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1.
Sodium nitroprusside treatment for psychotic symptoms and cognitive deficits of schizophrenia: A randomized, double-blind, placebo-controlled trial.
Wang, X, Zhao, J, Hu, Y, Jiao, Z, Lu, Y, Ding, M, Kou, Y, Li, B, Meng, F, Zhao, H, et al
Psychiatry research. 2018;:271-277
Abstract
Schizophrenia presents with a broad range of negative, positive, and cognitive symptoms, and comprehensive treatment is still a challenge. Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms and improve cognitive functions in patients with schizophrenia, providing a new possible direction for treatment. In this study, we tested whether SNP can improve psychotic symptoms and cognitive function in schizophrenia patients with longer disease history. This was a randomized, double-blind, placebo-controlled trial conducted between May 2016 and April 2017. Forty-two schizophrenia patients aged 18-45 years were recruited from Henan Province Mental Hospital. Baseline psychiatric symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and baseline cognitive functions were measured using the Wechsler Adult Intelligence Scale. Patients received two SNP or placebo infusions (0.5 μg/kg per min for 4 h) at a one-week interval. We reassessed psychiatric symptoms and cognitive functions using the same tests shortly after the first and second infusions and 4 weeks after the second infusion. We did not find any significant effect of SNP over placebo on psychotic symptoms or cognitive functions, although SNP was relatively well tolerated with a good safety profile.
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2.
A Pilot Study of the Effectiveness of Lithium Versus Quetiapine Immediate Release Monotherapy in Patients With Bipolar Spectrum Disorders.
Gao, K, Goto, T, Yuan, C, Brownrigg, B, Conroy, C, Chan, PK, Serrano, MB, Ganocy, SJ, Fang, F, Calabrese, JR
Journal of clinical psychopharmacology. 2018;(5):422-434
Abstract
OBJECTIVE The aim of this study was to compare the effectiveness of lithium versus quetiapine immediate release (IR) monotherapy in patients with bipolar I, II, or subthreshold bipolar disorder at any phase. METHODS Eligible patients were randomized to lithium or quetiapine IR for 16 weeks. The difference in the time to discontinuation from study due to "all causes" between lithium and quetiapine IR groups and changes from baseline to 8 and 16 weeks in depression, mania, anxiety, quality of life (QOL), metabolic profiles, and proinflammatory markers were compared. RESULTS Of the 42 patients randomized to lithium (n = 18) and quetiapine IR (n = 24), the median time to discontinuation due to "all causes" was 6 weeks (95% confidence interval, 2-12 weeks) in the lithium group and 8 weeks (95% confidence interval, 6 weeks to not calculable) in the quetiapine IR group. The mean time to discontinuation due to "all causes" was 7.7 ± 1.1 weeks for lithium versus 8.4 ± 0.8 weeks for quetiapine IR (P = 0.54). There was no significant difference between lithium and quetiapine IR in changes in the severity of depression, mania/hypomania, anxiety, and QOL as a whole or only in patients with depressive index episode. The decrease in total cholesterol was significantly larger with lithium than with quetiapine IR (P = 0.05) as a whole, but not only in patients with depression index episode. There was no other significant difference in changes in metabolic panels and inflammatory markers between the 2 groups. CONCLUSIONS The difference in effectiveness between lithium and quetiapine IR monotherapy in a real-world bipolar population was minimal. Large-sample studies are needed to support or refute this finding.
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3.
QTc prolongation in short-term treatment of schizophrenia patients: effects of different antipsychotics and genetic factors.
Spellmann, I, Reinhard, MA, Veverka, D, Zill, P, Obermeier, M, Dehning, S, Schennach, R, Müller, N, Möller, HJ, Riedel, M, et al
European archives of psychiatry and clinical neuroscience. 2018;(4):383-390
Abstract
Antipsychotics are effective in treating schizophrenia but may lead to a higher cardiovascular risk due to QTc prolongation. Besides drugs, genetic and clinical factors may contribute to QTc prolongation. The aim of this study is to examine the effect of candidate genes known for QTc prolongation and their interaction with common antipsychotics. Thus, 199 patients were genotyped for nine polymorphisms in KCNQ1, KCNH2, SCN5A, LOC10537879, LOC101927066, NOS1AP and NUBPL. QTc interval duration was measured before treatment and weekly for 5 weeks while being treated with risperidone, quetiapine, olanzapine, amisulpride, aripiprazole and haloperidol in monotherapy. Antipsychotics used in this study showed a different potential to affect the QTc interval. We found no association between KCNH2, KCNQ1, LOC10537879, LOC101927066, NOS1AP and NUBPL polymorphisms and QTc duration at baseline and during antipsychotic treatment. Mixed general models showed a significant overall influence of SCN5A (H558R) on QTc duration but no significant interaction with antipsychotic treatment. Our results do not provide evidence for an involvement of candidate genes for QTc duration in the pathophysiology of QTc prolongation by antipsychotics during short-term treatment. Further association studies are needed to confirm our findings. With a better understanding of these interactions the cardiovascular risk of patients may be decreased.
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4.
Psychopharmacological Treatment in the RAISE-ETP Study: Outcomes of a Manual and Computer Decision Support System Based Intervention.
Robinson, DG, Schooler, NR, Correll, CU, John, M, Kurian, BT, Marcy, P, Miller, AL, Pipes, R, Trivedi, MH, Kane, JM
The American journal of psychiatry. 2018;(2):169-179
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Abstract
OBJECTIVE The Recovery After an Initial Schizophrenia Episode-Early Treatment Program compared NAVIGATE, a comprehensive program for first-episode psychosis, to clinician-choice community care over 2 years. Quality of life and psychotic and depressive symptom outcomes were found to be better with NAVIGATE. Compared with previous comprehensive first-episode psychosis interventions, NAVIGATE medication treatment included unique elements of detailed first-episode-specific psychotropic medication guidelines and a computerized decision support system to facilitate shared decision making regarding prescriptions. In the present study, the authors compared NAVIGATE and community care on the psychotropic medications prescribed, side effects experienced, metabolic outcomes, and scores on the Adherence Estimator scale, which assesses beliefs related to nonadherence. METHOD Prescription data were obtained monthly. At baseline and at 3, 6, 12, 18, and 24 months, participants reported whether they were experiencing any of 21 common antipsychotic side effects, vital signs were obtained, fasting blood samples were collected, and the Adherence Estimator scale was completed. RESULTS Over the 2-year study period, compared with the 181 community care participants, the 223 NAVIGATE participants had more medication visits, were more likely to receive a prescription for an antipsychotic and more likely to receive one conforming to NAVIGATE prescribing principles, and were less likely to receive a prescription for an antidepressant. NAVIGATE participants experienced fewer side effects and gained less weight; other vital signs and cardiometabolic laboratory findings did not differ between groups. Adherence Estimator scores improved in the NAVIGATE group but not in the community care group. CONCLUSIONS As part of comprehensive care services, medication prescription can be optimized for first-episode psychosis, contributing to better outcomes with a lower side effect burden than standard care.
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Increase in serum HDL level is associated with less negative symptoms after one year of antipsychotic treatment in first-episode psychosis.
Gjerde, PB, Dieset, I, Simonsen, C, Hoseth, EZ, Iversen, T, Lagerberg, TV, Lyngstad, SH, Mørch, RH, Skrede, S, Andreassen, OA, et al
Schizophrenia research. 2018;:253-260
Abstract
BACKGROUND A potential link between increase in total cholesterol and triglycerides and clinical improvement has been observed during antipsychotic drug treatment in chronic schizophrenia patients, possibly due to drug related effects on lipid biosynthesis. We examined whether changes in serum lipids are associated with alleviation of psychosis symptoms after one year of antipsychotic drug treatment in a cohort of first-episode psychosis (FEP) patients. METHODS A total of 132 non-affective antipsychotic-treated FEP patients were included through the Norwegian Thematically Organized Psychosis (TOP) project. Data on antipsychotic usage, serum lipids (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (TG)), body mass index (BMI) and clinical state were obtained at baseline and after 12months. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptoms. Mixed-effects models were employed to examine the relationship between serum lipids and psychotic symptoms while controlling for potential confounders including BMI. RESULTS An increase in HDL during one year of antipsychotic treatment was associated with reduction in PANSS negative subscores (B=-0.48, p=0.03). This relationship was not affected by concurrent change in BMI (adjusted HDL: B=-0.54, p=0.02). No significant associations were found between serum lipids, BMI and PANSS positive subscores. CONCLUSION We found that an increase in HDL level during antipsychotic treatment is associated with improvement in negative symptoms in FEP. These findings warrant further investigation to clarify the interaction between lipid pathways and psychosis.
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Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis.
Sakuma, K, Matsunaga, S, Nomura, I, Okuya, M, Kishi, T, Iwata, N
Psychopharmacology. 2018;(8):2303-2314
Abstract
RATIONALE This study aims to examine whether folate/folic acid/methylfolate/folinic acid supplemented to antipsychotics (FA + AP) is beneficial in schizophrenia treatment. OBJECTIVE We conducted a comprehensive systematic review and meta-analysis of double-blind, placebo-controlled, randomized clinical trials (RCTs) of FA + AP for schizophrenia. METHODS The primary outcome was an improvement in total symptoms. Other outcomes were psychopathology subscales (positive, negative, general, and depressive symptoms), discontinuation due to all-cause and adverse events, and individual adverse events. The meta-analysis evaluated the effect size based on a random-effects model. RESULTS Although we included ten RCTs with 925 patients in total (seven folic acid RCTs (n = 789), two methylfolate RCTs (n = 96), and one folinic acid RCT (n = 40)) in the systematic review, only seven RCTs were included in the meta-analysis. Pooled FA + AP treatments were not superior to placebo + AP in the improvement of total (N = 7, n = 340; standardized mean difference (SMD) = - 0.20, 95% confidence interval (CI) = - 0.41, 0.02, p = 0.08, I2 = 0%), positive, general, or depressive symptoms. Pooled FA + AP treatments were more effective than placebo + AP for negative symptoms (N = 5, n = 281; SMD = -0.25, 95% CI = -0.49, -0.01, p = 0.04, I2 = 0%). Although pooled FA + AP treatments were associated with a lower incidence of serious adverse events than placebo treatments (N = 4, n = 241; risk ratio = 0.32, 95% CI = 0.12-0.82, p = 0.02, I2 = 0%; number needed to harm = not significant), there were no significant differences in other safety outcomes between both treatments. CONCLUSIONS Our findings suggest that pooled FA + AP treatment improves negative symptoms in schizophrenia patients. Moreover, this treatment was well tolerated. However, because our results might exhibit a small-study effect, future studies with a larger sample should be conducted to obtain more robust results.
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Contribution of parasympathetic muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia.
Rickels, MR, Perez, EM, Peleckis, AJ, Alshehabi, E, Nguyen, HL, Stefanovski, D, Rickels, K, Teff, KL
American journal of physiology. Endocrinology and metabolism. 2018;(2):E250-E257
Abstract
Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized 15 healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet- and activity-controlled inpatient conditions. Before and after 7 days of study drug administration, subjects underwent frequently sampled intravenous glucose tolerance tests with either saline or atropine infused on subsequent days to assess insulin secretion and hepatic insulin extraction in the absence or presence of muscarinic blockade. We found that olanzapine led to an increase in the acute insulin response to glucose, which was not seen with placebo, and was attenuated in the olanzapine group by atropine. Deconvolution of C-peptide data confirmed an increase in insulin secretion with olanzapine, which was blocked by atropine, with a modest reduction in hepatic insulin extraction with olanzapine. These results support the contribution of muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia, and provide a mechanism for the compensatory hyperinsulinemia that normally serves to prevent deterioration of glucose tolerance under conditions of metabolic challenge.
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Differences in Metabolic Factors Between Antipsychotic-Induced Weight Gain and Non-pharmacological Obesity in Youths.
Pisano, S, Coppola, G, Catone, G, Carotenuto, M, Iuliano, R, D'Esposito, V, Cabaro, S, Miraglia Del Giudice, E, Bravaccio, C, Formisano, P
Clinical drug investigation. 2018;(5):457-462
Abstract
BACKGROUND Youth exposed to antipsychotics may experience several metabolic consequences that often limit the effectiveness of this class of drugs. OBJECTIVES The aim of this study was to compare several metabolic markers between subjects who experienced antipsychotic-induced weight gain and untreated obese patients. METHODS Nineteen non-diabetic youth (mean age 159 months, mean body mass index z-score 1.81) experiencing antipsychotic-induced weight gain and an age-, sex-, and body mass index-matched group of non-diabetic obese patients with no record of treatment (n = 19, mean age 147 months, mean body mass index z-score 2) were compared for a wide range of metabolic factors using a Bioplex Multiplex system. RESULTS C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin were significantly higher in the antipsychotic-induced weight gain group, whereas visfatin was significantly higher in the untreated obese patients. When age, sex, pubertal status, and body mass index were controlled, C-peptide, glucose-dependent insulinotropic polypeptide, and visfatin remained significant, whereas adipsin fell slightly below the threshold of statistical significance. No other statistically significant difference emerged. CONCLUSIONS Antipsychotic-induced weight gain and untreated obesity showed some similarities, confirming that levels of some hormones, such as leptin and ghrelin, are related to body mass index rather than to antipsychotic exposure. Some differences were also noted; for example, the antipsychotic-induced weight gain group displayed higher C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin, which may reflect β-cell stress and may suggest susceptibility to insulin resistance and lower visfatin, possibly indicating a lower inflammatory status.
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Assessment of the efficacy of omega-3 fatty acids on metabolic and inflammatory parameters in patients with schizophrenia taking clozapine and sodium valproate.
Behdani, F, Roudbaraki, SN, Saberi-Karimian, M, Tayefi, M, Hebrani, P, Akhavanrezayat, A, Amlashi, SV, Ferns, GA, Ghayour-Mobarhan, M
Psychiatry research. 2018;:243-247
Abstract
Omega-3 fatty acid (FA) supplementation has been reported to improve several cardio-metabolic risk factors. We aimed to assess the efficacy of omega-3 fatty acids on metabolic and inflammatory indices in patients with schizophrenia who were taking clozapine and sodium valproate. All patients were on a stable dose of 300-400mg of clozapine for 3 months. Subjects were randomized to treatment with either omega-3 fatty acid (4gr/day) or a placebo for 8 weeks. Height, weight, abdominal circumference, serum lipid profile, fasting blood glucose (FBG), and serum high sensitivity-C-reactive protein (hs-CRP) were determined at baseline and after 8 weeks of treatment. Fifty six subjects were recruited into the study. Patients with schizophrenia who were in the group receiving omega-3 FA capsules had an improvement in some anthropometric indices including weight, BMI, wrist and waist circumference, compared to the placebo group. Only changes in waist circumferences remained significantly different after adjustment for serum fasted TG. Our results showed omega-3 FA supplementation can improve some anthropometric indices in patients with schizophrenia who are taking clozapine pharmacotherapy.
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Clinical and neuroimaging spectrum of hyperglycemia-associated chorea-ballism: systematic review and exploratory analysis of case reports.
Gómez-Ochoa, SA, Espín-Chico, BB, Pinilla-Monsalve, GD, Kaas, BM, Téllez-Mosquera, LE
Functional neurology. 2018;(4):175-187
Abstract
Hyperglycemia-associated chorea-ballism (HCB) is an infrequent neurological syndrome occurring predominantly in elderly females and in the setting of non-ketotic hyperglycemia (NKH). A systematic review was conducted in accordance with the PRISMA statement. Studies published between 1980 and 2018 that reported demographic, clinical, laboratory and imaging features from patients with HCB were screened. 136 studies describing 286 patients were included in the analysis. The patients included had a median age of 72 years; those with ketotic hyperglycemia (KH) were older (p<0.001). Women and NKH patients were the most frequently affected (63% and 92%, respectively). The median glucose level at admission was 420 mg/dL (IQR 328-535), and was significantly higher in KH (p=0.009). Moreover, the absence of a clear lesion on imaging studies and the finding of bilateral imaging evidence of lesions were each more frequent in the KH group (p=0.036 and p=0.008, respectively). 48 cases (19.4%) presented with bilateral CT/MRI lesions, having higher values of plasma osmolarity compared with the patients with unilateral lesions (p=0.011). Every patient received hypoglycemic treatment, but only 174 (60.84%) were prescribed neuroleptics. 213 patients (84.86%) showed a total recovery, after a median of 14 days (IQR 3-31). Bilateral chorea-ballism was supported by bilateral imaging evidence of involvement in only 60% of the cases (positive predictive value). Patients not prescribed neuroleptics, with negative lentiform nucleus involvement, and age within the third tertile (≥ 78 years) had an odds ratio of 6.6 (CI 95% 1.18-141.10) for a complete clinical recovery. Significant differences were identified between types of hyperglycemia and regarding the clinical and imaging laterality features. Furthermore, the predictor variables evaluated showed potential utility for assessing the prognosis of HCB patients.