Abstract
The Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA) trial by the MTA Cooperative Group [1, 2] has been praised as a successful trial with important implications for clinical services [3]. The results of the trial concluded that for attention deficit hyperactivity disorder (ADHD) symptoms, active medication management, titrated for optimal dose, and regularly monitored for side-effects, was superior to behavioural treatment and to routine community care that included medication. Combined, intensive medication and behavioural treatment (parent, school and child components) did not yield significantly greater benefits than active medication management alone, for core ADHD symptoms. However, it is important to note that combined treatment outcomes were achieved with significantly lower medication doses than used in medication management alone.
It should also be noted that while the MTA treatments (most notably combined treatment) offered greater benefits than community care (including medication) for oppositional/aggressive behaviours, including internalizing symptoms, peer interactions, parent–child relations and reading achievement, behavioural treatment surpassed community care in children with ADHD plus anxiety, and approached medication-based treatments in this group. Thus, while an active medication regimen may suffice for the core symptoms of ADHD, the trial also indicates the benefits of multimodal interventions for comorbid symptoms. The significantly lower total daily doses of medication in the combined arm, and the question of degree of benefit from intensive behavioural treatments are of public health importance.
According to Taylor [3] the main conclusion of the study, that a carefully executed (actively titrated and regularly monitored) regimen of medication management is superior to alternative treatments, and nearly as good as combined treatment, calls for services to make medication available for ADHD. Although this conclusion may appear simple, Taylor [3] points out that practice is different in North America than in much of the rest of the world. Numbers of prescriptions suggest that stimulants are used between 10 and 30 times more frequently in the USA than in the UK. As with other treatments, medication use is often influenced by the traditions of child mental health in different countries and cultural settings.
As far as Australia is concerned, considerations for clinical services should include service traditions and organization, workforce issues, diagnostic considerations, including comorbidity, cost implications and, last but not least, ethical and philosophical considerations.
Service delivery
In general, Australian child mental health services are organized via Community Mental Health, Child and Family teams. These multidisciplinary teams ideally consist of child psychiatrists, psychologists and social workers. On the other hand, Child Development Centres, which traditionally provide services for children diagnosed with degrees of developmental delay, are staffed by paediatricians, psychologists and social workers. In Australia (with the possible exception of Queensland) only child psychiatrists and paediatricians are able to prescribe stimulant medications, which are controlled by State laws. As the use of stimulant medication has increased, albeit more slowly than in the USA as a result of increased parental awareness (including the Internet), the response of public services has varied. As shown by the MTA study, careful titration and monitoring of stimulant response requires considerable professional input. Community Mental Health services and Child Development Centres have limited medical resources, and as a result stimulant prescription has often been carried out in the private paediatric sector, certainly in New South Wales and Western Australia. In both of these States, guidelines, which are provided by Health Department ‘Stimulant Committees’, have generally proved helpful in providing guidelines and monitoring and educating professionals. Nonetheless, prescribing practice has often largely been according to the interests or biases of individual paediatricians, and not subject to systematic research. The traditions of Child and Family teams are strongly influenced by the theoretical training of the staff. Whether this training is psychodynamic, cognitive–behavioural or narrative, it is often more influenced by theory and belief, than by outcome. It has unfortunately been true that neither paediatricians nor child psychiatrists have had extensive training in child psychopharmacology. Future services will require paediatrician/child psychiatrist cooperation where possible. Such cooperation may involve joint services. Meanwhile, practitioners will need to share experience with old and newer medications, as well as opinions and support in relation to difficult and complex cases. The question can also be raised whether either paediatricians or child psychiatrists have sufficient time and resources for the intensive medication monitoring alogarithms used in the MTA study, and whether, in future, computerized communication systems would be helpful between clinicians and schools.
Diagnostic considerations
The MTA trial treated 579 children diagnosed as having ADHD, combined type, aged 7–9.9 years, for 14 months. Initial diagnosis was via structured interview: the Diagnostic Interview for children, and diagnostic status was assessed prior to randomization. The presence of comorbid conditions, such as oppositional defiant disorder, conduct disorder, internalizing disorder or specific learning disability, did not lead to exclusion from the study. Nonetheless, the study examined treatment responses in the most severe ADHD subtype, with combined inattentive and hyperactive/impulsive symptoms. Thus the question of whether medication is equally effective for the other subtypes remains. This is particularly important for the predominantly inattentive subtype [3, 4] where overlap with learning disability is also likely in a high percentage of patients.
The MTA trial did not include a remedial learning arm (remediation was sporadic and left to schools). It could be that a remedial education arm may have produced a different result. This has important service implications for Child and Family, and Child Development Teams. It is likely that for a subgroup of children diagnosed with ADHD, remedial education is a neglected aspect of treatment [5]. If so, any strategy for clinical services should include assessment and planning for remedial programmes. Such programmes should include speech pathology, remedial reading and occupational therapy interventions. In fact, ideally, teams working with ADHD children should include or have close access to speech pathology services.
Developmental considerations
A recent publication by Zito et al. [6] drew attention in the USA, to the use of psychotropic medications in preschoolers. Prescription records from two State Medicaid programs and a Health Maintenance Organization (HMO) were used to perform a population-based analysis of three 1-year cross-sectional data sets for the years 1991–1995. Stimulant treatment of preschoolers increased approximately threefold (mainly methylphenidate), while sizeable increases in the prevalence of clonidine and antidepressant use were noted in children younger than 5 years of age. The authors comment on the current lack of knowledge about the long-term safety of psychotropic medications, particularly in light of earlier ages of initiation and longer durations of treatment. Because the possibility of adverse effects on the developing brain cannot be ruled out, active surveillance mechanism for ascertaining subtle changes that the developing personality may undergo, as a result of psychotropic drugs impact on brain neurotransmitters, are recommended.
Pharmacogenomics
With the completion of the Human Genome Project, there has been considerable interest in the development of molecular genetic insights which will not only improve genetic prediction of drug response, but also give rise to an expanding array of gene products for use as drug therapies. For example, increased knowledge of the role of catecholamine neurotransmittors and related genes in attention processes [7] may allow the development of more tailored medications. For example, future researchers may put cloned genes in various cells and watch how they produce proteins, since proteins do the real work of genes. Disease occurs when proteins are produced incorrectly. The more scientists can learn about them, the more they can learn about disease.
DNA chips (microarrays) are thin slices of glass or silicon on which threads of synthetic nucleic acid are arranged. Sample probes are added, and matches read with an electronic scanner. Capacity is rapidly increasing to hold hundreds of thousands of nucleic acids. These techniques enable detection of single nucleotide polymorphisms (SNPs), which are small DNA variations that give people different hair colours, make individuals more prone to certain diseases, or determine how people react to drugs. These developments hold considerable promise for some of the unanswered questions in relation to prediction of drug response, including psychostimulant and other psychotropics. Genetic tests could predict positive and adverse responses, as well as matching drugs to subgroups most likely to benefit.
While these developments are potentially exciting, Rutter [8] points out that the extent to which genetic effects are dependent on combination with environmental risk factors (gene–environment interaction) is an important and unresolved issue. Evidence is available on risk indicators, but much less on risk mechanisms. According to Rutter [8], finding genes may prove the easiest (albeit difficult) first step in determining causal neural processes.
Ethical, philosophical and social implications
It is now frequently pointed out that the genetic revolution raises issues in relation to privacy in health insurance and employment. The use and interpretation of genetic information will require both public and professional education. Issues less often discussed are the philosophical implications of the technological revolution we are currently experiencing. This is particularly relevant in relation to the pharmacotherapy of children.
Cole-Turner [9] has discussed the issue of whether the ‘means-to-an-end’ are themselves important. New technology is often accepted as good or moral because it helps us achieve established ends more easily or efficiently. Cole-Turner raises the question of whether the means by which heightened cognitive performance is achieved, either through classic educational strategies, or possibly, in the not too distant future, by genetic techniques, would, in this way make a morally significant difference to the result achieved. The argument is cogent in relation to socialization of children, previously the exclusive domain of family, school and church. For example, the laboratory assessment of slow-release stimulant medications in the USA [10] utilizes a measure of attention and deportment in the home and at school to assess medication response.
If administration of a medication such as methylphenidate results in a child, previously stubbornly oppositional, becoming more amenable to sitting in a classroom and learning society's morays, or ‘fitting in’ with family life at home, is this a legitimate way to socialize a child? At a practical level, should a child with subthreshold ADHD symptoms and comorbid oppositional symptoms be treated with stimulants, as one suspects may sometimes occur? The decision to treat may depend on access to multimodal treatments, social and economic circumstances, as well as clinical judgement.
While official indications for stimulant medications are for ADHD subtypes, uncomfortable questions in relation to socialization issues are often posed [11, 12]. According to Diller [11], the line between treating a disorder and enhancing a particular aspect of personality is ‘cosmetic psychopharmacology’. He raises questions about the fairness of situations where two children have similar borderline attention problems, and one achieves higher grades with the aid of a stimulant. Diller [11] goes on to discuss whether or not a diagnosis of Attention- Deficit Disorder should be sufficient to argue diminished responsibility in a court of law. De Grandpre [12] argues that the modern tendency to reduce all human traits to the level of biological destiny allows society to escape responsibility for the environment in which these traits develop. Cole-Turner [9] believes that there are physical and technological means that affect the body and even the brain, but there are also social, psychological, intellectual and spiritual means that affect the self or the social, and that these two categories do not compete or overlap with each other.
In relation to the above socialization questions, it is important to ask whether the long-term outcome of social compliance achieved via medication, is equal to, less than or even better than that achieved via the rough and tumble, tears and sweat of family life and peer relations. Fortunately, these latter continue to occur, whether a child is on medication or not, and some evidence [13] suggests that the positive interactions achieved while an ADHD child is on medication are preferable to the otherwise constant negative feedback experienced by the child. Nonetheless, the increasing use of psychotropic medications in young children [6] raises important philosophical, as well as scientific, questions.
Cole-Turner [9] argues that even when new means such as psychopharmacology and genetic alteration are easier than traditional means, they may cheat us of the value to be found in old means. There is, he says, a glory and dignity to human accomplishment attained ‘the old-fashioned way’. It remains to be seen if the new means of childrearing will rob us of old-fashioned values, or whether the old-fashioned values will continue to be argued in the therapeutic and educational context. Child psychiatrists will be required to have an understanding of technological developments, if they wish to contribute to these debates. Rutter [8], in a discussion of ethical issues, concludes that ‘one of the key messages of genetic research is that genetic factors are not just concerned with disease. To the contrary, they affect the whole of human behaviour and carry no implications with respect to medicalization.’
Conclusions
The MTA study has important implications for the organization of treatment services for children with ADHD and comorbid behaviour and learning disorders. While active medication treatment may be sufficient for the core symptoms of ADHD, combined medication with behavioural treatments allow for lower dose regimens, and multimodal treatments are useful for comorbid symptoms. The study raises both philosophical and scientific questions in relation to socialization of children in an increasingly technological society.