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Confirmations, advances and recommendations for the daily care of schizophrenia based on the French national FACE-SZ cohort.
Fond, G, Godin, O, Schürhoff, F, Berna, F, André, M, Aouizerate, B, Capdevielle, D, Chereau, I, D' Amato, T, Dubertret, C, et al
Progress in neuro-psychopharmacology & biological psychiatry. 2020;:109927
Abstract
BACKGROUND The National FondaMental Centers of Expertise (FACE) for Schizophrenia (SZ) have been created to shorten the gap between research and clinical practice. OBJECTIVES To synthetize in a review the 10-year findings issued from the FACE-SZ cohort analyses. METHODS More than 1000 patients were evaluated in 10 expert centers since 2010 with a 2-day long comprehensive standardized battery including neuropsychological testes and physical health assessment and followed-up for 3 years. RESULTS 1. The phase 0 cross-sectional analyses have confirmed well-known data: over-prescription of first-generation antipsychotics, antipsychotic polytherapy and long-term benzodiazepine and under-prescription of clozapine, 13% of drug-induced parkinsonism, 18% of akathisia, a mean duration of untreated psychosis of 18 months, one third of poorly-adherent patients, 24% of metabolic syndrome and 52% of current tobacco smokers with poor care for physical illnesses; a yearly mean financial cost of 15,000 euro/patient. 2. FACE-SZ also yielded additional data in insufficiently explored area: a half of major depression issues (among them one third of undiagnosed major depression and 44% of treated patients with unremitted depression), major depression having a strong impact on Quality of Life independently of negative symptoms, 22% of moderated to severe untreated physical pain. 3. FACE-SZ has explored emerging fields of research, including development of 4 stages- model of schizophrenia, chronic low-grade peripheral inflammation, latent Toxoplasma infection, hypovitaminosis D, and a model for relapse prediction at 2 years. DISCUSSION The associated factors and implications for public health programs were discussed. Based on the FACE-SZ findings and literature, the FACE-SZ group has yielded recommendations to improve daily care for schizophrenia and for future research.
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Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics.
Cernea, S, Dima, L, Correll, CU, Manu, P
Drugs. 2020;(17):1763-1781
Abstract
Fasting hyperglycemia, impaired glucose tolerance, prediabetes, and diabetes are frequently present in patients treated with second-generation antipsychotics (SGAPs) for schizophrenia, bipolar disorder, and other severe mental illnesses. These drugs are known to produce weight gain, which may lead to insulin resistance, glucose intolerance, and metabolic syndrome, which constitute important risk factors for the emergence of diabetes. The aim of this review was to formulate therapeutic guidelines for the management of diabetes in patients treated with SGAPs, based on the association between SGAP-induced weight gain and glucose dysregulation. A systematic search in PubMed from inception to March 2020 for randomized controlled trials (RCTs) of diabetes or prediabetes in patients treated with SGAPs was performed. PubMed was also searched for the most recent clinical practice guidelines of interventions for co-morbid conditions associated with diabetes mellitus (DM) (arterial hypertension and dyslipidemia), lifestyle interventions and switching from high metabolic liability SGAPs to safer SGAPs. The search identified 14 RCTs in patients treated with SGAPs. Drug therapy using metformin as first-line therapy and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or perhaps sodium-glucose cotransporter-2 (SGLT2) inhibitors as add-on therapy, might be preferred in these patients as well, as they favorably influence glucose metabolism and body mass index, and provide cardio-renal benefits in general to the DM population, although for the SGLT-2 inhibitors there are no RCTs in this specific patient category so far. Metformin is also useful for treatment of prediabetes. Arterial hypertension should be treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and statins should be used for correction of dyslipidemia. The outcome of lifestyle-changing interventions has been disappointing. Switching from clozapine, olanzapine, or quetiapine to lower cardiometabolic-risk SGAPs, like aripiprazole, brexpiprazole, cariprazine, lurasidone, or ziprasidone, has been recommended.
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Meta-analysis of ghrelin alterations in schizophrenia: Effects of olanzapine.
Goetz, RL, Miller, BJ
Schizophrenia research. 2019;:21-26
Abstract
OBJECTIVE Schizophrenia is associated with an increased prevalence of the metabolic syndrome. Patients receiving antipsychotic medications, including olanzapine, are at further risk. Ghrelin is an appetite-stimulating peptide hormone, although whether blood levels are altered by antipsychotic treatment, remains unclear. We performed a systematic review and meta-analysis comparing blood ghrelin levels in patients with schizophrenia before and after treatment with olanzapine. METHOD Two authors independently searched major electronic databases from inception until February 2018 for studies measuring blood ghrelin levels among patients with schizophrenia before and after olanzapine therapy. Random effects meta-analysis calculating standardized mean difference (SMD) and 95% confidence intervals (CI) and meta-regression analyses were performed. RESULTS Six studies met the inclusion criteria. Across these studies, there were 111 patients with schizophrenia (mean age 40, 85% male, baseline BMI 22, and endpoint BMI 23). Olanzapine treatment (mean [standard deviation] duration = 12.3 [7.6] weeks) was associated with a significant decrease in blood ghrelin levels with a medium effect size (SMD = -0.48, 95% CI -0.88 to -0.08, p = 0.018). Age, sex, baseline BMI, geography, olanzapine dose and duration, year of publication, study quality, inpatient status, and antipsychotic washout did not moderate this association. CONCLUSION Our results suggest that in patients with schizophrenia, olanzapine therapy is associated with decreased blood ghrelin levels, a paradoxical phenomenon known to occur in obesity. Future studies should investigate the contribution of dietary factors (e.g., caloric intake) and physical activity to this association, as well as the effects of other antipsychotics on ghrelin levels.
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Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial.
Lin, CH, Lin, CH, Chang, YC, Huang, YJ, Chen, PW, Yang, HT, Lane, HY
Biological psychiatry. 2018;(6):422-432
Abstract
BACKGROUND Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. This study aimed to examine the efficacy and safety of a D-amino acid oxidase inhibitor, sodium benzoate, for schizophrenia patients who had poor response to clozapine. METHODS We conducted a randomized, double-blind, placebo-controlled trial. Sixty schizophrenia inpatients that had been stabilized with clozapine were allocated into three groups for 6 weeks' add-on treatment of 1 g/day sodium benzoate, 2 g/day sodium benzoate, or placebo. The primary outcome measures were Positive and Negative Syndrome Scale (PANSS) total score, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, and Global Assessment of Functioning. Side effects and cognitive functions were also measured. RESULTS Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms. The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score, PANSS-positive score, and Quality of Life Scale. Sodium benzoate was well tolerated without evident side effects. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS-total score and PANSS-positive score in the sodium benzoate group. CONCLUSIONS Sodium benzoate adjuvant therapy improved symptomatology of patients with clozapine-resistant schizophrenia. Further studies are warranted to elucidate the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia.
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Exercise, diet and educational interventions for metabolic syndrome in persons with schizophrenia: A systematic review.
Gurusamy, J, Gandhi, S, Damodharan, D, Ganesan, V, Palaniappan, M
Asian journal of psychiatry. 2018;:73-85
Abstract
INTRODUCTION Individuals with major psychotic disorders such as schizophrenia are at increased risk for developing metabolic syndrome due to lifestyle- and treatment-related factors. Numerous interventions have been tested in inpatient and outpatient mental health settings to decrease risk factors. Diet and exercise represent the mainstay of weight loss treatment. With this background the review aimed to evaluate the effects of psychoeducation, diet and physical activity interventions on reduction of metabolic syndrome risk factors such as BMI, Body weight, biochemical profiles in schizophrenia. METHODS The authors conducted database searches of PsychINFO, MEDLINE, Pubmed, Proquest, EBSCO and the Cochrane Database of Systematic Reviews, and manual searches from 1968 to 2017. Search indentified 11 studies that met the inclusion criteria. Study quality was critically appraised by 2 reviewers using established criteria. The outcome measures were body mass index, body weight, waist circumference, lipid profile, fasting glucose. RESULTS Interventions led to significant weight reduction (8 studies), reduced body mass index (5 studies), decreased waist circumference (4 studies) and lower blood glucose levels (5 studies). Dietician and nurse led interventions (6 studies). The studies showed non pharmacological interventions were effective in reducing risk factors. CONCLUSION This review was able to demonstrate effectiveness of peychoeducation, diet and physical activity interventions were helpful to decrease and manage antipsychotic-induced weight gain. Results showed lifestyle interventions are safer and effective for promoting decrease or maintenance of weight and it can be delivered at low cost, safe and improves quality of life.