Systematic review and exploratory meta-analysis of the efficacy, safety, and biological effects of psychostimulants and atomoxetine in patients with schizophrenia or schizoaffective disorder

CNS Spectrums ◽  
2018 ◽  
Vol 24 (5) ◽  
pp. 479-495 ◽  
Author(s):  
Marco Solmi ◽  
Michele Fornaro ◽  
Kuniyoshi Toyoshima ◽  
Andrè F. Carvalho ◽  
Cristiano A. Köhler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Problem Solving ◽  
Executive Functions ◽  
Negative Symptoms ◽  
Biological Effects ◽  
Meta Analysis ◽  
Cortical Activation ◽  
Therapeutic Effects ◽  
Double Blind ◽  
Relapse Prediction

ObjectiveOur aim was to summarize the efficacy and safety of atomoxetine, amphetamines, and methylphenidate in schizophrenia.MethodsWe undertook a systematic review, searching PubMed/Scopus/Clinicaltrials.gov for double-blind, randomized, placebo-controlled studies of psychostimulants or atomoxetine in schizophrenia published up to 1 January 2017. A meta-analysis of outcomes reported in two or more studies is presented.ResultsWe included 22 studies investigating therapeutic effects of stimulants (k=14) or measuring symptomatic worsening/relapse prediction after stimulant challenge (k=6). Six studies of these two groups plus one additional study investigated biological effects of psychostimulants or atomoxetine. No effect resulted from interventional studies on weight loss (k=1), smoking cessation (k=1), and positive symptoms (k=12), and no improvement was reported with atomoxetine (k=3) for negative symptoms, with equivocal findings for negative (k=6) and mood symptoms (k=2) with amphetamines. Attention, processing speed, working memory, problem solving, and executive functions, among others, showed from no to some improvement with atomoxetine (k=3) or amphetamines (k=6). Meta-analysis did not confirm any effect of stimulants in any symptom domain, including negative symptoms, apart from atomoxetine improving problem solving (k=2, standardized mean difference (SMD)=0.73, 95% CI=0.10–1.36,p=0.02, I2=0%), and trending toward significant improvement in executive functions with amphetamines (k=2, SMD=0.80, 95% CI=−1.68 to +0.08,p=0.08, I2=66%). In challenge studies, amphetamines (k=1) did not worsen symptoms, and methylphenidate (k=5) consistently worsened or predicted relapse. Biological effects of atomoxetine (k=1) and amphetamines (k=1) were cortical activation, without change in β-endorphin (k=1), improved response to antipsychotics after amphetamine challenge (k=2), and an increase of growth hormone–mediated psychosis with methylphenidate (k=2). No major side effects were reported (k=6).ConclusionsNo efficacy for stimulants or atomoxetine on negative symptoms is proven. Atomoxetine or amphetamines may improve cognitive symptoms, while methylphenidate should be avoided in patients with schizophrenia. Insufficient evidence is available to draw firm conclusions.

scholarly journals The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Rasmus Lorentzen ◽  
Tuan Dang Nguyen ◽  
Alexander McGirr ◽  
Fredrik Hieronymus ◽  
Soren Dinesen Ostergaard
Keyword(s):  
Systematic Review ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Negative Symptoms ◽  
Meta Analysis ◽  
Preliminary Evidence ◽  
Pooled Analysis ◽  
P Value ◽  
Number Needed To Treat ◽  
Double Blind

Several trials have shown preliminary evidence for efficacy using Transcranial Magnetic Stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature using a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The standardized mean difference (SMD, Cohen's d) with 95% confidence intervals (CI) was calculated for each study (TMS vs. sham) and pooled across studies using an inverse variance random effects model. We identified 56 studies with a total of 2550 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD=0.37, 95%CI: 0.23; 0.52, p-value <0.00001), corresponding to a number needed to treat of 4.85. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex, using a stimulation frequency >1 Hz, and a stimulation intensity at or above the motor threshold, was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters have yet to be resolved.

scholarly journals T175. THE GUT-MICROBIOTA AS A TARGET FOR THE TREATMENT OF NEGATIVE SYMPTOMS OF SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CONTROLLED TRIALS OF ADD-ON STRATEGIES

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S298-S298
Author(s):  
Amedeo Minichino ◽  
Natascia Brondino ◽  
Marco Solmi ◽  
Cinzia Del Giovane ◽  
Christoph U Correll ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Sodium Benzoate ◽  
Negative Symptoms ◽  
Mixed Model ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Controlled Trials ◽  
Double Blind

Abstract Background None of the currently available treatments are effective for negative symptoms of schizophrenia, which represent a long-lasting burden on sufferers, their families and on wider society. The gut-microbiota has been emerging as a putative novel target of intervention for negative symptoms of schizophrenia. This hypothesis has been welcomed with enthusiasm by the scientific community as showed by the growing number of commentaries and not-systematised reviews on the topic. To date, only few clinical trials tested the efficacy of interventions with the a-priori rationale of targeting the gut-microbiome in schizophrenia, with contrasting results. However, there is a number of trials that used compounds, such as antibiotics, antimicrobials, pre- and pro-biotics with a clear potential of modifying the gut-microbiome in patients. Interpreting and analysing data from these studies will help to shed light on the potential of the gut-microbiome as a therapeutic target in schizophrenia. Here we provide the first systematic review and meta-analysis on augmentation strategies targeting the gut-microbiome in schizophrenia. Methods Following PRISMA guidelines, we searched from inception to August 2019 all the randomised double-blind controlled trials of add-on antibiotics, antimicrobics, pre/probiotics, and fecal transplant in schizophrenia. Primary outcomes were negative symptoms at end of follow-up and acceptability of treatment. Data were independently extracted by multiple observers and a random-mixed model was used for the analysis. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results. Results We identified 28 placebo-controlled trials: 21 investigated antibiotics, 4 antimicrobials, 3 pre/probiotics, none faecal transplant. None of the investigated compounds were effective for treating negative symptoms of schizophrenia, with the exception of the antimicrobial Sodium benzoate. It was possible to perform individual meta-analyses on three compounds for the outcome negative symptoms: (i) D-Cycloserine vs placebo (10 studies, N=389; SMD, -0.15; 95% CI -0.39, 0.10; P=0.24; I2: 26.4%); (ii) Minocycline vs placebo (7 studies, N=713, SMD: -0.35; 95% CI -0.70, 0.00; P=0.05, I2:77.7%) (iii) Sodium benzoate vs placebo (2 studies, N=107, SMD, -0.83; 95%CI -1.12, -0.42; P&lt;0.001; I2:0%) Acceptability of interventions was similar to placebo. Qualitative and quantitative subgroup analyses suggested that baseline severity of negative symptoms and stage of illness have the potential to influence treatment outcomes. Discussion None of the available treatment with a putative action on the gut-microbiome are effective for the treatment of negative symptoms of schizophrenia, with limited evidence supporting the use of the antimicrobial Sodium benzoate. However, this latter finding is likely to be related to the central effect of the compound. The effect of some compounds might be beneficial if timing of intervention and clinical heterogeneity are taken into account. A more detailed characterisation of the gut microbiome and the pathophysiological path linking it with schizophrenia is needed before engaging in further trials

scholarly journals Antipsychotic combinations in schizophrenia

2017 ◽  
Vol 26 (5) ◽  
pp. 462-465 ◽  
Author(s):  
C. Gastaldon ◽  
D. Papola ◽  
G. Ostuzzi
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Negative Symptoms ◽  
Partial Agonist ◽  
Meta Analysis ◽  
Open Label ◽  
Double Blind ◽  
D2 Antagonist ◽  
Randomised Controlled ◽  
Meta Analyses

In the treatment of resistant schizophrenia, a number of meta-analyses attempted to quantify the efficacy and tolerability of antipsychotic (AP) polypharmacy v. monotherapy with contradictory results. Recently, a systematic review and meta-analysis of randomised controlled trials investigated the efficacy and tolerability of AP combination v. monotherapy in schizophrenia. It included 31 studies: 21 double-blind (considered high-quality studies) and 10 open-label (considered low-quality studies). The meta-analysis showed that, overall, the combination of two APs was more effective than monotherapy in terms of symptom reduction (standardised mean difference (SMD) = −0.53, 95% confidence interval (CI) −0.87 to −0.19); however, this result was confirmed only in the subgroup of low-quality studies. Negative symptoms improved when combining a D2 antagonist with a D2 partial agonist (SMD = −0.41, 95% CI −0.79 to −0.03) both in double-blind and open-label studies. In the present commentary, the results of this systematic review are critically discussed in terms of their clinical and research implications.

Executive functions in children with heart disease: a systematic review and meta-analysis

2021 ◽  
pp. 1-9
Author(s):  
William M. Jackson ◽  
Nicholas Davis ◽  
Johanna Calderon ◽  
Jennifer J. Lee ◽  
Nicole Feirsen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Executive Functions ◽  
Data Extraction ◽  
Meta Analysis ◽  
Executive Dysfunction ◽  
Cochrane Library ◽  
Planning Problem ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Increased Risk

Abstract Context: People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported. Objective: To examine differences in executive functions in individuals with CHD compared to healthy controls. Data sources: We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library. Study selection: Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three. Data extraction: Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model. Results: The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: −0.628 (−0.726, −0.531) for cognitive flexibility and set shifting, −0.469 (−0.606, −0.333) for inhibition, −0.369 (−0.466, −0.273) for working memory, −0.334 (−0.546, −0.121) for planning/problem solving, −0.361 (−0.576, −0.147) for summary measures, and −0.444 (−0.614, −0.274) for reporter-based measures (p < 0.001). Limitations: Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity. Conclusions: Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.

scholarly journals Toxoplasma gondii Infection and Clinical Characteristics of Patients With Schizophrenia: A Systematic Review and Meta-analysis

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Arjen L Sutterland ◽  
David A Mounir ◽  
Juul J Ribbens ◽  
Bouke Kuiper ◽  
Tom van Gool ◽  
...  
Keyword(s):  
Systematic Review ◽  
Toxoplasma Gondii ◽  
Publication Bias ◽  
Clinical Characteristics ◽  
Negative Symptoms ◽  
Age Of Onset ◽  
Meta Analysis ◽  
Random Effects Models ◽  
Duration Of Illness ◽  
Toxoplasma Gondii Infection

Abstract Schizophrenia is associated with an increased prevalence of IgG antibodies against Toxoplasma gondii (T. gondii seropositivity), whereby the infection seems to precede the disorder. However, it remains unclear whether a T. gondii infection affects clinical characteristics of schizophrenia. Therefore, a systematic review and meta-analysis was conducted following PRISMA guidelines examining the association between T. gondii seropositivity and severity of total, positive, or negative symptoms or age of onset in schizophrenia. PubMed, Embase, and PsycInfo were systematically searched up to June 23, 2019 (PROSPERO #CRD42018087766). Random-effects models were used for analysis. Furthermore, the influence of potential moderators was analyzed. Indications for publication bias were examined. From a total of 934 reports, 13 studies were included. No overall effect on severity of total, positive, or negative symptoms was found. However, in patients with a shorter duration of illness T. gondii seropositivity was associated with more severe positive symptoms (standardized mean difference [SMD] = 0.32; P &lt; .001). Similar but smaller effects were seen for total symptoms, while it was absent for negative symptoms. Additionally, a significantly higher age of onset was found in those with T. gondii seropositivity (1.8 y, P = .015), although this last finding was probably influenced by publication bias and study quality. Taken together, these findings indicate that T. gondii infection has a modest effect on the severity of positive and total symptoms in schizophrenia among those in the early stages of the disorder. This supports the hypothesis that T. gondii infection is causally related to schizophrenia, although more research remains necessary.

scholarly journals Psychological and psychosocial interventions for negative symptoms in psychosis: Systematic review and meta-analysis

2017 ◽  
Vol 210 (5) ◽  
pp. 324-332 ◽  
Author(s):  
Danyael Lutgens ◽  
Genevieve Gariepy ◽  
Ashok Malla
Keyword(s):  
Systematic Review ◽  
Negative Symptoms ◽  
Psychotic Disorders ◽  
Meta Analysis ◽  
Psychosocial Interventions ◽  
Detailed Examination ◽  
Behavioural Therapy ◽  
Integrated Treatment ◽  
Treatment As Usual

BackgroundNegative symptoms observed in patients with psychotic disorders undermine quality of life and functioning. Antipsychotic medications have a limited impact. Psychological and psychosocial interventions, with medication, are recommended. However, evidence for the effectiveness of specific non-biological interventions warrants detailed examination.AimsTo conduct a meta-analytic and systematic review of the literature on the effectiveness of non-biological treatments for negative symptoms in psychotic disorders.MethodWe searched for randomised controlled studies of psychological and psychosocial interventions in psychotic disorders that reported outcome on negative symptoms. Standardised mean differences (SMDs) in values of negative symptoms at the end of treatment were calculated across study domains as the main outcome measure.ResultsA total of 95 studies met our criteria and 72 had complete quantitative data. Compared with treatment as usual cognitive–behavioural therapy (pooled SMD −0.34, 95% CI −0.55 to −0.12), skills-based training (pooled SMD −0.44, 95% CI −0.77 to −0.10), exercise (pooled SMD −0.36, 95% CI −0.71 to −0.01), and music treatments (pooled SMD −0.58, 95% CI −0.82 to −0.33) provide significant benefit. Integrated treatment models are effective for early psychosis (SMD −0.38, 95% CI −0.53 to −0.22) as long as the patients remain in treatment. Overall quality of evidence was moderate with a high level of heterogeneity.ConclusionsSpecific psychological and psychosocial interventions have utility in ameliorating negative symptoms in psychosis and should be included in the treatment of negative symptoms. However, more effective treatments for negative symptoms need to be developed.

scholarly journals Brief Psychotherapy for Depression: A Systematic Review and Meta-Analysis

2012 ◽  
Vol 43 (2) ◽  
pp. 129-151 ◽  
Author(s):  
Jason A. Nieuwsma ◽  
Ranak B. Trivedi ◽  
Jennifer McDuffie ◽  
Ian Kronish ◽  
Dinesh Benjamin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Problem Solving ◽  
Cognitive Behavioral Therapy ◽  
Systematic Reviews ◽  
Behavioral Therapy ◽  
Meta Analysis ◽  
Cognitive Behavioral ◽  
Evidence Based ◽  
Brief Psychotherapy ◽  
Problem Solving Therapy

Objective: Because evidence-based psychotherapies of 12 to 20 sessions can be perceived as too lengthy and time intensive for the treatment of depression in primary care, a number of studies have examined abbreviated psychotherapy protocols. The purpose of this study was to conduct a systematic review and meta-analysis to determine the efficacy of brief psychotherapy (i.e., < 8 sessions) for depression. Methods: We used combined literature searches in PubMed, EMBASE, PsycINFO, and an Internet-accessible database of clinical trials of psychotherapy to conduct two systematic searches: one for existing systematic reviews and another for randomized controlled trials (RCTs). Included studies examined evidence-based psychotherapy(s) of eight or fewer sessions, focused on adults with depression, contained an acceptable control condition, were published in English, and used validated measures of depressive symptoms. Results: We retained 2 systematic reviews and 15 RCTs evaluating cognitive behavioral therapy, problem-solving therapy, and mindfulness-based cognitive therapy. The systematic reviews found brief psychotherapies to be more efficacious than control, with effect sizes ranging from −0.33 to −0.25. Our meta-analysis found six to eight sessions of cognitive behavioral therapy to be more efficacious than control (ES −0.42, 95% CI −0.74 to −0.10, I2 = 56%). A sensitivity analysis controlled for statistical heterogeneity but showed smaller treatment effects (ES −0.24, 95% CI −0.42 to −0.06, I2 = 0%). Conclusions: Depression can be efficaciously treated with six to eight sessions of psychotherapy, particularly cognitive behavioral therapy and problem-solving therapy. Access to non-pharmacologic treatments for depression could be improved by training healthcare providers to deliver brief psychotherapies.

scholarly journals Clinical Therapeutic Effects of Aspirin in Combination with Fufang Danshen Diwan, a Traditional Chinese Medicine Formula, on Coronary Heart Disease: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 39 (5) ◽  
pp. 1955-1963 ◽  
Author(s):  
Jianchun Huang ◽  
Xiaojun Tang ◽  
Fangxing Ye ◽  
Junhui He ◽  
Xiaolong Kong
Keyword(s):  
Systematic Review ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Aspirin Therapy ◽  
Therapeutic Effects ◽  
Chinese Medicine Formula

Background/Aims: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. Methods: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. Results: Fourteen randomized controlled trials enrolling 1367 subjects were included. Meta-analyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD −1.12; 95% CI −1.49 to −0.76); 2) reduction of TG level (SMD −0.94; 95% CI −1.15 to -0.74); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. Conclusion: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease.

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