Althealth

ADHD - A UK Review

A UK Review

A UK Review

By Dr p.V.F. Cosgrove
Consultant Child and Adolescent psychiatrist,
The Bristol priority Clinic,
pO Box 2043,
Bath BA2 5YD, UK

This Review was also published in; primary Care psychiatry (1997) 3, 101-113 - Rapid Science publishers

parents, and some affected adults, are increasingly coming to their Gps with the belief that they or their child suffers from the attention deficit hyperactivity disorder. Often they are armed with information leaflets, some of which are written by experts in this disorder. The response of the practitioner can range from outright rejection to an intrigued willingness to learn more and to facilitate appropriate referral. An increasing number of Gps are becoming fascinated by the global and sometimes dramatic improvements in their young patients on medication. This article is written in order to provide a range of information that can assist the Gp with both the attention deficit hyperactivity disorder-enthusiastic parent or patient and those who need encouragement to consider seriously this childhood onset disorder.

Introduction

The attention deficit hyperactivity disorder (ADHD) is here to stay in the UK. The parents organisations, of which there are more than 120 local groups in Britain will ensure this through the media and through information dissemination. There are two reasons why parents are so enthusiastic about diagnosis and treatment. First ADHD defies ordinary parenting skills with the result that society blames the parents for the chronic behavioural and educational problems of these children. A medical treatment, which removes this stigma as well as markedly improving the function of the child, is a cause of great joy to parents. Second, these parents have often invested many hours in some form of counselling which has produced no benefit in the behaviour and academic performance of their child. They feel that they have received the best that the professionals can give and yet nothing substantial has been achieved. To then experience improvements in their childs social, educational and personal (e.g. self-esteem) life by the administration of some tablets can make them feel better at what they perceive to be the ignorance of child psychiatrists, psychologists and social workers. They become motivated to tell others about ADHD, which they now realise is already well known and researched into in countries outside the UK.

ADHD is a real disorder of childhood in spite of the fact that the vast majority of UK doctors were not introduced to it during their training. It is real in the sense that, like major depressive disorder, schizophrenia, autism and obsessive-compulsive disorder (for examples) is found in the two international classifications of mental disorders, ICD 10 1 and DSM-IV 2. The waters of knowledge have been muddied by a British diagnosis called the hyperkinetic disorder, with the result that two similar but not identical disorders have competed for the attention of British doctors. It is helpful, however, to see ADHD as a spectrum of severity with the hyperkinetic disorder being found at the severe end of this spectrum 3. Alternatively, hyperkinetic disorder can be abandoned altogether by the clinician because it is included within the wider range of ADHD, is not used by parents and laypeople, and is an incomprehensible Greek word. A further reason for rejecting the hyperkinetic disorder is that it grossly overemphasises the importance of hyperactivity at the expense of the other debilitating features of ADHD. Hyperkinetic is interpreted by British specialists as being severe hyperactivity which, if absent, will cause the clinician to decide not to prescribe medication. This is tragic because the poor concentration or the impulsiveness may be crippling the patient even though the hyperactivity is residual and trivial at the time of assessment.

In 1970, the publication of a book called A Neuropsychiatric Study in Childhood 4 symbolised the rift between British and European child psychiatry on one hand and the North Americans on the other. The British view, annunciated by the influential figures of professors Rutter and Graham, was that hyperactivity is rare and that it is usually associated with intellectual deficit or epilepsy. This was repeated in the opening paragraph of a paper co-authored by professor Rutter as late as 1986 5. The British position is that hyperactivity (or hyperkinesis) is an extreme state of excessive activity; is highly uncommon; and usually occurs in conjunction with other signs of brain damage (such as epilepsy, hemiplegia or mental retardation) or a clear history of brain injury such as trauma or infection 6. In clear contrast, the North American position is that hyperactivity is not necessarily associated with brain damage, injury or demonstrable pathology; is a greater than normal level of activity (as opposed to an extreme state of excessive activity); and is fairly common in children 7. This parting of the ways in the late 1960s has meant that research on ADHD and its treatment has been largely ignored by British academic child psychiatry and that medical students and trainee doctors have been denied the opportunity to assess for themselves the relative merits of ADHD and the hyperkinetic disorder. One consequence is that the vast majority of the medical profession in The UK, in addition to child psychiatrists, are finding themselves at a disadvantage when a parent comes into the surgery or clinic wanting to discuss ADHD.

The Genetics of ADHD

The first important twin study on hyperactivity and attention deficit was conducted by two British researchers who compared 29 monozygotic and 45 dizygotic same-sex twins 8. They found that 51% of the monozygotic twins were concordant for hyperactivity compared with 33% of the dizvgotic twins. There was no evidence that hyper-activity was related to perinatal adversity. They concluded that the link between hyperactivity and adverse family relationships is weak, with family pathology more plausibly being a consequence of hyperactivity rather than a cause. The Colorado Reading project 9 studied 81 monozygotic and 52 same-sex dizygotic twins in whom reading disability happened to be a problem. Eighty-one per cent of monozygotic twins and 29% of dizygotic twins were concordant for ADHD. Gillis et al. 10 focused on 37 monozygotic and 37 same-sex dizygotic twins where ADHD had already been diagnosed in one member of each twin pair. Seventy-nine per cent of monozygotic twins but only 32% of dizygotic twins were concordant for ADHD (p<0.001). Stevenson 11 compared 91 monozygotic twins and 105 same-sex dizygotic twins and concluded that there was a significant genetic contribution to level of activity and attention.

Molecular biologists are studying components of the dopamine system in order to discover genes linked to ADHD. Coming et al 12 reported an association between the dopamine D2 receptor gene and ADHD; Cook et al 13 proposed an association between the dopamine transporter gene and ADHD; and La Hoste et al 14 suggested that a sevenfold expansion of part of the dopamine D4 receptor gene may be associated with ADHD symptoms. Unfortunately, none of these studies has been replicated by others, but researchers are continuing to, examine the human genome for genes responsible for ADHD. A significant association has been found between expanded dopamine D4 receptor genes and a personality characteristic made up of impulsiveness, excitability and extravagance in normal subjects 15,16. Dopamine neurotransmission is being targeted in ADHD gene research because of the consistent effectiveness of Ritalin (methylphenidate; Ciba, Horsham, UK) and Dexedrine (dexamphetamine; Evans, UK) for this condition. These two medicines are known to influence dopaminergic function either by dopamine reuptake inhibition (Ritalin) or by the release into the synaptic cleft of dopamine stored in vacuoles in the presynaptic neurone (dexamphetamine).

Robert plomin, who is professor of Behavioural Genetics at the Institute of psychiatry, London, has stated that studies on ADHD over the last three years have consistently and surprisingly shown very substantial genetic influences of the order of 60% heritability 17; a 60% heritability can be considered to be high. Biederman et al 18 compared the first degree relatives (n = 822) of ADHD boys aged between 6 and 17 years (n = 140) and of normal control individuals (n = 120). They found that relatives of ADHD sufferers were 5.6 times more likely to have ADHD. Interestingly, they also discovered that the relatives were 2.4 times more likely to have major depressive disorder, 3.2 times more likely to have generalised anxiety disorder, approximately twice as likely to be drug or alcohol dependent, and 2.3 times more likely to have conduct disorder or antisocial personality disorder. It seems that ADHD is a poisoned well for much common psychopathology seen in surgeries.

Brain Dysfunction in ADHD

Faced with the genetic evidence and the consistently better than placebo response to Ritalin, ADHD should manifest evidence of brain dysfunction. Giedd et al 19 used magnetic resonance imaging to assess the frontal circuitry in 18 ADHD boys in comparison to 18 matched controls. They found that two anterior regions of the corpus callosum (the rostrum and the rostral body) were significantly smaller and concluded that this was evidence for frontal lobe dysfunction and abnormal development. The callosal fibres in the rostral body relate to the premotor cortex which is critical for the suppression of relatively automatic responses to certain sensory stimuli 20. This is consistent with a defect in the persons ability to inhibit responses, which is considered by Barkley to be the fundamental deficit in ADHD 7. Castellanos et al 21 found that the normal asymmetry between the volumes of right and left caudate nuclei was absent in ADHD children. The right caudate is normally larger than the left (as in their controls) but in the ADHD children the volume of the right caudate was similar to the left. This abnormality in the right caudate nucleus was reflected in a by Lou et al 22 who discovered that cerebral bloodflow in ADHD children was not only reduced in the region of the caudate nuclei but was more reduced on the right than on the left. It does appear that there is dysfunction between the prefrontal cortex and the striatum (i.e. caudate and putamen) in ADHD sufferers.

It is only in recent years that blood flow studies have shown consistent abnormalities in brain metabolism in clinical depression and in schizophrenia. In 1997, Ebmeier and colleagues 23 concluded in regard to depression that there now remains little doubt that depressive symptom changes are associated with functional processes in the cingulate gyrus and associated limbic structures. Similar consistency of reduced frontal lobe metabolism has been demonstrated in regard to the negative features of schizophrenia 24-26. Even in normal individuals, blood flow (and, therefore, neuronal metabolic) changes occur when feelings of happiness or of sadness are induced. George et al. 27 showed that, in 11 healthy women, blood flow increased in sadness in the prefrontal cortex, cingulate cortex and other neuronal groups. In happiness, blood flow decreased in the prefrontal and temporal cortices. It would be surprising, therefore, if cerebral metabolism did not show ADHD sufferers to be different from normal individuals in view of the considerable interference in attention and in impulse and motor control in ADHD. Zametkin et al 28 showed that glucose metabolism was reduced in the premotor and superior prefrontal cortex in adults who had been hyperactive since childhood. They pointed out that these two cortical areas have been previously shown to be important in the control of attention and motor activity. These positron emission tomography and single photon emission computed tomography studies involved the use of radioactivity which means that there have been few studies in children, who are the main sufferers of ADHD. The study of regional brain metabolism in ADHD children has, therefore, been disadvantaged in comparison with such research in schizophrenia and depression. It is to be hoped, however, that the nonradioactive transcranial magnetic stimulation will reveal further abnormalities of brain structure and function in childhood ADHD.

poor concentration with a short attention span, distractibility and a tendency to flit from one interest to the next are regular features of ADHD. In writing about the function of the prefrontal cortex, Weinberger 29 stated that the ability to concentrate and to purposely direct attention tends to be affected by dysfunction of the prefrontal cortex...prefrontal dysfunction may result in impairment on a broad spectrum of tasks (page 246). One such task is the Eye Movement Task, otherwise known as the Oculomotor Delayed Response Task, which is considered to reflect prefrontal cortical function. Ross et al 30 compared 13 children with ADHD with ten normal control individuals (aged 9 - 12 years) and found that the ADHD children were less able to delay their response and would move their gaze too soon. This demonstrates dysfunction in prefrontal cortical activity. Shue and Douglas 31 gave six frontal lobe tasks to 24 ADHD and 24 normal control children. The ADHD children were significantly different from the controls on the frontal lobe tasks but not on those for temporal lobe function. The authors concluded that the features of ADHD are features of frontal lobe dysfunction.

Diagnosis

In Britain today, underdiagnosis of ADHD is serious and extremely worrying in the delivery of health care to the public. It has been estimated that only 10% of hyperkinetic disorder children are diagnosed in the UK 3. It is amazing that child psychiatrists and paediatricians fail to recognise 90% of those children with the severest form of ADHD, namely the hyperkinetic disorder. The essential feature of ADHD is a persistent pattern of behaviour made up of poor concentration, impulsiveness, hyperactivity and poor motivation in comparison with peers of similar age and same sex. These symptoms need to be present from before about the age of 7 years. It is important to ask the parents to complete individually an ADHD rating scale so that due weight is given to each and all of the features of ADHD. It should not be a matter of embarrassment to the doctor that diagnosis depends in no small part on information supplied by the parents since other diagnostic categories in psychiatry also rely on information from the patient or relative, unlike other investigations such as blood tests or X-rays.

Because diagnostic failure with regard to ADHD is the norm in Britain today, the following points are considered to be important:

The spectrum of hyperactivity ranges from mild through moderate to severe In older primary school children, adolescents and young adults, the hyperactivity may have lessened from earlier years to a level where it is barely recognisable. Whatever level of residual hyperactivity remains, diagnostic emphasis should be given to the poor concentration, impulsiveness and poor motivation. ADHD sufferers often seek help not for their fidgetiness and overactivity but for the other features of ADHD.

pervasiveness of attention deficit hyperactivity disorder symptoms may not be apparent to the clinician

ADHD usually manifests itself in more than one situation so that parents and teachers or parents and clinician are united in their concern. Sometimes, however, the teacher does not recognise the ADHD symptoms (being too busy in a large class, being prejudicially biased against ADHD or being unwilling to commit to paper the worrying signs). The doctor should never reject the experience of the parents obtained over many years and many situations on the grounds that he or she cannot see evidence of poor concentration, hyperactivity, poor motivation or impulsiveness in the clinic or surgery. The DSM-IV recognises that signs of the disorder may be minimal or absent (page 79) when the person is in the clinic, under strict control, in a novel setting, engaged in interesting activities, or in a one to one situation with the clinician 2. It is unusual for the child to display the same level of dysfunction in all situations or at all times within the same setting. pervasiveness of ADHD does not mean that the symptoms have to be present all the time. The clinician should err on the side of treatment if the problems are moderate to severe at home but apparently absent or minimal at school.

Attention deficit hyperactivity disorder does continue into adolescence and adulthood Dismissal of a diagnosis of ADHD on the grounds that the child is postpubertal is a serious error. The sex hormones have little or no effect on the persistence of ADHD symptoms. It is estimated that about 70% of children will take their ADHD into adolescence, and 10% into adulthood (i.e. beyond 25 years) 32. ICD10 states that the diagnosis of hyperkinetic disorder (i.e. the severe end of the ADHD spectrum) can still be made in adult life. The grounds are the same... (page 265) 1. The DSM-IV similarly states In most individuals, symptoms attenuate in late adolescence and adulthood, although a minority experience the full complement of ADHD symptoms into mid-adulthood (page 82) 2.

The clinical features of ADHD include the following:

  • the individual has difficulty sustaining attention to tasks;
  • is easily distracted;
  • often does not seem to listen;
  • often shifts from one uncompleted activity to another;
  • often loses things necessary for tasks;
  • often interrupts or intrudes on others;
  • has difficulty awaiting turn in groups;
  • often blurts out answers to questions;
  • often engages in physically dangerous activities without considering the consequences;
  • often talks excessively;
  • has diffficulty playing quietly;
  • has difficulty remaining seated;
  • often fidgets or squirms in seat;
  • has difficulty following instructions.

Where eight or more of these apply, ADHD is likely to be present.

The more inexperienced and timid the specialist is in using anti-ADHD medication, the less likely it is that a diagnosis of ADHD will be made when the condition is present. Training in effective diagnosis includes observing the beneficial effects of treatment following a diagnosis. He who rarely treats rarely diagnoses.

Treatment

Counselling is seen by society to be the best intervention for behaviour problems. In contrast, science has not demonstrated this to be true for ADHD sufferers. Hinshaw et al. 33 found no advantage in adding cognitive behavioural therapy to Ritalin in hyperactive boys aged between 8 and 13 years; Ritalin alone was just as effective. Cognitive training did not improve behaviour in children with residual problems while taking Ritalin. In fact, following a period on placebo, the majority of the children needed to restart medication regardless of whether they had received cognitive training or not 34. A great many other studies have come to the same conclusion, namely, that the combining of some form of counselling or training with medication does not increase the benefit already obtained by the medication alone 35-42. Klein 43 has stated The additional use of various forms of psychotherapy (behavioural treatment, parent training, cognitive therapy) with stimulants (i.e. Ritalin and dexamphetamine amine) has not resulted in superior outcomes than medication alone (page 1223).

Ritalin and dexamphetamine are licensed in the UK for use in children with ADHD. The fact that they are licensed for ADHD is official approval for their sufficient safety in children. Dexamphetamine is licensed for use in children down to 3 years which indicates both the manufacturers and the licensing authoritys confidence in the use of this drug in young children. Dexamphetamine is licensed in adults for narcolepsy despite societys disapproval of illicit amphetamine usage (e.g. Metamphetamine or Speed). In contrast, the manufacturers of Ritalin have not applied for a licence for its use in adults. In view of the licences authorized under government approval, Ritalin and dexamphetamine amine can be prescribed with medicolegal confidence by any registered medical practitioner.

Bradley 44 was the first to prescribe an amphetamine to children. He used benzedrine on inpatients and noted the dramatic improvement in their behaviour and academic performance. After two decades of silence on this method of treatment, Laufer et al. 45, Eisenberg 46 and Connors 471 reported, as Bradley 44 had done previously, on the efficacy of amphetamine and also of Ritalin (commercially available since 1957) on childrens behaviour. A search through the manufacturers database produced 45 double-blind, placebo-controlled trials from 1984 to 1994 comparing Ritalin with placebo. This makes Ritalin the most researched psychotropic drug in children and, possibly, in the whole of psychiatry. Each of these 45 studies demonstrated the greater efficacy of Ritalin over placebo on wide range of problems: attention deficit, impulsiveness, aggression, comprehension, arithmetic, reading, spelling, persistence with problem solving, non-compliance, hyperactivity, acquisition of information, work output, cognitive functioning, shortterm memory, and on-task behaviour.

The use of psychotropic medication in children in the UK is in its infancy. It is, therefore, sensible for a Gp to prescribe under the supervision of a specialist. It is probably not wise for a Gp to initiate treatment for ADHD; however, the act of writing a prescription for Ritalin or dexamphetamine by a Gp is totally legal and acceptable. The Gp can reasonably expect clear dosage guidance from the specialist.

Regular blood tests are not required for dexamphetamine or Ritalin usage. A balance needs to be struck because of the suffering the child endures while having blood taken as well as the struggle often needed to obtain the blood sample. When the child is ill (as happens to any child from time to time), it may then be worthwhile taking blood for a full blood picture and for liver function tests when this would not normally be done. A mild neutropenia can occur in children not taking medication and without obvious cause. Regular blood pressure recordings are not necessary but the Gp may like to obtain some blood pressure figures in the early months of treatment in order to demonstrate that a drug-induced hypertension is not occurring.

Regular weighing is needed to provide a weight trajectory. If this is in a positive direction and is consistent with health and a good appetite, then weighing of the child becomes superfluous. Height recordings are of interest but parents have usually accepted the possibility of some reduction in final height in order to obtain the benefits of drug treatment for their ADHD child. From the study by Klein and Manuzza 48, the general rule is that if the final height of a child is to be over six feet, then a loss of up to 1 inch might occur. If the final height is to be less than six feet, a loss of up to 1 cm is possible. This only applies if the Ritalin cannot be stopped before bone-growth ceases. A rebound of vertical growth occurs if the Ritalin is stopped before the epiphyses fuse with the result that Ritalin-treated children have the same final height as children who have never been treated with Ritalin. parents are invariably willing to accept a final height loss of up to 1 inch (above 6 feet) or up to 1 cm (below 6 feet) in order to gain the behavioural, social, emotional and academic benefits of drug treatment for their ADHD child. It is not known whether the above applies to dexamphetamine.

Dosage

Large variations in plasma drug level have been noted between children on the same oral dosage 49. Some children will be fast hepatic metabolizers and others slow. Intestinal absorption of the medication may also vary between patients. The total daily dosage therefore needs to be titrated against academic, behavioural and emotional benefit and not against the age or weight of the child. One deduction from this is that the licensed recommended maximum dosage should never influence the clinician in seeking the optimal dosage for the patient. The recommended maximum dosage only applies in law (Medicines Act 1968) to the manufacturers and distributors of the drug, and leaves doctors and pharmacists (dentists and nurses also) totally exempt from this or any other restrictions in the licence 50.

Evidence is accumulating that timepoint dosages need to be around lmg/kg for Ritalin for good clinical effectiveness. If there are, say, three to four timepoint dosages in a day (i.e. tds or qds), the total daily dose is very likely to exceed the daily recommended maximum. It is, however, the level of the timepoint dosage which is important and not the amount given over 24 h. Since Ritalin (and dexamphetamine) have clinically effective durations of 3-5 hours, repeated dosages of Ritalin of about lmg/kg will be necessary thus making the total daily dose unimportant in and of itself. Some children require daily Ritalin dosages of between 60 and 100 mg per day (and sometimes higher) and any reduction below these levels produces a suboptimal drug response. Children on higher daily dosages are likely to be requiring medication more frequently, but the actual mg level at each timepoint dose may be the same as the child on a lower daily amount. For example, a child on 90mg Ritalin daily receives 15mg at six timepoints in the day, whereas another child on 15mg tds has a daily dose of 45mg. In each case, the timepoint dose is 15mg, and it is this dose that should be seen in terms of mg kg rather than the total daily dose.

Even after finding the optimal dosage of dopamine-releasing agent through the day, the patient may be experiencing symptoms such as obsessions and compulsions or severe anxiety or tics or continuing aggression. The specialist should be willing to add a selective serotonin reuptake inhibitor (like fluoxetine or citalopram) for obsessive-compulsive features, propranolol for anxiety, pimozide or haloperidol or clonidine for tics, and risperidone (low dosage) and clonidine, or both, for aggression. In a small number of children and adolescents, bipharmacy or even polypharmacy is necessary. For example, a child with a genetic predisposition to multiple motor tics may begin ticing once on Ritalin or dexamphetamine. The addition of pimozide effectively treats the tics but induces a mild dystonia which then requires procyclidine. It is important that the specialist does not give up and abandon the treatment of ADHD because certain other symptoms require additional medication.

Side Effects

Ritalin and dexamphetamine are gentle drugs as indicated by being licensed for use in young children. Appetite reduction is invariable although, paradoxically, food intake can increase in some children because the medication enables them to sit still and concentrate for longer on the process of eating. The appetite reduction usually normalizes over time especially as the rate of dosage increase falls; however, occasionally this normalization of appetite does not occur and the child loses weight. In these circumstances, low dose risperidone will act as an antidote and increase the appetite 50. Delay in falling asleep can occur although, paradoxically, the quality of sleep usually improves as shown by increased restfulness at night. If the wakefulness cannot be tolerated, once again low dose risperidone will enable the Ritalin or the dexamphetamine to be continued while allowing the child to get to sleep at a reasonable time 51. Alternatively, a bedtime dose of clonidine can be used. Occasionally, a child will remain aggressive on Ritalin or dexamphetamine. This may necessitate changing from Ritalin to dexamphetamine (or vice versa) or it may require the addition of low dose risperidone which usually removes the aggression 51. Clonidine is useful for continuing aggression. Abdominal pain rarely occurs, usually initially, and is helped by an osmotic laxative. Headaches are very uncommon and, in fact, many ADHD sufferers with chronic headaches resistant to antimigraine and other treatments have found total relief when their ADHD is treated with Ritalin or dexamphetamine.

parents and society are understandably concerned about addiction to Ritalin or dexamphetamine. Barkley 7 stated that there have been no reported cases of addiction or serious drug dependence with these medications. He referred to Gadows examination of several studies 52 and concluded that children on Ritalin or dexamphetamine are no more likely to abuse other substances than those not taking them. Clinical evidence indicates that children on these medications wish for discontinuation of treatment particularly as they get older. Gualtieri 53 followed up adults with ADHD (n = 47) and with traumatic brain injury (n = 31) who had been treated with a dopamine releasing agent. Of these 78 adult patients, none abused the taking of the medication, there was no evidence of inappropriate drug seeking behaviour, no patients expressed the need for dosage increase over time, there were no cases of social disruption, disorganization on or toxic psychosis, and no patients progressed to other drugs of abuse. The majority of these patients discontinued medication after 6-18 months. Recent publicity in the US over secondary school children selling Ritalin to peers was debunked by Newsweek Magazine in 1996 54. Newsweek examined the evidence cited by the Drug Enforcement Agency and rejected it as unconvincing and altogether too anecdotal. Its own research provided no evidence to support the medias hype on alleged secondary school age abuse of Ritalin.

The manufacturers do list a large number of clinical events which have occurred in patients taking Ritalin or dexamphetamine. This list is provided for their medicolegal legal defence and should not be seen as indicating a causal relationship between their licensed drug and the clinical problem cited. With hundreds of thousands of children taking Ritalin over forty years since 1957, clinical diseases and dysfunctions are bound to occur anyhow while some children are on Ritalin.

The Longer Term

There is no evidence that Ritalin and dexamphetamine have no benefit over the longer term. On the contrary, Loney et al. 55 found that treatment in childhood was associated in adolescence with better parent ratings, less drunken driving and less police contact for alcohol and drug abuse. Hechtman et al. 31 compared two groups of adults; one group had been treated with Ritalin for at least 3 years at primary school age and the other group, similarly afflicted with ADHD, had received no medication. The adults given Ritalin as children had less psychiatric treatment, fewer car accidents, more independence and were less aggressive. This suggests a better adult outcome for treated ADHD children. A follow up study 56 found that conduct disorder in adolescents occurred almost exclusively in those who were still showing features of ADHD. This indicates that effective treatment of ADHD before adolescence would reduce the frequency and severity of conduct-disordered behaviour and, therefore, of delinquency and crime.

Although science needs to carry out further studies of the long-term outcome of Ritalin and dexamphetamine treatment for ADHD, a common sense approach to this matter is valid. Who would not agree that the long-term outcome for a 12 year old boy, threatened with expulsion from mainstream education, is not immeasurably improved by medication which enables him to remain in mainstream classes and then go on to obtain, say, 9 GCSEs at 16 years of age Between 30 and 40% of diagnoses in adolescents in care by Social Services are conduct disorder or ADHD, or both 57. Because the outlook for young people leaving care is generally poor, who would disagree that the treatment of ADHD in the primary school years (thus avoiding care proceedings and allowing the developing child to stay with his family) does not have long-term benefits even after the medication has been stopped Because ADHD is linked to delinquency and crime in many sufferers through the onset of conduct disorder in adolescence, then treatment of ADHD in the young child could prevent contact with the penal system in later years.

As has been stated, about 70% of ADHD children continue to have ADHD in adolescence, and about 10% of childhood sufferers will take their ADHD into adulthood 31. ADHD is, therefore, a chronic long-term dysfunction and the clinician should always be willing to diagnose and to treat even if the onset of ADHD symptoms was many years ago. parents whose child was failing educationally before treatment do not have difficulty accepting the advice to keep their child on medication until school leaving age in order to obtain the maximum benefit from the years of schooling. Of course, they have the right to stop the medication at any time and to test, for example once per year, whether their child needs to continue to take the tablets. It can, though, be argued that, because the brain does not reach its adult maturity (e.g. full myelination of the prefrontal cortex) until the mid-twenties, there is still a need for medication after leaving school in some young people. Further education or simply learning to stay in employment may make it necessary for the adolescent to continue taking the Ritalin or the dexamphetamine after the school years are completed.

Future Ideas

Adult psychiatry

Because childhood ADHD persists into adulthood in about 10% of cases, it is essential that adult psychiatrists begin to acknowledge the reality of ADHD and learn to treat it effectively. Spencer et al. 58 found a highly statistically significant difference between Ritalin and placebo in 23 adult ADHD patients where the Ritalin dosage was at a level of lmg/kg day. Adult psychiatrists have been trained to believe that the dopamine-releasing agents necessarily trigger psychosis in adults ever since Connells Maudsley Monograph Amphetamine psychosis was published in 1958 59. Connells patients, most of whom became psychotic, were taking overdosages of amphetamine. For a 70kg patient, a therapeutic dose of dexamphetamine of 5mg tds is 0.2mg/kg/day and for 10mg tds it is 0.4mg kg/day whereas the mean daily dosage in Connells 39 patients was 3.2mg kg day (8-16 times as much). The modal average dose in his study was 4.6 mg kg/day and two people had taken 14mg kg day. Even in the five patients who had apparently taken therapeutic doses of between 20 and 40mg day, it is not known whether they had taken this daily dosage at just one time in the day, whether their report of the amount they had taken was true, or whether any other unprescribed drugs had been taken as well. Connells patients are in no way indicative of how adult ADHD sufferers will respond to therapeutic doses of dexamphetamine or Ritalin. Adults taking prescribed doses rarely become psychotic. In the study by Spencer et al. 58, none of the 23 patients became psychotic. In addition, on the rare occasions that thought disorder or frank psychosis does occur on therapeutic doses (due to a psychotic predisposition as opposed to the effects of the drug itself), the addition of an antipsychotic, such as risperidone in low dosage, will allow the dexamphetamine or Ritalin treatment to be continued.

At a psychopharmacology conference in Belfast organized by the British Association for psychopharmacology, a desire for better and more consistently effective antidepressant drugs was expressed. It was suggested that adult psychiatry did not have to wait for the pharmaceutical industry to produce yet another antidepressant because Ritalin and dexamphetamine have considerable antidepressant properties in and of themselves. The dopaminergic system is recognized as being involved in the experience of pleasure, and both electroconvulsive therapy and a number of dopamine facilitating drugs (e.g. monoamine oxidase inhibitors and dopamine agonists, bromocriptine and piribedyl, and the dopamine reuptake inhibitor, buproprion) are known to relieve depression through their effects on dopamine 60. Biedermans family study 18 that first degree relatives of known ADHD sufferers are 2.4 times more likely to suffer from depression should alert adult psychiatry to the value of trying Ritalin or dexamphetamine in cases of adult depression with a family history of ADHD. Certainly, the drug treatment of ADHD in children characteristically raises self-esteem and makes the chronically unhappy child observably happier. It would be surprising if this did not also occur in adult ADHD sufferers.

No adult should be allowed to undergo leucotomy without first being assessed for ADHD. preoperative assessment requires that a full social, educational and psychological history be obtained for the adults childhood as far back as pre-school years. Interviewing parents or, if these are not available, siblings is necessary. School reports should be obtained and studied for evidence of childhood ADHD. If there is any suspicion of childhood-onset ADHD, a trial of a dopamine releasing agent must be given before a final decision to operate neurosurgically is made.

Adult ADHD patients are not only often depressed but also anxious. Clinical experience of Ritalin or dexamphetamine is that they are good anxiolytics.

personality Disorder

personality disorder (including psychopathic personality) is considered by adult psychiatrists to be untreatable in spite of the enthusiasm of a small minority. Although any associated depression, anxiety, psychosis or drug abuse is managed or treated, the core diagnosis of personality disorder is viewed as chronic, untreatable and ameliorated only by age. A significant number of adults, labelled as suffering from personality disorder, are misdiagnosed and are, in fact, unrecognized adult ADHD sufferers. In a seminal study of 91 men followed up from their hyperactive childhood to a mean age of 26 years, Mannuzza et al. 61 found that antisocial personality disorder (known as psychopathic personality disorder in Britain) was 10 times more likely to occur in the group of individuals who had been hyperactive since childhood than in a control group also followed up from childhood. In other words, psychopathic personality disorder was hugely more common in those patients with a diagnosis of ADHD in their primary school years. This gives rise to the idea that psychopathic personality disorder is an adult manifestation of child and adolescent ADHD and would respond to Ritalin or dexamphetamine.

Hill 62 was the first to use amphetamine for the treatment of personality disorder; he found that responsiveness to treatment was predicted by hyperactivity in childhood. Cowdry and Gardner 63 described the same childhood hyperactivity prediction with regard to responsiveness to treatment with monoamine oxidase inhibitors in borderline personality disorder, and monoamine oxidase inhibitors have a dopamine releasing action on neurotransmission. Wood et al. 64 found that Ritalin was significantly more effective for temper control and concentration in personality disordered adults with a childhood history of hyperactivity. Wender et al. 65 reported that the weaker dopamine releasing agent, pemoline, was superior to placebo in these personality disordered patients for temper, impulsiveness, stress intolerance and concentration and, once again, in those subjects with a history of childhood hyperactivity (ADHD in todays terminology).

Adult psychiatrists should never make a diagnosis of personality disorder without first checking that hyperactivity, poor concentration, impulsiveness and poor motivation were not present from young childhood. A diagnosis of personality disorder or psychopathy is a painful label for many patients to bear and it is usually a diagnosis of therapeutic nihilism and clinical rejection. The studies cited above indicate that the dopamine releasing agents are beneficial where there has been a childhood history of ADHD and these should be tried even if there has been illicit drug abuse.

prevention of Delinquency & Crime

This may seem pretentious but most crime is committed by the few. A senior probation officer stated that 5% of children commit two-thirds of all crime (BBC Radio 4 Today programme, March 1997). If this small number of school children and older adolescents can be identified either before or during the phase of criminal behaviour, and if those with ADHD can be recognized and effectively treated, a dramatic fall in delinquency and crime would occur. It has already been observed from a number of treatment studies of personality disordered individuals that they suffered from ADHD in childhood, and antisocial personality disorder is associated with crime in adults. Farrington 66 has shown that hyperactivity, impulsiveness and attention deficit at the age of 8 years predict delinquency in adolescence. Coid 67 describes the common experience of clinicians that ADHD develops into conduct disorder. Research into conduct disorder is hampered by the difficulty in finding case which have not been preceded by ADHD in earlier childhood. Szatmart et al 68 found that ADHD males are 14 times more likely to have conduct disorder than those without ADHD, and that ADHD females are 40 times more likely to have conduct disorder. Conduct disorder is a persistent pattern of behaviour in which major rules of society are violated, especially the basic rights of others. The behaviour of conduct disorder can be grouped into four divisions: aggression, damage to property, theft and Iying, and truancy from home and school 2. Clearly, the 5% of children who commit two-thirds of all crime have conduct disorder. The evidence suggests that they also have ADHD which has preceded the onset of their conduct disorder and which is so eminently treatable with Ritalin or dexamphetamine. Because up to one-half of child guidance clinic referrals are suffering from conduct disorder, the prevention of much delinquency and crime is within the grasp of British child psychiatry and paediatrics.

Conclusion

It is not easy for Gps to be told about an unknown disorder by their patients; however, most Gps realize that their patients do not expect them to know about every possible condition in medicine, so they readily accept any information brought to the surgery. patients respect their doctor for having an open mind and for being willing to take them seriously. It is to be hoped that this article will rectify the imbalance in the knowledge of this condition that is occurring in surgeries up and down the land.

Onward referral to a specialist in ADHD can be a problem for the Gp: although the parents or adult patient often bring recommendations with them.

A list of AD/HD 'aware' Doctors and Specilaists is available, and more information on the disorder is available from the AD/HD Library.

References

  1. World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: clinical descriptions and diagnostic guidelines, pp. 262-265. WHO, Geneva.
  2. American psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th edition, pp.78 85. American psychiatric Association, Washington.
  3. Anonymous (1995) The Management of Hyperactive Children. Drug and Therapeutics Bulletin, 33, 57-60.
  4. Rutter M, Graham p. and Yule W (1970) A Neuropsychiatric Study in Childhood. Heinemann Medical, London.
  5. Taylor E, Everitt G, Thorley R, Schachar R, Rutter M and Wieselberg M (1986) Conduct disorder and hyperactivity: II. A cluster analytic approach to the identification of a behavioural syndrome. British Journal of psychiatry, 149, 768 777.
  6. Taylor E (1988) Diagnosis of hyperactivity - a British perspective. In: Attention Deficit Disorder Criteria, cognition and intervention. (Eds L Bloomingdale and J Sergeant), pp. 141-160. pergamon press, New York.
  7. Barkley RA (1990) History. In: Attention Deficit Hyperactivity Disorder (Ed RA Barkley), pp. 3-38. Guilford press, New York.
  8. Goodman R and Stevenson J (1989) A twin study of hyperactivity-II. The aetiological role of genes, family relationships and perinatal adversity Journal of Child psychology and psychiatry and Allied Disciplines, 30, 691-709.
  9. GilgerJW, pennington BF and DeFries JC (1992) A twin study of the etiology of comorbidity Attention deficit hyperactivity disorder and dyslexia. Journal of the American Academy of Child and Adolescent psychiatry, 31, 343-348.
  10. Gillis JJ, Gilger JW pennington BF and DeFries JC (1992) Attention deficit disorder in reading-disabled twins: evidence for a genetic etiology. Journal of Abnormal Child psychology, 2O, 303-315.
  11. Stevenson J (1992) Evidence for a genetic etiology in hyperactivity in children. Behavior Genetics, 22, 337-343.
  12. Comings DE, Comings BG, Muhleman D, Dietz G, Shahbahrami B, Tast D, Knell E, Kocsis p, Baumgarten R, Kovacs BW et al. (1991) The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. Journal of the American Medical Association, 266, 1793-1800.
  13. Cook EH, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE and Leventhal BL (1995) Association of attention deficit disorder and the dopamine transporter gene. American Journal of Human Genetics, 56, 993-998.
  14. La Hoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N and Kennedy JL (1996) Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Molecular psychiatry, 1, 121-124.
  15. Benjamin J, Li L, patterson C, Greenberg BD, Murphy DL and Hamer DH (1996) population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nature Genetics, 12, 81-84.
  16. Ebstein Rp, Novick 0, Umansky R, priel B, Osher Y, Blaine D, Bennett ER, Nemanov L, Katz M and Belmaker RH (1996) Dopamine D4 receptor exon 111 polymorphism associated with the human personality trait of novelty seeking. Nature Genetics, 12, 78 80.
  17. Mozdy AD (1997) pay attention Rover! New Scientist, 10 May. 30-33.
  18. Biederrman J, Faraone SV, Keenan K, Benjamin J, Krifcher B, Moore C, Sprich-Buckminster S, Ugaglia K, Jellinek MS, Steingard R et al. (1992) Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Archives of General psychiatry, 49, 728 738.
  19. Giedd JN, Castellanos FX, Casey BJ, Kozuch p, King AC, Hamburger SD and Rapoport JL (1994) Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder. American Journal of psychiatry, 151, 665-669.
  20. Wise Sp (1985) The primate premotor cortex; past, present and preparatory. Annual Review of Neuroscience, 8, 1-19.
  21. Castellanos FX, Giedd JN, Eckburg p, March WI, Vaituzis AC, Kaysen D, Hamburger SD and Rapoport JL (1994) Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder. American Journal of psychiatry, 151, 1791-1796.
  22. Lou HC, Henriksen L, Bruhn p, Borner H and Nielsen IB (1989) Striatal dysfunction in attention deficit and hyperkinetic disorder. Archives of Neurology, 46, 48 - 52.
  23. Ebmeier Kp, OCavanagh Jp, Moffat Ap, Glabus MF, OCarroll RE and Goodwin GM (1997) Cerebral perfusion correlates of depressed mood. British Journal of psychiatry, 170, 77-81.
  24. Andreasen NC, Rezai K, Alliger R, Swayze VW 2nd, Flaum M, Kirchner p, Cohen G and oleary DS (1992) Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Archives of General psychiatry, 49, 943-958.
  25. Buchsbaum MS, Haier RJ, potkin SG, Nucchterlein K, Bracha HS, Katz M, Lohr J, Wu J, Lottenherg S, Jerabek pA et al. (1992) Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenics. Archives of General psychiatry, 49, 935-942.
  26. Wolkin A, Sanfiiipo M, Wolf Ap, Angrist B, Brodie JD and Rotrosen J (1992) Negative symptoms and hypofrontality in chronic schizophrenia. Archives of General psychiatry, 49, 959-965.
  27. George MS, Ketter TA, parekh pl, Horwitz B, Herscovitch p and post RM (1995) Brain activity during transient sadness and happiness in healthy women. American Journal of psychiatry, 152, 341-351.
  28. Zametkin AJ, Nordahl TE, Gross M, King AC, Semple WE, Rumsey J, Hamburger S and Cohen RM (1990) Cerebral glucose metabolism in adults with hyperactivity of childhood onset. New England Journal of Medicine, 323, 1361-1366.
  29. Weinberger DR (1993) A connectionist approach to the prefrontal cortex. Journal of Neuropsychiatry, 5, 241-253.
  30. Ross RG, Hommer D, Breiger D, Varley C and Raclant A (1994) Eye movement task related to frontal lobe functioning in children with attention deficit disorder. Journal of the American Academy of Child and Adolescent psychiatry, 33, 869-874.
  31. Shue KL and Douglas Vl (1992) Attention deficit hyperactivity disorder and the frontal lobe syndrome. Brain and Cognition, 20, 104-124.
  32. Hechtman L, Weiss G and perlman T (1984) Young adult outcome of hyperactive children who received long-term stimulant treatment. Journal of the American Academy of Child psychiatry, 23, 261-269.
  33. Hinshaw Sp, Henker B and Whalen CK (1984) Self control in hyperactive boys in anger-inducing situations: effects of cognitive-behavioural training and of methylphenadate Journal of Abormal Child psychology, 12, 55-77.
  34. Abikoff H and Gittelman R (1985) Hyperactive children treated with stimulants. Is cognitive training a useful adjunct Archives of General psychiatry, 42, 953-961.
  35. Bugental DB, Whalen CK and Henker B (1977) Casual attributions of hyperactive children and motivational assumptions of two behaviour-change approaches: evidence for an interactionist system. Child Development, 48, 874-884.
  36. Wolraich M, Drummond T, Salomon M, OBrien ML and Sivage C (1978) Effects of methylphenidate alone and in combination with behaviour modification procedures on the behaviour and academic performance of hyperactive children. Journal of Abnormal psychology, 6, 149-161.
  37. Brown RJ (19S()) Impulsivity and psychoeducational intervention in hyperactive children. Journal of Learning Disabilities, 13, 249-254.
  38. Gittelman Klein R, Abikoff 11, pollack E, Klein DF, Katz S and Mattes JA. A controlled trial of behaviour mockfication and methylphenidate in hyperactive children. In: Hyperactive Children: The Social Ecology of Identification and Treatment (Eds CK Whalen and B Henker), pp. 221-243. Academic press, New York.
  39. Firestone p, Kelly MJ, Goodman JT and Davey J (1981) Differential effects of parent training and stumulant medication with hyperactives: a progress report. Journal of the American Academy of Child psychiatry, 20, 135-147.
  40. Cohen NJ, Sullivan J, Mincle K, Novak C and Helwig C (1981) Evaluation of thc relative effectiveness of methylphenidate and cognitive behaviour modification in the treatment of kindergarten-aged hyperactive children. Journal of Abnormal Child psychology, 9, 43-54.
  41. pelham WE, Bender ME, Caddell J, Booth S and Moorer SH (1985) Methylphenidate and children with attention deficit disorder. Dose effects on classroom academic and social behaviour Archives of General psychiatry, 42, 948 952.
  42. Brown RT, Wynne ME and Medenis R (1985) Methylphenidate and cognitive therapy: a comparison of treatment approaches with hyperactive boys. Journal of Abnormal Child psychology, 13, 69 87.
  43. Klein RG (1987) pharmacotherapy of childhood hyperactivity: an update. In: psychopharmacology: The Third Generation of progress. (Ed HY Meltzer), p. 1223. Raven press, New York.
  44. Bradley WC (1937) The behaviour of children receiving benzedrine. American Journal of psychiatry, 94, 577-585.
  45. Laufer M, Denhoff E and Solomons G (1957) Hyperkinetic impulse disorder in childrens behaviour problems. psychosomatic Medicine, 19, 38-49.
  46. Eisenberg L (1966) The management of the hyperkinetic child. Developmental Medicine and Child Neurology, 8, 593-598.
  47. Connors CK (1966) The effects of dexedrine on rapid discrimination and motor control of hyperkinetic children under mild stress. Journal of Nervous and Mental Disease, 142, 420-433.
  48. Klein RG and Manuzza S (1988) 111 Hyperactive boys almost grown up. Archives of General psychiatry, 45, 1131-1134.
  49. Gualtieri CT, Wargin W, Kanoy R, patrick K, Shen CD, Youngblood W, Mueller RA and Breese GR (1982) Clinical studies of methylpher date serum levels in children and adults. Journal of the American Academy of Child psychiatry, 21, 19-26.
  50. Anonymous (1992) prescribing unlicensed drugs or using drugs for unlicensed indications. Drug and Therapeutics Bulletin, 30, 97-99.
  51. Cosgrove p V F (1996) Risperidone added to methylphenidate in attention deficit hyperactivity disorder. European Neuropsychopharmacology, 6(Suppl 3), 11-12.
  52. Gactow KD (1981) prevalence of drug treatment for hyperactivity and other childhood behaviour disorders In: psychosocial Aspects of Drug Treatment for Hyperactivity (Eds KD Gadow and J Loney), pp. 13-70. Westview press, Boulder, Colorado.
  53. Gualtieri CT (1990) Neuropsychiatry and Behavioural pharmacology. Springer-Verlag, Berlin.
  54. Newsvacek 18 March 1996.
  55. LoneyJ, Kramer J and Kosier T (1981) The hyperactive child grows up: predictors of symptoms, delinquency and achievement at followup. In: psychosocial Aspects of Drug Treatmentfor Hyperactivity (Eds KD Gadow and J Loney), pp. 381-415. Westview press, Boulder, Colorado.
  56. Gittelman R, Mannuzza S, Shenker R and Bonagura N (1985) Hyperactive boys almost grown up. 1. psychiatric status. Archives of General psychiatry, 42, 937-947.
  57. McCann JB, James A, Wilsoll S and Dunn G (1996) prevalence of psychiatric disorders in young people in the care system. British Medical Journal, 313, 1529-1530.
  58. Spencer 1; Wilens T, Biederman J, Faraone SV, Ablon JS and Lapey K (1995) A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention deficit hyperactivity disorder. Archives of General psychiatry, 52, 434-443.
  59. Connell pH (1958) Amphetamine psychosis. Maudsley Monograph (No 5). Chapman & Hall, London.
  60. Cosgrove p V F (1997) The place of Drugs in Treatment. In: Depression in Children and Adolescents (Eds KN Dwivedi and Vp Varma), pp. 94-105. Whurr, London.
  61. Mannuzza S, Klein RG, Bessler A, Malloy p and Lapadula M (1993) Adult outcome of hyperactive boys. Educational achievement, occupational rank and psychiatric status. Archives of General psychiatry, 50, 565-576.
  62. Hill D (1944) Amphetamine in psychopathic states. Briti.sh Journal of Addiction, 44, 50-54.
  63. Cowdry R and Gardner DL (1988) pharmacotherapy of borderline personality disorder Archives of General psychiatry, 45, 111-119.
  64. Wood RD, Reimherr FW and Wender pH (1976) Diagnosis and treatment of minimal brain dysfunction in adults. Archives of General psychiatry, 33, 1453-1460.
  65. Wender pH, Reimherr FW and Wood RD (1981) Attention deficit disorder (minimal brain dysfunction) in adults. Archives of General psychiatry, 38, 449 456.
  66. Farrington Dp (1993) Childhood origins of teenage antisocial behaviour and adult social dysfunction. Journal of the Royal Society of Medicine, 86, 13-17.
  67. Coid J (1993) Current concepts and classifications of psychopathic disorder. In: personality Disorder Reviewed. (Eds p Tyrer and G Stein), pp. 113-164. Gaskell, London.
  68. Szatmari p, Boyle M and Offord DR (1989) ADHD and conduct disorder: degree of diagnostic overlap.

Many Thanks to Dr Cosgrove for supplying this review.
Contributions/Suggestions to: addnet@web-tv.co.uk

Buy 6 for the price of 5 Reduced UK postage available on orders over £35, maximum discount of £2.50 applies

We ship out to the UK, EU and all over the world. In the UK, and reduced shipping on all orders over £35. We have a special offer of 'Buy 5, get 1 free' some of our special offers are even better than this with 'Buy 3 get 1 free', 'Buy 2, get 1 free' and even 'BOGOF' (Buy 1, get 1 free) on selected products. View our special offers page for full details.

© AltHealth 2017 | All rights reserved | Site by Cultrix