Positive And Negative Syndrome Scale General Scores Research Articles

Quality of Life and C-Reactive Protein in Patients with Schizophrenia: A Cross-Sectional Study.

The connection between chronic inflammation and the quality of life (QOL) in individuals diagnosed with schizophrenia lacks clarity. This study aimed to achieve 2 primary objectives: (1) assess the QOL among outpatients with schizophrenia and (2) explore the potential correlation between reduced QOL and heightened levels of C-reactive protein (CRP) in patients with schizophrenia. The research included 129 outpatients diagnosed with schizophrenia who were receiving care at the psychiatry department of the University Hospital Mohamed VI in Marrakech, Morocco. Disease severity was evaluated using the Positive and Negative Syndrome Scale (PANSS), while the QOL was measured using the Moroccan Arabic version of The Schizophrenia Quality of Life questionnaire. Patients were categorized into 2 groups based on their CRP levels: normal CRP (≤5.0 mg/L) and high CRP (>5.0 mg/L). A comparative analysis of sociodemographic, clinical, biological, and quality of life factors was conducted between the 2 groups (normal CRP and high CRP). The group with elevated CRP levels exhibited higher scores in various PANSS categories, including PANSS total score (P ≤ .01), PANSS positive score (P ≤ .01), PANSS negative score (P ≤ .01), and PANSS general score (P ≤ .01). After adjusting for sociodemographic and clinical variables, individuals with elevated CRP levels demonstrated lower QOL compared to those with normal CRP levels (OR = 0.57, 95% CI = 0.46-0.68). Significant associations were noted between male gender (OR = 0.047, 95% CI = 0.01-0.26), earlier onset of the condition (OR = 0.54, 95% CI = 0.33-0.82), current tobacco smoking (OR = 0.015, 95% CI = 0.00-0.08), and heightened CRP levels. Our study suggests that higher CRP is associated with lower QOL levels in schizophrenia.

The Therapeutic Role of Intermittent Theta Burst Stimulation in Schizophrenia: A Systematic Review and Meta-analysis.

Schizophrenia affects approximately 1% of the population worldwide. Multifactorial reasons, ranging from drug resistance to adverse effects of medications, have necessitated exploring further therapeutic options. Intermittent theta burst stimulation (iTBS) is a novel high-frequency form of transcranial magnetic stimulation, a safe procedure with minor adverse effects with faster and longer-lasting poststimulation effects with a potential role in treating symptoms; however, the exact target brain regions and symptoms are still controversial. Therefore, we aimed to systematically investigate the current literature regarding the therapeutic utilities of iTBS using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Twelve studies were included among which 9 found iTBS effective to some degree. These studies targeted the dorsolateral prefrontal cortex and the midline cerebellum. We performed a random-effects meta-analysis on studies that compared the effects of iTBS on schizophrenia symptoms measured by the Positive and Negative Syndrome Scale (PANSS) to sham treatment. Our results showed no significant difference between iTBS and sham in PANSS positive and negative scores, but a trend-level difference in PANSS general scores ( k = 6, P = 0.07), and a significant difference in PANSS total scores ( k = 6, P = 0.03). Analysis of the studies targeting the dorsolateral prefrontal cortex showed improvement in PANSS negative scores ( k = 5, standardized mean difference = -0.83, P = 0.049), but not in PANSS positive scores. Moderators (intensity, pulse, quality, sessions) did not affect the results. However, considering the small number of studies included in this meta-analysis, future works are required to further explore the effects of these factors and also find optimum target regions for positive symptoms.

Features of Psychotic Symptoms in Methamphetamine Use Disorder Patients and Ketamine Use Disorder Patients: A Cross-Sectional Study.

BackgroundMethamphetamine and ketamine are commonly used club drugs. Both of them have been reported to mimic psychotic symptoms of schizophrenia. However, the prevalence and detailed features of psychotic symptoms among methamphetamine use disorder (MUD) and ketamine use disorder (KUD) patients are largely unknown. This study aimed to measure psychotic symptoms among patients with MUD and KUD.MethodsA total sample of 842 patients from voluntary drug rehabilitation centers, including 462 MUD patients and 380 KUD patients, were invited to this study. The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychotic symptoms in these two groups of patients.ResultsThe prevalence of psychotic symptoms was significantly higher among MUD patients than KUD patients (75.1 vs. 50.5%, 95% CI: 3.532 – 11.858, p < 0.001). Compared with KUD patients, MUD patients were more likely to experience positive symptoms (PANSS positive scores: 11.5 ± 6.07 vs. 15.1 ± 8.22, P < 0.001) and negative symptoms (PANSS negative scores: 12.4 ± 6.60 vs. 14.5 ± 8.63, P < 0.001), but not general symptoms (PANSS general scores: 31.2 ± 13.90 vs. 32.2 ± 15.13, P < 0.001).ConclusionsThe current study found that more than half of MUD and KUD patients experienced psychotic symptoms, and that patients with MUD are more likely to experience positive and negative symptoms than patients with KUD. The findings provide a new perspective for exploring the neuropathological mechanism of psychotic symptoms of schizophrenia.

A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia.

Purpose: Metabolomics has attracted attention as a new method for understanding the molecular mechanisms of psychiatric disorders. Current metabolomics technology allows us to measure over hundreds of metabolites at a time and is a useful indicator of the consequences of complex and continuous changes in metabolic profiles due to the execution of genomic information and external factors of biological activity. Therefore, metabolomics is imperative to the discovery of biomarkers and mechanisms associated with pathophysiological processes. In this study, we investigated metabolites changes in hospitalized patients with chronic schizophrenia compared to that in healthy controls, and examined the correlations between the metabolites and psychiatric symptoms.Patients and Methods: Thirty patients with schizophrenia and ten healthy controls participated in this study between September 2019 and June 2020. The mean duration of disease in patients with schizophrenia was 26 years. Clinical and neuropsychiatric symptoms of patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS). Metabolomics was conducted using Capillary Electrophoresis Fourier Transform Mass Spectrometry (CE-FTMS), using serum samples from patients with schizophrenia and healthy controls. Metabolomics assigned a candidate compound to the 446 (cation 279, anion 167) peaks. Hierarchical cluster analysis (HCA), principal component analysis (PCA), logistic regression analysis, receiver operating characteristic (ROC) analysis, and linear regression analysis were used to analyze the metabolites changes, identifying the disease and the relationship between metabolites and psychiatric symptoms.Results: HCA showed that approximately 60% of metabolites had lower peak values in patients with schizophrenia than in healthy controls. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in patients with schizophrenia. PCA showed a clear separation between patients with schizophrenia and healthy controls in the first principal component (the contribution ratio of the first principal component was 15.9%). Logistic regression analysis suggested that the first principal component was a predictor of disease (odds = 1.36, 95%CI = 1.11–1.67, p = 0.0032). ROC analysis showed a sensitivity of 93% and a specificity of 100% for the diagnosis of schizophrenia with a cut-off value of the first principal component; −3.33 (AUC = 0.95). We extracted the high factor loading for the first principal component. Gamma-glutamyl-valine (γ-Glu-Val) was significantly negatively correlated with PANSS total scores (r = −0.45, p = 0.012) and PANSS general scores (r = −0.49, p = 0.0055). Gamma-glutamyl-phenylalanine (γ-Glu-Phe) was significantly negatively correlated with PANSS total score (r = −0.40, p = 0.031) and PANSS general score (r = −0.41, p = 0.025). Tetrahydrouridine was significantly positively correlated with PANSS negative scores (r = 0.53, p = 0.0061).Conclusion: Metabolites changes in hospitalized patients with chronic schizophrenia showed extensive and generalized declines. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in the schizophrenia group. Metabolomic analysis was useful to identify chronic schizophrenia. Some glutamate compound metabolites had a relationship with psychiatric symptoms.

Antipsychotic-Associated Weight Gain and Clinical Improvement Under Clozapine Treatment.

Antipsychotic-associated weight gain is a common adverse effect with several negative outcomes in the clinical evolution of patients, which might also affect patients' self-identity from physical appearance and imply treatment discontinuation. However, recent research has drawn attention to an unexpected clinical improvement associated with weight gain, mostly in patients under treatment with clozapine or olanzapine. Twenty-three treatment-resistant psychosis patients initiating clozapine were evaluated. Longitudinal psychopathological assessment through the Positive and Negative Syndrome Scale (PANSS) and anthropometric evaluation were performed at baseline, week 8, and 18. Body mass index (BMI) change during clozapine treatment was associated with clinical improvement measured with PANSS total score at week 8 (P = 0.021) while showed a trend at week 18 (P = 0.058). The PANSS general score was also associated with weight gain at week 8 (P = 0.022), whereas negative subscale score showed a trend at week 8 (P = 0.088) and was associated between week 8 and 18 (P = 0.018). Sex differences applied at week 8 for PANSS total score, where clinical improvement was significantly associated with BMI in male subjects (P = 0.024). We also stratified for time to initiate clozapine, finding significant associations in negative symptom at week 8 (P = 0.023) and week 18 (P = 0.003) for subjects, which started clozapine after 3 years of illness. Our results suggest that in subjects initiating clozapine, clinical improvement is associated with BMI increase, mostly in negative symptom and in patients after 3 years of antipsychotic use. Our findings were already described in the preantipsychotic era, suggesting some pathophysiological mechanism underlying both conditions.

Association Between Serum Insulin-Like Growth Factor 1 Levels and the Clinical Symptoms of Chronic Schizophrenia: Preliminary Findings.

Purpose: Insulin-like growth factor 1 (IGF-1) is a trophic mediator that is regulated by growth hormone and associated with the proliferation, development, and growth of neural cells. IGF-1 may be associated with the pathophysiology of schizophrenia, but this association remains controversial. This study aimed to investigate the relationship between serum IGF-1 levels and psychiatric symptoms in patients with chronic schizophrenia.Patients and Methods: A total of 65 patients were recruited from the University of Occupational and Environmental Health, Komine Eto Hospital, Moji Matsugae Hospital, Shin-Moji Hospital, and Tsutsumi Hospital in Kitakyushu between September 2019 and June 2020. Further, 20 healthy age- and sex-matched control participants were recruited from the Komine Eto Hospital and the University of Occupational and Environmental Health. Patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Drug-Induced Extrapyramidal Symptoms Scale. Serum levels of free plus albumin-bound IGF-1 (IGF-1) were measured by immunoradiometric assay. The measurements were performed using antibody beads for bound/free separation. Associations between serum IGF-1 levels and the PANSS scores were determined. We also examined the associations between serum IGF-1 levels and diabetes, antipsychotic drug use, and disease duration.Results: No significant difference was found in the serum IGF-1 level between patients with schizophrenia and healthy controls. Serum IGF-1 levels were significantly negatively correlated with the PANSS total score (R2 = 0.06, p = 0.015) and PANSS general score (R2 = 0.088, p = 0.008), but not with the PANSS positive scores and PANSS negative scores. Serum IGF-1 levels were not related to the prevalence of diabetes (p = 0.64). However, a significant correlation was observed between serum IGF-1 levels and age (B = −1.88, p < 0.0001). Serum IGF-1 levels could not distinguish patients with schizophrenia and healthy controls.Conclusion: The association between serum IGF-1 levels and psychiatric symptoms may be complicated in patients with chronic schizophrenia.

Matrix Metalloproteinase 9 Blood Alterations in Patients With Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis.

Matrix metalloproteinase 9 (MMP-9), an extracellular network protease implicated in glutamatergic signaling, may be part of the pathophysiology of schizophrenia spectrum disorders (SSD). We performed a systematic review in PubMed/Embase until July 15, 2020, conducting a random-effects meta-analysis of studies comparing MMP-9 blood levels in SSD vs healthy controls (HCs) and psychiatric controls (PCs), calculating between-group differences in standardized mean differences (SMDs) ± 95% confidence intervals (CIs). Meta-regression analyses included sex, age, illness duration, antipsychotic dose, and Positive and Negative Syndrome Scale (PANSS) total/subscales. Subgroup analyses included first-episode patients (FEP) vs non-FEP, each vs HCs and vs PCs, and blood sample type. Study quality was assessed using the Newcastle-Ottawa scale. Four, five, and two trials were rated as high, fair, and low quality. In 11 studies (n = 1443), 643 patients (age = 36.7 ± 14.1 years, females = 42.9%) were compared with HCs (n = 631), with 4 studies including also 169 PCs. MMP-9 levels were higher in SSD vs HCs (SMD = 0.52, 95%CI = 0.20-0.85, P = .002), but not in PCs vs HCs (n = 132, after removing one implausible outlier [SMD = 0.33, 95%CI = -0.16 to 0.85, P = .082]). MMP-9 differences between SSD and HCs were associated with higher PANSS total (coefficient = 0.02, 95%CI = 0.01-0.02, P < .001), PANSS positive (coefficient = 0.08, 95%CI = 0.02-0.13, P = .006), and PANSS general scores (coefficient = 0.02, 95%CI = 0.01-0.03, P < .001). MMP-9 level differences vs HCs did not vary significantly between FEP (n = 103, SMD = 0.44, 95%CI = 0.15-0.72, P = .71) and non-FEP patients (n = 466, SMD = 0.59, 95%CI = 0.38-0.80; P = .34) (FEP vs non-FEP: P = .39). In four high-quality studies, MMP-9 levels remained significantly higher in SSD vs HCs (SMD = 0.82, 95%CI = 0.03-1.61). Findings suggest MMP-9 upregulation in SSD, requiring further validation and understanding of related pathways.

T194. SUBJECTIVE ANOMALIES OF IMAGINATION AGGREGATE IN SCHIZOPHRENIA-SPECTRUM DISORDERS AND ARE ASSOCIATED WITH DISORDERS OF BASIC SELF

BackgroundImagination is the formation of ideas or images of something known not to be present to the senses. Clinical psychopathology has few notions addressing this domain apart from obsession and rumination. Some classic psychopathological notions such as Jaspers’ concept of pseudohallucination or the pseudo-obsession are relevant to this area. In a recent research project, informed by contemporary philosophy of mind and phenomenology, we have developed novel concepts targeting subjective disturbances of imagination and fantasy life with a focus on the schizophrenia-spectrum. Patients describe a spatialization of images, i.e., stable imagery with an articulated spatial structure being liable to inspection ‘from afar in the mind’ and often undergoing an autonomous development independently of the will of the patient (‘like watching a movie in the head’). Other notions address tacit, non-psychotic erosions of the demarcation of fantasy life from perception and memory. A broad range of ideations (such as ‘daydreams’, ‘fears’, anticipations, intrusions, paranoid or suicidal ideation) may involve such structural disturbances of experience. Here, we present data from the first, cross-sectional study investigating the distribution of anomalies of imagination in different diagnostic groups and healthy controls as well as their association with positive symptoms, negative symptoms and disorders of basic selfhood.MethodsThe sample (N=81) included in- and outpatients with schizophrenia or another non-affective psychosis (N=32), outpatients with schizotypal disorder (N=15) or other mental illness (N=16) and healthy controls (N=18). The sample was 70% female with mean age 29.9 (SD 6.8; range 18–42) years. Anomalies of imagination were assessed with the Examination of anomalous fantasy and imagination (EAFI), which is an instrument recently developed in our group for a semi-structured interview exploring these experiences. The EAFI has shown very good reliability with average Kappa of 0.84. Disorders of basic self were assessed with the Examination of anomalous self experience (EASE) and positive, negative and general symptoms with the Positive and Negative Syndrome Scale (PANSS).ResultsAnomalies of imagination aggregated significantly (p < 0.000, Kruskall-Wallis test) in the schizophrenia-spectrum disorders compared to other mental illness with no significant difference between schizophrenia and schizotypal disorder. The group of healthy controls very rarely reported these anomalies and scored significantly lower (p < 0.000) than all diagnostic groups. In multivariate linear regression analysis (R2 = 0.66), EAFI score was significantly associated with EASE score (β = 0.62, p < 0.000), PANSS positive (β = 0.34, p = 0.01) and PANSS negative (β = 0.29, p = 0.02), but not PANSS general score (β = -0.29, p = 0.07). More than 79% of the schizophrenia-spectrum patients retrospectively reported the onset of these experiences to adolescence or earlier.DiscussionThe results of this cross-sectional study support that the subjective anomalies of imagination, targeted with the EAFI, are associated with the schizophrenia-spectrum. The association with disorders of basic self, which has been shown to have trait-like characteristics and to predict transition to schizophrenia-spectrum disorders, may reflect that the anomalies of imagination share a common experiential core-structure with self disorders. We suggest that the anomalies of imagination belong to an early onset level of psychopathology in the schizophrenia-spectrum and may have a relevance for differential diagnosis and early detection.

Decreased plasma levels of gasotransmitter hydrogen sulfide in patients with schizophrenia: correlation with psychopathology and cognition.

Aberrant N-methyl-D-aspartate receptor (NMDAR) function has been implicated in the pathophysiology of schizophrenia. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that regulates NMDAR function. The current study investigated the relationship between plasma H2S levels and both psychopathological and cognitive symptoms in schizophrenia. Forty-one patients with schizophrenia and 40 healthy control subjects were recruited in present study. Schizophrenic symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was evaluated with a neuropsychological battery including seven neurocognitive tests. Plasma H2S levels were measured by reversed-phase high-performance liquid chromatography (RP-HPLC). Patients with schizophrenia performed worse in all of the cognitive tests than the healthy controls except for the visual memory. Plasma H2S levels were significantly lower in patients with schizophrenia relative to healthy control subjects (F= 3.821, p= 0.007). Correlation analysis revealed a significant negative correlation between the H2S levels and the PANSS general scores (r= - 0.413, p= 0.007). Additionally, a positive association was observed between plasma H2S levels and working memory (r= 0.416, p= 0.007), visual memory (r= 0.363, p= 0.020), or executive function (r= 0.344, p= 0.028) in patients. Partial correlation analysis showed that the correlations between the H2S levels and the PANSS general scores, working memory, visual memory, or executive function were still significant when controlling for age, gender, years of education, BMI, duration of illness, and age of onset. The significant relations observed in the current study between H2S and the general psychopathological as well as cognitive symptoms suggest that decreased H2S is involved in the psychopathology and cognitive deficits of schizophrenia, and it might be a promising peripheral biomarker of schizophrenia.

S158. REWARD ALTERATIONS IN ANTIPSYCHOTIC NAïVE FIRST-EPISODE-PSYCHOSIS PATIENTS BEFORE AND AFTER TREATMENT WITH A PARTIAL DOPAMINE AGONIST

BackgroundAlterations of the brain reward system is a common finding in patients with psychoses and it may be affected by antipsychotic medication. There are however only few longitudinal studies on medication effect and the effect of a partial dopamine agonist have not previously been examined in patients. The aim of the present study is to explore reward abnormalities in first episode psychotic patients and matched heathy controls (HC) before and after treatment with a partial dopamine agonist (aripiprazole), and relate the findings to dopamine synthesis capacity (F-DOPA-PET), glutamate and GABA levels in the brain (MRS at 3T) and treatment outcome. Here we present preliminary baseline and follow up analyses on functional magnetic resonance imaging (fMRI) only.MethodsThe project is a part of a multimodal prospective cohort study. Reward related brain activity was examined with fMRI using a variant of the Monetary Incentive Delay Task before and after 6 weeks, where patients were treated with individual doses of aripiprazole. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Whole brain voxel-wise group comparison was performed at baseline and follow up using two sample t-test with a corrected cluster significant threshold of P=0.05. Likewise, the effect of time and group time interaction was analyzed voxel-wise.ResultsInclusion is ongoing and data have been analyzed for 19 patients, age 22.9(4.6), 9 males (47%) and 24 HC, age 22.1(2.7), 11 males (46%). Mean medication dose was 11.7 (6) mg aripiprazole at follow up.Psychopathology: At baseline patients were moderately ill with a mean PANSS total score of 69 (14). Paired t-test showed a significant reduction over time for PANSS total score to 57 (12) (P<0.001), with significant improvements in PANSS positive, PANSS negative and PANSS general scores (all p<0.05).fMRI: There were no group differences at baseline.At follow up, patients had an increased signal in medial frontal cortex and Anterior Cingulate Cortex (ACC) compared to HC during anticipation of monetary gain. During outcome evaluation, patients likewise had an increased signal in right striatum and paracingulate gyrus in the win contrast, increased signal in left ventral part of striatum and ACC in the lose contrast, and increased signal in right striatum and ACC in the miss contrast compared to HC. There was only a significant effect of time in patients in the anticipation to win contrast and no significant group time interaction.DiscussionThe data represent work in progress and should be taken with precaution. The group-differences at follow up which were not found at baseline may suggest that treatment with a partial dopamine agonist lead to alterations of reward processing in patients. This is further supported by the effect of time in patients in the anticipation to win contrast. The data collection is still ongoing, and we expect to increase the size of the cohort and plan to relate the findings to measures of dopamine, GABA, glutamate and psychopathology.

The Interaction of Polymorphisms of IL10 and DBH Was Associated with General Symptoms of PANSS with TD in Chinese Han Schizophrenic Patients

ObjectiveTardive dyskinesia (TD) is a human hyperkinetic movement disorder as a result of potentially irreversible long-term chronic first-generation antipsychotic medications. Unfortunately, mechanisms involved in the development of TD have been poorly understood. Previous studies have indicated that some genetic polymorphisms of immune system and dopamine beta-hydroxylase (DBH) genes may be involved in the pathogenesis of TD. Rs1800872 and rs72393728 are located on the promoter of interleukin-10 (IL10) and DBH gene, respectively. The genetic association between the rs1800872 and TD is unclear. Previous studies have indicated that genetic variations of IL 10 and DBH are implicated in the positive and negative symptoms in schizophrenia. However, the interaction of two variations with severity of TD and symptoms of schizophrenic patients with TD has not been reported. The present study investigated whether these variations and their interaction were associated with clinical phenotypes of TD with schizophrenia in a genetically homogeneous northern Chinese Han population.MethodsRs1800872 and rs72393728 were genotyped in schizophrenic patients with TD (n = 372) and without TD (NTD; n = 412). The Abnormal Involuntary Movement Scale (AIMS) and Positive and Negative Syndrome Scale (PANSS) were applied to assess the severity of TD and psychopathology of schizophrenia, respectively.ResultsThe allele and genotype frequencies of rs1800872 and rs72393728 did not significantly differ between TD and NTD patients (p>0.05). No significant difference was found in the AIMS total score among the genotypes of two loci (p>0.05). Interestingly, the interaction of rs1800872 and rs72393728 showed a significant association with the PANSS general score (p = 0.011), and a trend toward to the PANSS total score (p = 0.055).ConclusionThese findings suggest that the interaction of rs1800872 and rs72393728 variants may play a role in psychopathology of the general symptoms on PANSS in schizophrenic patients with TD in a northern Chinese Han population.

Selective Serotonin 3 Receptor Antagonist Treatment for Schizophrenia: Meta-analysis and Systematic Review

Double-blinded, randomized, placebo-control trials of selective serotonin 3 receptor antagonists (5-HT3R-ANTs) for schizophrenia have differed in outcome. This meta-analysis tests the hypothesis that 5-HT3R-ANTs are effective for the treatment for schizophrenia. We searched PubMed, the Cochrane Library database, and PsycINFO up to June 15, 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing 5-HT3R-ANTs add-on therapy with placebo. The risk ratio (RR), 95% confidence intervals (CI), and standardized mean difference (SMD) were calculated. A random-effects model was used. Six studies (total n=311) were identified. These included one granisetron plus risperidone study, one ondansetron plus risperidone study, one ondansetron plus haloperidol, and three tropisetron plus risperidone studies. The statistically significant effects of 5-HT3R-ANTs add-on therapy on Positive and Negative Syndrome Scale (PANSS) total scores were SMD=-1.03, CI=-1.70 to -0.36, p=0.003 (I (2)=82%, 5 studies, n=261); on negative scores were SMD=-1.10, CI=-1.82 to -0.39, p=0.002 (I (2)=84%, 5 studies, n=261); and on PANSS general scores were SMD=-0.70, CI=-1.23 to -0.17, p=0.01 (I (2)=73%, 5 studies, n=261). However, 5-HT3R-ANTs add-on therapy was not superior to placebo in PANSS positive scores (SMD=-0.12, p=0.33). Dropout due to all cause (RR=0.80, p=0.50), inefficacy (RR=0.76, p=0.65), or adverse events (RR=0.84, p=0.75) was similar in both groups. Constipation occurred significantly more often with 5-HT3R-ANTs than placebo (RR=2.05, CI=1.07-3.91, p=0.03, NNH=11, p=0.02). 5-HT3R-ANTs add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia, and 5-HT3R-ANTs seem to be well-tolerated treatments.