[Crystalline polymorphism of eflucimibe]. / Polymorphisme cristallin de l'éflucimibe.

The importance, in therapeutics, of the concept of bioavailability and on-going quality research in the formulation of a drug has prompted us to examine the crystalline polymorphism of eflucimibe as from the research phase. This study has been carried out by re-crystallization of the product in organic solvents having a different polarity in a variety of experimental temperature and pressure conditions, then, subsequently, by re-cooling the previously dissolved substance. The analytical methods applied to identify and then describe the polymorphic forms are thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction from synchrotron radiation (XRPD), infrared spectrometry (IR), solid-state nuclear magnetic resonance spectrometry (SSNMR) and lastly maximum solubility measurements. By means of XRPD, two polymorphic forms called A and B have been clearly identified at ambient temperature. These two crystalline forms were obtained in a reproducible way, then described by DSC, XRPD, IR and SSNMR. Differential scanning calorimetry analysis has shown for polymorphic form A two endothermic phenomena with low energy at about 35 masculine and 118 degrees C attributed by XRDP to conformational polymorphism. The complex endothermic event that extends between 75 masculine and 105 degrees C appears to correspond to successive alterations of a lamellar structure. The solid-solid transition observed at 110 degrees C is due to a change of crystalline phase, then the melting point occurring at about 130 degrees C. For form B, two changes of crystalline phase are clearly observed at about 80 masculine and 120 degrees C. The reversibility of these changes was observed by thermomicroscopy in polarized light. Form A, which is less soluble in absolute ethanol than form B, is the more stable thermodynamically in the temperature range from 25 masculine to 50 degrees C where the data have been obtained. The Van't Hoff diagram layout for each polymorphic form appears to reveal an A<-->B transition temperature in a temperature range lower than 25 degrees C. This study, undertaken as from the research phase, has enabled us to highlight the polymorphism of this new chemical entity by means of XRDP by explaining the nature of the endothermic phenomena observed by DSC, and lastly identify the thermodynamically more stable polymorphic form, thus contributing to a better knowledge of this future drug.

Electroconvulsive therapy in adolescents with mood disorder: patients' and parents' attitudes.

The aim of the study was to assess retrospectively patients' and parents' experiences and attitudes towards the use of electroconvulsive therapy (ECT) in adolescence. The experiences of subjects (n=10) who were administered ECT in adolescence for a severe mood disorder and their parents (n=18) were assessed using a semi-structured interview after a mean of 4.5 years (range, 19 months to 9 years). Their attitudes were mostly positive and ECT was considered a helpful treatment. Concerns were frequently expressed, probably because ECT was not fully understood by the patients and their families. Most complaints were of transitory memory impairment. The parents were satisfied with the consent procedure, while all but one patient did not remember the consent procedure. We concluded that, despite negative views about ECT in public opinion, adolescent recipients and their parents shared overall positive attitudes towards the use of ECT in this age range.

Electroconvulsive therapy in adolescence.

The aim of this work is to discuss the ethical issues regarding the use of electroconvulsive therapy (ECT) in adolescents. Ethical implications of ECT in adolescents are analyzed in the light of general medical ethics, which include five prominent principles with respect to autonomy, nonmaleficence, beneficence, justice, and cautiousness. As adults, adolescents with acute psychotic impairment raise an inherent conflict between the respect for the patient's autonomy, on the one side, and the principle of beneficence on the other. However, this age group presents particular dilemmas: (i) As any adolescent suffering from a psychiatric illness is a highly vulnerable subject, society asks for particular attention. The consequence of potential overprotection is that the adolescent may remain untreated because of unrealistic fears regarding ECT. (ii) Some of these fears are linked to the cognitive secondary effects of ECT. Although preliminary data are reassuring, more empirical research on this population should be encouraged. (iii) Cautiousness recommends the use of ECT in limited indications catatonia, mood disorders, and intractable acute psychotic disorders. We conclude that there is no ethical reason to ban the use of ECT in adolescents. Ethical options in clinical practice must be evaluated empirically with respect to the consequences for the patient. Dogmatic views should be set aside.

Absence of cognitive impairment at long-term follow-up in adolescents treated with ECT for severe mood disorder.

OBJECTIVE: Cognitive functions of adolescents treated with ECT for mood disorder were evaluated at long-term follow-up. METHOD: At an average of 3.5 years (SD=1.7) after the last ECT, 10 subjects treated during adolescence with bilateral ECT for severe mood disorder completed a clinical and cognitive evaluation, including the California Verbal Learning Test and Squire's Subjective Memory Questionnaire. The same assessments were given to 10 psychiatric comparison subjects matched for sex, age, and diagnosis. RESULTS: All cognitive test scores of the patients treated with ECT were similar to those of the comparison subjects and did not differ from norms from the community. Six of the 10 ECT-treated patients reported having had memory losses immediately after the ECT course, but only one complained of subjective memory impairment at follow-up. CONCLUSIONS: The results suggest that adolescents given ECT for severe mood disorder do not suffer measurable cognitive impairment at long-term follow-up.

Case series: catatonic syndrome in young people.

This article reviews all recent (1977-1997) reports on catatonic adolescents and summarizes the 9 consecutive cases seen at the authors' institution during the past 6 years. Catatonia occurs infrequently in adolescents (0.6% of the inpatient population), but it appears to be a severe syndrome in adolescents of both sexes. Diagnoses associated with catatonia are diverse, including in this series: schizophrenia (n = 6), psychotic depression (n = 1), mania (n = 1), and schizophreniform disorder (n = 1). Two patients had a previous history of pervasive developmental disorder. In the literature, catatonia was also reported in children with organic condition (e.g., epilepsy, encephalitis). Therapeutic management depends on the specific causes, but several points need to be stressed: (1) the frequency of neuroleptic-induced adverse effects; (2) the potential efficacy of sedative drugs on motor signs; (3) the possible use of electroconvulsive therapy; and (4) the necessity to manage family reactions and fears, which are frequent causes of noncooperation. It is concluded that catatonia is an infrequent but severe condition in young people. While symptomatology, etiologies, complications, and treatment are similar to those reported in the adult literature, findings differ with regard to the female-male ratio and the relative frequencies of associated mental disorders.

[Use of electroconvulsive therapy in the adolescent]. / Utilisation de l'électroconvulsivothérapie chez l'adolescent.

Despite the progress of pharmocotherapy, electroconvulsive therapy (ECT) is still used in a majority of countries to treat severe intractable mental disorders of the youth, yet few studies have been conducted to assess its use for individuals under 20-year-old. Efficacy, indications, side effects, technical characteristics and outcome are uncertain. A review of the 96 cases reported in the literature shows that: 1) its average frequency in adolescent psychiatric practice is similar throughout western nations and can be estimated around one ECT every year per million people; 2) intractable mood disorders, both manic and depressive episodes, are its main indications, since ECT treated more than 90% of the 66 cases reported; ECT can also offer an interesting alternative in some schizoaffective and schizophrenic episodes, in particular catatonic ones; 3) tolerance appears to be good, although secondary effects may occur. The most serious ones are infrequent spontaneous seizures and more common memory loss. Although no prospective studies are available on the evolution of cognitive side effects, they seem to disappear within a few weeks.

Use of electroconvulsive therapy in adolescents.

Electroconvulsive therapy (ECT) is used in adolescent psychiatric practice, yet few studies have been conducted to assess its use for 13-19-year-olds. Efficacy, indications, side effects, technical characteristics, and outcome are uncertain. We retrospectively reviewed the medical records of 21 adolescents treated with bilateral ECT in our department from 1984 through 1995. In our series, ECT was effective in treating both maniac and depressive episodes, with a high rate of relapse at 1 year follow-up (approximately 40%). Clinical improvement was only partial and in schizophrenia and schizoaffective episodes. Seizure threshold was associated with gender, but not with the cumulative number of treatments. Adverse effects were frequent, but were usually transient with only moderate discomfort, even in patients with concomitant medical problems. We conclude that ECT is a safe and effective treatment for adolescents with severe and intractable mental illness, and it has the same indications and effects as in adults.

Cotard's syndrome in a 15-year-old girl.

We here describe a case of Cotard's syndrome in a 15-year-old girl who exhibited a short period of malignant catatonia, and the positive effect of electroconvulsive therapy (ECT) on her disorder. A psychopathological hypothesis is proposed.

The outcome of adolescent suicide attempts.

A sample of 265 adolescents hospitalized between 1971 and 1980 in a psychiatric unit following a suicide attempt was studied to evaluate outcome. After an average of 11.5 years, 48% of the original sample, or 127 subjects, could be traced. Thirty-nine per cent of these subjects showed signs of improvement, 22% appeared to be unchanged and 33% were worse. Substantial dropout rates were found in postdischarge care, only 32% of the patients having been followed up for a sufficient amount of time. Fifteen subjects had died, only one of whom from a natural cause. Of the remaining 14, 5 had committed suicide and 9 had died from unnatural or violent causes other than suicide, the cause of death appearing in all cases to be closely linked to the subject's adolescent disorders. The implications of these findings for suicide prevention are discussed.

[The adolescent's lexicon: study of lexical variations in normal adolescents depending upon the listener]. / Le lexique de l'adolescent: étude chez des adolescents normaux des variations lexicales selon l'interlocuteur.

Clinicians and parents are familiar with the fact that adolescents have a special vocabulary, but very few studies have examined this. Linguists describe it as deeply metaphoric, creative and lively, thus showing that young people have a deep knowledge of language and truly experience pleasure using words. This contrasts with teachers' complaints about the little taste adolescents show for oral school activities and how poorly they express themselves. Some of them link this to the use of this polysemic and all purpose vocabulary. The context of locution is probably the explanation for these diverging opinions. Using this hypothesis, we have realised a quantitative study of the lexical variations depending on the person the adolescent is talking to in two groups (20 and 19 subjects), from very different social and educational backgrounds. Each teen-ager had to perform the same linguistic task: the description of a photograph on two occasions, once with an adult examiner and once with a friend. We studied the lexical differences between the two narratives. When adolescents are together they use their particular vocabulary four times more than when with an adult. But this qualitative difference is not a quantitative one, such as the length of the narrative or the number and repetition of whole words, and isn't correlated with the lexical stock. The use of this vocabulary runs across gender and social class categories. It can equally be found in high performance and upper class students as well as in underprivileged youngsters of technical schooling. It is the only variable that does not change between the two high schools. Thus this special vocabulary would not be connected to the subject's lexical competence, nor to gender or social background. It is the psychological function of this language that seems to be prominent.

[Cognitive disorders and psychiatric manifestations in the fragile X syndrome. Autism and fragile X]. / Dysfonctionnement cognitif et manifestations psychiatriques dans le syndrome de l'X fragile. Autisme et X fragile.

The fragile X syndrome is one of the main etiologies of mental retardation in human beings. Some of its specific cognitive and language disturbances are nowadays well known. Disturbances of behavior are frequent. They are akin to psychotic manifestations and are mainly described in terms of autistic syndromes. The question of the possible links between autism and the fragile X syndrome is being discussed since 1980. The authors give a synthetic and critic overview of the studies reporting on the frequency of co-occurrence of these syndromes and offer some reflexion on the true questions at stakes in the debate. They emphasize the determining role of future clinical research in autism in order to objectively contribute to the progression of knowledge in this field.

[Use of electroconvulsive therapy in adolescence]. / Utilisation de l'ECT chez l'adolescent.

Few studies report the use of ECT in adolescents. Within a period of 3 years, 9 patients aged 15 to 19 were treated by ECT in our department. Indications were acute schizophrenia, delusional depression and delusional mania, resistant to usual medication. ECT proved to be a safe treatment with good short-term outcome. Long-term outcome did not seem to be modified by treatment. These results are discussed in relation to the use of ECT in adults and adolescents reported in the literature.

[A case of dysthymic pathology in a 16-year-old adolescent]. / Un cas de pathologie dysthymique chez une adolescente de seize ans.

Dysthymia in children and adolescents, illustrated by a sixteen-year-old-girl's clinical history, raises different diagnostic, therapeutic and prognostic problems. Diagnostic, since dysthymia in children and adolescents has specific peculiarities (often mixed manic episodes, variable expression of depressive affect according to age, problem of the meaning of "masked depression"; Diagnostic again, since it is difficult to collect clearcut evidence ascertaining the diagnosis of manic-depressive syndrome in children: genuine periodicity in the occurrence of dysthymic episodes, family history of psychoses (manic-depressive syndrome, periodic psychosis, or other types of psychosis) and effectiveness of lithium are reliable criteria; Finally, differential diagnosis with the two other types of childhood psychosis: affective psychoses and severe dysthymic disorders; Therapeutic: the problem is to know when and on what evidence treatment with lithium can be started and, if called for, discontinued.

[The child as a symptom of his parents]. / L'enfant, symptôme de ses parents.

The child psychiatrist is often consulted for symptoms which apparently belong to the child but, in fact, betray a much broader problem. This is substantiated by three clinical observations. The child's symptoms may be the only manifestation of a pathological family organization. The problem often originates in the parents' relationship: the parents can stay together only if the unconscious conflict between them remains hidden; however, the repressed pulsions remain active and provide the child with a basis for building a symptomatic complex which, as for neurotic arrangements, is a compromise between expression and repression of unconscious pulsions. In other cases, the child's symptoms represent an actualization or a revival of the parents' repressed phantasms. Thus, the child becomes a symptom of a pathological situation which affects the whole family. The child's experiences during the first years of life are often found to have been deficient. Inferiority of one of the parents, usually the father, compared to the other, is often noted. In all cases, the therapeutic approach requires special caution.