[Brief history of the development of valproate in bipolar disorders]. / Historique du développement du valproate dans les troubles bipolaires.

The anticonvulsant properties of N-dipropylacetic acid (valproic acid) were discovered in 1967 by Meunier and Carraz. It very soon became widely used in epilepsy, generally in the form of sodium valproate. Divalproate, an equimolar combination of valproic acid and sodium valproate has been available in the United States for this indication since 1983. The development of this drug for use in bipolar disorders occurred in two stages. Antimanic and prophylactic activity was demonstrated for valpromide, a primary amide of valproic acid (Lambert et al., 1968-71). The preliminary studies conducted by Lambert were not repeated outside France and it was only much later that the efficacy of derivatives of valproic acid in bipolar disorders was demonstrated in studies undertaken in Germany with sodium valproate (Enrich and Von Zerssen, 1980-85), and then in the USA with divalproate in the last decade. The majority of controlled studies were performed with divalproate and demonstrated the efficacy of this drug in monotherapy during manic episodes (Pope et al., 1991) (Bowden et al, 1994), and divalproate was approved by the FDA in 1995 in this indication. The results of the study by Bowden and the findings of other open studies suggest a wider spectrum of activity for divalproate than for lithium with a good efficacy profile in subtypes of mania in which the effects of lithium are mediocre: dysphoric mania, rapid cycling mania and forms of mania secondary to organic brain disease. The prospective studies by Puzynski and Klosiewicz (1984) and by Lambert and Venaud (1992) demonstrated the prophylactic activity of valpromide, with slightly greater efficacy being noted against manic episodes than against depressive episodes. The study by Bowden et al. (2000) shows that good efficacy of divalproate in acute manic episodes in a given patient may be predictive of efficacy of the drug in maintenance therapy. The field of bipolar disorders currently appears much wider and more heterogeneous than has long been held. Current therapeutic strategy is dominated by thymoregulators. In such long-term therapy where poor compliance constitutes a risk factor for treatment failure, use of valproate (valpromide, divalproate) has the twin advantage of being easy to manage and well tolerated in the long-term. During coadministration of thymoregulators, which is often necessary due to their limited individual efficacy, general consensus exists regarding the therapeutic value of combined divalproate and lithium.

Consensus on the Practical Use of Amisulpride, an Atypical Antipsychotic, in the Treatment of Schizophrenia.

Clinical expectations in schizophrenia treatment have greatly increased since the introduction of new atypical antipsychotics, but the choice of therapeutic strategy has become more complex and reference guidelines are scarce. This paper summarizes the consensus of a broad range of professionals after long-term commercialization in France of an atypical antipsychotic, amisulpride. Participants were from psychiatric hospitals, private clinics, out-patients settings and research; all were experienced with the drug. Discussions focused on the practical use of amisulpride, as, in addition to the double-blind trials information, it may be useful for psychiatrists of other countries to intuitively understand the therapeutic properties of amisulpride. The topics selected include acute psychotic episodes, short- and long-term follow-up, feasibility of treating the initial phase, the elderly and switching treatments. The French experience emphasizes the central role of amisulpride as a first-line treatment of schizophrenia.

Amisulpride has a superior benefit/risk profile to haloperidol in schizophrenia: results of a multicentre, double-blind study (the Amisulpride Study Group).

In a multicentre, double-blind, flexible-dose study, 199 patients with paranoid schizophrenia or schizophreniform disorders received haloperidol (10-30 mg/d) or amisulpride (400-1200 mg/d) for four months. More patients in the haloperidol group withdrew prematurely (44% vs 26%; P = 0.0077) due to a higher incidence of adverse events. Amisulpride was at least as effective as haloperidol in reducing the Brief Psychiatric Rating Scale (BPRS) total score (-27.3 vs -21.9) (non-inferiority test; P < 0.001). The PANSS positive score improved to a similar extent in both groups whilst improvement in the PANSS negative score was significantly greater with amisulpride (-10.5 vs -7.2; P = 0.01). The percentage of responders on the Clinical Global Impression scale was also significantly greater with amisulpride (71% vs 47%; P < 0.001). Both the Quality of Life Scale (QLS) and the Functional Status Questionnaire (FSQ) improved to a significantly greater extent under amisulpride. Haloperidol was associated with a greater incidence in extrapyramidal symptoms and with a greater increase in the Simpson-Angus score than was seen with amisulpride (0.32 vs 0.02; P < 0.001). In conclusion, amisulpride is globally superior to haloperidol in the treatment of acute exacerbations of schizophrenia and significantly improves patients' quality of life and social adjustment.

[The importance of classifications in psychiatry]. / L'intérêt des classifications en psychiatrie.

The classifications currently used in psychiatry have different aims: to facilitate communication between researchers and clinicians at national and international levels through the use of a common language, or at least a clearly and precisely defined nomenclature; to provide a nosographical reference system which can be used in practice (diagnosis, prognosis, treatment); to optimize research by ensuring that sample cases are as homogeneous as possible; to facilitate statistical records for public health institutions. A classification is of practical interest only if it is reliable, valid and acceptable to all potential users. In recent decades, there has been a considerable systematic and coordinated effort to improve the methodological approach to classification and categorization in the field of psychiatry, including attempts to create operational definitions, field trials of inter-assessor reliability, attempts to validate the selected nosological categories by analysis of correlation between progression, treatment response, family history and additional examinations. The introduction of glossaries, and particularly of diagnostic criteria, marked a decisive step in this new approach. The key problem remains that of the validity of diagnostic criteria. Ideally, these should be based on demonstrable etiologic or pathogenic data, but such information is rarely available in psychiatry. Current classifications rely on the use of extremely diverse elements in differing degrees: descriptive criteria, evolutive criteria, etiopathogenic criteria, psychopathogenic criteria, etc. Certain syndrome-based classifications such as DSM III and its successors aim to be atheoretical and pragmatic. Others, such as ICD-10, while more eclectic than the different versions of DSM, follow suit by abandoning the terms "disease" and "illness" in favor of the more consensual "disorder". The legitimacy of classifications in the field of psychiatry has been fiercely contested, being variously dubbed "a reductive academic exercise of no relevance to patients", "a dehumanizing labelling system, and a potential source of social and political violence", "a destructive prognostic guide", and so on. Other critics point to various aspects of certain classifications: the abandonment of theoretical concepts, the arbitrary nature of certain categories, the selection of definitions and criteria, the privileged position systematically accorded to the notion of category over that of general dimension. Multiaxial systems such as those proposed in successive versions of DSM or the classifications used in child psychiatry go some way towards meeting these criticisms. They go beyond simple labelling and place the patient in an overall medicopsycho-social setting. Nosographical indicators do not constitute an obstacle to psychopathological understanding. No classifications are capable of satisfactorily fulfilling all needs, namely those of daily practice, research and health statistics. The has led to the development of specialized diagnostic criteria and instruments, as in research for example. It should also be noted in this context that different versions of ICD-10 exist for psychiatrists, general practitioners, researchers and healthcare managers. The greatest danger posed by classifications is the potential reification of hypothetical approaches, arbitrary categorization and the dulling of reflection, all of which have created a need for regular revisions underpinned by field trials.

[Psychotic women and their children]. / Les femmes psychotiques et leurs enfants.

With desinstitutionalization, the social life of psychiatric patients and particularly that of psychotics has arisen in new terms over the past twenty years. In particular, relationships and sexuality of these patients are manifest realities to which few studies are devoted. 61 schizophrenic and 21 bipolar women (18-45 years of age, mean 34 in-or outpatients) were interviewed with a battery of instruments (PANSS, Carpenter's criteria of schizophrenia with deficit syndrome, axis V of DSM-III-R) and with a semi-structured questionnaire related to clinical data, sexuality, relationships, children and motherhood. Half of the schizophrenic women have an active sexual life, and children. The study provides information about the reproduction rate of schizophrenic women, the precocity of their pregnancies and the outcome of their children. The study also treats these women's ability to rear their children, their desire to have children and any hospitalizations during the perinatal period. These results, as well as those related to abortion and contraception, are discussed in the light of those of the bipolar control group.

Sexual victimization in women with schizophrenia and bipolar disorder.

Exposure of populations with psychosis to traumatic events (among them sexual trauma) has seldom been studied. In addition, the clinical features developed by victims with psychosis after a traumatic event are rarely taken into account. Sixty-four women with schizophrenia and 26 women with bipolar disorder (DSM-III-R diagnosed, 18-45 years, inpatients and outpatients) were interviewed using a clinician-rated battery of instruments, including a semi-structured questionnaire concerning sexual victimization and its impact. In childhood or adolescence, 36% of women with schizophrenia (vs 28% of those with bipolar disorder) had been victims of sexual abuse involving body contact. In the women with schizophrenia, this sexual abuse was associated with addictions, suicide attempts and becoming psychiatric patients earlier. Over their lifetime, the prevalence of rape was 23% in the two clinical groups. In women with schizophrenia, rape was associated with a greater severity of their disorder and addictions. Moreover, a frequent repetition of sexual trauma was observed in women with schizophrenia, whereas such repeated traumas were less frequent in those with bipolar disorder. The results suggest that these two clinical groups are at risk of rape and the study highlight clinical features in victims with schizophrenia that have been described for other groups of victims of sexual abuse.

Folates and post partum depression.

Hypofolatemia can cause psychiatric disturbances of a depressive nature. Pregnancy and delivery are often associated with hypofolatemia. This study was conducted to determine if hypofolatemia at day 3 post partum is a risk factor for baby blues or post partum depression. To study this hypothesis, 131 post partum women were followed prospectively for the 3 months immediately following delivery. 19% were found to have 'baby blues', as defined by a score greater than 20 on Pitt's scale (Pitt, 1968, J. Psychiatry 114, 1325-1335) and 12% had post partum depression as defined by a score greater than 7 on QD2A scale (Pichot et al., 1984, Rev. Psycholog. App. 34, 229-250, 323-340), within the three months post partum. No relationship was observed between the serum or erythrocyte folate levels on the third day following delivery and the maternal post partum depression scores. A statistically significant correlation between post partum depression and previous psychiatric disturbance was, however, observed.

[Mental disorders in elderly hospitalized patients. Epidemiological study in an internal medicine department]. / Troubles mentaux chez les sujets âgés hospitalisés. Etude épidémiologique dans un service de médecine interne.

This epidemiological transversal study conducted on 100 patients older than 65 years hospitalized in the Internal Medicine department of a University hospital demonstrates the frequency of psychiatric pathology in these patients: dementia 19 percent; other psycho-organic disorders 17 percent; affective disorders 23 percent and other psychological disturbances 4 percent. Thus, 63 percent of this patient population had a mental disorder as defined by the DSM III criteria. These disorders are generally not or imperfectly identified by the internists in charge of these patients.

[Assays of arylsulfatase activity in psychotic patients. Review of the literature and results of a study of 22 patients]. / Dosages de l'activité de l'arylsulfatase chez les malades psychotiques. Revue de la littérature et résultats d'une étude chez 22 patients.

After a clinical and biological description of arylsulfatase A and metachromatic leucodystrophy, we present the results of a study of leucocyte arylsulfatase A in a population of 22 adult psychotic inpatients. The patients, clinically defined, filled the criteria of DSM III of schizophrenic disorders. All of them were treated by neuroleptics. None of these 22 patients showed a level of arylsulfatase A different from the range of 27 healthy adult controls. These results differ from those of most precedent studies of arylsulfatase A in "psychiatric populations". Some explanations of this difference are suggested. The concept of "purely psychiatric" form of adult metachromatic leucodystrophy is discussed.

[Current clinical aspects of obsessive disorders]. / Clinique et aspects actuels des troubles obsessionnels.

The clinical approach to obsessional troubles has barely evolved since the symptoms were first referenced throughout the 19th century. Recent developments in active therapeutics have led to studies on large series of patients. Thus, the various clinical and evolutive aspects, the borderline forms and associated pathologies (other anxiety troubles, depression and mental anorexy) have been delineated.

[Seasonal affective disorders, a new clinical category]. / Les troubles affectifs saisonniers, une nouvelle catégorie clinique.

Seasonal affective disorders have recently been individualized by American authors. According to these authors, this subgroup of affective diseases deserve to be regarded as a clinical category owing to its specific symptoms, its epidemiological features and its response to treatment. They are characterized by the triad: hypersomnia, hyperoxia, weight gain, associated with usual symptoms of depression. Moreover, contrary to the bipolar manic-depressive psychosis, they seem to predominate among women. Finally, phototherapy, the various protocols of which are discussed here, is said to be effective. The influence of latitude combined with the effectiveness of phototherapy has led to original pathogenic hypotheses, among which the presence of a chronobiological disorder (abnormality of the season-induced circadian rhythm), although attractive and supported by a strict clinical study, has yet to be demonstrated. Also hypothetical is the role played by melatonin: is this hormone the principal "mediator" or an epiphenomenon?

Anxiety disorders in a French general psychiatric outpatient sample. Comparison between DSM-III and DSM-IIIR criteria.

In a general psychiatric outpatient sample (n = 1271) gathered through a cross-national French survey, anxiety and somatoform syndromes were assessed according to DSM-III and DMS-III-revised criteria. Lifetime and one-month prevalence rates in this population are provided and the high level of comorbidity between the anxiety syndromes is noted. The patient symptom profiles for panic syndrome, simple attacks, agoraphobia and generalized anxiety are displayed. The conspicuous consequences of the modifications brought in by the Revision-anticipatory anxiety in panic syndrome, and restricted period criteria for generalized anxiety- are discussed, with the conclusion that more field study assessment is required before further revision.

[Tyrer's Brief Scale for Anxiety used with outpatients. First validation in the French language]. / L'échelle brève d'anxiété de Tyrer en pratique extrahospitalière. Première validation en langue française.

The brief scale for anxiety of Tyrer is a subdivision of the comprehensive psychopathological scale. We studied a serie of 105 anxious outpatients treated for chronic or reactive anxiety, without depressive or psychotic symptoms. We confirm its sensitivity to change, prove its concurrent validity in regard to the Hamilton anxiety rating scale and demonstrate that the brief scale for anxiety is a reliable instrument to assess anxiety with outpatients. Nevertheless the assessment of its internal validity raises the question of the item's selection at the time of the elaboration of the rating scales according to the scale's purpose. Indeed, must we attempt to register all the symptoms of the anxious syndrome, with the risk of including less specific items? Or must we choose the most characteristic and specific items with the risk of obtaining a more reductionist inventory, but more reliable in a "transnosographic" perspective?

[Study of the relation of gynecologic and obstetric findings and psychological disorders of pregnancy and the puerperium]. / Etude des relations entre données gynéco-obstétricales et troubles psychiques de la grossesse et du post-partum.

The relationship between gynaecological and obstetrical parameters and psychological troubles in pregnancy and after delivery are a matter of much debate. This arises partly because of different methods of studying the conditions and because of epidemiological studies that have been carried out on this subject. This longitudinal prospective study has been carried out on 211 women who were delivered in the maternity department of Louis Mourier Hospital. The figure for anxiety (in the de Bonis scale of greater than or equal to 20) was 13 to 15% at different times in the pregnancy, of depression (in the CESd scale greater than or equal to 16) was between 11 and 14.5%. 34.5% of those women who had delivered suffered from "baby blues", while 20% had symptoms of depression (CESd greater than or equal to 16 in the first week post-partum) and 6% had a quite obvious syndrome of depression (MADRS greater than or equal to 20). Finally, 18 to 24.5% of women had a major episode of depression (according to the DSM III test) in the year following delivery. As far as risk factors were concerned there was a statistically significant correlation between anxiety and depression in pregnancy and induction of labour, as well as difficulties with the third stage of labour and with an Apgar score of less than 9 in the infant. There was poor correlation between "baby blues" and gynaecological and pathological changes except where vaginal delivery was not spontaneous and where large episiotomies were carried out. On the other hand, women who had pathological labours or cesareans or a general anaesthetic for the third stage had more troubles than others in the year following delivery. Finally, women who showed signs of anxiety or depression in pregnancy or had "baby blues" after delivery were less likely to be able to breast feed their children.