Pierre Michel Llorca

Predicting suicidal risk in schizophrenic and schizoaffective patients in a prospective two-year trial

BACKGROUND Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide. METHODS This study followed 980 patients at high risk for suicide in a multicenter prospective study for 2 years after randomization to clozapine or olanzapine. A priori predictors related to diagnosis, treatment resistance, and clinical constructs of disease symptoms were evaluated as possible predictors of subsequent suicide-related events. RESULTS Ten baseline univariate predictors were identified. Historical predictors were diagnosis of schizoaffective disorder, history or current use at baseline of alcohol or substance abuse, cigarette smoking, number of lifetime suicide attempts, and the number of hospitalizations in the previous 36 months to prevent suicide. Predictive clinical features included greater baseline scores on the InterSePT scale for suicidal thinking, the Covi Anxiety Scale, the Calgary Depression Scale (CDS), and severity of Parkinsonism. Subsequent multivariate analysis revealed the number of hospitalizations in the previous 36 months, baseline CDS, severity of Parkinsons, history of substance abuse, and lifetime suicide attempts. Clozapine, in general, was more effective than olanzapine in decreasing the risk of suicidality, regardless of risk factors present. CONCLUSIONS This is the first prospective analysis of predictors of suicide risk in a large schizophrenic and schizoaffective population judged to be at high risk for suicide. Assessment of these risk factors may aid clinicians in evaluating risk for suicidal behaviors so that appropriate interventions can be made.

Psychopathological features of a patient population of targets of workplace bullying

BACKGROUND A strong association between workplace bullying and subsequent anxiety and depression, indicated by empirical research, suggests that bullying is an aetiological factor for mental health problems. AIMS To evaluate levels of stress and anxiety-depression disorder developed by targets of workplace bullying together with outcome at 12 months and to characterize this population in terms of psychopathology and sociodemographic features. METHODS Forty-eight patients (36 women and 12 men) meeting Leymann Inventory of Psychological Terror criteria for bullying were included in a prospective study. Evaluations were performed at first consultation and at 12 months using a standard clinical interview, a visual analogue scale of stress, the Hospital Anxiety and Depression (HAD) scale, the Beech scale of stress in the workplace and a projective test (Picture-Frustration Study). RESULTS At first consultation, 81% of patients showed high levels of perceived stress at work and 83 and 52% presented with anxiety or depression, respectively. At 12 months, only 19% of working patients expressed a feeling of stress at work. There was a significant change in symptoms of anxiety while there was no change in symptoms of depression. Stress at work and depression influenced significatively capacity to go back to work. At 12-month assessments, workers showed a significantly better score on the HAD scale than non-workers. Over half the targets presented a neuroticism-related predominant personality trait. CONCLUSION Workplace bullying can have severe mental health repercussions, triggering serious and persistent underlying disorders.

The InterSePT scale for suicidal thinking reliability and validity

BACKGROUND The InterSePT Scale for Suicidal Thinking (ISST) is a 12-item instrument for the assessment of current suicidal ideation in patients with schizophrenia and schizoaffective disorders. We report the psychometric characteristics of this new scale based on two studies. METHOD In Study 1, 22 inpatients with schizophrenia and schizoaffective disorders, who had recently attempted suicide or engaged in suicidal ideation, were rated by three trained independent raters to examine interrater reliability. In Study 2, a total of 980 patients with schizophrenia or schizoaffective disorder with a history of suicidal ideation in the past 36 months were enrolled in a 2-year industry-sponsored suicide prevention study. At baseline, these patients were administered the ISST and the Clinical Global Impression Scale for Severity of Suicidality (CGI-SS) by the Principal Investigator (PI) and by a blinded rater (BR), who also administered the Positive and Negative Symptom Scale (PANSS), the Calgary Depression Scale (CDS), and the Scale of Functioning (SOF). Indices of internal reliability, construct and discriminant validity were examined. RESULTS The intraclass correlation coefficient (ICC) for the total ISST score for the 22 subjects in Study 1 was 0.90 and mean weighted item kappa coefficients ranged from 0.66 to 0.92. In Study 2, internal reliability (Cronbach alpha) was high, ranging from 0.86 to 0.89 for the individual items, and the overall Cronbach alpha coefficient for all items was 0.88. The ISST (PI) total score was highly correlated with the CGI-SS by the blind rater (r = 0.61, p < 0.0001). ISST total scores significantly differentiated the different levels of CGI-SS (F = 519.2; p < 0.0001). Results of construct and discriminant validity analyses are also presented. CONCLUSION The ISST is a reliable and valid instrument for the assessment of current suicidal thinking in patients with schizophrenia and schizoaffective disorder by both clinicians and researchers.

Benzodiazépines et schizophrénie, revue de la littérature.

AIn this work, the authors have analysed the principal studies on the interest in the use of benzodiazepines in schizophrenia. The first double-controlled study concerning this question was conducted in 1961. The results of the first studies are criticisable due to the variability of the diagnostic and clinical assessment criteria, as well as to the divergences between the different conclusions. Through this review of literature, the authors wish to clarify the questions and hypothesis raised specify certain therapeutic strategies. MECHANISM OF GABA-ERGIC TREATMENTS: The analysis of the principle works on this question provides evidence on the use of benzodiazepines in schizophrenia. By fixing on their receptors, benzodiazepines facilitate GABA-ergic transmission. GABA is an inhibitor neurotransmitter. The GABA stimulation induced by benzodiazepines may be at the origin of a reduction of the pre-synaptic release of dopamine in the mesolimbic region. The GABA stimulation may also delay the post-synaptic adaptation of the dopaminergic neurons to neuroleptics. This phenomenon may enhance the activity of neuroleptics in resistant schizophrenia. Benzodiazepines would also have an effect on the mesoprefrontocortical regions where neuroleptics may be less efficient. It is interesting to note that this cerebral region is particularly sensitive to stress. This effect of benzodiazepines on the mesoprefrontocortical region might explain a preferentially beneficial effect in patients who have radiographic signs consistent with prefroncortical atrophy, although this observation remains preliminary. BENZODIAZEPINES IN MONOTHERAPY: In monotherapy their action on productive and deficient psychotic symptoms is greatly discussed and not very convincing. The main studies in the use of benzodiazepines alone ) are heterogeneous for their diagnosis criteria, their methodology and their results. The conclusions of the publications are not totally clear, and different points are to be criticized: heterogeneity of assessment criteria, heterogeneity and variability of methodology, use of non standardized scales, most of the studies are open studies, variability of benzodiazepines dose. BENZODIAZEPINES IN ASSOCIATION WITH NEUROLEPTICS: In few controlled studies, most authors have underlined ) the advantage of the association of benzodiazepines with neuroleptics. This association may act either on positive symptoms (hallucinations, delusions) or on negative symptoms. The latent period and the length of the effect of benzodiazepines in the treatment of psychotic patients remain unclear. According to certain studies, the therapeutic effect may appear in a short time, and then disappear within the fourth week. The association of benzodiazepines with neuroleptics is particularly helpful for patients with great anxiety, whether they have neuroleptic intolerance or not. There is no robust convergence about the type of benzodiazepines and their optimal dose in the treatment of schizophrenia. Their use may permit a reduction in the neuroleptic dose. They could increase the plasma concentration of neuroleptics and they might act on the mesoprefrontocortical regions where there are fewer dopaminergic auto receptors. BENZODIAZEPINES AND ANXIETY IN SCHIZOPHRENIA: States of anxiety, and in particular panic disorders that would participate in the exacerbation of psychotic symptoms, would benefit from the use of benzodiazepines. Anxiety can be considered as a major symptom of schizophrenia: insecure feelings and impressions of threatening events are frequent during schizophrenia. Interpretations or brutal hallucinations can lead to the feeling of imminent catastrophe or anxiety. Nevertheless, anxious phenomenons are under-estimated for many reasons: on the one hand, positive symptoms may hide anxiety, and on the other, the symptoms that are observed in patients treated with neuroleptics are often attributed to the neuroleptic side effects rather than linked to anxiety. Benzodiazepines and catatonia - Lorazepam has demonstrated its efficacy on catatonia. This effect seems to be specific of small doses of lorazepam (<5 mg/day). It should be compared to the effect of zolpidem in the same conditions. This prescription should be limited to acute catatonia, with no effect on chronic catatonia. Benzodiazepines and neuroleptic side effects - The use of benzodiazepines to treat some side effects of neuroleptics such as akathesia is reported by certain authors but remains little explained. They may have no effect or only small effects on tardive dyskinesia, but could reduce their incidence with the use of the smallest doses of neuroleptics in association with benzodiazepines. Safety of use - The safety of use of benzodiazepines in schizophrenia, particularly in association with neuroleptics is admitted, however recommended precautions with clozapine are to be noted. Benzodiazepine combined with clozapine clearly increases the frequency of cardiovascular and respiratory accidents. Some studies point out the risk of behavioural desinhibition and dysphoria. Their use should also be limited to patients with good compliancy, in order to avoid exacerbation of symptoms in the case of brutal interruption of the treatment. Dependency, which is an important issue in the use of benzodiazepines, seems much lesser in schizophrenia than in personality disorders and anxiety. Conversely, some studies point out the benefits of benzodiazepine use in schizophrenia, with their efficacy in the treatment and prevention of drug abuse. Finally, benzodiazepines contribute to the establishment of a good patient-doctor relationship, and may guarantee enhanced treatment compliancy.

Validation study of the Medication Adherence Rating Scale. Results from the FACE-SZ national dataset

OBJECTIVE The Medication Adherence Rating Scale (MARS) is one of the most widely used measurements of adherence in schizophrenia (SZ). However, the data available regarding its psychometric properties are scarce. The aim of this study was to provide new data regarding the psychometric properties of the MARS in a multicenter community-dwelling sample of SZ patients. METHODS This study was conducted in the French National network of the 10 FondaMental Expert Centers for SZ. The MARS was tested for construct validity, reliability, external validity and acceptability. In addition, data pertaining to sociodemographic information, clinical characteristics using the Positive and Negative Syndrome Scale (PANSS), the Scale to Assess Unawareness in Mental Disorder (SUMD), the Calgary Depression Scale for Schizophrenia (CDRS) and therapeutic adherence using the Brief Adherence Rating Scale (BARS) were collected. RESULTS Three hundred and nineteen patients were included. The 3-factor structure of the MARS was confirmed using confirmatory factor analysis: RMSEA=0.05, CFI=0.95, and WRMR=0.88. The unidimensionality of each factor was supported by the satisfactory INFIT statistics. Item internal consistencies were all higher than 0.15 and the Kuder-Richardson were close to 0.6, except for factor 2, which was close to 0.5. Significant associations with BARS, PANSS, CDRS showed satisfactory external validity. The acceptability was excellent as all patients complete the MARS, without missing values. CONCLUSION The MARS is a short self-administered instrument with acceptable psychometric properties that yields important information about adherence to pharmacological treatment. Some improvements might be considered to enhance its validity and reliability.

L'information du sujet schizophrène en pratique clinique : données actuelles

Resume En France, la conception traditionnelle du soin, ancree dans une medecine paternaliste et hermetique, fait aujourd’hui figure de vestige. Elle n’a pu resister aux courants de pensee post-modernes ayant erige en dogme la diffusion de l’information (elevee au rang du savoir) au nom de la liberte individuelle ou du bien collectif. Le medecin devient le partenaire d’un consommateur de soin qui devra, en son âme et conscience, choisir ce qui lui semble le mieux pour sa sante. Mais pour choisir, il devra etre avise – c’est-a-dire informe – par le medecin de sa pathologie, ses caracteristiques, son evolution et des risques inherents aux choix (ou non-choix) therapeutiques. Cette evolution de la relation medecin-malade vers une contractualisation de fait enterine l’emancipation de l’individu face au savoir. Ce n’est plus celui qui sait qui choisit, mais bien celui qui subit, et la maladie et son remede. La limite de cette evolution est la capacite a diffuser la connaissance (sera-t-elle clairement comprise ?) et la capacite du patient a faire un choix. Ce probleme se posera de facon accrue si le patient presente une pathologie alterant ses capacites a acceder a une information et a clairement et positivement l’utiliser. On l’aura compris, le champ de la maladie mentale, et en particulier de la schizophrenie, pose des questions particulieres face a l’evolution des courants de pensee medicaux et juridiques en ce qui concerne la relation medecin-malade, et plus specifiquement l’information, base de l’obtention du consentement aux soins. Existe-t-il une specificite de l’information des patients schizophrenes ? Quel type d’information peut-on leur delivrer ? A qui peut-on la delivrer et par quels moyens ? L’annonce du diagnostic ne risque-t-elle pas de declencher un refus de soin chez un sujet souvent ambivalent vis-a-vis de la prise en charge, ou bien peut-on, en accroissant le champ de connaissance que le patient pourrait avoir sur la maladie, esperer obtenir de sa part une participation dans le soin effective et benefique ? Nous allons dans cet article tenter de repondre a ces questions, en mettant en exergue l’evolution de la pensee vis-a-vis de cette problematique.

Mediation Analyses of Insight, Quality of Life, Depression, and Suicidality

OBJECTIVE The relationship between greater insight and increased risk of suicide in patients with schizophrenia is debated. The purpose of this study was to assess whether quality of life (QoL) and depression mediated the association between insight and suicidality. METHODS Between March 2010 and December 2015, 527 community-dwelling adults with stable schizophrenia according to DSM-IV criteria were included in a multicenter cross-sectional study, the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study. Structural equation modeling was used for mediation analyses among insight, QoL, depression, and suicidality, controlling for the global level of schizophrenic symptoms. RESULTS The model provided a good fit for the data (χ²₃ = 1.4, P = .708, Tucker-Lewis index = 1, comparative fit index = 1, root mean square error of approximation = 0, standardized root mean square residual = 0.008) and explained 27% of the variance in suicidality. Poorer QoL and greater severity of depression mediated 68.4% of the positive association between insight and suicidality (full mediation). Poorer QoL mediated 48% of the positive effect of insight on depression (partial mediation). The severity of depression mediated 91.2% of the negative relationship between QoL and suicidality (full mediation). CONCLUSIONS Insight appears to be an indirect risk factor for suicide in patients with schizophrenia, with the link being mediated by poorer QoL and worse underlying depression, mainly by a sequential pathway but also by a less important parallel pathway.