Nouveaux enjeux de la recherche clinique en psychopharmacologie chez l’enfant et l’adolescent

A large proportion of medicines used in children are actually prescribed off-label, which can place children at a direct risk of under- or overdosing and a delayed risk of long-term adverse effects, and children have often been denied access to new or innovative medications. Many generations of paediatricians and other physicians have learned to live with the situation. But because such situation is nowadays considered as unethical, the need to obtain paediatric information for medicines used in children seems a matter of consensus on a global basis. If the therapeutic effects of amphetamines in hyperactive children were first described in 1937, thus, preceding the major discoveries of adult psychopharmacology, since this little innovation has occurred in paediatric psychopharmacology. However, it is widely recognized that mental disorders in children and adolescents lead to a major burden for them and for their families. Over the past decade, under the impulsion of the US paediatric legislation, the number of high quality paediatric psychopharmacological studies has dramatically increased. Like what happened in the US, it was clear in European Union, that there was a need for a legal obligation for Pharmaceutical Companies to perform studies in paediatric populations, and a new Paediatric European Regulation came into force in 2007, opening a new era in the history of European regulation with the ambition of improving the health of children and adolescents. Therefore drug development is changing; the concern of protecting children against clinical research fading away, a new paradigm is now emerging, i.e. protecting children through clinical research. In Europe, paediatric development is no longer an option but needs to be truly integrated in clinical development plans with paediatric evaluations being a regular part of every drug development process. It seems reasonable to anticipate that more research may occur as well in paediatric psychopharmacology and more studies will be enrolling paediatric patients all over the world in the forthcoming years. But paediatric clinical development is difficult and the hurdles of conducting clinical trials in paediatric population are numerous. This article presents briefly the new European Paediatric Regulation, illustrates its purpose through the example of antidepressants in children and adolescents, and discusses new research challenges in paediatric psychopharmacology. Ultimately, it is through well-conducted research that children will gain access to new medications and receive safe and optimal drug therapy.     

Les ateliers de l’atopie

Atopic dermatitis is a chronic disease, which is a burden with putative major repercussions. Its management could be complex. The workshops of atopy gather therapeutic education psychological help. Such interventions are not possible for all patients. They are very useful and efficient since clinical controlled trials have demonstrated that Scorad, a score of severity for atopic dermatitis, was decreased whereas topical steroids were globally less used.     

Le devenir des idées en pédopsychiatrie, à travers l’histoire de l’autisme

The history of autism can serve as a model for the understanding of the history of child psychiatry. One can observe the controversies between the inborn or acquired nature of the child psychic troubles, between the primacy of psychiatric care or education, between handicap or disease and about the specificity of the child psychopathology. The 19th century was dominated by the educational model. The goals were, first, to civilize wild children, then to develop by education the mind of idiotics, imbeciles, mentally retarded children, ranged on a one-dimension scale of intellectuel level. At the turn of the century, under the influence of psychoanalysis but also of a more humanistic conception of psychiatry, psychopathology has developed as a new approach, against the pessimistic view of heredity, giving birth to the new concept of infantile autism included in the more general frame of infantile psychosis and fostering the development of various forms of psychotherapy articulated with educative methods. After World War II, in France, the movement of “sector public child psychiatry” has represented a major trend in favor of social and psychological reintegration of abnormal children. Nowadays, parents have received some of psychodynamic theories as a way of making them responsible of their child pathology. They ask for a turn towards mere education and fight against the therapeutic methods. This backward movement may, by neglecting the need for care and therapy, hinder a regard for the emotional life of the child and be detrimental for his/her evolution. Under the pressure of the families exaction, the influence of drug industry, the financial shortage due to economic conditions, child psychiatry is in need of more historical knowledge in order to insure its transmission and its ethics.     

Les thymoregulateurs chez l’enfant et l’adolescent

Background

In child and adolescent psychiatry, mood stabilizers are mainly prescribed for bipolar disorders (BD). Recognition of BD in adolescent is now clearly established. However, whether bipolarity exists in children is more controversial. To distinguish different clinical presentation in youth, it is recommended to use severe mood dysregulation (SMD) or temper dysregulation disorder (TDD) regarding previously called BD not otherwise specified. This point is currently in discussion for DSM 5. This distinction is very important as recent studies showed that treatment efficacy depends on diagnosis.

Methods

We reviewed pharmacological treatment approaches for BD in children and adolescents focusing both on short-term efficacy, prevention of relapse and adverse effects.

Results

We found 16 double blind randomized controlled trials (DBRCT) with rigorous methodological criteria assessing short-term efficacy of medications in BD in children and/or adolescents. Four used mood stabilizers (lithium, n = 2; valproate, n = 1; divalproate, n = 1; oxcarbamazepine, n = 1); eight second-generation antipsychotics (SGA); two compared divalproate with an SGA; one compared lithium, valproate and risperidone; and one combined divalproate plus quetiapine. We found at least one DBRCT showing superiority to placebo for lithium, valproate, as compared to SGA (aripiprazole, risperidone, quetiapine, olanzapine and ziprasidone). Finally, we found only one relapse prevention DBRCT comparing lithium and divalproate. In sum, most studies refer to SGA short-term efficacy and trials remain too rare regarding mood stabilizers. However, anti-epileptics’ secondary effects are more evaluated compared with SGA or lithium because of their use in treating epilepsy.

Conclusion

Current state of data and recent studies bring us to stay very careful regarding use of mood stabilizers in pre-pubertal child with BD. In contrast, these treatments are indicated for adolescent BD in addition to psychotherapeutic treatment and educational care although the number of studies is still limited.     

Symptomatologie dépressive à l’adolescence : rôle de la personnalité et de la conscience émotionnelle

Aim of the study

The aim of the study was to analyze the relating contribution of personality dimensions referring to Cloninger's model and emotional awareness to depressive symptoms intensity, in a community sample of adolescents. Our purpose was also to investigate the mediating role of the emotional awareness on the personality-depression relationship.

Method

A sample of 372 school students completed the following questionnaires: the Tridimensional Personality Questionnaire (TPQ), the Level of Emotional Awareness Scale (LEAS), and the Center for Epidemiologic Studies Depression Scale (CES-D).

Results

Correlationnal and multiple hierarchical regressions analysis confirmed the existence of direct links between each personality dimensions and depression, and the partial mediating effect of emotional awareness, but only for the novelty seeking and the harm avoidance dimensions.

Conclusion

Our results confirm the relationships observed in previous research between emotion awareness and depression on one hand, and between personality and depression on the other hand. They highlight the major role played by personality and emotional processing in the vulnerability to present depressive symptoms. The importance of taking in account and assess the emotional processing in the adolescent's depression clinical support is discussed.     

SociaBillyQuizz,un jeu pour l’entraînement aux habiletés sociales chez l’enfant et l’adolescent : étude exploratoire

Background

The SociaBillyQuizz is a therapeutic game designed for social skills training groups with children and adolescents. Using an entertaining method, this media requests several dimensions: exposure, cognition, communication skills, imagination, emotional expression and sign decoding. In this preliminary study, the setting includes two groups of six adolescents, one with social anxiety disorder and the other with Asperger syndrome.

Objective

To evaluate, in an exploratory study, the effects of a therapeutic device involving this game for these two clinically different groups of adolescents.

Methods

During 26 of 1 hour weekly sessions, two adolescents groups participate to a program including the SociaBillyQuizz and cognitive behavioral therapies. The groups are moderated by two therapists. The SociaBillyQuizz is a board game for two to six players; its goal is to collect points by answering instructions from the different thematic cards. There are four thematic cards: action cards (players have to do something), brainstorming cards (players have to use their imagination and demonstrate cognitive flexibility), interview cards (players have to express themselves about what they think or feel) and mystery cards (unexpected instructions). According to the groups’ clinical characteristics, some aims are specifically highlighted. In the anxiety disorder group, the cognitive dimension is privileged and in the Asperger syndrome group, we emphasise the pretend, cognitive flexibility and theory of mind. The effects are measured by the Rathus Assertiveness Schedule and the Fear Avoidance Hierarchy (FAH) for the social anxiety disorder group and by the Faux Pas Recognition Test and the Social Responsiveness Scale (parent version) for the Asperger group.

Results

These assessment tools indicate, for both groups, a significant increase of the scores corroborating the observed clinical effects. For eleven of the twelve adolescents, a clinical interview 6 months after the retest shows a continuity of therapeutic benefit.

Discussion

These early results suggest that a social skills training device featuring the SociaBillyQuizz produces clinical improvements in these two groups of adolescents. In future researches, with control group and more complete follow-up, nature and effectiveness of its contribution should be specified.

Conclusion

In this preliminary study, the SociaBillyQuizz appears to be an interesting therapeutic tool that can increase implication, motivation, participation and cohesiveness of the group. It also makes easier the cognitive-behavioural-strategies learning.     

Adolescents obèses : évaluation de l’image du corps,de l’estime de soi,de l’anxiété et de la dépression

Background

Adolescence is identified as a critical period for obesity and its complications.

Objective

To evaluate body image, self-esteem, anxiety and depression in obese adolescents.

Methods

Hundred and six obese adolescents benefited from an exploration of body image (Body Prominence, BPQ; Figure Rating Scale, FRS; Questionnaire of Body Preoccupation, QPC), self-esteem (Self-Esteem Scale, SES), anxiety (Revised children Manifest Anxiety Scale, RCMA-S), depression (Center for Epidemiologic studies–Depression Scale, CES-D).

Results

Globally, body image is disturbed. The BPQ shows a level of body consciousness greater in girls. Concerning the choice of the perceived figure, boys position themselves more frequently than girls in plump figures. For wished figures, girls choose more slim figures. However, there is no sex difference concerning body dissatisfaction that is relatively important for both sexes. The QPC indicates that girls have higher body preoccupation level than boys with specific focus on certain body area according to sex. The SES indicates that one out of two adolescents shows a low self-esteem and according to the RCMA-S, one out of three shows a high anxiety level without sex difference. Moreover, from the CES-D, one out of five adolescents, more frequently girls, exhibits a moderate to severe depression.

Conclusion

These results, with a differential interpretation (statistical vs clinical), partly confirm the data from the literature, and underline the need to perform a comprehensive investigation of body image, self-esteem, anxiety and depression in obese adolescents. In order to optimize the quality of the management provided to these youths, we proposed to physicians a pragmatic guide as “the somato-psychic pyramid”. It is important to remind that while escaping from the rule of the body fat regulation, obese adolescents may demonstrate a transgression and an adaptative marginalization.     

L’impact du cannabis à l’adolescence sur la transition psychotique de l’adulte

It is now well known that cannabis can precipitate the onset of psychosis. The epidemiological studies have shown that the increased risk is significant from ‘recreational’ consumptions (ten times exposure at the age of 18), but the effect is more important with higher doses (dose-dependent effect) and more marked in adolescent (with a two-fold increase of exposure at the age of 15 compared to 18). The effect is also dependent on the composition in cannabinoids: delta-9-tetrahydrocannabinol have psychotomimetic effects while cannabidiol has anxiolytic and possibly antipsychotic. This question is timely since some production of cannabis includes genetic modifications that tend to decrease the level of cannabidiol. Cannabis interferes with endogeneous cannabinoides systems, involved in the maturation processes at adolescence, and adolescence seems a critical period of sensitivity to the deleterious effects of cannabis. The recent literature in human and animal have demonstrated that exposure to cannabis at adolescence can result in chronic deleterious effect on cognition in adulthood. While the reliable data are compelling, we now need to disseminate these informations in an appropriate way, without militant excess but without complaisance. It is also needed to identify the markers that shall alert the environment of the adolescent or young adults and identify subjects at risk of complications when exposed to cannabis. It is already established that exposure at adolescence should not be minimized since adolescence per se appears as a risk factor for chronic cognitive deleterious effect and sometimes psychotic complications, even after relatively minor exposure.     

Relations sociales entre pairs à l’adolescence et risque de désinvestissement scolaire

Objective

This paper emphasizes the variety of peer relationships and their impact on the psychological and social-emotional development of adolescents of their attachment to school. In greater detail, this study analyzes the impact of social status on school commitment/disengagement within suburban schools (socially disadvantaged areas). We define social status as the social position of a person in a group: popular, rejected, lonely profile, etc. We study it based on the integration of an adolescent to a peer group, on the acknowledgment than he gets back, on the quality of his relationships with the other members of the group and on the fact he is/is not able to curb the peer pressure.

Methods and population

We asked 186 adolescents, pupils of a suburban school (58% of them are girls and 42% are boys). Most families live on low (or medium) incomes with a low educational attainment. A Decreasing Hierarchical Classification (DHC, Alceste, a method which consists of providing clusters by bringing them together according to their similarity) was used to identify five adolescents’ profiles: “followers/aggressive”, “popular”, “rejected”, “lonely” and “estimates”. This approach allowed us to set up typical adolescent profiles based on their social status and illustrated with their school disengagement.

Results

It was revealed that adolescents with “extreme” relationships (profiles: famous, aggressive or rejected) are those experiencing more difficulties at school. Their relationships are based either on power, on research for conformity or on strong emotional dependence. This leads them to bad school behaviors (practicing other activities at school, inattention, or being passive during class) because of their values too far from school requirements. Adolescents who have balanced and satisfying relationships succeed better. The support and the security from peers make them more cognitively available during class. The adolescents who do not belong to any group are also good performers: this way, they avoid social pressure so that they can concentrate on school activities.

Conclusion

After all, these results underlie that the social status of a adolescents in his group of peers can generate individual problems affecting his personality, his self-esteem, his sociability, his values and, as a consequence, his whole school journey.     

La régulation des émotions par le coping chez les enfants et adolescents de sept à 16 ans placés à l’Aide sociale à l’enfance

Objective

The aim of this paper was to compare foster care and typical children's and adolescent's use of emotion regulation processes through coping. Developmental shifts in coping strategies were expected to change coping profiles during the transition from childhood to adolescence and enhance a less adaptive coping style in foster adolescents.

Methods and population

One hundred and forty-two children and adolescents, from 7 to 16 years, participated to this study, 46 were in foster care and 96 were in typical families. Most families lived on medium incomes with a low to medium educational attainment. An Hierarchical Classification Ascendant (method consisting to build a partition of the population into homogeneous clusters [low within-variability] which are different one from another [high between-variability]) was used to identify three coping profiles in children and adolescents: “flexible”, “avoidant”, and “active”. This method allowed us to set up children and adolescent profiles as a function of their ages, their social status and their gender.

Results

It was revealed that 30% of foster care children and adolescents used a “flexible” coping profile in the same proportion as in the control population. In both populations, there was an increase of the adaptive “flexible” coping profile with age. However, a placement in foster families after 6 years old increased adolescents’ vulnerability since between 12 and 16, they used less the “active” coping profile and more the “avoidant” coping style when faced with a stressor. The coping profiles of foster care girls differ significantly from those of girls in typical families with a greater proportion of “avoidant” coping profiles.

Conclusion

These results suggest that the transition from childhood to adolescence alters emotion regulation in both populations. They are discussed within the framework of clinical intervention following the resilience perspective.     

Déficience sensorielle,utilisation de l’espace et constitution de l’espace psychique. Psychothérapie d’un enfant aveugle

Based on material from psychotherapy with sensory deficient patients (blind or deaf children and adults) this paper analyses subjects’ use of physical space in transference as well as in the elaboration of psychical spaces. Through the psychotherapy of Tom, a blind child, drawing upon Winnicott's work, we will show how this space, which is at first unapproachable, is progressively assimilated into a shared reality. This space is first experienced as suffering, before being ultimately used creatively and playfully as transitional space. This transformation occurs through the integration of aggressiveness induced by the occupation of this space. Any discontinuity is experienced by the patient as a rupture of the relationship. Furthermore, discontinuity is associated with the elaboration of separations and an increase in the patient's capacity to distinguish the self from the object. We thus hypothesize that differentiation from the object may pose a particular challenge for sensory deficient patients. The absence of the visual or vocal bond accentuates adhesive identifications (Bick, 1986 [6]). These pathological identifications can be repeated in transference, where they take the form of the patient's excessive need for continuous vocal tactile or visual contact. Supported by the therapist, these adhesive identifications can be overcome, and the patient's access to a three-dimensional world can be facilitated.