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Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.

Background: Neurological soft signs (NSS) and minor physical anomalies (MPA) are frequent in patients with schizophrenia and their biological relatives. We examined whether the NSS and MPA are related to the genetic loading in schizophrenia., Methods: Patients with schizophrenia (DSM-IV) (n=61), nonpsychotic parents of these patients (n=76) and healthy comparison subjects (n=44) took part in the study. Parents were further classified as "presumed carriers" of the genetic loading (n=26) if they had a second relative with schizophrenia in their ascendants and/or collaterals (first or second degree) or as "presumed noncarriers" (n=50). NSS and MPA were compared in these groups., Results: A multivariate analysis indicated that total NSS and MPA scores, adjusted for age and gender, were significantly related to group status. Univariate tests showed higher scores in motor coordination and integration subscores (p=0.005 and 0.008, respectively) in presumed carriers than in presumed noncarriers. In addition, a discriminant function analysis based on total NSS and MPA scores correctly classified 71% of nonpsychotic parents in presumed carriers or presumed noncarriers., Conclusions: Neurological impairments and slight morphological anomalies seem to be associated with the genetic risk for schizophrenia, even when the disease itself is absent. Their presence might be a valuable composite intermediate phenotype for genetic studies.

The frequency of minor physical anomalies (MPAs) in patients with schizophrenia suggests an early disturbance in the development of the neuroectoderm. To improve the phenotypic delimitation of this disorder, we used a comprehensive scale of MPAs (41 items) in patients with schizophrenia and their first-degree relatives. This scale, adapted from a revised version of the Waldrop Scale (Ismail et al. Minor physical anomalies in schizophrenic patients and their siblings, American Journal of Psychiatry 155, 1998a, 1695-1702), introduced new items assessing facial and limbs asymmetry. The interrater reliability between two examiners was good: intraclass correlation coefficient: 0.68 (0.42-0.92). Patients with schizophrenia (n=40; mean=5.8, S.D.=4) and their non-psychotic parents (n=45; mean=4.7, S.D.=2.8) had significantly more MPAs than healthy comparison subjects (n=42; mean=2.2, S.D.=1.2). A logistical regression model showed the ability of several items to predict group status, including facial asymmetry, cleft palate, hair whorls and abnormal palmar crease. The high prevalence of facial asymmetry in patients with schizophrenia and their first-degree relatives provides new insights into the underlying dysembryogenic processes. This revised scale thus appears to be a useful complementary tool in pathophysiological studies aiming at the identification of developmental factors in schizophrenia.

Alzheimer's disease has definitively emerged from its ghetto and has been identified as a (priority) public health concern in view of the increasing age of the population. Considerable advances have been made in this disease over the last 15 Years, with progress in the following fields: knowledge of the underlying aetiopathogenetic, genetic and biochemical mechanisms; semiological, clinical and paraclinical approaches; creation of early diagnostic centres and multidisciplinary care networks; therapy available to patients or currently under development. The four existing acetylcholinesterase inhibitors having confirmed symptomatic action in patients with mild to moderate Alzheimer's disease have now been joined by memantine (Ebixa), a non-competitive agonist of N-methyl-D-aspartate (NMDA) receptors. One pathogenic mechanism of Alzheimer's disease appears to be hyperactivity of the glutaminergic neurons. Various preclinical studies have shown that memantine (Ebixa) inhibits glutaminergic hyperactivity in Alzheimer's disease through modulation of NMDA receptors. Since the early 1990s, several controlled clinical trials in patients with moderate to severe Alzheimer's disease (3

Depression is one of the most common health disorders in elderly people. It is still often considered as a natural consequence of aging, arising in reaction to a medical disease, cognitive or functional decline, or a loss of social fabric. Many studies have highlighted the low rates of diagnosis and treatment of depression, especially in the primary care setting. Major depression in old age is characterized by the same core symptoms as in other periods of life. However, aging may accentuate some symptoms and alleviate others. Somatic concern, marked anxiety, poor subjective memory, psychotic ideation, and recurrent thoughts of death can mask sadness and anhedonia. Organic factors and adverse life events are often intricately linked with the pathogenesis of depressive states in the elderly. The role of cerebrovascular lesions has also been established, particularly in late-onset depressive disorders. The management of depressive disorders in older people, as in younger adults, involves pharmacological and psychological treatments. Electroconvulsive therapy can be beneficial in some cases. Transcranial magnetic stimulation is being evaluated in this setting.

Background: The therapeutic efficacy of adding lithium to an ongoing antidepressant in resistant depression is well known. However there is less data concerning the efficacy of giving lithium and antidepressant concurrently from the start of treatment., Methodology: The primary objective of this study was to compare the efficacy of a combination of clomipramine+lithium (C+L) with that of clomipramine+placebo (C+P) in-patients with unipolar major depression, during the first 11 days of treatment. Secondary objectives were the assessment of effectiveness after 6 weeks and assessment of the safety of the combination clomipramine and lithium carbonate. C+L and C+P groups were compared for 6 weeks in a multicenter randomized trial of 141 patients hospitalized with a DSM-IV diagnosis of major depression. Efficacy was evaluated using the standard MADRS and CGI scales., Results: Analysis of the 'as treatment ITT' population showed: the percentage reduction in MADRS scores between D0 and D11 in this population was better in the C+L group but not statistically significant (C+L: 32.1 vs. C+P: 27.4, P=0.07). Nevertheless, the comparison of mean MADRS scores showed a significant difference in the C+L group on days 4 (C+L: 25.1 vs. C+P: 27.8) and 7 (C+L: 18.6 vs. C+P: 21.5), P<0.05, and approaching significance on day 11 (C+L: 14.6 vs. C+P 17.2, P=0.054). On day 7, the number of patients in total remission was threefold higher in the C+L group than in the C+P group (15 vs. 4%, P<0.05) and twofold on day 11 (29 vs. 14%, P<0.05). CGI severity score showed C+L was superior to C+P on days 4, 7 and 11 and CGI improvement score was better in C+L group on day 11 (P<0.05). After 6 weeks of treatment no statistical difference was found between the two groups from the clinical point of view. Safety based upon clinical and laboratory parameters was satisfactory in both groups during the 6 weeks of the study., Limitations: Patients with bipolar disorder, previously treated with clomipramine or with any other mood stabilizers during the previous week; or with suicide attempt during the current episode with a score > or =3 for item 10 of the MADRS were excluded from the study., Conclusion: The results of this study suggests that lithium slightly to moderately potentiates antidepressant treatment in unipolar non-refractory patients with severe major depression in the first days of treatment but not as significantly as for the bipolar population.

Rationale and Method: Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D-7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score < 15 or decrease > or = 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology., Results: Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p < 0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 +/- 3.5 to 14.8 +/- 6.4 in the 5 mg group vs a decrease from 31.6 +/- 4.7 to 18.6 +/- 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatments a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties in falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse events in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups., Conclusion: Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a dose at least as effective and slightly better tolerated than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

Unlabelled: The high prevalence of psychoactive substance abuse or dependence among schizophrenic patients has now been well established. Mueser et al. stressed the need to assess the abuse of specific classes of substances and analyse the data accordingly. The objective of this study was to compare the socio-demographic correlates and the clinical features in a group of schizophrenic patients with a lifetime cannabis abuse or dependence according to the DSM III-R with a group of schizophrenic patients who had never presented any abuse or dependence., Subjects and Methods: The study included 124 subjects with diagnoses of schizophrenia or schizoaffective disorders according to the DSM III-R. Inclusion criteria for participation in the study were age 18 years or older and willingness to provide consent to participate in the study. The inpatients were evaluated when their condition was stabilised. Assessment tools were the psychoactive substance use disorder section of the Composite International Diagnostic Interview (CIDI), the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning Scale (GAF). Subjects with cannabis abuse or dependence during their lifetime were compared with subjects without abuse or dependence, using chi(2) test for categorical variables and analyses of covariance (ANCOVA) for quantitative variables., Results: Forty-nine subjects (42,6%) presented lifetime abuse or dependence on one or more substances. Since 19 patients with alcohol, stimulant, sedative or opiate abuse or dependence were excluded, the study finally included 96 subjects including a first group of schizophrenic patients with cannabis abuse (n=6) or dependence (n=24) and a second group without any psychoactive substance abuse (n=66). Thirteen (11.3%) patients presented cannabis abuse or dependence within the 6 months prior to the assessment. The mean SD age of onset of cannabis abuse or dependence was 19.6 +/- 3.0 years. Cannabis abuse/dependence preceded the first psychiatric treatment in 70% of the subjects (n=21). 83.3% of the schizophrenic patients with cannabis abuse or dependence were male (n=25) compared to 62.1% in the group without substance abuse (n=41) (chi(2)=4.32, df=1, p=0.04). Schizophrenic patients with cannabis abuse were significantly younger (mean age: 28.9 +/- 6.3 vs 37.0 +/- 12.7, ANCOVA, F=7.2, df=1,96 p=0.009). There was no significant difference between the two groups for marital status, (chi(2)=5.34, df=2, p=0.07), level of education, (chi(2)=0.93, df=2, p=0.62) professional status, (chi(2)=8.7, df=5, p=0.11), on PANSS total score (ANCOVA, F=0.42, df=1,93, p=0.52), GAF score (ANCOVA, F=0.06, df=1,92, p=0.80), mean number of hospitalizations (ANCOVA, F=3.25, df=1,85, p=0.08), mean age of first psychiatric contact (ANCOVA, F=0.74, df=1,93, p=0.39), and neuroleptic dosages (ANCOVA, F=0.03, df=1,90, p=0.87). In contrast, the total duration of hospitalization was significantly longer for the group with cannabis abuse. Patients with cannabis abuse were more likely to have an history of suicide attempts than subjects without substance abuse (chi(2)=11.52, df=1, p=0.0007)., Discussion: The prevalence rates for substance abuse and the socio-demographic characteristics of the population of our study are consistent with findings of previous studies. Male gender and age were significantly related to history of cannabis abuse or dependence. Cannabis abuse frequently preceded the onset of psychiatric treatment. However, both schizophrenia and substance abuse tend to develop gradually, with no clear demarcation for the onset of schizophrenia. The absence of any link between the scores for the subscales of the PANSS and cannabis abuse, both in our study and in some retrospective previous studies, is not suggestive of cannabis abuse as a self-medication of positive or negative symptoms of schizophrenia. Self-medication could concern other symptoms, such as cognitive deficits. In addition, the hypothesis of self-medication has especially been suggested in cocaine abuse or dependence. Some limitations to this study can be discussed. First, although the recruitment was systematic and done in a public mental health service, the patients of our study are not necessarily representative of all schizophrenic patients. Secondly, as in any retrospective study, the prevalence of lifetime substance abuse may have been under-estimated. Urinary toxicology tests may have been able to improve the sensitivity of the diagnosis of recent substance abuse, but structured interviews are more appropriate for the diagnosis of lifetime substance abuse in schizophrenic patients than urinary toxicology tests., Conclusion: The socio-demographic characteristics of cannabis abuse or dependence in schizophrenia are similar to those found in general population. Cannabis using schizophrenic patients were more likely to be younger and male than non users. The duration of hospitalization was significantly longer for the group with cannabis abuse. Prevalence of suicide attempts in schizophrenia is closely correlated to cannabis abuse.

Agomelatine (S 20098) has a unique and new pharmacological profile. It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder (DSM-IV criteria). The methodology used was a conventional double-blind design comparing three different doses of agomelatine (1, 5 and 25 mg once a day) with placebo over an 8-week treatment period. Paroxetine was used as the study validator. Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were included. On the pivotal analysis, the mean final HAM-D total score (Full Analysis Set LOCF) demonstrated agomelatine 25 mg to be statistically more effective than placebo. This was confirmed by other analyses and criteria (responders, remission, subpopulation of severely depressed patients, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression-Severity of Illness). Agomelatine 25 mg alleviated the anxiety associated with depression, as measured on Hamilton Anxiety Scale. Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to validate the study methodology and population. Agomelatine, whatever the dose, showed good acceptability with a side-effects profile close to that of placebo. In conclusion, this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose.

Rational and method - Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist -MASSA), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D -7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score<15 or decrease 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. Results - Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p<0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 3.5 to 14.8 6.4 in the 5 mg group vs a decrease from 31.6 4.7 to 18.6 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatment a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties for falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse event in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. Conclusion - Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a at least as effective and slightly better tolerated dose than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

A number of side effects occurring during IFN therapy have been described. Psychiatric side effects include cognitive, behavioural and affective changes, confusion and, less commonly, psychotic symptoms. We report the case of a 52-year-old patient who had been treated for almost three years with IFN alpha for a chronic myelogenous leukemia and who presented an acute confusional episode with delusions, following the reintroduction of IFN alpha after a therapy suspension of 2 weeks. Clinical improvement occurred quite rapidly after cessation of the IFN treatment; this evolution and the normality of the biological tests, EEG and cerebral imagery suggest a causal relationship between this treatment and the psychiatric symptoms.

Lifetime substance abuse comorbidity is frequent in schizophrenic patients, but the clinical correlates remain unclear. We have explored the chronological relations between substance abuse and course of schizophrenia, and compared several clinical characteristics and personality dimensions in 50 schizophrenic patients with or without lifetime substance abuse or dependence. Abuse occurred mainly after the first prodromal symptoms and just before the first psychotic episode. Substance-abusing patients were not different from non-substance-abusing patients on the Chapman Physical Anhedonia Scale, PANSS total score, negative subscore or depression item, CGI, treatment response and demographic variables. In contrast, substance-abusing patients had higher scores on the Barratt Impulsivity Scale (total, cognitive and non-planning scores) and had attempted suicide more often. In patients with schizophrenia, as in the general population, substance abuse or dependence appears associated with higher impulsivity and suicidality. High impulsivity could facilitate substance abuse as a maladaptive behavior in response to prodromal symptoms, precipitating the onset of a characterized psychosis.

Unlabelled: Minor Physical Anomalies represent valuable indices of disturbance in early neurodevelopment. They are frequently observed in individuals with various brain disorders, including mental retardation, autism, epilepsy, hyperactivity, foetal alcohol syndrome and schizophrenia. The high prevalence of Minor Physical Anomalies in schizophrenia provides considerable support for a neurodevelopmental model in this disorder. However, studies in large sample using standardised scale are lacking. Such studies are needed in order to confirm their actual frequency and study the clinical correlates or morphological anomalies., Objective: The aim of this study was to revise and validate a French version of a scale designed for the evaluation of Minor Physical Anomalies in adult psychiatric patients and notably in patients with schizophrenia., Methodology: The scale was revised from the Waldrop scale. The choice of items was done on the basis of frequency, reliability in the adult, reliability of rating. Some new items, related to know syndroms with comportmental symptoms were added. Both raters had previously had a short initiation to the rating of the scale. Interrater reliability between two examiners, blind with regards to the diagnosis was evaluated., Results: The interrater reliability was good, with an intraclass correlation coefficient at 0.97. Patients had significantly more minor physical anomalies than comparison subjects, and also more Minor Physical Anomalies than their parents. Fathers and mothers of these schizophrenic patients had significantly more Minor Physical Anomalies than normal comparison subjects., Conclusion: Although the evaluation of physical anomalies relies on subjective appreciation of normal vs abnormal, the revised version of minor physical anomalies scale (French version) was found to be a reliable tool, provided that a short initiation to the rating is performed. The scale differentiated schizophrenic patients from their parents, and the latter from the normal controls. A lot of questions remains unanswered concerning the neurodevelopmental hypothesis of schizophrenia. This scale appeared as a useful complementary tool to help in the determination of the developmental phenotypic status of the patients enrolled in pathophysiological studies aiming the identification of developmental factors in schizophrenia.

Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest. A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks. At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters. In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety. Copyright 1999 Elsevier Science B. V. All rights reserved.

Eye movement anomalies are more frequent in schizophrenic patients than in healthy subjects. This study deals with visually guided saccadic eye movements in seventeen schizophrenic patients [ten untreated (neuroleptic-naive or free), seven treated patients] and their correlations between symptoms presented by patients and oculomotor performances. There was no significant difference between the patients and the control group in visually guided saccades tasks. However, negative correlations between oculomotor performance and positive or disorganisation symptomatology were found. Thus, although no major oculomotor dysfunction in response to external stimulus was seen in schizophrenic patients, some symptoms were linked to oculomotor performance impairment. Thus psychiatric symptoms might share some common cerebral circuits which those involved in oculomotor tasks.

Unlabelled: Psycho-behavioural inhibition is characteristic of major depressive disorder and frequently recedes after the other depressive symptoms. This may induce an important psychosocial impairment which could be a risk factor for relapse., Methods: The aim of this eight weeks, multicentric, randomized, double blind, placebo controlled trial was to assess the efficacy and safety of sulbutiamine (Arcalion) [600 mg p.d.] on the symptoms of psycho-behavioural inhibition of inpatients with DSM III-R defined Major Depressive Episode (MDE) treated by adjusted doses of clomipramine [75 to 150 mg pd]. Moderate doses of hypnotics and anxiolytics without potential activity on the mood were authorized during the trial. The MDE was assessed with the MADRS, HAM-A and CGI scales. Patients who did not respond adequately to the antidepressant treatment were prematurely withdrawn from the trial. The three Sheehan Disability Scales (SDS), the Norris Visual Analogue Scale (VAS) and the Depressive Psychomotor Retardation Scale (ERD) were used to monitor psycho-behavioural inhibition., Results: The mean intake scores were, as expected, fairly high: MADRS (32), HAMA-A (23), CGI (5) and ERD (27). The SDS and EVA scores showed that the patients felt severely handicapped in their social, professional and family life functioning as well as in their emotional, affective, cognitive and behavioural performances. At four weeks the MADRS, HAM-A and CGI scores indicated that the global improvement of the MDE was comparable in both treatment groups. However, the scores at the EVA and SDS scales showed that the patients treated with sulbutiamine were significantly less incapacitated than the placebo group in all of the various facets (affective, cognitive, emotional, behavioural) of psycho-behavioural inhibition. Furthermore, the safety data shows that both treatment groups were comparable and in particular that sulbutiamine had not induced any inappropriate behaviour, including suicide attempts, or mania., Conclusions: Sulbutiamine has no antidepressive effect but it can hasten the resorption of psycho-behavioural inhibition occurring during major depressive disorder and thereby facilitate the rehabilitation of patients in their social, professional and family life functioning.

Though the concept of impulsiveness is controversial, there are many attempts being made to measure this dimension. In this context, only psychometric measures are widely considered valid and are routinely in use. Barratt developed the first scale that specifically measured impulsiveness. Subsequently, various refinements have improved the validity of results. We have translated, without any significant problems, the tenth validated version of this scale (BIS 10) into French, and we have completed a factorial analysis. The scale was coupled with a self-administered questionnaire designed to assess anxiety. A sample of 280 subjects between the ages of 18 and 79 years (average age, 36.9) were recruited from the general population. Subject age was found to have a weak but nevertheless significant correlation with the impulsiveness rating. A principal component analysis (PCA) resulted in the first 9 factors explaining 55.6% of the variance. Another PCA of these factors allowed the identification of a second tier of 3 second order factors; these were closely related to Barratt's ranking. Our study confirms results from the scale's initial analysis--results which could not be subsequently reproduced. To our knowledge, this is the first French translation of an instrument that specifically measures impulsiveness and the first in which a factorial structure has been tested in the general population.

A role of histaminergic neuronal systems in schizophrenia was suggested by an association with several polymorphisms located in the coding region of the histamine H2-receptor (H2R) gene (Orange et al, Mol Psychiatry 1996; 1: 466-469). Using either the reference method of direct sequencing or restriction endonuclease digestion of PCR products amplified from DNA, we could not confirm the existence of these polymorphisms in 53 Swedish controls, 52 French controls and 88 French schizophrenics. In contrast, we detected a G543A transition in the coding region of the gene that was not found in the British population. This allelic variation, which was observed in 15% of the controls with no homozygotes, did not change the amino acid sequence of the receptor. We also analyzed a 1.8-kb nucleotide sequence of the promoter region in which we detected two additional polymorphisms that may modulate the expression of the H2R gene. The first one was a A-592G transition located in the minimal promoter of the gene and found in;10% of controls with no homozygotes. The second one was a G-1018A transition located in an enhancer element of the promoter and was found in;20-30% of controls (with;2-4% homozygotes). DNA analysis of the 88 French schizophrenic subjects revealed that the incidence of the three polymorphisms was not significantly different in this population. In conclusion, the present findings may suggest a surprisingly high variability of the H2R gene polymorphisms in different geographical areas but do not support an association of these allelic variations with schizophrenia.

Background: Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest., Methods: A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks., Results: At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters., Conclusions: In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety.

Clinical symptoms of bipolar disorders onset act as a prognostic risk-factor. Discrepancies of data are related with geographical or cultural conditions. Within a patient population of bipolar (ICD 10) in and out patients of a psychiatric department, manic or hypomanic disorders initiate the space disease in 33% of the cases theses features are similar within the western psychiatric population. In a maghrebian population this proportion reaches 50%. A percentage of 65% of bipolar 1 patients was found within our sample. Sex ratio is 1 for bipolar 1, when, for bipolar 2 disorders sex-ratio was superior to 1, in favor of females. Mean age of the first episode of the disease was younger for patients with a familial history of the disease.

Medical information for the general public, patients and their families is a current Public Health priority. What information can be given to a patient suffering from schizophrenia, whose understanding and judgement capacities are supposedly affected by this mental disease? In the United States, 70% of psychiatrists inform patients of schizophrenia and diagnosis of schizophreniform disorder, while in Japan less than 30% do this. The lack of information given to the general public on the disease may contribute to reinforcing the difficulty in announcing the diagnosis. Indeed, the beliefs and attitudes of the patient, his/her family, the general population and health carers concerning the disease do not match up. However, the first two years seem to be a main issue for the subsequent evolution of the disease. No specific data on the attitude of French clinicians with respect to the announcement of the diagnosis is available. In the current legal context and in view of the advances in treatment, we have carried out a survey among French psychiatrists. It is an auto-questionnaire, transversal epidemiological, descriptive and analytical. The questionnaire was sent to a population of 12,958 psychiatrists. It comprised 48 questions: 7 referred to the socio-demographic and professional characteristics of the subjects, 22 to the attitude with respect to the announcement of the diagnosis to the patients, and the last 18 concerned the attitude with respect to the announcement of the diagnosis to the families. 1,691 questionnaires were returned by free post and analysed. The socio-demographic characteristics of the sample are close to those of French psychiatrists as a whole. The number of patients suffering from schizophrenia in the active files of the psychiatrists is 24% (+/- 21.4) on the entire sample. Approximately a third (37.8%) of psychiatrists deem it necessary to announce the schizophrenia diagnosis and approximately two thirds (69.5%) declare that they sometimes announce it. Among the patients suffering from schizophrenia in the active files of the psychiatrists who responded, approximately a third (34%) were informed of their diagnosis. The main reasons for not announcing the diagnosis are firstly the "reticence to give a diagnosis label" and secondly "the functional incapacity of the patient to understand the concept". The alternative diagnosis term most commonly used is "psychosis" (46.5%). However, 48.1% of practitioners state that the announcement of a specific diagnosis allows a better therapeutic combination. Depending on the proportion of patients suffering from schizophrenia in their active file presented in two categories (< 10% and > 10%), psychiatrists significantly most frequently announce the specific diagnosis (17.3% vs 25.3%, p < 10(-3). A statistically significant proportion of younger psychiatrists (44.4 vs 46.3, p < 10(-3) with fewer years of practice (14.1 vs 15.8), more often believe that it is necessary to announce the diagnosis. The rate of response (13.5%) for this type of survey seems high, which could indicate a high interest among psychiatrists with respect to this question. Our data showed the existence of a correlation between age, number of years in practice, type of practice and the proportion of patients suffering from schizophrenia in the active file on the one hand and the attitude of the psychiatrists with respect to the announcement of the diagnosis on the other hand. It is possible that the multi-disciplinary team work of public practice psychiatrists and the fact that they are more often confronted with schizophrenic disease facilitate the announcement of this diagnosis. In the survey population, the inability to give a diagnosis may be related to the questions of the practitioners about the capacity of the subjects to understand, the lack of precision of this diagnosis, the fear of disheartening the patients and the absence of curative treatment. The risk of suicide does not seem to be one

In an association study of the Bal I polymorphism in the dopamine D3 receptor (DRD3) gene in a French Caucasian population, global comparison of patients with schizophrenia (n = 89, DSM-III-R criteria) and controls (n = 52) led to non-significant differences. However, the homozygosity was significantly more frequent in schizophrenic patients with lifetime substance abuse comorbidity (n = 36) as compared to patients with no history of substance abuse (P = 0.010) or to controls (P = 0.047) and in neuroleptic responder patients as compared to treatment-refractory patients (n = 19; P = 0.037). The combined characteristics treatment response and lifetime substance abuse were strongly associated with homozygosity. We propose that homozygosity for the Bal I polymorphism DRD3 gene is associated with predisposition to substance abuse and/or the pharmacosensitive characteristic of schizophrenia rather than with schizophrenia itself, an hypothesis in agreement with the positive association of this polymorphism with opiate dependence (see companion article by Duaux et al) and the involvement of DRD3 in both pharmacodependence mechanisms and antipsychotic effects of neuroleptics.

Anatomical, pharmacological and human post-mortem studies suggest the dopamine D3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Bal I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zückerman scale) than controls (P = 0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P = 0.038) or controls (P = 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Bal I polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).

Behavioral modifications induced by psychotropic drugs result primarily from their pharmacological properties. According to classification of psychotropic drugs, sedative compounds contrast with psychostimulating medications. Behavioural effects of psychotropic drugs depend on dosing, subject's status (patient or healthy volunteer), acute or chronic administration, and environment. Some psychotropic compounds, particularly sedative drugs, decrease the level of mental alertness and cognitive functioning. But those deleterious effects tend to disappear during the course of a repeated administration. Some psychotropic drugs, especially benzodiazepines, induce a tolerance effect, eventually a psychic or a physiological dependence state evidenced by withdrawal reactions. Such similar dependence processes have been reported with other psychotropic drugs. Forensic problems have been attributed to some psychotropic compounds, like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism. Psychotropic drugs usually can confer a positive effect on behaviour owing to their therapeutic action by the way of improving the illness and consequently the life of patients in the cases of depression, anxiety or schizophrenia.

Several arguments are in favour of the use of antidepressant drugs in alcohol-dependent patients, especially those acting on the serotoninergic system: (1) neurochemical data indicate the interaction between alcohol and 5-HT metabolism, (2) pharmacological studies show an improvement in the behaviour of alcoholized animals treated with antidepressants, (3) depression is a frequent disease in alcoholic patients. Tianeptine has been shown to be active in the treatment of depression in patients with history of alcohol abuse or dependence. In a first double-blind study performed versus amitryptiline, depression after withdrawal was improved by tianeptine, and biological abnormalities usually related to chronic alcohol intake tended to decrease. Similar results were found in an open study carried out on 277 alcoholic patients treated for 1 year. As these patients were depressed, no definite conclusion could be drawn from these results in respect of a specific action of tianeptine on alcohol dependence. Thus, a multicentre double-blind study has been performed which compared tianeptine (12.5 mg t.i.d) and placebo in 342 non-depressed patients fulfilling DSM-III-R criteria for Psychoactive Substance Dependence (alcohol). Other inclusion criteria were: daily alcohol intake higher than 80 g, minimum score of 3 on the Short-Mast Questionnaire, mean corpuscular volume above 98 fl and/or gamma Gt more than twice the upper limit of normal. The patients were treated for 9 months. The intention-to-treat population and the per protocol population were made up of 327 patients and 111 patients, respectively. The main efficacy criterion was the absence of alcoholic relapse (abstinence) defined by the patient's statements, the investigators clinical judgement and some biological parameters: alcohol blood levels, gamma Gt levels. Secondary criteria were the evolution of the alcohol consumption in the patients who relapsed, cumulative abstinence duration, a visual analogue scale for the evaluation of the appetence for alcohol and the clinical global impressions scale. The statistical analysis showed no difference between both groups in respect of the maintenance of abstinence (intention-to-treat and per protocol populations). In spite of the methodological problems of the studies in dependence (choice of the inclusion and efficacy criteria, especially), the preliminary results obtained with the serotoninergic antidepressants were not confirmed in the different trials performed in the maintenance of alcohol abstinence. The indication of tianeptine should be restricted to the treatment of depressive syndromes, which have a high lifetime prevalence in the alcoholic patient, and which have a noticeable role on the alcoholic relapse.

Behavioural modifications induced by psychotropic drugs results primarily from their pharmacological properties. According to classification of psychotropic drugs, sedative compounds contrast with psychostimulating medications. Behavioural effects of psychotropic drugs depend on dosing, subject's status (patient or healthy volunteer), acute or chronic administration, and environment. Some psychotropic compounds, particularly sedative drugs, decrease the level of mental alertness and cognitive functioning. But those deleterious effects tend to disappear during the course of a repeated administration. Some psychotropic drugs, especially benzodiazepines, induce a tolerance effect, eventually a psychic or a physiological dependence state evidenced by withdrawal reactions. Such similar dependence processes have been reported with other psychotropic drugs. Forensic problems have been attributed to some psychotropic compounds, like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism; Psychotropic drugs usually can confer a positive effect on behaviour owing to their therapeutic action by the way of improving the illness and consequently the life of patients in the cases of depression, anxiety or schizophrenia.

In contrast to the well known chlorpromazine-induced cholestatic hepatitis, we report the case of a schizophrenic patient who presents a cytolytic hepatitis, without any prior hepatic disease. Mr G. was first hospitalized for depressive symptomatology. A pseudo-nevrotic schizophrenia was diagnosed. Pretherapeutic clinical and biological data were normal. A treatment with chlorpromazine 400 mg/day was given. At day 8, the patient was still anxious and began to be agitated. An increase to 500 mg/day of chlorpromazine posology and an addition of haloperidol 200 mg/day was implemented. At day 10, the following clinical symptoms appeared: 38.6 degrees C fever; headache; myalgia; epigastralgia and hypocondrium pain. Biological hepatitis disturbances (ALAT, 984 U/L; ASAT, 414 U/L) and hypereosinophilia with normal white cell count were found. Clinical and biological investigations were normal. Blood-culture, A, B, C hepatitis, HIV and CMV serologies were negative. Neuroleptic treatment was discontinued. Evolution to normality of the disturbances and biological data suggested a cytolytic hepatitis. Mr G... remained treated with flupentixol without side-effects. Phenothiazine-induced cholestatis is frequent, mild, and recovers spontaneously. The biological mechanism is supposed to be immunologic. Prevalence of biological hepatic disturbances is 10 to 20% with chlorpromazine in long-term treatment. More often, symptomatology is the same; jaundice, pruritus, abdominal pain, fever. Although pharmacological data suggest for a cytotoxic activity of phenothiazines, cytolytic hepatitis is poorly described. Maximum range of transaminase blood level reported in previous studies is about 400 U/l. This level is not clearly correlated with hepatic cell lysis. Few cases of hepatic necrosis have been reported. In all cases, preexistent hepatic injuries were observed. Chlorpromazine-induced cytolytic hepatitis is uncommon and cholestatic hepatitis mild. Biological hepatic parameters investigations remain necessary during neuroleptic treatment.

The concept of addiction is now of interest in psychiatry, but is a great subject of controversies. It is now recognized that as different disorders as alcoholism, drug addiction, bulimia, kleptomania, trichotillomania, pathological gambling are to be considered as addictive states. Other pathological behaviours could be included in the addictive spectrum (i.e. suicidal behaviours, compulsive spending). The comorbidity rates of these disorder are elevated in these populations. For example, high comorbidity rates are found between kleptomania and bulimia or drug addiction and pathological gambling. Polyaddictive states are well established. For some subjects, more than one addiction is present in life-time, but not occurring in the same period. We present three patients in whom different addictive states occurred alternately. All the patients had a history of compulsive spending and kleptomania, two of them had a history of bulimia and sexual compulsion. Some clinical characteristics were common: recurrent mood disorder, depression preceeding the addictive state, no psychoactive substance disorder. In all patients, severity of depressive state decreased when addiction appeared. Depressive symptoms varied inversely to addiction severity. The hypothesis about psychopathological links between kleptomania and bulimia on one hand and mood disorders on the other hand has been known for a long time. Kleptomania as other impulsive disorders is, for some authors, understood in the meaning of a "spectrum affective disorder". For these three patients, an antidepressant effect of the behavioural addictions is suggested. In fact, the addictions appeared alternately. The possibility of common psychopathological and/or biological mechanisms for behavioural addiction is supported by these clinical observations, that could contribute to the addiction concept validity.

Objectives: Münchhausen syndrome by proxy has been well described in the case of a women producing or pretending symptoms in one of her children, leading that child to have numerous medical interventions. The case of two adults has been seldom described and the differences in the psychopathological features of the two situations are not well known., Methods: We report our observation of a Münchhausen syndrome in a married couple where the wife injected tranquilizers to her husband, inducing repeated episodes of coma. Complex interactions between the pathological personalities of the husband and wife were present. Prominent features of the wife's personality included a narcissistic deficiency, poor defenses and signs of depression., Discussion: Practioners should be aware of this peculiar pathology to avoid delayed diagnosis and its dramatic consequences. Appropriate medical, psychiatric, as well as legal measures must be taken.

In Münchhausen syndrome by proxy, a subject, usually a mother, pretends her child has a serious medical disorder. After simulating ficticious symptoms, or even producing clinical signs such as convulsions, fever, bleeding, vomiting, diarrhea or skin eruptions, the mother repeatedly takes her child to different hospitals for care. During hospitalization, the mother shows great concern for the child and is highly cooperative with the health care team. The consequences may be unwarrented, often invasive, investigations and therapy with a very high risk of morbidity and mortality. The underlying psychopathological structure is difficult to apprehend. Narcissic fragility and borderline personality are the must frequent, but passive-dependent hysteric personality or sadomasochist behavior can be found and depression is often associated. The main, if not the sole, benefit for the mother lies in the leading role she plays during the repeated hospitalizations in front of the admizing medical staff. Rare cases of adult-adult Münchhausen syndrome by proxy have also been reported. Physicians should be aware of this syndrome in order to avoid unintentional participating in this morbid scenario by performing useless invasive examinations or by prescribing dangerous medication. Psychiatric treatment and sometimes legal action are required to avoid this particular kind of child abuse.

Recent advances in knowledge about calcium's role as an intracellular regulator allow to broaden understanding of possible pathophysiologic mechanisms in affective disorders. An hypothesis emerge that bipolar illness arise from disorders in calcium-regulated functions. Given this hypothesis, some authors propose to describe the common profiles of action of the different mood-stabilizers: all the neural mechanisms that are hypothesized to explain various psychopharmacological treatments of bipolar illness involve functions that are critically controlled by calcium. Moreover, in every instance, a known action of lithium on calcium-dependent processes could account for lithium's prophylactic results. Similarities exist between the action of lithium and calcium antagonists like verapamil and nimodipine. From these considerations the hypothesis emerge that calcium antagonists could be an alternative pharmacological agent in the maintenance treatment of bipolar illness. Calcium antagonists have been found useful in this indication by a number of investigators. Given the safety and relative lack of side effects of calcium channel blocking agents, their potential efficacy in mood disorders, it is concluded that calcium antagonists may be an alternative choice in prophylactic treatment for bipolar illness, especially in patients who cannot be treated with lithium or carbamazepine. There is evidence for using verapamil at 240 to 320 mg a day, in 2 to 4 times. Some studies suggest that the association of lithium with calcium antagonist resulted more effective than lithium alone or calcium antagonist alone in the reduction of episodes of affective disorders. However, concomitant administration of a calcium channel antagonist and lithium present adverse interactions (lithium toxicity, cardiovascular accidents), probably because of synergistic toxic effects. Therefore, authors advise care in monitoring patients receiving the combination of these medications.

Depressive syndromes are very frequent in drug-addicted patients. Their study is particularly difficult on account of the toxic intake which disturbs the clinical analysis. Methadone has improved our understanding of these pathologies. In fact, methadone permits treatment of some depressive disorders typically linked to addiction, such as a motivational symptoms and depressive mood following intoxication. It brings to the fore the other mood disorders which are often associated with drug intake.

In the course of the international development of tianeptine (T), depressed patients were recruited by 18 centres from Belgium, Italy, Mexico, Portugal, Spain and Switzerland in a double-blind parallel group study versus placebo (P) and imipramine (I). Efficacy and safety of tianeptine were evaluated in 187 depressed inpatients (56% female, 44% male), who fulfilled criteria for either major depression, single episode (24.6%) or recurrent (66.8%), or depressed bipolar disorder (8.6%). After a seven-day run-in placebo pre-inclusion period, patients were treated in double-blind conditions with tianeptine (37.5 mg/d) or imipramine (150 mg/d) or placebo for 14 days, including an increasing daily dose period of three days. After the fourteenth day and until the end of the sixth week of treatment, a flexible dosage was introduced in accordance with the therapeutic efficacy and/or the potential adverse events (T: 25-50 mg/d; I: 100-200 mg/d; P; 2-4 capsules). Discontinuation of treatment occurred in 57 patients (30.5%) with more inefficacy on placebo and tianeptine (P: 16/23; T: 11/17; I: 7/17), and more side-effects on imipramine (P: 1/23; T: 1/17; I: 7/17). Final MADRS scores in intention-to-treat analysis were 22.3 +/- 1.5, 17.3 +/- 1.6 and 18.4 +/- 1.5 for placebo, tianeptine and imipramine, respectively. Statistical analysis demonstrated the antidepressive efficacy of tianeptine and imipramine versus placebo (P = 0.012 and P = 0.034, respectively), and no difference between tianeptine and imipramine. In patients treated for 42 days (n = 129) the MADRS scores dropped from 62.3% on tianeptine, 54.2% on imipramine and 48.5% on placebo. These results confirmed the efficacy of tianeptine (37.5 mg/d) in the treatment of major depression and depressed bipolar disorder when compared to placebo. No difference was found between tianeptine and imipramine (150 mg/d) for the efficacy and between tianeptine and placebo for all safety criteria. The following adverse events were significantly more frequent with imipramine than with tianeptine or placebo: dry mouth (P < 0.001), constipation (P = 0.007), and hot flushes (P = 0.011). No difference in adverse events was found between tianeptine and placebo. While the usual cardiovascular signs of tricyclic antidepressants were observed in the imipramine group, no difference between tianeptine and placebo was shown in respect to heart rate or blood pressure (supine or standing). The assessment of haematological, renal, metabolic and hepatic parameters confirmed the safety of tianeptine.

The adverse effects of electroconvulsive therapy (ECT) become rare due to the increased progress specially in avoiding cardiovascular side effects. In fact, several studies report ECT treatment performed with success and without side effects, in depressive patients presenting serious cardiovascular diseases (aortic anevrysm, cerebral venous angioma, cerebral infarct, aortic dissection...). Occurrence of cardiovascular complications can be prevented if an elevation of blood pressure or an arythmia occurring during the seizure are previously and correctly detected and managed. Hence an adequate anaesthetic premedication must be implemented. Usual protocols use atropine, hydralazine and hydro-chlorothiazide. However, ECT treatment should be avoided in patients requiring urgent surgical correction of their cardiovascular abnormalities. Also, patients and families must be informed on the benefit derived from ECT treatment and reassured on the therapeutic issue when ECT treatment is correctly managed. This case report concerns an 89 year old woman presenting a melancholic depressive state complicated with an aortic anevrysm, successfully treated with ECT.

The widespread use of antidepressants since the late 1950s and especially the ambulatory treatment of the majority of depressive patients raises the issue of the state of knowledge of the effects of these drugs on cognitive function. This review aims at synthesizing information about differential effects of antidepressants on cognitive function to facilitate good prescription. The first part of this review tries to summarize the main tasks used to explore global reactivity, attention, memory and psychomotor performances. The second part of this work presents the differential cognitive effects of antidepressants with a discrimination between substances which have a sedative impact, antidepressants with no cognitive effect, and drugs which seem to have a positive cognitive action. The differenciation is established for single and repeated administration, for healthy volunteers and depressed subjects. For each substance, the dose, the tasks selected and cognitive effect are discussed and the question of the real benefit of this cognitive impact is raised. The specificity of cognitive effects of antidepressants related to age and to the combination with alcohol are also tackled. Then the discussion raises the difficulty and the biases encountered to perform neuropsychological studies and particularly evaluation of cognitive effects of antidepressants. Finally the conclusion of this review gives some advice to select and prescribe antidepressants according to their cognitive effects.

A decreased thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) has been noted in major depression. Some authors found a positive correlation between baseline TSH levels and TSH response to TRH, especially with sensitive assays of TSH. Serum TSH was assayed by a sensitive method in 55 depressed patients and 38 healthy volunteers. Patients were subclassified according to DSM-III as suffering from major depression (n = 40) and non-major depression (n = 15). The patients' mean score on the Hamilton Rating Scale for Depression (HRSD) was 50 (SD = 10). The TSH value was significantly lower in depressed patients compared with healthy control subjects, and in major compared with non-major depression. No differences in TSH levels distinguished the various subtypes of major depression. There was a significant negative correlation between global HRSD scores and TSH concentrations. The most anxious patients tended to have significantly lower TSH values compared with the least anxious subjects. Total HRSD insomnia scores correlated negatively with TSH concentrations after log transformation. The sensitive determination of TSH may also provide an index of thyroid function in depression that is simpler to implement than measurements of the TSH response to TRH.

Because of pharmacological characteristics methadone is an interesting substitutive opiate compound. However, the most important aspect of maintenance treatment consists of the accompanying global medico-social care. Useful as a therapeutic alternative in some severe and chronic heroin addictions, methadone is useless and even dangerous in other cases. Its efficacy in preventing AIDS epidemics has not been clearly established.

The systematic and long term association of anti-parkinsonian drugs to neuroleptics is questioned by many authors because of their side effects and their toxicomanogenous risks whereas their efficiency in extrapyramidal effects of prophylaxis is not certain. This work aims at evaluating the interest of prescribing long term parkinsonian drug in association with neuroleptics. The study centered on 101 psychotic patients treated with neuroleptics, and followed on an ambulatory bases. 97% of this patients systematically received antiparkinsonian drugs. Extrapyramidal symptoms of varied intensity have noted for 61% of patients. The authors have compared, in double blind, the effects of the progressive and abrupt withdrawal of anti-parkinsonian drugs for 37 patients among the 101. These patients have been regularly treated for at least 6 months by neuroleptics (fluphenazine or pipothiazine) in association with trihexyphenidyle. They were randomly divided into 3 groups, and statified by sex and type of neuroleptic. For group I, composed of 13 patients, trihexyphenidyle is abruptly withdrawn and replaced by a placebo. For group II, composed of 11 patients, withdrawal is progressive for 2 weeks, trihexyphenidyle being replaced by a placebo. Group III, composed of 13 patients, is a sample group which went on receiving trihexyphenidyle. The results of this study showed that within the brutal withdrawal group (group I), 10 patients over 13 needed trihexyphenidyle again, whereas only 3 patients over 11 needed it in the progressive withdrawal group (group II). In the sample group (group III), one patient over 13 showed extrapyramidal symptoms, necessitating his leaving school. The global chi 2 is significant with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Distinction between relapse and recurrence is a major difficulty in studies assessing the efficacy of long term antidepressant treatment. A four to six months symptom-free period is required to talk of recovery from depression and plan a preventive treatment, i.e. prevention of recurrence. Compounds are not selected according to their biochemical profile; the most recent antidepressant drugs were studied in that indication through long term controlled trials. In unipolar patients, recent studies favour the prescription of high doses of antidepressant drugs during at least five years. In bipolar patients, combination of long term antidepressant to lithium treatment may be of benefit to patients whose index episode was of depressive type, but appears useless in other cases. In all cases, joint psychotherapy and the quality of the relationship between the patient and the prescribing physician influence compliance and outcome. Dysthymia, panic disorder and obsessive-compulsive disorder constitute other acknowledged cases for long term prescription of antidepressants. These indications remain empirical till controlled trials have not specifically assessed each antidepressant compound.

Cognitive functions are known to be impaired by ECT. The aim of this study is to differentiate the effects of electroconvulsive therapy on some cognitive functions according to the mode of application of the electrodes. The brief-pulse Thymatron DG apparatus allows to control four electrical parameters and to assess electroencephalographic data. The preliminary sample comprises nine patients suffering of major depressive disorder; they are randomly assigned to the mode of application of the electrodes, bilateral or unilateral to the non dominant hemisphere. Clinical evolution is surveyed by the Montgomery and Asbert Depression Rating Scale. Non mnesic functions are assessed: arousal by CFF (Critical Fusion Frequency), and attentional, motor and decisional abilities by CRT (Choice Reaction Test). Different mnesic function are studied by selective reminding test, cued recall test, block tapping test and picture fragmentation test. After treatment by ECT, verbal mnesic functions assessed by selective reminding test are impaired with the bilateral application. Whereas they are not modified with the unilateral application. The variance of CFF regains a physiological value in the bilateral group, but remains altered in the unilateral.

The authors present the development and the application of a structured interview guide for 4 depression scales: Hamilton Depression rating scale 17 items (HDRS-17), Montgomery-Asberg Depression rating scale (MADRS), Widlöcher Depressive Retardation Scale and also a fourth scale designed to evaluate the symptoms other than depression core symptoms (based on Depression and mania rating scale of P. Pichot). The final version of the guide was tested with 60 french depressed inpatients. This guide provides clinical information that permits the rating of the 4 scales in approximatively 45 minutes.

Since the last decade of the nineteenth century, psychiatric nosology has been dominated by Kraepelin's binary system: the notion that the distinction between manic-depressive illness and schizophrenia identifies two separate diseases with differing symptom patterns and outcomes. However, Kraepelin recognised that intermediate states, as exemplified by Kasanin's concept of "schizoaffective" illness are common. In contrast to Kraepelin's separation of manic-depressive illness from schizophrenia, the concept of a continuum of psychosis implies that there are gradations of illness between unipolar depressive, through bipolar affective and schizoaffective illness, to schizophrenia. This concept is strongly supported by the majority of family studies. Moreover, no simple clinical demarcations of affective from schizophrenic illnesses can be made. The family findings are compatible with the hypothesis that the same gene or genes contribute to susceptibility to both schizophrenia and affective disorder: a single locus that may be variable between generations, and that is represented by homologous loci on the X and Y chromosomes.

In this review the authors propose to study the impact of antidepressants on attention, memory and motor functions in healthy volunteers and depressed patients on single and long-term administration. After reviewing the principal cognitive functions, we examine the actual investigation means to conclude that the Critical Flicker Fusion Test (CFFT) is one of the most drug-sensitive tests. It permits a categorization in: sedative antidepressants that in single administration lower CFFT; compounds with no effect on CFFT and no deleterious cognitive effect; and finally substances that raise CFFT and may have psychostimulating properties. On single administration amitriptyline is the most sedative antidepressant on attention or motor level. It seems to produce negative effects on memory level. However, experimental trials give contradictory results. Imipramine in single administration also has sedative effects on memory and car driving capacity. However divergent results of experimental trials do not allow any conclusions of a clearcut negative cognitive effect. Memory impairments with imipramine appear at administration levels of 150 mg. Mianserin has a sedative impact on attention and motor level at low doses (10 mg). Among the tricyclics, nortriptyline has a highly dose dependent sedative effect that has been shown on attention tests (Time Reaction:TR, Digit Symbol Substitution Test: DSST). Among non-tricyclic compounds, doxepine lowers attention and motor performances. Maprotiline (75 mg) lowers CFFT and has a dose dependent effect. Trazodone also has a negative impact on attention tests. Finally viloxazine lowers CFFT but does not impair other attention or motor tests on a 100 mg doses. Buspirone, lofepramine, midalcipran and zimelidine are antidepressants with no effect on CFFT and do not have any positive or negative cognitive effect. On the other hand nomifensine, paroxetine and fluoxetine raise CFFT in healthy volunteers on single administration. Improvement of CFFT performances was found in an isolated manner for nomifensine and paroxetine on 30 mg doses with no other memory or motor effects. MAO-Inhibitors do not impair attention or motor function; thus moclobemide has no negative impact on memory, attention or car driving tests. Cognitive impact of antidepressants in depressive patients seems the same with those of healthy volunteers on single administration. In long-term administration antidepressants have different effects in healthy and depressed subjects. In healthy volunteers cognitive effects of most compounds are normalized after the second week of treatment. However, attention and motor performances with amitriptyline are normalized after 3 weeks of treatment. Sedative motor or cognitive effects of imipramine do not exceed 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)