Stimulant treatment for attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is often associated with other behavioural or emotional problems and academic failure. In clinical trials, approximately 70% of affected children derive clinically significant benefits from treatment with stimulant medication, especially if this is augmented with behavioural management. However, 35-40% have a similar responseto placebo. Drug treatment has few shortterm hazards if the patients are adequately assessed and monitored. Possible longterm hazards are unknown.

Attention deficit hyperactivity disorder (ADHD) is characterised by persistent over activity, impulsivity and inattention inappropriate for the child's mental age.¹ It was formerly known as attention deficit disorder. The exact prevalence in Australia is unknown and depends on whether the U.S.A. or European diagnostic criteria are used. The European diagnostic criteria are more conservative and yield a lower prevalence.² In Europe, the condition is known as hyperkinetic syndrome. The condition seems to affect boys 5-10 times more commonly than girls, but the gender ratio may be biased by the diagnostic criteria which reflect boyish behaviours. Brain imaging suggests altered function in the limbic and frontal regions.^3,4

A small group of children have ADHD following a brain injury, but in most affected children, the condition is thought to be inherited. Although the disorder is usually apparent from early childhood, children are often not referred for clinical assessment until they reach school age. The hyperactive behaviours usually remit by early adolescence, but the problems with impulse control and inattention may persist into adulthood. A significant minority of teenagers and young adults with ADHD develop antisocial behaviours, abuse alcohol and other drugs, or develop other psychiatric disorders. Academic and vocational underachievement are common.

If the commonly used U.S.A. criteria (DSM-IV) are used to make the diagnosis, the child's symptoms must have begun before the age of 7 years. The symptoms must be maladaptive, inappropriate for the child's age, lead to significant impairment and be present in at least two settings e.g. home and school.

To fulfill the diagnosis of attention deficit hyperactivity disorder under DSM-IV criteria, the child must fulfill 6 of the inattention items and 6 of the hyperactivity/impulsivity items (see box). It is now possible to make a diagnosis of inattention without hyperactivity/impulsivity, and a diagnosis of hyperactivity /impulsivity without inattention, although the clinical utility of these categories has yet to be proven.

The rate of diagnosis is quite variable in different parts of Australia. This, rather than differences in State regulations (Table 1), may explain the varying prescribing rate for stimulants (Table 2). It would appear that prescribing doctors are often using different assessment procedures based on varying theories to make their diagnoses of ADHD. The condition is probably both over diagnosed and under diagnosed in different regions of Australia.

The validity of ADHD as a distinct syndrome remains controversial. This is because the symptoms vary in different settings and the majority of ADHD sufferers have associated problems. These problems may include conduct disturbance, learning difficulties, emotional disorders and family dysfunction. Maladaptive parenting behaviours are common, but may be a consequence of the child's symptoms rather than a cause for them. There is a very specific overlap with Tourette's syndrome, since three quarters of Tourette's sufferers have clinically significant ADHD. Many developmentally delayed children manifest some behaviours similar to ADHD, but do not fulfill the diagnostic criteria if their mental age is taken into account.

Due to the considerable publicity given to ADHD in recent years, parents are generally very well informed about the disorder. They are likely to present to the general practitioner with quite clear expectations about what may be done medically to help their child. A doctor who is asked to see a child with possible ADHD should screen for obvious developmental delay, speech, language, hearing, visual and neurological problems. The practitioner should ask the parents to arrange for the child to be seen by the school counsellor, if they have not already seen one. The counsellor may identify specific learning problems, and may be able to advise the teachers how to manage disruptive behaviour in the classroom. There are several useful treatments for ADHD, so it is reasonable to express optimism to the child and the parents.

General practitioners should seek a specialist opinion if they suspect that a child has ADHD. The specialist usually confirms the diagnosis by obtaining histories and standardised behaviour checklist information from several sources to determine whether symptoms are pervasive. Specialised EEG and psychometric examinations are offered by some clinics, but it is controversial whether these help the diagnostic process.

Treatment usually includes educating the child, parents and teachers about the nature of the problem and its likely course. Parents may be offered strategies to manage disruptive behaviour. A small minority of ADHD sufferers benefits from the assessment and management of food hypersensitivities, although the role of this approach remains controversial. The evidence for a specific association between allergic disorders and attention deficit hyperactivity disorder is equivocal.^5,6 The treating doctor is often asked to play an advocacy role for the child in obtaining specialist educational services and disability benefits.

Pharmacotherapy remains the single most effective treatment strategy, although its efficacy is enhanced by involving the parents and teachers in behavioural management. The stimulants dexamphetamine and methylphenidate are the most widely prescribed treatments for ADHD. Tricyclic antidepressants, clonidine, moclobemide and thioridazine are second line treatments which have been used alone or in combination with a stimulant for some patients. While the tricyclics have a similar efficacy to the stimulants, the efficacy of the other drugs has yet to be established.⁷

Action

Some of the many actions of the stimulants include inhibition of the reuptake of noradrenaline and dopamine. They exert their effect, not as was once thought, by paradoxical sedation of the hyperactive child, but by preferentially stimulating inhibitory pathways. The effect is dose dependent, and if the therapeutic dose is exceeded, the stimulants become activating. The stimulants are only clinically effective in most children for 3-4 hours, necessitating at least two doses if the child is to receive adequate cover during the school day. Most children require their treatment 7 days of the week, but the development of tolerance is unusual.

Efficacy

Attention may improve with low doses, but higher doses seem to be required to control hyperactivity and impulsivity adequately. Short term efficacy in improving performance on tasks requiring sustained attention is well established. In clinical trials, 70% of children show a clinically significant response, but the placebo response in these trials is 35-40%.^8,9 However, there is only equivocal evidence that the stimulants improve the longer term functioning of children with ADHD.¹⁰ Most parents and clinicians hope that stimulant therapy will reduce the child's risk of developing secondary problems such as conduct disturbance, but the drugs do not exert a direct effect on behaviour or learning problems. Improving the child's attention and reducing impulsivity may improve compliance with instructions. This may help the child to benefit from special education programs and so indirectly improve academic performance.

Dexamphetamine and methylphenidate appear to be equally effective. There is no way of predicting which drug will be the most suitable for an individual child.

Adverse effects

Appetite suppression and initial insomnia are common unwanted effects of treatment. As children with ADHD may already be indifferent or fussy eaters, and have trouble settling down to sleep, these adverse effects can pose a significant problem to parents. Some children will also complain of headaches and gastrointestinal discomfort or pain after taking a stimulant.

As children are unlikely to eat much while the drugs are active, a useful strategy is to give the child a substantial breakfast before the morning dose, accept that lunch will probably come home untouched, and allow the child to snack before bedtime. Children who develop insomnia while taking stimulants should not receive medication later than 1 p.m. In contrast, children who do not develop insomnia may be helped significantly by a dose after school which covers them for homework.

Occasionally, even low doses of stimulants may be very activating. Stimulants have also been known to uncover tics and other stereotyped behaviours. Despite this, the majority of Tourette's sufferers treated with stimulant medication do not experience an increase in tic frequency or intensity. Caution is needed if the child has a history of seizures, since the stimulants will lower the seizure threshold. Stimulant toxicity may present with agitation, hyperarousal, delusional thinking, hallucinations and confusion.

Children may express realistic fears of being teased or harassed by their classmates. When this is a problem, it often reflects ambivalent attitudes to treatment held by school staff. Liaison with the school will usually circumvent this problem. Mood lability is sometimes seen in treated children, but again, this is already a vulnerable group. Emotional blunting is not usually observed unless the dose of stimulant is excessive. Persistent depression and suicidal preoccupation are serious symptoms which should be assessed urgently by a child psychiatrist.

No specific problems associated with long term stimulant use have yet been identified. Early concerns about effects on growth have not been supported by recent research.¹¹

Prescribing

Drug treatment is not recommended for children less than 4 years old. My practice is to confirm that the child's symptoms are disabling at school. This means that I rarely prescribe stimulants until the child has attended school for at least a year. Often, in negotiation with the parents, I elect to wait to see if the symptoms improve without drugs.

The decision to prescribe stimulants is based on an assessment of the degree of social or academic disability caused by the child's symptoms. The parents' attitude to drug treatment and their ability to supervise its use should also be assessed.

Contraindications to treatment include the presence of anxiety or a severe mental disturbance such as a psychosis. Tics and abnormal movements are relative contraindications. If there is a history of these problems in the child or the family, the child should be assessed by a specialist with experience in managing these disorders. Stimulants may still be prescribed, but the parents and the child should be fully informed of the risks. 8 The child will need to be monitored closely in case the abnormal movements are exacerbated.

Before commencing treatment with stimulants, the practitioner should enquire about any personal or family history of tics or other abnormal movements. The child's height and weight should be recorded, as should pulse rate and blood pressure. The school should be informed that the child will be receiving medication. The child should begin with a dose at the low end of the recommended range based on weight, and gradually increase until an optimal response is obtained. Recommended doses are 0.15-0.5 mg/kg per day for dexamphetamine, and 0.3-1.0 mg/kg per day for methylphenidate. In Australia, dexamphetamine and methylphenidate are only available in 5 mg and 10 mg tablets respectively. This does limit the flexibility of dosing, but the tablets are easily broken in half.

At subsequent visits, the practitioner should enquire about any adverse effects, and routinely check height, weight, pulse and blood pressure. The response to treatment may be monitored using behaviour rating scales, but often the narrative comments made by the teacher at the end of the school report are just as informative. In the early phases of treatment, children should, if possible, be seen every few weeks, with the frequency of visits tapering off as the child becomes stabilised on treatment. If the child fails to respond to an adequate trial of one stimulant, then it is reasonable to try the alternative drug. In contrast, if the child experiences a marked adverse reaction to one drug, the alternative will probably have the same effect and a second line drug should be considered.

The optimum duration of therapy is uncertain, but the need for treatment should be reviewed every 6months. In most States, evidence of a significant relapse in symptoms when medication is withheld may be required to justify the continuation of the permission to prescribe. A more reliable indication of relapse is obtained if the drug is withheld during the school term, when the child's attention capacity is most greatly taxed, and when observations can be made by both parent and teacher.

The decision to cease treatment should be based on the overall functioning of the child, and on the extent to which symptoms return during breaks from treatment. Adverse withdrawal symptoms are rarely encountered, but the rebound in symptoms can be quite distressing to parents and teachers if symptoms have been well controlled with medication.

It is important that the practitioner remains reasonably available to the parents by telephone. The decision to treat a child with stimulant medication requires a long term commitment to the patient and his/her parents.

The following statements are either true or false.

1. Stimulants are more effective than the behavioural management of attention deficit disorder.

2. The height and weight of children taking stimulants should be monitored as the drugs may stimulate growth.