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1.
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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2.
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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3.
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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4.
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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5.
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.
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6.
Metabolic outcomes of bergamot polyphenolic fraction administration in patients treated with second-generation antipsychotics: a pilot study.
Bruno, A, Pandolfo, G, Crucitti, M, Maisano, A, Zoccali, RA, Muscatello, MRA
The Journal of nutritional biochemistry. 2017;:32-35
Abstract
Second-generation antipsychotics (SGAs) are notoriously associated with a marked increase in body weight and with a wide range of metabolic adverse effects, and their chronic use is related with an increased risk for the development of metabolic syndrome (MS). Different adjunctive treatments have been proposed to reduce SGAs-induced weight gain and/or metabolic abnormalities with inconsistent or too limited evidence to support their regular clinical use, thus suggesting the need to find new possible treatments. Bergamot polyphenolic fraction (BPF) has been proven effective in patients with MS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to explore the efficacy and safety of BPF treatment on metabolic parameters in a sample of subjects receiving atypical antipsychotics. Fifteen outpatients treated with SGAs assumed BPF at the oral daily dose of 1000 mg/day for 30 days. Fasting levels of glucose, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides were determined. BPF administration resulted in a statistically significant reduction of body weight (P=.004) and in a trend for body mass index decrease (P=.005). No significant differences in other and metabolic parameters were observed. Our findings suggest that BPF, at the daily dose of 1000 mg for 30 days, could be an effective and safe agent to prevent weight gain associated with atypical antipsychotic use. However, further clinical trials with adequately powered and well-designed methodology are needed to better explore the BPF effectiveness on the SGAs-induced weight gain and metabolic side effects.
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7.
Risperidone and Cardiometabolic Risk in Children and Adolescents: Clinical and Instrumental Issues.
Matera, E, Margari, L, Palmieri, VO, Zagaria, G, Palumbi, R, Margari, F
Journal of clinical psychopharmacology. 2017;(3):302-309
Abstract
PURPOSE/BACKGROUND Although second-generation antipsychotics are used to treat and manage symptoms for several psychiatric disorders, data about their adverse effects in developmental age are limited. The aim of this prospective observational study was to verify the cardiovascular and metabolic risk in a sample of antipsychotic-naive children/adolescent patients starting risperidone therapy. METHODS Twenty-two patients, younger than 18 years, were recruited. The assessment included anthropometric data, cardiovascular parameters, blood tests, and ultrasonographic abdominal study. RESULTS After an average follow-up period of 7.6 months, statistically significant increases in mean values of waist circumference, body mass index (BMI), BMI percentile, BMI z score, total cholesterol, and prolactin were found. Other cardiometabolic parameters showed an upward trend in time. Subjects in pubertal/postpubertal stage and female patients were more susceptible to developing cardiometabolic changes. Moreover, significant correlations between changes in anthropometric and several metabolic parameters were found. A tendency to change in constitution of the liver parenchyma and distribution of the abdominal fat mass with ultrasonographic abdominal study was also evident. CONCLUSIONS In our sample, several metabolic parameters showed a sensitivity to risperidone treatment. Because most of these parameters are age dependent, metabolic syndrome criteria used for adults were inappropriate in children and adolescents. Periodic clinical and instrumental evaluations and guidelines for monitoring of any metabolic, laboratory, and instrumental complications are necessary in the perspective of even long-time second-generation antipsychotics treatment in children and adolescents.
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8.
Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment.
Sjo, CP, Stenstrøm, AD, Bojesen, AB, Frølich, JS, Bilenberg, N
Journal of child and adolescent psychopharmacology. 2017;(10):884-891
Abstract
OBJECTIVES Mental illness is often accompanied by poor physical health and shorter life expectancy. Second-generation antipsychotics (SGAs) are suspected of increasing cardiovascular risk, possibly through development of metabolic syndrome (MetS), and the risk of adverse outcome is even higher if obesity or metabolic aberration starts in childhood or adolescence. METHODS Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were determined through regular follow-ups. RESULTS The sample included 35 SGA-naive patients aged 7-19 (mean: 15.5) with a diagnosis of psychosis. Over 12 months, the overall rate of MetS changed significantly (from 0% to 20% [p < 0.016]). There was a significant increase in BMI (18.4% [p < 0.001]), WC (14.3% [p < 0.001]), TG (25.2% [p = 0.039]), and FBG (3.6% [p = 0.038]), whereas there was a significant decrease in HDL (-11.5% [p < 0.001]). No significant change was found for BP. Compared with the 2014 Danish references BMI-for-age charts, after 12 months the participants' BMI had increased from 0.5 to 1.57 standard deviation (SD) above the 50th percentile for age and gender (p = 0.0001). CONCLUSION To our knowledge, this is the first study to include all the aspects of MetS in a sample of drug-naive adolescents followed over the first 12 months after starting SGA treatment. A significant shift in all parameters (except BP) toward MetS was found, presumably due to SGA use. Therefore, these adolescents will need proper follow-up, consisting of not only monitoring but also preventive measures to diminish these effects of SGA use.
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9.
[The association of schizophrenia with chronic non transmissible diseases].
Orellana, G, Rodríguez, M, González, N, Durán, E
Revista medica de Chile. 2017;(8):1047-1053
Abstract
The life expectancy of patients with schizophrenia (SCH) is 11 to 20 years less than the general population. There is an association between SCH and various diseases and chronic conditions, highlighting the cardio-metabolic diseases. This association has been attributed to the use of antipsychotics, however, evidence has also shown intrinsic susceptibility of schizophrenic patients the development of chronic conditions. This review aims to update knowledge about chronic conditions such as cardiometabolic risk and sleep, bone and kidney disorders related to SCH. These patients have a high prevalence of risk behaviors, including smoking and poor diet. They have a worse metabolic profile than the general population and a greater likelihood of developing metabolic syndrome, diabetes and cardiovascular disease. SCH has also been associated with other chronic diseases such as osteoporosis and chronic kidney disease. The high prevalence of these comorbidities in schizophrenic population is not explained solely by the antipsychotic treatment, therefore intrinsic mechanisms associated to SCH are postulated to be associated with these conditions. This new information requires a change in the multidisciplinary medical approach for the study and management of schizophrenic patients.
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10.
Psychotic and Bipolar Disorders: Antipsychotic Drugs.
Holder, SD, Edmunds, AL, Morgan, S
FP essentials. 2017;:23-29
Abstract
Antipsychotic drugs block dopamine receptors and are used to manage psychosis as well as other mental illnesses that may or may not have psychotic features, such as bipolar disorders and major depressive disorder. First-generation antipsychotic drugs are more likely to cause adverse effects such as extrapyramidal symptoms and tardive dyskinesia. Adverse effects of second-generation antipsychotic drugs typically are related to metabolic abnormalities such as weight gain, abnormal blood glucose levels, and elevated lipid levels. Neuroleptic malignant syndrome is a rare but serious adverse effect of antipsychotic drugs that causes mental status changes, hyperthermia, and generalized rigidity. Timely diagnosis is essential due to a high risk of related morbidities if the syndrome remains untreated. Some adverse effects of antipsychotics can be identified and managed so that patients can continue beneficial therapy while minimizing the physiologic consequences. Patients taking antipsychotic drugs should be monitored regularly for adverse effects. Antipsychotics are also associated with potential drug interactions, the most lethal being prolongation of the QT interval, which can lead to fatal arrhythmias. Antipsychotic drugs can be used in special populations, such as pregnant women, children, and elderly patients, per recommendation from a mental health subspecialist.