDF - all reviews)

Functional Neuroimaging in Child Psychiatry

Handbook of Cultural Psychiatry

The Empathetic Healer: An Endangered Species?

Cognitive Rehabilitiation: An Integrative Neuropsychological Approach

The Madness of Adam and Eve: How Schizophrenia Shaped Humanity

Letters to the Editor
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Evidence-Based Psychiatry

Evidence-Based Psychiatry: Response

Research Ethics and Forensic Psychiatry: A Comment on Regehr and Others

Research Ethics and Forensic Psychiatry: Response

Repetitive Transcranial Magnetic Stimulation is Useful for Maintenance Treatment

The Mood Disorder Questionnaire for Assessing Bipolar Spectrum Disorder Frequency

Capgras Syndrome and Blindness: Against the Prosopagnosia Hypothesis

Re: New Centry: Overcoming Stigma, Respecting Differences—Dr Myers' Superlative Presidential Address

Steroid-Induced Psychosis Treated With Risperidone

Review Paper

Attention-Deficit Hyperactivity Disorder: Critical Appraisal of Extended Treatment Studies

Russell Schachar, MD, FRCPC1, Alejandro R Jadad, MD, DPhil2 , Mary Gauld, BA3,
Michael Boyle, PhD4, Lynda Booker, BA5, Anne Snider, MEd6, Marie Kim, MD, FRCPC7, Charles Cunningham, PhD8


We undertook a systematic review of the literature on the long-term treatment of attention-deficit hyperactivity disorder (ADHD). We used systematic strategies to identify randomized treatment studies in which treatment was administered for 12 weeks or more. We included 14 studies involving 1379 subjects. Because of the limited number of high-quality studies and the heterogeneity of outcome measures, we did not perform metaanalysis. We rated 5 studies as adequate for methodological quality. Five studies followed children for more than 26 weeks. Pharmacologic interventions were studied more frequently than nonpharmacologic ones. Six studies permitted evaluation of the effects of combined drug and behavioural intervention. Twenty-five different outcomes were measured using 26 different tests. Stimulant medication appears to reduce ADHD (7 studies), dysfunctional social behaviour (6 studies), and internalizing symptoms (2 studies). Available studies provide little evidence for improved academic performance with stimulants (3 studies). Medications other than stimulants have not been studied extensively (3 studies). Only 1 study showed that combination therapy adds to the effects of medication. Rigorous treatment research among representative samples of ADHD individuals is needed.

(Can J Psychiatry 2002;47:337–348)

Acronyms and Abbreviations Used in this Paper

Clinical Implications

  • Systematic reviews are important tools for decision makers but the methodological rigour of randomized controlled trials (RCTs) of long-term attention-deficit hyperactivity disorder (ADHD) treatment is low.
  • These studies do not clarify the effect of treatment on important outcomes.
  • Combined pharmacologic and nonpharmacologic interventions yield the best outcomes.


  • The effects of nonpharmacologic treatment and drugs other than stimulants are little studied.
  • Systematic review of available studies is limited by the wide array of outcomes, designs, diagnostic measures, and other critical study elements.
  • RCTs may not be the best design to evaluate the effectiveness of long-term therapy.

Key Words: attention-deficit hyperactivity disorder, ADHD, systematic review, treatment, stimulants, behavioural therapy

Résumé : Trouble d’hyperactivité avec déficit de l’attention : évaluation critique des études sur le traitement de longue durée

Attention-deficit hyperactivity disorder (ADHD) (1) is a common psychiatric disorder occurring in approximately 5% of school-aged children, adolescents, and adults (1,2). It is a frequent reason for referral to mental health services (3). ADHD is first evident in the preschool years (4) and persists in as many as 70% of individuals throughout childhood and adolescence and into adulthood (5,6). Affected individuals are at risk for oppositional defiant disorder (ODD), conduct disorder (CD), depression, anxiety, and learning disability (LD) (7). They are also at risk for the development of delinquency or criminality, and for school suspension, academic underachievement, low self-esteem, and substance abuse (8). Treatments must be of sufficient intensity to have an immediate impact on the core ADHD symptoms, and they must be of adequate duration and intensity to alter adverse outcomes, many of which do not develop for several years.

In 1997, the Agency for Healthcare Research and Quality charged the McMaster Evidence-based Practice Centre with the conduct of a comprehensive, systematic review of the literature on ADHD treatment . Our first objective was to conduct a formal critical appraisal of existing systematic reviews and metaanalyses. In addition to other issues, we wished to determine whether existing reviews had adequately evaluated the evidence on the effectiveness of extended treatment for ADHD. The main conclusion from the appraisal of published reviews (9) was that most existing systematic reviews and metaanalyses had extensive flaws due to poor description of the methods used to identify, select, assess, and synthesize information. Of the 13 reviews (3,10–21), only 2 (10,13) had minimal flaws, but these reviews were narrowly focused on treatment effects as measured on the Continuous Performance Task (13) or on school-based interventions (10). Only 1 review (15) specifically evaluated evidence for long-term ADHD treatment, but that study had significant methodological limitations. Consequently, the evidence for the effectiveness of long-term pharmacologic and nonpharmacologic interventions for ADHD was not addressed by previously published reviews.

This article systematically appraises the methods and results of published studies in which ADHD treatment persisted for more than 12 weeks (Table 1, 22–35). Although ADHD treatment typically continues for many years (36), we identified those studies in which treatment persisted for a minimum of 12 weeks under randomized conditions. This criterion was arbitrary but ensured that the review would identify the longest studies from which to draw preliminary conclusions. This distinction does not, of course, imply that 3 months of treatment defines optimal extended therapy. The entire report is available at (
). We focused on evidence provided by randomized controlled trials (RCTs) because they are the simplest and most powerful research designs in which to evaluate the efficacy and effectiveness of interventions.


Selection of Studies

Inclusion and Exclusion Criteria. We regarded as potentially eligible full reports published in peer-reviewed journals, in any language, that focused on the treatment of ADHD in humans. We selected any reported RCT in which treatment persisted for a minimum of 12 weeks under randomized conditions. Where studies included subjects with conditions other than ADHD, they were selected only if they provided separate analyses for patients with ADHD.

Search Strategy. Potentially eligible studies were identified through a systematic search of Medline (from 1966), CINAHL (from 1982), HEALTHStar (from 1975), Psycinfo (from 1984), and EMBASE (from January 1, 1984, to November 30, 1997). (The search strategy may be obtained from the principal author.) We also searched the Cochrane Library (issue 4, 1997). Finally, we searched the reference lists of any eligible article from these sources, as well as files of research team members and partner organizations.


Data Extraction

We developed and tested data extraction forms for this project ( Two reviewers independently extracted data from each full report. Differences were resolved by consensus and by referring to the information in the original report. Any differences that the 2 reviewers could not resolve were resolved by a third reviewer. The original reports were not masked because masking is time-consuming and does not have an important impact on the results of systematic reviews (37).

Data were extracted on each of the treatment arms, outcomes, and tests used in each study. Information on outcomes was extracted regardless of the instrument or test used within each study. Only information gathered during the subjects’ participation in the randomized groups was extracted: no data gathered after discontinuation of therapy were sought.

The outcomes of interest, selected a priori by the panel of experts (led by the AAP Task Force), were as follows:

Behaviour Symptoms: observed core symptoms of inattention, hyperactivity, and impulsivity, and the results of a laboratory test of attention.

Academic Performance: results of achievement tests and grades, as well as verbal, reading, mathematics, and spelling skills.

Social Behaviour, Conduct, and Oppositional Disturbance: diagnosis of ODD or CD, degree of aggressiveness and social competence.

Internalizing Symptoms: depression, anxiety, crying, sadness, global mood, and level of emotional well-being and self-esteem.

Assessment of Study Quality

We assessed the methodological quality of the studies in several ways.

Quality Assessment Scale. The methodological quality scale (38) produces a minimum score of 0 points and a maximum score of 5 points. This scale assesses whether the study includes a description of appropriate methods to generate the randomization sequence (2 points), double blinding (2 points), and a detailed account of withdrawals and dropouts (1 point). The higher the score, the better the methodological quality of the RCT. Studies with a score of less than or equal to 2 points have been shown to exaggerate estimates of intervention effects by more than 30%, on average (39). Blinding helps prevent ascertainment bias and protects the randomization sequence after allocation, but cannot always be implemented, as was the case for most trials in this review (40). Even when a trial was not double-blind, a study could still be awarded 3 points if it included a description of randomization and adherence.

Concealment. We determined whether the allocation of individuals to the different study groups had been concealed until after their consent was obtained. Studies in which allocation was unclear or inadequately concealed have been shown to exaggerate estimates of intervention effects, by more than 35%, on average (39,40). Allocation concealment prevents selection bias, protects the randomization sequence before the interventions are given to study participants, and can always be implemented.

Relation with Industry. We also sought information on any association between the investigators and the pharmaceutical or a related industry. It has been shown that reports of trials sponsored by pharmaceutical companies are more likely to favour the experimental intervention than are trials not sponsored by pharmaceutical companies (41,42).