O. Blanc

The influence of therapeutic alliance and insight on medication adherence in schizophrenia

Background: Poor adherence is one of the leading problems affecting the effectiveness of treatment in schizophrenia. It is an identified factor for relapse and hospitalizations with major social and economic consequences. Various determinants of poor adherence have been identified but few studies investigate the role of therapeutic alliance on medication adherence in routine mental healthcare. Aims: To investigate links between therapeutic alliance insight and medication adherence in routine care and community psychiatry. Methods: In this cross-sectional study, 38 inpatients that met ICD-10 criteria for schizophrenia or schizoaffective disorder were recruited and independently interviewed just before discharge. Various rating scales were used: the self-reported 4-Point ordinal Alliance Scale (4PAS), the Medication Adherence Rating Scale (MARS) and the Scale to assess Unawareness of Mental Disorder (SUMD). In addition, we investigated the relationships between medication adherence and clinical variables through uni- and multivariate analysis. Results: Therapeutic alliance was significantly correlated with adherence (r = 0.663, P < 0.0001) and insight (r =−0.664, P < 0.0001). Poor adherence was associated in patients with substance or alcohol use disorders (5.4 vs. 2.9, P = 0.0075, t = 2.83). No significant difference was found between the demographic characteristics of the sample, the characteristics of the treatments and adherence. Conclusions: A weak therapeutic alliance and low insight are associated with poor adherence in patients with schizophrenia or schizoaffective disorder who were hospitalized. Specific psycho-educational programs to improve therapeutic alliance and insight should be implemented to achieve better therapeutic adherence and outcome.

Hypersexuality and pathological gambling in Parkinson's disease: A cross-sectional case–control study†‡§

Substance and behavioral addictions have already been described separately or in combination in Parkinsons disease. However, no comparisons of the prevalence of addictive behaviors in patients with Parkinsons disease and the general population have been published. The objective of this study was to compare the prevalence and characteristics of addictions (gambling, hypersexuality, tobacco, and alcohol) in patients with Parkinsons disease and in a matched, paired sample from the general population.

Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: Results from the FACE-SZ cohort

OBJECTIVE Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. METHOD 240 SZ patients (age=31.4years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360μmol/L. RESULTS MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR=5.9, IC95 [1.7-21.4]) and in subjects with high waist circumference (OR=3.1, IC95 [1.1-8.3]) or hypertriglyceridemia (OR=4.9, IC95 [1.9-13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. CONCLUSIONS The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

Clinicians' Attitudes Toward the Use of Long-Acting Injectable Antipsychotics

Abstract Depot formulations are not widely used in everyday practice. This study aimed to assess psychiatrists’ attitudes toward the use of long-acting injectable (LAI) antipsychotics in schizophrenia. We interviewed 113 French psychiatrists about the factors that influenced their prescription of LAI antipsychotics. Multidimensional and cluster analyses were used to detect correlations. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk for extrapyramidal symptoms; and for second-generation LAI, it is the unavailability of the equivalent oral formulation. Four factors incite the psychiatrists to prescribe LAI. Two different clusters of patients can also be identified. Most factors influencing the clinicians’ attitudes toward the use of LAI antipsychotics are shared in many countries. Conversely, some attitudes related to organizational aspects, particularly the relevance of health care costs, may vary from one country to another.

CAGE, RAPS4, RAPS4-QF and AUDIT Screening Tests for Men and Women Admitted for Acute Alcohol Intoxication to an Emergency Department: Are Standard Thresholds Appropriate?

AIMS A number of screening instruments are routinely used in Emergency Department (ED) situations to identify alcohol-use disorders (AUD). We wished to study the psychometric features, particularly concerning optimal thresholds scores (TSs), of four assessment scales frequently used to screen for abuse and/or dependence, the cut-down annoyed guilty eye-opener (CAGE), Rapid Alcohol Problem Screen 4 (RAPS4), RAPS4-quantity-frequency and AUD Identification Test (AUDIT) questionnaires, particularly in the sub-group of people admitted for acute alcohol intoxication (AAI). METHODS All included patients [AAI admitted to ED (blood alcohol level ≥0.8 g/l)] were assessed by the four scales, and with a gold standard (alcohol dependence/abuse section of the Mini International Neuropsychiatric Interview), to determine AUD status. To investigate the TSs of the scales, we used Youdens index, efficiency, receiver operating characteristic (ROC) curve techniques and quality ROC curve technique for optimized TS (indices of quality). RESULTS A total of 164 persons (122 males, 42 females) were included in the study. Nineteen (11.60%) were identified as alcohol abusers alone and 128 (78.1%) as alcohol dependents (DSM-IV). Results suggest a statistically significant difference between men and women (P < 0.05) in performance of the screening tests RAPS4 (≥1) and CAGE (≥2) for detecting abuse. Also, in this population, we show an increase in TSs of RAPS4 (≥2) and CAGE (≥3) for detecting dependence compared with those typically accepted in non-intoxicated individuals. The AUDIT test demonstrates good performance for detecting alcohol abuse and/or alcohol-dependent patients (≥7 for women and ≥12 for men) and for distinguishing alcohol dependence (≥11 for women and ≥14 for men) from other conditions. CONCLUSION Our study underscores for the first time the need to adapt, taking into account gender, the thresholds of tests typically used for detection of abuse and dependence in this population.

Pharmacogenetic of response efficacy to antipsychotics in schizophrenia: pharmacodynamic aspects. Review and implications for clinical research

Pharmacogenetics constitutes a new and growing therapeutic approach in the identification of the predictive factors of the response to antipsychotic treatment. This review aims to summarize recent finding into pharmacodynamic approach of pharmacogenetics of antipsychotics and particularly second generation. Studies were identified in the MEDLINE database from 1993 to July 2008 by combining the following Medical Subject Heading search terms: genetic, polymorphism, single nucleotide polymorphism, pharmacogenetics, antipsychotics, and response to treatment as well as individual antipsychotics names. Only pharmacodynamics studies were analyzed and we focused on efficacy studies. We also reviewed the references of ll identified articles. Most studies follow a polymorphism‐by‐polymorphism approach, and concern polymorphisms of genes coding for dopamine and serotonin receptors. Haplotypic approach has been considered in some studies. Few have studied the combinations of polymorphisms of several genes as a predictive factor of the response to antipsychotics. We present this gene‐by‐gene approach while detailing the features of the polymorphisms being studied (functionality, linkage disequilibrium) and the features of the studies (studied treatment(s), prospective/retrospective study, pharmacological dosage). We discuss the heterogeneity of the results and their potential clinical implications and extract methodological suggestions for the future concerning phenotype characterization, genotypes variants studied and methodological and statistical approach.

Optimizing treatment of schizophrenia to minimize relapse

One of the most important predictors of relapse in schizophrenia is medication status. Continuous prophylactic antipsychotic treatment reduces the risk of relapse by approximately 70% [1]. Therefore, on one hand, relapse may be caused by discontinuation of antipsychotic medication and there is a real need to optimize patients’ adherence in clinical practice. On the other hand, relapse may be related to a lack of efficacy of antipsychotic treatment that can be improved. However, we must keep in mind that there is no consensual operational criteria for defining ‘relapse’ and that there can be a bias when comparing the different long-term studies evaluating efficacy of antipsychotics. In this editorial we will highlight the factors contributing to partial compliance and propose strategies that could help to improve adherence to treatment and also how to improve the effectiveness of treatment in schizophrenic patients.

A double amino-acid change in the HLA-A peptide-binding groove is associated with response to psychotropic treatment in patients with schizophrenia

The choice of an efficient psychotropic treatment for patients with schizophrenia is a key issue to improve prognosis and quality of life and to decrease the related burden and costs. As for other complex disorders, response to drugs in schizophrenia is highly heterogeneous and the underlying molecular mechanisms of this diversity are still poorly understood. In a carefully followed-up cohort of schizophrenic patients prospectively treated with risperidone or olanzapine, we used a specially designed single-nucleotide polymorphism (SNP) array to perform a large-scale genomic analysis and identify genetic variants associated with response to psychotropic drugs. We found significant associations between response to treatment defined by the reduction in psychotic symptomatology 42 days after the beginning of treatment and SNPs located in the chromosome 6, which houses the human leukocyte antigen (HLA). After imputation of the conventional HLA class I and class II alleles, as well as the amino-acid variants, we observed a striking association between a better response to treatment and a double amino-acid variant at positions 62 and 66 of the peptide-binding groove of the HLA-A molecule. These results support the current notion that schizophrenia may have immune-inflammatory underpinnings and may contribute to pave the way for personalized treatments in schizophrenia.

Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Clinical predictors of response to olanzapine or risperidone during acute episode of schizophrenia

The study attempted to identify clinical variables which could predict the response to a second-generation antipsychotic treatment during acute episodes among schizophrenic patients. Socio-demographic, premorbid and clinical variables were studied in a population of 95 diagnosed with schizophrenia, as defined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSMIV), during an acute treated phase, in a multicentre prospective study. Patients were assigned to olanzapine or risperidone treatment in an open design. Clinical evaluations were performed at D0, D42 and D180. Good response to treatment was defined as a Positive and Negative Syndrome Scale (PANSS) reduction greater than 20% and a Brief Psychiatric Rating Scale (BPRS) score lower than 35. Univariate analysis revealed earlier age at onset of schizophrenia and earlier age at first prescription of antipsychotic among non-responders compared with good responders at D42. Non-responders also had a clinical profile at the onset of antipsychotic treatment characterised by more severe forms of the acute episode as shown by higher scores at the positive, general and overall PANSS scale and on CGI-S and BPRS scores. With a multivariate logistic regression model, age at onset and overall duration of illness remained the only clinical criteria identified as predictors of response to antipsychotic treatment at D42. Clinical variables do not clearly appear to be good predictors of treatment efficacy.