The Intervention Triad Prevention Treatment and Enhancement

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This chapter on interventions in developmental psychopharmacotherapy will be subdivided into preventative interventions, treatment in a developmental perspective, and enhancement (and restraint). These three forms of intervention have to be distinguished. Treatment and enhancement are currently discussed for many new interventions in the brain represented in this book.

Preventative interventions or interventions at an early state of development influencing brain development and therefore future personality traits are little discussed. However, as the example of novel antipsychotics in the prevention of schizophrenia shows, the question of preventative intervention in the brain raises many ethical considerations. The same is true for the debate on the potential use of interventions for restraint.

Experts in neurosciences are increasingly speculating about issues of prevention and neuroprotection. If, in a few years' time, we are able to define specific targets in order to enable us to offer protection to the neural system, some parents would certainly wish to use these techniques for the benefit of their children. The wish to have a healthy and well born (eugenic) child is a very natural and ancient one. But this possibility raises troubling questions. Who will defend the children's rights in these decisions? What are the ethical questions arising from clinical trials aimed at preventing potential neuropsy-chiatric illnesses in seemingly healthy children, especially when the risk of morbidity is a relative risk, depending on multiple factors in the environment? What justifies interventions in nature, where nurture can also be protective and when there is only a risk rather than the certainty of developing a severe psychiatric disease?

Enhancement of sensory functions is well accepted because we usually presume that prosthetic interventions only improve natural functions or replace impaired functions without changing the personality. What about psychopharmacological agents changing attention and behaviour in school, school success etc.? The use of stimulants in children and adolescents not only for the treatment of ADHD but also for cognitive enhancement during examination periods appears to be growing, especially in the United States (Fegert et al. 2002; McCabe et al. 2005). The President's Council on Bioethics in its study "Beyond Therapy - Biotechnology and the Pursuit of Happiness" summarises:

It is precisely the effectiveness in improving attentiveness, focus, and steady conduct - coupled with the absence of serious side effects, when they are properly administered in small doses - that makes these drugs attractive also for the treatment of inattention, distractibility, and impulsivity in children who do not manifest the full disorder. Indeed, these drugs have the capacity to enhance alertness and concentration in children without any symptoms whatsoever. All these reasons conspire to make the use of stimulants to control behaviour a fascinating and important case study for the pursuit of 'better children' through psychopharmacol-ogy. (President's Council on Bioethics 2003:74)

Emotional enhancement is another issue of intervening in the psyche and the personality in the so-called "ProzacĀ® Generation". Isn't it justified that even normal individuals want to escape from natural mood changes by using for example SSRIs to improve their emotional stability in a society where good mood and optimism is a real need for success in the work place?

Another ethical debate concerns the potential for abuse of psychophar-macological substances as means of chemical restraint. Interventions in the brain can also limit the autonomy of people especially if they could harm themselves or others. The debate about restraint is somewhat similar to the ethical debate about enhancement but reflects the other side of the coin with regard to intervening in the brain to reduce potential risks even against the will of a person.

In the psychopharmacotherapy of psychiatric disorders, neurotransmitters, receptors, signal transduction and so-called second messengers all play an important role. A neurotransmitter is a substance synthesised and released from neurons. It is released from nerve terminals in a chemically or pharmacologically identifiable form and interacts with postsynaptic receptors, causing the same effects as are seen with stimulation of the pre-synaptic neuron. Cell surface receptors have two major functions: They have to identify specific molecules (neurotransmitters, hormones, growth factors and sensory signals) and they have to activate a response via effectors. Among the different neurotransmitter and neuropeptide systems we can describe the seroton-ergic system, the dopaminergic system, the noradrenergic system, the gluta-matergic system and the GABAergic system. For this context, the monoaminergic systems are the best studied, because most current effective antidepressants and antipsychotics target these systems. Generally we distinguish different substance classes:

- Antidepressants and anxiolytics including tricyclic and tetracyclic drugs, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other mostly combined reuptake inhibitors such as Venlafaxine, Duloxetine and so on. These substances are usually used for the treatment of (major) depression, anxiety disorders and obsessional compulsive disorders.

- Other anxiolytics: Benzodiazepines are used for the treatment of anxiety disorders and acute states of agitation or panic.

- Antipsychotics. Classic antipsychotic medications are the phenothiazines, Butyrophenone, neuroleptics such as Haloperidol, and different derivatives. These classic conventional antipsychotic drugs have a multitude of well known effects and side effects. They are used for the treatment of schizophrenia and schizoaffective disorder, substance induced psychosis, mania, personality disorders, Tourette's syndrome and different states of aggression or self-injurious behaviour. The so-called atypical novel antipsychotics are Clozapine, Olanzapine, Quetiapine, Risperidone, Arip-

iprazole, Ziprasidone and others. All these antipsychotic substances can also be used for the acute treatment of mania but there is another substance group for the treatment of bipolar disorders, the "mood stabilisers".

- Mood stabilisers and drugs for the treatment of bipolar disorder. Lithium is the oldest and best studied substance that can prevent relapse in bipolar affective disorders. It is effective in reducing suicide rates in this population, but feared for its narrow therapeutic window (the effective versus toxic plasma levels) in treatment. It can be also used for the treatment of aggressive behaviours in children and adolescents, if other interventions have failed (Gerlach et al. 2006). Antiepileptic drugs like Valproate, Car-bamazepine, Lamotrigine and Topiramate are also used as mood stabilisers.

- Sedatives-hypnotics. Barbiturates can be used as sedatives, for example in order to induce sleep.

- Psychostimulants like Methylphenidate, Amphetamine and Modafinil are used for the treatment of children with attention deficit hyperactivity disorder.

We will limit our discussions of interventions in a developmental perspective to a few practical examples of ethical problems and debates in the use of psychopharmacological substances in childhood and adolescence. We will focus on the three most commonly used substance classes in this age group: stimulants, antidepressants and antipsychotics. Therefore, we will deliberately omit other important substance classes such as mood stabilisers and/or antiepileptic drugs, anxiolytic drugs and sedatives. The example of the abuse of anxiolytic drugs and the tragedy of a generation of women dependant on prescription drugs is well known and does not need to be illustrated in this chapter. Before starting with the main chapter on interventions we will give a short overview of the history of developmental psy-chopharmacology. At the end of this chapter we will focus on aspects of the different roles of doctors, researchers, the industry and the state in medical innovations. This chapter is not intended to be an exact or detailed history of child psychopharmacology, nor is it meant to detail the neurobiological foundations of treatment. Instead, it will offer some insights into future perspectives of drug development and an overview of the different conflicts of interests influencing medical progress. The main aim of this chapter is to use well-known examples of conflicts and problems in developmental psychophar-macology in children and adolescents to highlight future perspectives in the ethical debate on novel techniques and medical innovations.

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