N-acetyl-cysteine in a double-blind randomized placebo-controlled trial: Towards biomarker guided treatment in early psychosis

2017 ◽  
Vol 41 (S1) ◽  
pp. s806-s806
Author(s):  
P. Conus ◽  
M. Fournier ◽  
L. Xin ◽  
P. Baumann ◽  
C. Ferrari ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Negative Symptoms ◽  
Controlled Trial ◽  
Early Psychosis ◽  
Antipsychotic Treatment ◽  
Positive Symptoms ◽  
Double Blind ◽  
Significant Difference ◽  
Oxidation Status ◽  
Acetyl Cysteine

PurposeRecent evidence points to a critical role of redox dysregulation induced oxidative stress in the pathophysiology of early phases of schizophrenia. An add-on trial with n-acetyl-cysteine (NAC) led to a reduction in negative symptoms in chronic schizophrenia patients. Aim of this study was to explore impact of addition of NAC to standard treatment in early psychosis (EP) patients.MethodsDouble-blind, randomized, placebo-controlled trial of addition of NAC, 2700 mg daily, to antipsychotic treatment over 6 months. Monthly assessment of PANSS, GAF, SOFAS and antipsychotics treatment; quantification of brain glutathione levels (GSHmPFC) by 1H-magnetic-resonance-spectroscopy and of blood cells glutathione (GSHBC) and glutathione peroxidase activity (GPxBC) as marker of oxidation status at the beginning and end of treatment.ResultsOverall, 63 patients were included. Spectroscopy data showed that GSHmPFC increased by +23% in the NAC group, while it tended to decrease by −5% in the placebo group (P = 0.005). No significant difference between NAC and placebo was observed on global changes in negative symptoms, positive symptoms or functional outcome. However, in patients with high-baseline oxidation status (GPxBC>22.3U/gHb), subgroup explorations revealed an improvement of positive symptoms over time compared to patients with low-baseline GPx (P = 0.02).ConclusionsWhile addition of NAC induced an increase of brain GSH, it had no impact on symptomatic and functional outcome in EP patients. However, in patients with high oxidation status, addition of NAC leads to significantly greater improvement in positive symptoms. Future studies on antioxidant interventions in EP should consider biomarker-guided treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Adjunctive simvastatin treatment in schizophrenia patients; a double blind randomized and placebo controlled trial

2021 ◽  
Vol 7 (1) ◽  
pp. e02-e02
Author(s):  
Somaieh Ashrafi ◽  
Seyyed Mohammad Ghaffari ◽  
Hatam Boostani ◽  
Somaieh Raz ◽  
Negar Ebadi ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Mixed Model ◽  
Controlled Trial ◽  
Repeated Measure ◽  
Antipsychotic Treatment ◽  
Double Blind ◽  
Exact Test ◽  
Beneficial Effects ◽  
Significant Difference ◽  
Double Blinded

Introduction: Statins such as simvastatin are recently introduced as agents that may have beneficial effects in schizophrenia regarding their prominent anti-inflammatory properties. Objectives: This study was designed to evaluate the effects of simvastatin on schizophrenia symptoms. Patients and Methods: In a double-blinded randomized clinical trial, 40 hospitalized schizophrenia patients (according to the DSM-IV-TR criteria) were studied for 6 weeks. One group of the patients (n=20) received simvastatin (with the dose of 40 mg/d) and the other group received (n=20) placebo. The patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms. Data were analyzed with mixed model repeated measure ANOVA, t test, and χ2 test or Fischer’s exact test by SPSS software. The significant cutoff was considered at P<0.05. Results: The mean age of the patients was 34.05±9.74 years and 50% of them were men. There was not a significant difference between the two groups regarding negative symptoms reduction. Conclusion: Our study demonstrated that adding simvastatin on atypical antipsychotic treatment had no significant beneficial effects on the negative and positive symptoms in patients with schizophrenia disorder. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT2017052034046N1; https://en.irct.ir/trial/26134, ethical code; ETH-457).

scholarly journals SA19. N-Acetyl-Cysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

2017 ◽  
Vol 43 (suppl_1) ◽  
pp. S119-S120
Author(s):  
Kim Do ◽  
Larry J. Seidman ◽  
Margot Fournier ◽  
Lijing Xin ◽  
Martine Cleusix ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Early Psychosis ◽  
Double Blind ◽  
Acetyl Cysteine

Efficacy and safety of MIN-101: A new drug for the treatment of negative symptoms in schizophrenia a 12-week randomized, double blind, placebo-controlled trial

2017 ◽  
Vol 41 (S1) ◽  
pp. S191-S191
Author(s):  
R. Luthringer
Keyword(s):  
Primary Endpoint ◽  
Negative Symptoms ◽  
Controlled Trial ◽  
Specific Treatment ◽  
Positive Symptoms ◽  
Double Blind ◽  
Five Factors ◽  
Symptom Scores ◽  
Clinically Significant ◽  
Metabolic Indices

ObjectiveTo compare the efficacy, safety, and tolerability of MIN-101, a compound with high affinities for sigma 2 and 5-HT 2A receptors, to placebo in treating negative symptoms, in stabilized patients with schizophrenia.MethodsThis multi-national phase 2b trial enrolled 244 patients with schizophrenia who were symptomatically stable for ≥ 3 months prior to entering the trial and had scores ≥ 20 negative subscale of the PANSS. Patients were randomized to monotherapy with MIN-101 32 mg/day, MIN-101 64 mg/day or placebo in a 1:1:1 ratio. The primary endpoint was the PANSS negative symptom score based on the five factors (pentagonal) model.ResultsStatistically significant reduction in the primary endpoint score was demonstrated for MIN-101 32 mg and 64 mg compared to placebo (P ≤ 0.022, ES 0.45 and ≤ 0.003, ES 0.58, respectively). This was supported by similar effects on most of the secondary measurements including: the PANSS three factors negative symptoms subscale, PANSS total score, CGI, BACS, CDSS, and PSP. There were no statistically significant differences in PANSS positive subscale scores between MIN-101 and placebo. No weight gain or clinically significant changes in vital sings, prolactin levels, routine laboratory values, metabolic indices and extrapyramidal symptom scores (EPS) were observed.ConclusionsSince positive symptoms and EPS did not change, the improvement in negative symptoms was not secondary to improvement in positive symptoms or EPS, suggesting that MIN-101 might be the first specific treatment to have a direct effect on negative symptoms.Disclosure of interestI have received consultant fees from Minerva Neuroscience the sponsor of this trial and own stock of Minerva Neuroscience

Treatment of Negative Symptoms in Schizophrenia with Amisulpride

1995 ◽  
Vol 166 (1) ◽  
pp. 68-72 ◽  
Author(s):  
P. Boyer ◽  
Y. Lecrubier ◽  
A. J. Puech ◽  
J. Dewailly ◽  
F. Aubin
Keyword(s):  
Negative Symptoms ◽  
Controlled Trial ◽  
Positive Symptoms ◽  
Receptor Blockade ◽  
Low Doses ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Dopaminergic Transmission ◽  
Parallel Group ◽  
Primary Evaluation

BackgroundThe efficacy of low doses of certain neuroleptics in improving negative symptoms is still controversial. This study assessed the efficacy of amisulpride, a benzamide which increases dopaminergic transmission at low doses via presynaptic dopamine receptor blockade, on negative symptoms of schizophrenia.MethodThe study was designed as a parallel-group, double-blind, placebo-controlled trial. Patients had to fulfil DSM–III criteria for schizophrenia, Andreasen's criteria for negative schizophrenia, and to have a total score of at least 75 on the SANS; those treated with neuroleptics or antidepressants underwent a six-week placebo wash-out. One hundred and four in-patients were randomly assigned to amisulpride 100 mg/d, amisulpride 300 mg/d, or placebo for six weeks; 85 patients completed the study.ResultsBoth amisulpride doses were significantly more effective than placebo on the primary evaluation criterion (SANS total score, MANOVAP< 0.02). No significant changes were found in positive symptoms or in extrapyramidal symptoms.ConclusionsNegative symptoms can be improved by low doses of amisulpride, favouring the hypothesis of dopaminergic hypofunction as one of the causes of negative symptoms.

A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder

2016 ◽  
Vol 51 (3) ◽  
pp. 241-249 ◽  
Author(s):  
Olivia M Dean ◽  
Kylie M Gray ◽  
Kristi-Ann Villagonzalo ◽  
Seetal Dodd ◽  
Mohammadreza Mohebbi ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Autistic Disorder ◽  
Controlled Trial ◽  
Demographic Data ◽  
Fixed Dose ◽  
Social Responsiveness ◽  
Vineland Adaptive Behavior Scales ◽  
Double Blind ◽  
Significant Difference ◽  
Acetyl Cysteine

Objective: Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. Method: This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children’s Communication Checklist–Second Edition and the Repetitive Behavior Scale–Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. Results: A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1–9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. Conclusion: This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

scholarly journals Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis

2019 ◽  
Vol 45 (4) ◽  
pp. 622-631 ◽  
Author(s):  
Yuya Mizuno ◽  
Robert A. McCutcheon ◽  
Stefan P. Brugger ◽  
Oliver D. Howes
Keyword(s):  
Negative Symptoms ◽  
Meta Analysis ◽  
Treatment Resistance ◽  
Study Groups ◽  
Antipsychotic Treatment ◽  
Double Blind ◽  
Significant Difference ◽  
Randomised Controlled ◽  
Positive And Negative Symptoms ◽  
Relative Variability

AbstractTwo important clinical questions are whether there is a subtype of schizophrenia which responds differently to clozapine relative to other antipsychotics, and whether greater efficacy of clozapine is dependent on the degree of treatment-resistance. The authors address this by examining both variability and magnitude of response in patients treated with clozapine and other antipsychotics for both treatment-resistant schizophrenia (TRS) and non-resistant schizophrenia. Double-blind randomised controlled trials comparing clozapine with other antipsychotics in patients with schizophrenia were identified using five databases. Standard deviations and means of change in total, positive, and negative symptoms were extracted. Variability ratio (VR) and coefficient of variation ratio (CVR) were used to quantify relative variability in symptom change. Hedges’ g was used to quantify mean differences. Ten TRS studies (n = 822) and 29 non-TRS studies (n = 2566) were meta-analysed. Relative variability in change of total symptoms did not differ significantly between clozapine and other antipsychotics in TRS studies (VR = 1.84; 95%CI, 0.85–4.02). These findings were similar with CVR, and for positive and negative symptoms. Clozapine was superior to other antipsychotics in improving total symptoms in both TRS (g = 0.34; 95%CI, 0.13–0.56) and non-TRS (g = 0.20; 95%CI, 0.08–0.32) studies. Furthermore, clozapine was superior in improving positive symptoms in both study groups, but not for negative symptoms. Pooled effect sizes showed no significant difference between TRS and non-TRS studies. These findings do not support a subtype of schizophrenia which responds specifically to clozapine. Clozapine is more effective than other antipsychotics irrespective of treatment-resistance, arguing for its use more generally in schizophrenia. PROSPERO CRD42018086507

scholarly journals Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e045559
Author(s):  
Xuelei Zhang ◽  
Anxin Wang ◽  
Jing Yu Zhang ◽  
Baixue Jia ◽  
Xiaochuan Huo ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Endovascular Treatment ◽  
Functional Outcome ◽  
Acute Ischaemic Stroke ◽  
Controlled Trial ◽  
Intravenous Thrombolysis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Ischaemic Injury ◽  
Study Results

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

scholarly journals Adjunctive Garcinia mangostana Linn. (Mangosteen) Pericarp for Schizophrenia: A 24-Week Double-blind, Randomized, Placebo Controlled Efficacy Trial: Péricarpe d’appoint Garcinia mangostana Linn (mangoustan) pour la schizophrénie : un essai d’efficacité de 24 semaines, à double insu, randomisé et contrôlé par placebo

2020 ◽  
pp. 070674372098243
Author(s):  
Alyna Turner ◽  
Andrea Baker ◽  
Olivia M. Dean ◽  
Adam J. Walker ◽  
Seetal Dodd ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Schizoaffective Disorder ◽  
Negative Symptoms ◽  
Controlled Trial ◽  
Safety Data ◽  
Rate Of Change ◽  
Adjunctive Treatment ◽  
Garcinia Mangostana ◽  
Double Blind

Objectives: Garcinia mangostana Linn. (“mangosteen”) pericarp contains bioactive compounds that may target biological pathways implicated in schizophrenia. We conducted a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp, compared to placebo, in the treatment of schizophrenia. Methods: People diagnosed with schizophrenia or schizoaffective disorder ( Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), recruited across 2 sites (Brisbane and Victoria, Australia), were randomized to receive 24 weeks of adjunctive mangosteen pericarp (1,000 mg/day) or matched placebo. The primary outcome measure was the Positive and Negative Symptom Scale total score. Secondary outcomes included positive and negative symptoms, general psychopathology, clinical global severity and improvement, participant reported overall improvement, depressive symptoms, functioning, quality of life, and safety data at 24 and 28 weeks (4 weeks postdiscontinuation). Data were collected from July 2016 to February 2019. Results: Baseline assessments were conducted on 148 people (mangosteen = 74, placebo = 74); data analyses were conducted on 136 (92%) participants with postbaseline data. The treatment group had significantly higher symptom severity compared to placebo, and both groups significantly improved on all symptom, functioning, and quality of life measures over time. No between-group differences were found for the rate of change between baseline and 24 or 28 weeks. Conclusion: Despite promising preclinical and clinical work, our results do not support mangosteen pericarp extract as an adjunctive treatment for schizophrenia or schizoaffective disorder.

scholarly journals Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2238
Author(s):  
Xiaomei Zhang ◽  
Shanbin Chen ◽  
Ming Zhang ◽  
Fazheng Ren ◽  
Yimei Ren ◽  
...  
Keyword(s):  
Mental Illness ◽  
Placebo Group ◽  
Rating Scale ◽  
Controlled Trial ◽  
Fermented Milk ◽  
Daily Consumption ◽  
Double Blind ◽  
Tnf Α ◽  
Significant Difference ◽  
Factor Α

Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8–12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.

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