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1.
Is Sitagliptin Effective for Modulating Metabolic Disturbances Associated With Olanzapine in Schizophrenia Patients? A Double-blind Placebo-controlled Clinical Trial.
Moghimi Sarani, E, Memari, E, Anushiravani, A, Mowla, A
Journal of clinical psychopharmacology. 2020;(5):487-490
Abstract
PURPOSE/BACKGROUND The mortality rate of patients with schizophrenia due to metabolic disturbances is high. Our aim is to survey the effects of sitagliptin on metabolic disturbances associated with olanzapine in patients with schizophrenia. METHODS/PROCEDURES In this 12-week double-blind placebo-controlled clinical trial, 71 patients taking olanzapine (10 to 30 mg) for at least 1 month were randomly allocated to enter 1 of the 2 treatment groups (olanzapine plus placebo or olanzapine plus sitagliptin). Sitagliptin was added to patients 'current medications with the dose of 100 mg/d. Physical examinations and measurement of anthropometric (body mass index and waist circumference) and laboratory parameters (fasting blood sugar, glycated hemoglobin, total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride) were measured at baseline, week 4, and week 12. The patients were assessed for any side effects of the medications in each visit. FINDINGS/RESULTS Sixty-one patients (30 in the sitagliptin and 31 in the placebo group) completed the trial. The anthropometric measurements at the end of the study did not differ between the 2 groups. glycated hemoglobin and total cholesterol were significantly lower in the sitagliptin group after 12 weeks. Other metabolic profile revealed either no change or minimal magnitude changes. No major side effect was reported. IMPLICATIONS/CONCLUSIONS Metabolic disturbances associated with olanzapine treatment in patients with schizophrenia can be modulated by sitagliptin.
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The effect of sublingual atropine sulfate on clozapine-induced hypersalivation: a multicentre, randomised placebo-controlled trial.
Mubaslat, O, Lambert, T
Psychopharmacology. 2020;(10):2905-2915
Abstract
BACKGROUND Hypersalivation and drooling are commonly reported in clozapine-treated patients. Current management strategies have been evaluated using subjective measures. Many case reports describe the successful use of atropine in the treatment of the condition. AIMS To measure the effect and safety of sublingual atropine on nocturnal unstimulated saliva secretion. Secondary aims were to evaluate the patient's satisfaction with the atropine effect on hypersalivation (or sialorrhea), drooling, and sleep. METHOD Twenty-one clozapine-treated patients with hypersalivation, or drooling, were randomised to take a single 600-μg dose of sublingual atropine drops or a matching placebo. The saliva secretion was measured over 5 min at baseline and 2 h after the administration of the study medication. RESULTS Sublingual atropine reduced the saliva secretion significantly more than the placebo (mean difference = - 57.21%, 95% CI: - 104.30, - 10.11, P = 0.02). A significant decrease in standing pulse rate was recorded in the participants in the atropine group (- 5.8 (- 9.54, - 2.15), P = 0.002). Subjectively, more patients in the atropine group found their pillow to have less saliva the following morning and found their sleep to be better. CONCLUSIONS Sublingual atropine drops significantly reduces nocturnal unstimulated clozapine-induced saliva secretion. More research is required to compare the effect of sublingual atropine with other anticholinergic medications and different dosage forms. TRIAL REGISTRATION ACTRN12618000051246.
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A Pilot Randomized, Placebo-Controlled Trial of Glycine for Treatment of Schizophrenia and Alcohol Dependence.
Serrita, J, Ralevski, E, Yoon, G, Petrakis, I
Journal of dual diagnosis. 2019;(1):46-55
Abstract
Objectives: The hypofunctioning of N-methyl-D-aspartate (NMDA) receptors are thought to play an important role in the pathophysiology of schizophrenia. The augmentation of the glutamatergic system through the NMDA receptor may attenuate alcohol craving and use. This study was designed to evaluate the efficacy of glycine, an agonist of the glycine B co-agonist site of the NMDA receptor on alcohol consumption and cravings as well as on negative symptoms in schizophrenia. Methods: Participants (N = 20) were given 0.8 g/kg glycine or matching placebo (provided in bottles with mixed in solution) each week for the duration of the 12-week trial. Primary outcome measures included drinking, craving for alcohol, and symptoms of schizophrenia. Cognitive functioning (attention, concentration, and memory) was also evaluated. Results: Glycine showed no benefit over placebo in the reduction of heavy drinking days or craving for alcohol over a 12-week treatment period. Nor was there an effect on negative symptoms of schizophrenia or on cognitive functioning. Conclusions: Although our study showed no beneficial effect of glycine over placebo, our results are consistent with the largest trial of glycine treatment in schizophrenia. Diagnosed schizophrenia and alcohol dependence might be more difficult to treat because of more severe psychopathology. This is the first study to date to examine an innovative treatment approach with an amino acid, glycine, as potentially acting on both alcohol intake and negative symptoms of schizophrenia.
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Curcumin as Add-On to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study.
Miodownik, C, Lerner, V, Kudkaeva, N, Lerner, PP, Pashinian, A, Bersudsky, Y, Eliyahu, R, Kreinin, A, Bergman, J
Clinical neuropharmacology. 2019;(4):117-122
Abstract
BACKGROUND Introduction of old and new generations of antipsychotics leads to significant improvements in the positive symptoms of schizophrenia. However, negative symptoms remain refractory to conventional trials of antipsychotic therapy. Recently, there were several open clinical human trials with curcumin. Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including antioxidative and neuroprotective effects. The studies showed that curcumin improved the negative symptoms of schizophrenia. The purpose of our study was to examine the efficacy of curcumin as an add-on agent to regular antipsychotic medications in patients with chronic schizophrenia. METHODS Thirty-eight patients with chronic schizophrenia were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 3000 mg/d curcumin or placebo combined with antipsychotics from January 2015 to February 2017. The outcome measures were the Positive and Negative Symptoms Scale (PANSS) and the Calgary Depression Scale for Schizophrenia. RESULTS Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. There was a significant response to curcumin within 6 months in total PANSS (P = 0.02) and in the negative symptoms subscale (P = 0.04). There were no differences in the positive and general PANSS subscales, and the Calgary Depression Scale for Schizophrenia scores between the treatment and placebo groups. No patient complained of any adverse effect. CONCLUSIONS The promising results of curcumin as an add-on to antipsychotics in the treatment of negative symptoms may open a new and safe therapeutic option for the management of schizophrenia. However, these results should be replicated in further studies.ClinicalTrials.gov Identifier: NCT02298985.
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Disparate effects of first and second generation antipsychotics on cognition in schizophrenia - Findings from the randomized NeSSy trial.
Veselinović, T, Scharpenberg, M, Heinze, M, Cordes, J, Mühlbauer, B, Juckel, G, Habel, U, Rüther, E, Timm, J, Gründer, G, et al
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2019;(6):720-739
Abstract
Cognitive impairment represents a core feature of schizophrenia. Uncertainty about demonstrable benefits of available antipsychotics on cognition remains an important clinical question relevant to patients' quality of life. The aim of our multi-center, randomized, double-blind "Neuroleptic Strategy Study" (NeSSy) was to compare the effectiveness of selected antipsychotics, conventionally classified as second- (SGAs) (haloperidol, flupentixol) and first generation antipsychotics (FGAs) (aripiprazole, olanzapine, quetiapine), on quality of life in schizophrenia. The effects on cognitive deficits represented a secondary outcome. We used an innovative double randomization for assignment of treatment group, and followed the patients with a neurocognitive test-battery upon six and 24 weeks of treatment. Psychopathology and quality of life were assessed using CGI, PANSS and SF-36. Assessment of cognitive performance was conducted in 114 of the 136 randomized patients. The SGA group (N = 62) showed beneficial effects of small to moderate effect size on cognition during the initial six weeks of treatment (executive functions, verbal fluency) and at 24 weeks (executive functions, working memory). In contrast, the FGA group (N = 52) showed moderately improved executive function, but a decline in verbal fluency at six weeks, with significant declines of moderate to large effect size in executive function, verbal learning and memory, and verbal fluency at 24 weeks. Our study indicates that SGAs present an advantage over FGAs regarding cognitive function during a medium-term treatment for schizophrenia. The results further emphasize a distinction between progression to detrimental effects of FGAs with prolonged treatment in contrast to more persistent cognitive benefits with SGA treatment.
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Prophylactic Haloperidol Effects on Long-term Quality of Life in Critically Ill Patients at High Risk for Delirium: Results of the REDUCE Study.
Rood, PJT, Zegers, M, Slooter, AJC, Beishuizen, A, Simons, KS, van der Voort, PHJ, van der Woude, MCE, Spronk, PE, van der Hoeven, JG, Pickkers, P, et al
Anesthesiology. 2019;(2):328-335
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Abstract
BACKGROUND Delirium incidence in intensive care unit patients is high and associated with impaired long-term outcomes. The use of prophylactic haloperidol did not improve short-term outcome among critically ill adults at high risk of delirium. This study evaluated the effects of prophylactic haloperidol use on long-term quality of life in this group of patients and explored which factors are associated with change in quality of life. METHODS A preplanned secondary analysis of long-term outcomes of the pRophylactic haloperidol usE for DeliriUm in iCu patients at high risk for dElirium (REDUCE) study was conducted. In this multicenter randomized clinical trial, nondelirious intensive care unit patients were assigned to prophylactic haloperidol (1 or 2 mg) or placebo (0.9% sodium chloride). In all groups, patients finally received study medication for median duration of 3 days [interquartile range, 2 to 6] until onset of delirium or until intensive care unit discharge. Long-term outcomes were assessed using the Short Form-12 questionnaire at intensive care unit admission (baseline) and after 1 and 6 months. Quality of life was summarized in the physical component summary and mental component summary scores. Differences between the haloperidol and placebo group and factors associated with changes in quality of life were analyzed. RESULTS Of 1,789 study patients, 1,245 intensive care unit patients were approached, of which 887 (71%) responded. Long-term quality of life did not differ between the haloperidol and placebo group (physical component summary mean score of 39 ± 11 and 39 ± 11, respectively, and P = 0.350; and mental component summary score of 50 ± 10 and 51 ± 10, respectively, and P = 0.678). Age, medical and trauma admission, quality of life score at baseline, risk for delirium (PRE-DELIRIC) score, and the number of sedation-induced coma days were significantly associated with a decline in long-term quality of life. CONCLUSIONS Prophylactic haloperidol use does not affect long-term quality of life in critically ill patients at high risk for delirium. Several factors, including the modifiable factor number of sedation-induced coma days, are associated with decline in long-term outcomes.
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[Metformin treatment of antipsychotic-induced dyslipidemia: analysis of two randomized, placebo-controlled trials].
Yang, Y, Wang, X, Kang, D, Long, Y, Ou, J, Guo, W, Zhao, J, Wu, R
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2019;(10):1128-1136
Abstract
To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L
(P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.
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Adjunctive telmisartan treatment on body metabolism in clozapine or olanzapine treated patients with schizophrenia: a randomized, double blind, placebo controlled trial.
Fan, X, Copeland, P, Nawras, S, Harrington, A, Freudenreich, O, Goff, DC, Henderson, DC
Psychopharmacology. 2019;(6):1949-1957
Abstract
OBJECTIVE This study examined the effect of adjunctive telmisartan on body metabolism in clozapine- or olanzapine-treated patients with schizophrenia. METHOD Each subject had been on stable dose of olanzapine or clozapine for at least 1 month. In a 12-week randomized, double-blind, placebo-controlled study, subjects received either telmisartan (80 mg once per day) or placebo. The homeostasis model of assessment of insulin resistance (HOMA-IR) was calculated based on fasting blood levels of insulin and glucose. Fasting blood levels of triglycerides and cholesterols, as well as serum levels of high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were measured. The whole-body dual-energy X-ray absorptiometry (DXA) was used to assess body composition. Lipid particles were assessed using nuclear magnetic resonance (NMR) spectroscopy. All assessments were conducted at baseline and repeated at week 12. RESULTS Fifty-four subjects were randomized and 43 completed the study (22 in the telmisartan group, 21 in the placebo group). There were no significant differences between the two groups in week 12 changes for HOMA-IR or fasting triglycerides (- 0.18 ± 1.24 vs 0.39 ± 1.39, p = 0.181; - 26 ± 76 vs - 10 ± 81 mg/dL, p = 0.679, respectively) (telmisartan vs placebo). Further, there were no significant between group differences in week 12 changes for other fasting lipids, body weight, body mass index, waist circumference, as well as various measures of lipid particles (p's > 0.100). The DXA assessment showed no significant differences between the two groups in week 12 changes for fat mass, lean mass, or total mass (p's > 0.100). CONCLUSION In the present study, adjunctive treatment of telmisartan did not seem to improve body metabolism in schizophrenia patients receiving olanzapine or clozapine. The implications for future studies were discussed. CLINICALTRIALS. GOV IDENTIFIER NCT00981526.
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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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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.