(9 1997 Martin Dunitz Ltd

International Journal of Psychiatry in Clinical Practice 1997 Volume 1 Pages 249-259

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Attention Deficit Hyperactivity Disorder (ADHD): Selected review of causes, comorbidity and treatment

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STUART FINE Department of Psychiatry, University of British Columbia

Correspondence Address Professor S. Fine, MB FRCP(C) FRCPsych, Director of ADHD Clinic, B.C.’s Children’s Hospital, 4480 Oak Street, C4, Vancouver, B.C. V6H 3V4, Canada Tel: +I 604 875 2031 Fax: +1 604 875 2099 Received 2 June 1997; revised 20 August 1997; accepted for publication 9 September 1997

A limited review of the causes, comorbidity, diagnosis and treatment is offered to emphasize the difficulties in diagnosing and treating Attention Deficit Hyperactivity Disorder and Hyperkinetic Disorder. Some of the difficulties include controversies about the existence of a separate disorder, the changes in symptoms with age, the short-lived improvement on medication and the claims of unsubstantiated treatments. This selected review should help the reader to consider recent findings in the aetiology, diagnosis and treatment of ADHD. (Int J Psych Clin Pract 1997 1: 249 - 259) Keywords

Attention Defcit Hyperactivity Disorder aetiology of ADHD

INTRODUCTION ttention Deficit Hyperactivity Disorder (ADHD)’ A and Hyperkinetic Disorder’ hold a great deal of fascination for researchers and clinician^.^-^ Depending on the definition of the disorder, the stated prevalence varies, but the rate often quoted is 3% to 5% of the school-aged p ~ p u l a t i o n .A~ higher prevalence was found in Ontario, Canada, where 6.3% of children aged between 4 and 16 years had Attention Deficit Disorder (ADD) with hyperactivity. The present paper selectively reviews advances since 1990 in knowledge of the causes, comorbid conditions and treatments of ADHD, to outline some of the difficulties in diagnosis and treatment of ADHD in children and adolescents. Those diagnosed with ADHD are more likely to suffer from academic difficulties at school and to have difficulties with peer and family relationships. They seem to suffer from a lack of ‘savoir faire’ and have a ‘social learning disability.’ As adults they are more likely to suffer from drug or alcohol abuse. Their work records are poor and they are less able to form lasting and close relationships4 The diagnosis of this condition and its treatment are fraught with controversy. It has elicited an enormous amount of investigation. There has been controversy as to whether ADHD or Hyperkinetic Disorder actually is a discrete condition, and if so, what may be the best way of managing it.8 With pharmacological treatment, the short-

Hyperkinetic Disorder treatment of ADHD

term response has been very good, but some symptoms may persist for many years, often into adulthood, and the toll on the child and the family is considerable. Using the diagnostic classification of the American Psychiatric Association, the diagnostic criteria for ADHD have differed over the years as the emphasis on different symptoms has changed. The most recent classification, DSM-IV, (1994) has three categories of diagnosis of ADHD: one predominantly inattentive, one predominantly hyperactive and impulsive, and one a combination of these two categories. For a diagnosis of ADHD using DSM-IV criteria, the patient needs to have six out of nine symptoms of poor attention or six of nine symptoms of hyperactivity and impulsiveness, or a combination of both. The symptoms must have been present from before the age of seven and they need to be present in at least two situations such as the home or at the school. The symptoms must result in significant impairment. Using the ICD-10 criteria for the diagnosis of hyperkinetic disorders, symptoms must be pervasive and present before the age of six. The ICD-10 diagnosis requires both hyperactive and inattentive symptoms, whereas DSM-IV has either hyperactivity or inattention. ICD-10 encourages the use of a single diagnosis, whereas DSM-IV encourages the use of multiple diagnosis. Field trials of DSM-IV diagnosis show that an increase in the prevalence of ADHD may indeed be found, because using these criteria will lead to more pre-school aged children and more girls being diagnosed with the d i ~ o r d e r . ~

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The three areas of hyperactivity, inattention and impulsiveness depend on the individual judgement of the observers. Moreover, symptoms of hyperactivity can occur in other psychiatric conditions such as anxiety disorders, depression, mania and autism, and they are present more frequently at certain stages of development, such as in younger children. Inattention is also seen in anxiety disorders and those who are showing apathy from whatever cause. Impulsiveness occurs in conduct disorders and the effects can be seen in behaviour that is inappropriately timed or intrusive; the impulsivenessmay result in more accidents. There are differences in how observers rate hyperactivity, inattention and impulsiveness and there are different connotations given to these behaviours. Many parents describe their children as exuberant and inquisitive when teachers have said they are overactive and intrusive. Other parents have said their child is thoughtful but very hesitant to write anything down, when teachers have called them day-dreamers and not productive. Yet other parents describe playful pranksters when teachers describe them as impulsive and prone to accidents. Sometimes parents see many symptoms at home and teachers see very few at school, and it is clear that the contexts for showing symptoms vary, as do the tolerance levels of different observers for certain types of behaviour. Frequently it is said that the child has an excellent ability to attend as he can play with Lego and play Nintendo for hours. These are novel interesting tasks that give immediate gratification and engage the child’s attention. In the doctor’s office, children with ADHD are often able to stay still and to attend because it is a novel, interesting situation where there is an authority figure. Most children with ADHD do seek other activities not related to the task at hand, unless they find the task interesting. There seems to be an impairment of their ability to regulate themselves and to inhibit extraneous responses. The child typically shows symptoms under boring conditions. Weiss and Hechtman6 have reviewed the concerns of several researchers about the poor interrater reliability in assessing the symptoms of ADHD and about the very existence of ADHD. They claim however, that there is little evidence of poor interrater reliability and stress that the observations should be made in several different settings. They do comment on some overlap between symptoms of ADHD and the symptoms of a conduct disorder. Schachar and Tannock” discuss four possible explanations of this overlap, but they show that ADHD and conduct disorder also occur as discrete entities. Van der Meere” reminds us that the tasks of attention can be divided into orientation, reorientation after getting distracted, information uptake (encoding), maintaining attention for a length of time and being able to attend to two or more tasks at the same time. Hyperactive children do not differ from controls in these areas but their task efficiency is highly sensitive to ‘state manipulation’ such as the rate of presentation of material. He suggests that parents and teachers often complain about different aspects

Table 1 Cormorbidity with ADHD

Anxiety disorders Conduct disorders Developmental disorders Generalized tic disorders and Tourette’s disorder Bipolar disorder Substance use disorder Autism and pervasive developmental disorders Central Auditory Processing Disorder

of poor attention or hyperactivity. Some of these ADHD children actually work more accurately if they have background music than if they are in a very quiet situation.

COMORBIDITY As the treatment of ADHD is affected by comorbidity, it is important to keep these other conditions in mind and to elicit whether there is a family history. Many dilemmas arise. For example, if there is comorbidity, which condition does one try to treat first, or can they be treated simultaneously? More research is required to answer these questions. Some comorbid conditions more commonly associated with ADHD will be mentioned. Biederman et all2 have reported the following ranges of rates of comorbidity with attention deficit disorders: conduct and oppositional disorders 30 - 50%; mood disorders 15- 75%; anxiety disorder 25%; learning disorders 10- 92%.Those with comorbid depressive disorder and anxiety disorders show higher levels of coexisting life stresses and parental symptoms. Anxiety disorders These have been found to be comorbid with ADHD in epidemiological and in clinical samples. About 25% of ADHD patients were comorbid with anxiety disorder.l 3 ADHD patients had more relatives with anxiety disorders than did normal controls, and patients with ADHD and comorbid anxiety were even more likely to have relatives with anxiety disorders than patients with ADHD without comorbid anxiety disorders. However, the genetic transmission of the two disorders seems to be independent. Conduct disorders The ICD-10 classification has two categories for the hyperkinetic child, one with and one without conduct disorder. There is some overlap in the symptoms of ADHD and conduct disorders.14*15Some ADHD children have no conduct disorder symptoms and it is suggested that this is an ADHD group that has more developmental abnormalities. The ADHD group with conduct disorder seems to be associated with more family dysfunction. This group, suffering from both, responds more poorly to treatment;

Attention Deficit Hyperactivity Disorder

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and in this combined type, symptoms of both hyperactivity and conduct disorder are more severe. Developmental disorders ADHD is often associated with developmental disorders and these include language delay, reading and spelling disorders and writing disorders.l6 Sometimes it is difficult to tell whether the ADHD symptoms are present because the child is finding it frustrating to learn to read or write; or whether the ADHD causes the difficulty in reading or writing. McGee and Share15 feel that in many cases treating the learning disorder improves the ADHD behaviour and that treating the ADHD does not have any long-term effect on the learning. Stevenson expands on how to consult with school staff about this, and he stresses that both ADHD and learning disorders have to be treated simultaneously.16 Generalized tic disorders and Tourette's disorder These are often preceded by attention deficit hyperactivity symptoms (up to 50% of cases).17Sometimes the onset of the tics occurs with the taking of stimulants, or, if the tics are already present, the stimulants may affect their severity and frequency. Often there is an increase in tics but occasionally they diminish.l8 If the frequency and severity are clearly increased by stimulants, other medications for the ADHD may be tried, but some, such as the tricyclic antidepressants and clonidine, can also increase tics. Bipolar disorder In children and adolescents this often begins with many of the symptoms of ADHD, including psychomotor restlessness, difficulty in concentrating, impulsiveness and poor judgement." When there is a family history of bipolar illness the diagnosis may come more readily to mind. Bipolar illness and ADHD can exist together. The drug treatment when both are present requires mood stabilizers (lithium, carbamazepine or valproate) and then the addition of stimulants. If stimulants are used first, the side-effects of appetite loss and insomnia may appear to exacerbate the symptoms of the bipolar disorder. Education of parent and patients and careful programming at school are also required. Milberger et alZ0 looked at the symptoms of major depression, generalized anxiety and bipolar disorder which overlap with those of ADHD. By using two different techniques (a subtracting technique and a proportion technique), they showed that these comorbid conditions maintained their integrity in most cases of ADHD, 79% of cases of major depression, 75% of cases of generalized anxiety and 56% of cases of bipolar disorder.

disorder as well as ADHD, it would be advisable to treat the ADHD with tricyclic antidepressants rather than stimulants, which can be abused or sold as street drugs. Autism and pervasive developmental disorders Many children diagnosed as having these show features of hyperactivity that interfere with their functioning. Although initially methylphenidate was not recommended to help the hyperactivity, as there was fear that it could worsen other symptoms,22more recent reports suggest that the hyperactivity may respond to stimulants without any deterioration of other symptom^.^^-^^ Central auditory processing disorder (CAPD) This is defined as "limitations in the ongoing transmission, analysis, organization, transformation, elaboration, storage, retrieval and use of information contained in audible signals," and is difficult to distinguish from ADHD.26Tests for difficulty with auditory reception and perception are used for CAPD. One of the interventions for CAPD is to fit a microphone in the ear so that the child pays attention to the words spoken by the teacher through a transmitter. CAPD and ADHD may both be present.

AETIOLOGY There are no known causes for ADHD but several contributory factors have been demonstrated. These seem to be genetic, biochemical or neuropathological factors as well as psychosocial factors2' Family studies have found an increased prevalence of ADHD in siblings of the ADHD patient (21% versus 6% of controls) and often a history of ADHD types of behaviour in the parents or their siblings.28 Other types of psychopathology have been noted in the parents, especially personality disorders and mood disorders. Twin studies

Biological factors Genetic factors Brain abnormalities Infections and toxins Neurotransmitter changes Temperament I Psychological Factors ADHD symPtoms+Poor attachment Pervasive anxiety

Social factors

Substance use disorder Symptoms can frequently mimic the symptoms of ADHD and the two can coexist. Patients on cannabis often show symptoms of ADHII.~' It is therefore important that the patient should be drug-free before embarking on drug treatment of the ADHD. In patients with substance use

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Multiple caretakers Institutional upbringing Physical and sexual abuse Figure 1 Aetiology of ADHD

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show an increased incidence of ADHD in the monozygotic twins of sufferers from ADHD, as compared to the incidence of ADHD in twins of dizygotic pairs.29 Adoption studies show that the adoptive relatives of ADHD children are less likely to have ADHD than are biological relatives of ADHD children. Because ADHD is more common in boys, this gender difference in prevalence should help to sort out the form of genetic transmission, but the results are contradictory. One would expect the relatives of girls with ADHD to have a greater incidence of the disorder, and some studies do show this, but others do not. In these studies the number of ADHD girls is small. The conclusion is that there is a genetic influence but the transmission seems to be c~mplicated.~' Brain abnormalities are suggested by imaging techniques, but only small numbers of children have been involved in these studies.31 Single-photon emission scans showed poorer perfusion of the frontal areas of the brain and the striatum in the midbrain. Positron emission studies on hyperactive parents of hyperactive children showed reduced uptake of glucose in the cerebral cortex, especially the frontal areas.32Magnetic resonance imaging has shown some abnormalities in the corpus callosum and more recently in fronto-striatal circuitry (prefrontal cortex and basal ganglia).33 Certain brain injuries do result in hyperactivity but also result in mental retardation. Toxins such as lead may cause various symptoms, and fetal alcohol syndrome or fetal alcohol effects from the intake of alcohol in the first trimester of pregnancy often result in quite severe ADHD that is very difficult to manage.34 Neurochemical studies have suggested that neurotransmitters play an important part in ADHD,35based upon the action of stimulants which inhibit re-uptake and increase release of monoamines, noradrenaline, dopamine and serotonin. Several studies on each monoamine have revealed the complexity of these systems and how they are interrelated, and Kado and Takagf6 write that "a single transmitter defect hypothesis cannot be valid." Psychosocial causes for ADHD have been suggested.37 Children who have had many different carers and those who could not bond well are frequently hyperactive and inattentive. This has been noted in children brought up in institutions, and is accepted as a cause of hyperactivity in ICD-10. It is listed separately as 'attachment disinhibition disorder', in which dependency in early childhood is replaced by indiscriminate over-affectionate behaviour and often associated with hyperactivity.

DIAG N0 s IS The diagnosis is made by taking a detailed history, including information from several observers, especially teachers. ADHD children have a history of kicking hard and often in the womb, getting into everything as a toddler

and having frequent cuts and bruises. They have also had many visits to the emergency ward, and show inattentive and disruptive behaviour at school and in peer groups. There is often a story of similar problems in other family members. A psychiatric interview must be carried out with the child. Sleator and Ullman have written that the "physician may not be able to diagnose hyperactivity in the office"3*as the child is in a novel, interesting situation and may not show any symptoms. Standardized history forms about the pregnancy and growth and development are often helpful. A physical (including a neurological) examination and an assessment of visual and hearing problems are necessary. It is largely a matter of personal preference which standardized rating scales to use. Many list the symptoms and grade their severity. An example is the Stony Brook Child Psychiatric Checklist,39 which has rating forms for both the parents and teachers. Another is the Child Behavior Checklist,4' and there are several others that are well standardized and have been described in other One commonly used in North America is Conner's rating scale, which includes questions on other conditions such as conduct disorders and anxiety disorders, and has different forms for the parents and the teacher. There is a shortened form of this scale; and another one, with only ten questions, is useful to monitor the response to m e d i ~ a t i o n .It~ ~is important to get other information from the teacher about grades, classroom and playground behaviour and educational psychologists' reports. The Wechsler Intelligence Scale for Children is often used to determine areas of deficit and also to measure freedom from distractibility, which is a combination of scores from the arithmetic, digit span and coding subtests. Barkley,' however, does not recommend using this factor as evidence for or against ADHD. Computerized tests for impulsivity, commission errors and omission errors are sometimes used clinically but are mostly used in research. In clinical practice the computerized tests are useful in assessing the response to medication; they are not reliable in clinically distinguishing ADHD from other conditions. One example of a computerized test is the continuous performance test, which can be obtained in various forms as software.42 Other special investigations may be required in individual cases. A speech and language assessment is helpful in assessing pathology. An occupational therapist may also reveal some difficulties in coordination and in the activities of daily living that need to be treated.

DEVELOPMENTAL FACTORS3r34 PRE-SCHOOL CHILDREN It is suggested that preschoolers should require more symptoms to qualify for the diagnosis of ADHD. Commonly the hyperactivity and impulsiveness are associated

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Attention Deficit Hyperactivity Disorder

with symptoms of aggression, and with symptoms of an oppositional defiant disorder. As the child gets older, the hyperactive features seem to diminish but the inattentiveness persists. Other features develop, such as poor self-esteem and depression. Frustration occurs with poor peer and family relationships, and this is even more likely in those with learning disorders. Many pre-school children appear to be hyperactive. Where there is a strong family history of ADHD and where the hyperactivity has started almost from conception the diagnosis is easier. When there is a difference between the ratings by parents and by preschool teachers, one needs to visit the preschool to see how the child compares with peers. If stimulants are to be used in treatment, dextroamphetamine seems to be more effective than methylphenidate, which is not recommended for children under the age of 6 years.

ADOLESCENTS In adolescents there may be fewer symptoms of ADHD than in the earlier years, but more evidence of comorbidity with bipolar disorders and conduct disorders: family history and dynamics may make these more apparent. The prognosis is worse if there is additional psychopathology. The adolescent is often wrestling with normal developmental tasks such as emancipation from adults, establishing a peer group or a close friendship, coming to terms with their sexuality and making some plans for their future; and these tasks may be more difficult for teenagers with ADHD. Teenagers will often not accept that they have ADHD, even when everyone else agrees that they do. When they agree that they have problems, they may be reluctant to try medication, often because they do not want to differ from peers. Also, they have heard that the medication can impair growth, or prevent them from taking alcohol or other street drugs, and they feel that they are giving up some control. If they improve on medication, they fear that it is only because of the medication and that this is not a true reflection of their abilities. For example, one teenager, an expert skateboarder, felt that he was taking unfair advantage of his competitors if he won a competition while taking methylphenidate. He accepted taking his medication when he was not competing, so that he would not get into so much trouble at school.

TEMPERAMENT In assessing and treating the ADHD child and adolescent, one must consider temperamental factors and how they play a part in the interaction with caretakers, teachers and peers. The child who has been active, persistent, irregular in sleep and eating patterns, negative in mood and poorly adaptable to new situations, is likely to run into some difficulties. This is even more so if those who care for him or her have a low tolerance for these characteristics. Temperament has been extensively studied, and certain

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core traits have been suggested which include the activity level, sociability and emotionality of the When the 'fit' between the caretakers and the child is poor, friction and acrimony can arise. Quite often a parent or teacher is hoping for a child with a certain temperament and the child may have a completely different one. This applies particularly to children with ADHD, where the hyperactivity may upset some carers a great deal more than others. It is important to assess carers' tolerance level for ADHD symptoms, as one needs to consider this when planning interventions.

TREATMENT There seems to be general agreement that treatment has to be m~ltimodal.',~~ This includes education about ADHD, some modification of behaviour using instantaneous rewards for good behaviour, and careful practising of socially appropriate behaviour. Also included are modifications in the environment at school, in the classroom and outside, at recess and lunch. Finally, treatment can include trylng medications and referring parents to parent support groups. There needs to be education of the parents, the child, the school staff involved with the child, and often of the extended family and the neighbours. They need to know that this is a child with a disorder which makes them more active and have difficulty in sitting still; they find it hard to listen to instructions and to curb the impulse to make themselves heard and to do dangerous actions. Educating parents about obtaining compliance from a child with ADHD is similar to teaching parenting skills to parents of normal children, but the immediacy of the parental response must be emphasized, as the ADHD child cannot wait, and also would prefer a small immediate reward to waiting for a deferred bigger reward. Barkley' has outlined a parenting course. Some sessions include "enhancing parental attending skills, giving commands more effectively, establishing a home token system, using a response Table 2 Treatment of ADHD

Multimodal approach 0 Behaviour modification 0 Teaching social skills and problem solving techniques (including anger management) 0 School interventions Medication 0 Stimulants: methylphenidate, dextroamphetamine and magnesium pemoline 0 Tricyclic antidepressants: desipramine, imipramine 0 Bupropion Parent education and parent support groups (Place of diet, biofeedback more controversial)

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cost, using time out and managing behaviour in public places."

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Behaviour modification Modifymg the child's behaviour by using star charts and ensuring immediate rewards for good behaviour often has to be carefully monitored. Parents and teachers frequently say this child has to learn to listen just like other children, and they are reluctant to give special attention to these children. Also, when the teachers have large classes they are unable to give the extra attention that is required.

in advising about the effects of various medications. Some schools have many teachers willing to help and some have very few, and this is probably determined by the principal and his or her attitude towards ADHD and its treatment. Public attitudes and budget constraints will have an effect on how the schools help.

MEDICATION

The possibility of using medications to modify behaviour is often recommended, as they are so effective in the short Social skills term.48 Several groups of drugs have been tried: the Teaching the children appropriate social b e h a v i o ~ r ~ ~stimulants .~~ (methylphenidate, dextroamphetamine and ('social skills') has been less successful than was hoped, magnesium pemoline), the tricyclic antidepressants (imias they seem to learn the appropriate behaviour but do not pramine and desipramine) and the alpha-adrenergic apply it, possibly because of their impulsivity. They do not agonists (clonidine and guanfacine). seem to be able to generalize their new knowledge of how to act, to other situations. Part of teaching social skills has Stimulants Seventy to ninety percent of those diagnosed with ADHD been anger management,5which includes recognizing the signs and symptoms of anger and learning some methods respond to the stimulants, and stimulants are the first to reduce anger (playing turtle where one 'withdraws into is going to be used. Parents raise c h o i ~ e ~if~ medication .~' oneself is a very useful visual picture to offer the child). concerns about the possible side-effects and the possibility Counting to ten, looking out of the window and thinking of of the child becoming addicted to the use of the drug. The something else are also effective techniques. These training most frequent side-effect is the loss of appetite. As the exercises are more effective if they are carried out in a effects of the drug usually only last for 4 hours, and it is school environment and they are enhanced by assigning a given twice or three times a day, the child usually eats more 'buddy' or peer tutor so that they can be reinforced. Brown in the evening; frequent snacks should also be encouraged. and Cantwell used siblings as therapists4' There is concern about retardation of growth. Recent studies show that ADHD children grow at a slower rate, School interventions16 whether placed on medication or not, but their average Contact with the teacher and other special education height at adulthood is the same as that of the general personnel and support staff is important so that one can p ~ p u l a t i o n .In ~ ~studies of the abuse of stimulants, those organize an individualized education plan. The teachers children who have been given medication were found to be need to know that the psychiatrist is interested in working no more likely than other children to abuse drugs.52Those with them to improve the behaviour of the children, and to who are medicated may be less impulsive and have higher try to help their academic progress. self-esteem, and should therefore be less likely to The difficulties arise in trying to contact teachers, as participate in the drug scene. they are only available at certain times and psychiatrists are Gualtieri et a153found little correlation between blood often not available at those times. When the teachers and levels of methylphenidate (MPH) and changes in behathe psychiatrists do talk to each other, they may be far apart viour. Elia et a154suggest that as long as one gives a high in their approaches. Often the psychiatrists recommend enough dose, 90% of subjects will respond to stimulants, behavioural approaches that take time and energy, and then although on higher doses the appetite-reducing side-effect they may recommend medications. Many teachers are and a feeling of dysphoria occur. Safer and Allen have against medications and talk about the "serious side- shown that tolerance to methylphenidate is rare.55There is effects." These include the alleged dangers of addiction and controversy about its differential effects on learning and "making the child so drugged that he does not know what social behaviour at different d o s a g e ~ . Sleator ~ ~ . ~ ~et a158 he is doing." discuss the responses of children to taking MPH and point Some teachers want advice about educational strategies. out that they will often say what they think will please the These could include structuring the timetable, having the interviewer rather than what they really think; this child sit near to the teacher and correcting any written becomes apparent when they are interviewed later by work as soon as possible. As the child gets older, helping in someone other than the person dispensing the medication. organization of materials and having a daily report card is Some children will claim they are taking medication helpful. Contingency management at school and at home is regularly when they are not. very important. Some children respond better to dextroamphetamine The psychiatrist may also want to enlist the teacher's than to methylphenidate, although the side-effects are said help in doing a drug placebo trial, and teachers are vital to be more pronounced with amphetamine^.^^ The

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Attention Deficit Hyperactivity Disorder

advantage of sustained-release dextroamphetamine over sustained-release methylphenidate is mentioned by many practitioners. There is concern that sustained-release methylphenidate does not enter the bloodstream as evenly as the dextroamphetamine. Some children are placed on a very high dose of methylphenidate to control their symptoms. There are not many reports on the effects of high doses. In one report by Ahlman et a1,60high-dose Ritalin (5 mgkg per dose) was found to cause more loss of appetite than low-dose (3 mg/ kg per dose). This may be associated over time with a loss of weight. It is interesting that these authors also cite papers where differences in efficacy of generic MPH and ritalin are reported. Recently Abbott Laboratories, the manufacturers of pemoline, have issued a warning about 12 deaths from liver failure from pemoline. This makes one reluctant to recommend pemoline, and certainly not as a first-line medication. However, when one 'inherits' a patient doing well on pemoline, in spite of the risks, the doctor, parents and patient have a difficult task in weighing the advantages of stayng on the medication. A drug/placebo trial is useful to help parents to decide whether to use stimulants. If it shows that the stimulants do work, parents can then decide to give the stimulants a longer trial. If the trial shows that the placebo is just as effective as the stimulant, it may dissuade parents from persisting in using stimulants. Trials can be done with placebo, low-dose stimulant and high-dose stimulant on different days, and parents, teacher and doctor should be blinded.61 Medication or placebo should be placed in gelatin capsules and the days on which each was given should be randomized. Others have done the trial by giving the low-dose and high-dose stimulant, and placebo, each, for a week at a time. There are however many pitfalls: for example, the teachers are requested to complete a rating of the child's behaviour each day, and they may often forget to do this, or forget to write the date on the rating. Some suggest that an active drug/placebo trial may only be necessary when the parents have major doubts about the use of stimulants. One study shows that the drug/placebo trial does improve patient acceptance of medication but not adherence.62 Antidepressants The use of desipramine for ADHD is in some disfavour because of reports of cardiac complications which were associated with death^.'^-^^ This question has been reviewed by Green66 and by Wilens et aP5 and they still use desipramine, with certain precautions. These include a baseline EKG and an EKG each time they increase the dose. They recommend EKGs each time the pulse rate is above 110- 130/min (110- 120/min in adolescents), the blood pressure above 120/80 mmHg (140/90 mmHg in adolescents), the QRS interval above 120 ms or 30% over baseline, and the QT interval 2 460 - 480 ms.

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Clonidine The use of clonidine for the hyperactive symptoms has been promoted by and his group. There have been reports of cardiac problems in the combined use of methylphenidate and clonidine, although the causal relationship for three deaths on this combination is questioned. Prince et a1 use clonidine with methylphenidate, using the clonidine at night to help the children settle and sleep.68 Cantwell et aP9 report one more death and three cases with adverse reactions among patients on clonidine and Ritalin, and they suggest that more research needs to be done before this practice should be accepted. Bupropion More recently, a trial of bupropion in comparison with methylphenidate has shown encouraging results.7o While bupropion was not quite as effective as methylphenidate, it was nearly so, and thus could be used in cases when the child is allergic to stimulants and where there is concern that other family members may abuse or sell the stimulants. Adherence Adherence to the medication regime can be a major problem. In one study, 20% of parents of ADHD children had stopped giving them their stimulant medication after 4 months, and 44% after 10 months, even when the medication was effe~tive.~' A more recent study has shown 18%stopping after 4 months and 27% after 12 months.72 To improve adherence, the patient and parents have to respect the doctor and believe that the medication is working without too many side-effects, and the medication needs to be easy to take and not result in the child being subjected to ridicule.73So that their peers don't see them take medication at school, many prefer the slow-release methylphenidate or dextroamphetamine. Moreover, there is public pressure not to take medication, from the media and from organizations like the Church of Scientology whose members feel that their teachings can eradicate the symptoms and the need to take medicines.

ATTRIBUTIONS How parents and teachers attribute the cause of certain behaviours will determine how they deal with them. If they think the child can control the symptoms, they will be more likely to punish him or her; different strategies are more likely to be considered if they believe that the misbehaviour is a result of a recognized disorder over which the child has little control.74 Related issues are the parents' feeling of competence in managing their child and their satisfaction with the services they receive. We hope that satisfaction with services will result in better adherence to treatment and that the carers will feel that they have become more competent. A study of what parents will accept for the treatment of the ADHD75showed that medication is frequently chosen

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last, and that a behaviour modification approach is preferred.

approach if a child responds to an elimination diet; and also, using several observers to assess the changes.

PARENTSUPPORT GROUPS

Thyroid abnormalities These are associated with symptoms of hyperactivity, anxiety and psychosis.” More recently, a higher prevalence of ADHD than in the general population was associated with the syndrome of generalized resistance to thyroid hormone (GRTH)?’ which is a rare inherited disorder. Initially it was hoped that thyroid abnormalities could be used as biological markers for ADHD. Two recent review^^^^^^ have suggested that thyroid testing should only be used when there are other symptoms of thyroid disorders (as well as ADHD), or when there is a history of thyroid disorder in the family.

These are generally well organized in Canada and in the United States. One of these is CHADD (Children and Adults with Attention Deficit Disorders), and there are many branches. Leading researchers present their latest findings at the annual meetings. Each group provides brochures and videotapes and they hold monthly meetings. These groups provide information and support. They can also put pressure on politicians for the provision of appropriate services.

OTHERINTERVENTIONS Diet This still seems to be a controversial intervention, as eliminating certain foods helps in only a small minority of those children with an atopic diathesis. One study by Egger et a176showed that children responded to dietary restriction if they also had other features of an allergy, but there were many placebo responders. There do seem to be some children who respond to the restriction of a dietary ingredient that also causes symptoms other than ADHD. A study by Kaplan et a177showed that 50% of 24 pre-school children with ADHD showed a 50% improvement of their ADHD, sleep and bedwetting behaviours, on a replacement diet. (The experimental diet eliminated food dyes, preservatives, monosodium glutamate, chocolate and caffeine over a 4-week period.) There was no challenge with large amounts of the ‘offending foods’, and this tends to minimize the importance of this study. Sugar It is commonly asserted that a high sugar intake will increase children’s activity level. Wolraich et a17’ tested a high sucrose diet, a high aspartame diet and a high saccharin diet (as a control) in 23 children aged between 6 and 12 who were reported to respond adversely to sugar, and in 25 normal pre-school children. There was no difference in behaviour or cognitive functioning among children fed on the three different diets, even though the school-aged children were identified as having been ‘sugar-sensitive.’ Kinsboume7’ summarizes the many studies done on food additives and sugar and writes: “Given the largely negative findings and failure of the occasional significant outcome to be confirmed in subsequent studies, it appears that any adverse effect of sugar is hardly as severe or as prevalent as uncontrolled observation and opinion would suggest.” He goes on to suggest that the public prefer external causes for disorders, such as diet, to genetic causes; however, he does admit that the behaviour of some hyperactive children may be aggravated by sugar. Because sugar-free diets are difficult to follow, he suggests only using this

Biofeedback A few studies claim good results using b i ~ f e e d b a c kThe .~~ child is taught to exercise some control over their brainwave speed and this is said to generalize into control over restlessness, impulsiveness and inattention. There have been no confirmatory studies of these claims. Perhaps one should present the evidence or lack of it to patients and their parents. If they still decide to try less recognized interventions, they could be encouraged to try more routine interventions afterwards, or even at the same time.

PROGNOSIS Cantwel14 has suggested three outcomes: ‘developmental delay’, where, as adults, the patients suffer no impairment from their symptoms (about 30%); ‘developmental decay’, where they may have an antisocial personality disorder and probably substance or alcohol abuse (30%); and finally ‘continual display’ of the symptoms, where symptoms persist, and this occurs in about 40% of patients. Hechtman and Weiss,6 in their 15-year follow-up, were quite optimistic about the outcome. Others” have found that in a 4-year follow-up, only 15% remitted, some before the age of 12. A family history of ADHD, psychosocial adversity, family discord and comorbidity are some predictive factors for persistence of the symptoms.

CONCLUSIONS Many things about ADHD are still unknown, including whether it is a homogeneous condition, and what the most salient causes may be. The different treatment approaches required when there are comorbid conditions make this a very challenging and yet rewarding area. Often symptoms of ADHD persist, and ADHD must be treated as a chronic condition. Although controversy still surrounds the diagnosis of ADHD, even the idea of adult The new findings ADHD is gaining more

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in the last decade suggest further parameters to consider in the aetiology, diagnosis and treatment. There is great activity on the research front in all of the disorders that are comorbid with ADHD, including developmental language and learning disorders, Tourette’s disorder, mood disorders and substance use disorders. From research at the genetic, biochemical and neurophysiological, and psychosocial levels, some new findings about the causes of ADHD and new techniques for treating it will surely be forthcoming.

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High comorbidity of ADHD Aetiology is multifactorial Treatment of ADHD with medication and individual psychotherapy as well as parent education

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