[Review of psychopharmacological treatments in adolescents and adults with autistic disorders].

Autism is an early developmental disorder. It leads to severe and durable disturbances. Given this problem, no treatment can be excluded a priori. Thus, many approaches are used to deal with autistic disorders. In France, pharmacological treatments are, for instance, largely and mostly used in adults. In the USA, these treatments concern 50% of persons with autism of any age. Nevertheless, they are rarely based on controlled studies. At the present, however, prescriptions and expected effects appear to be hard to localize. Furthermore, only few controlled studies validate their use. Aim - We offer a review of studies about medical treatments used in adolescents and adults with autism. They are classified in 3 categories: the first (category I) includes drugs used for their neurochemical effects focusing on autistic signs. The second (category II) covers drugs used for treatment of behavioural disorders frequently associated with autism. The third (category III) corresponds to a wide range of drugs or vitamins for wich only few case studies exist reporting irregular positive effects. The main hypothesis of this review is that autism involves a dysfunction of the neuromediation systems. This hypothesis opens new perspectives in the research of medical treatments in autism by focusing on molecules, which are supposed to have an effect on neuromediation systems. Method - Our review is based on studies, which have been published during the past twenty years. For many studies, data are limited to adolescents and adults. So we expanded our review to data available in children. The data bases that we have used are medline and psyclit. Keywords have been chosen according to: pharmacological considerations (psychotropic, psychoactive drugs, psychopharmacology) and clinical symptoms (autism, automutilations, aggressive behavior, and hyperactivity). Hypothesis of a dysfunction in the neuromediation systems in autism - Many studies exist about biochemical abnormalities in autism. As in schizophrenia and mental retardation, dysfunctions of the neuromediation systems are considered to be etiological factors. In 30% of people with autism the most regular dysfunction is the increase of serotonine. This led to the serotoninergic hypothesis in autism and to the use of active drugs in the serotonine system. However, the presence of other neurometabolic abnormalities also motivates the use of drugs, supposed to be active in other neuromediation systems. Pharmacological treatments in autism - Category I section sign 1 Active drugs in the dopamine system. Haloperidol (Dopamine antagonist): The effects of this molecule have been broadly studied in autism. Results indicate high efficiency in some symptoms of autism (lack in social behaviour, stereotypical behaviour) and in behavioural impairments that may be associated with autism (aggressive behaviour, hyperactivity). Its side effects, particulary the risk of late dyskinesy, make atypical antipsychotics preferable because of their lower risks. Risperidone (Dopamine and serotonine antagonist): Among several studies only few have been controlled. They indicate that Risperidone has positive effects on the behaviour and is quite well tolerated. section sign 2 Active drugs in the serotonine system. Clomipramine: after promising results, the medium-term efficiency has decreased and severe side effects have limited its use. Fluvoxamine, Fluoxétine, Sertraline (Specific serotonine drugs): Their efficiency has been mainly tested through open studies and their results are contrasted. In some cases, social behaviours have improved and aggressiveness and stereotyped behaviours have decreased. Fenfluramine: At present, this drug is removed from the market. Yet, some studies have suggested that it improves behavioural disturbances as well as performances in autism. section sign 3 Active drugs in the opiate system. Naltrexone: Several controlled studies have indicated an improvement in social and aggressive behaviours. Nevertheless, these studies have used small size sample and have not been replicated. Category II. This category correspond to drugs supposed to be active on neurochemical disturbances found in autism but their target symptoms are not autism specific signs as defined by the ICD 10. Buspirone: This serotonine agonist may have a good impact on emotional disorders and sleeping confusions. Methylphenidate: Most of the current studies about this noradrenergic drug concern children. The results are variable. Paradoxical effects may exist in children with severe mental retardation. Propanolol: Some isolated studies habe reported its efficiency on behavioural disturbances. Clonidine: This adrenergic drug treats efficiently some cases of aggressive behaviour and hyperactivity. Category III. This category contains a wide range of drugs, vitamins or method used in autism after sporadic observations of their positive effects. Secretine: An important improvement has been reported in isolated cases. However, controlled studies in children do not confirm these results. Vitamines B6, B12 and Magnesium: An improvement in socialization and in behavioural disorders have been reported in some cases, but these results are not yet confirmed. Lithium, Carbamazépine, Valproate: Results of some case studies have found it to be efficient in cyclic disorders. Gluten and casein free diet: An improvement of social behaviour have been reported by some parents after these diets. No controlled study has validated this observation. Conclusion - There is no consensus on the use of psychopharmacological treatments in autism. Although there exist many clinical observations, only few controlled studies have validated the efficiency and safety of these treatments. At the present time and until having sufficient studies, drugs are generally limited to severe disorders, for which usual psycho-educational approaches are insufficient.