Changes In Positive And Negative Syndrome Scale Scores Research Articles

Pharmacist-led Si-care (schizophrenia care) model to improve medication adherence and symptom management in schizophrenia

IntroductionSchizophrenia is a chronic mental disorder that requires long-term treatment, particularly antipsychotic medications. However, medication adherence among patients with schizophrenia is often suboptimal, leading to symptom relapse and poor outcomes. The Si-Care (Schizophrenia Care) program was developed as a pharmacist-led home intervention to improve medication adherence and support symptom control in patients with schizophrenia. This study aimed to evaluate the effectiveness of the Si-Care intervention in improving medication adherence and maintaining stability of symptoms among schizophrenia patients. MethodsA quasi-experimental study was conducted in three community health centers or Puskesmas in Banjarmasin, Indonesia. A total of 57 participants were recruited according to the sampling criteria. The Si-Care intervention consisted of seven home visits by trained pharmacists over four months, providing education, counseling, and medication monitoring. Adherence to medication was evaluated using the pill count method and severity of symptoms was measured using the Positive and Negative Syndrome Scale (PANSS) pre- and post-intervention. Data were analyzed using the Friedman test for adherence and the Wilcoxon test for PANSS scores. ResultsMean medication adherence improved significantly from 77.38 % ± 25.85 at baseline (T0) to 97.57 % ± 11.09 at the final visit (T4) (p = 0.000). However, the decrease in PANSS scores from 38.03 ± 9.14 to 37.81 ± 9.15 was not statistically significant (p = 0.089). Despite the lack of significant change in PANSS scores, symptoms remained stable throughout the intervention, suggesting effective symptom management. ConclusionsThe Si-Care intervention significantly improved medication adherence among people with schizophrenia, contributing to the maintenance of stable symptoms. Pharmacist-led home interventions provide valuable support to address adherence challenges and should be considered a critical component in schizophrenia care. Future studies should consider a more rigorous design, a larger sample size, and longer follow-up to better evaluate the sustainability, scalability, and applicability of the intervention in diverse healthcare settings.

Changes in IL-6, IL-12, IL-5, IL-10 and TGF-β1 Concentration in Patients with Treatment-Resistant Schizophrenia (TRS) Following Electroconvulsive Therapy (ECT)-A Pilot Study.

Background/Objectives: Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, IL-12, IL-5, IL-10 and TGF-β1 changes (pre- and post-ECT) and the effectiveness of ECT in TRS patients. The second aim is to search for correlations between serum concentrations of the above specified cytokines and psychometric assessments of clinical schizophrenia symptoms. Methods: The cytokine concentrations were measured in eight TRS patients on psychopharmacological treatment prior to and following ECT and in 13 control subjects. Psychopathology assessment was based on the Positive and Negative Syndrome Scale (PANSS). Results: Prior to ECT, IL-10 concentration was significantly higher in TRS patients, while IL-5 was decreased in comparison to the controls. A significant concentration decrease in the pro-inflammatory cytokines IL-6 (p = 0.012), IL-12 (p = 0.049) and anti-inflammatory IL-10 (p = 0.012) post-ECT vs. pre-ECT was observed, whereas concentrations of IL-5 and TGF-β1 did not significantly change. Also, a significant decrease in schizophrenia symptoms measured by the PANSS post-ECT was found. Furthermore, the pattern of correlations between PANSS scores and cytokine concentrations was different when comparing levels pre- and post-ECT. Additionally, correlations between changes in PANSS scores and cytokine concentrations were found. Conclusions: These results may indicate the probable impact of electroconvulsive therapy on the balance between pro- and anti-inflammatory cytokines, which may correspond to a neurobiological therapeutic effect of ECT in TRS patients.

Electrophysiological Markers Predicting Antipsychotic Treatment Response in Patients with Schizophrenia: A Retrospective Study.

This study aimed to provide an objective means of predicting treatment responses in patients with schizophrenia using quantitative electroencephalography (qEEG) as an electrophysiological indicator. We obtained qEEG recordings from patients with schizophrenia and explored them for patterns indicative of treatment responsiveness. The study included 68 patients had been diagnosed with schizophrenia spectrum disorder. After retrospectively gathering demographic information, clinical data such as qEEG, Positive and Negative Syndrome Scale (PANSS), a multiple regression analysis was performed. This analysis employed baseline qEEG findings as independent variables and PANSS score changes as dependent variables to discern causal relationships. The mean age of the participants was 38.4 years(SD =13.73). The mean PANSS score on admission was 92.97, decreasing to 67.41 at discharge. Multiple regression analysis revealed that delta waves in T4 (β=0.346, t=3.165, p=0.002), and high-beta waves in Fp2 (β=0.231, t=2.361, p=0.021) were associated with PANSS changes in absolute power. In addition, the delta waves of O2 (β=0.250, t=3.288, p=0.002); beta waves of T3 (β=-1.463, t=-5.423, p<0.001) and O2 (β=0.551, t=3.366, p=0.001); high beta waves of Fp1 (β=0.307, t=4.026, p<0.001), T3 (β=0.855, t=4.414, p<0.001) and T6 (β=-0.838, t=-4.559, p<0.001) of absolute power using the Z-score were also related to PANSS changes. Pearson's correlation analysis showed that only delta waves at Cz (r= 0.246, p=0.043) in absolute power correlated with changes in the PANSS. We found that certain qEEG wave patterns in patients with schizophrenia prior to antipsychotic treatment were linked to PANSS changes before and after treatment. Delta waves and beta waves, primarily in the frontal and temporal regions, were found to be significantly associated with changes in PANSS scores. In the future, the qEEG indicators identified in this study could serve as electrophysiological markers for predicting antipsychotic treatment responses in patients with schizophrenia.

OXTR polymorphisms associated with severity and treatment responses of schizophrenia

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = −0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.

Olanzapine-Samidorphan for Schizophrenia: A Systematic Review and Meta-Analysis.

United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse events (weight gain) in adult patients with schizophrenia and bipolar disorder. To opine about the safety and efficacy of OLZSAM, authors performed a systematic review and meta-analysis to convene justifiable evidence. A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, from inception to September 2022, with the keywords: 'olanzapine and samidorphan' and schizophrenia; and "ALKS3831" and "lybalvi." Clinical trials published in English that analyzed the efficacy and safety of OLZSAM were included. The significant outcomes included in this study were change from baseline (CFB) in Positive and Negative Syndrome Scale (PANSS) at the end of the study, the proportion of patients with weight gain at the end of the study, the proportion of patients with at least one adverse event, and the incidence of drug discontinuation due to adverse events. The change in PANSS score at the end of the study was comparable among groups receiving OLZSAM and olanzapine alone: standardized mean difference (SMD) = 0.04; 95% CI = -0.09 to 0.17; p = 0.57. The OLZSAM group reported less incidence of weight gain: risk ratio (RR) = 0.91; 95% CI = 0.62-1.34; p = 0.63, and any adverse event: RR = 0.99; 95% CI = 0.90-1.09; p = 0.81. Drug discontinuation incidence was higher in the OLZSAM group: RR = 1.22; 95% CI = 0.84-1.79; p = 0.30. The combination OLZSAM showed comparable efficacy to olanzapine alone in schizophrenia patients, with relatively less incidence of weight gain and adverse events; however, the drug discontinuation due to adverse events was more in the OLZSAM group.

Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone

BackgroundThis study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects.MethodsWe recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation.ResultsAmong the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01).ConclusionsThe genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes.

Clinical efficacy and safety of lurasidone in schizophrenia: 8 week randomized double blind active controlled trial

Background: Schizophrenia comprises a group of disorders with heterogeneous etiologies, it includes patients whose clinical presentations, treatment response, and courses of illness vary. This study was carried to study the clinical efficacy and safety of Lurasidone versus Risperidone on psychopathology and cognition in patients with first episode of schizophrenia.Methods: Patients diagnosed with first episode of schizophrenia were enrolled in the study. Patients were randomized to 80 mg/d (n = 27) of Lurasidone or 6mg/d (n = 27) of Risperidone. Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores, Schizophrenia cognition rating scale (SCoRS). IL-6 estimation was done and safety assessment was done using UKU side effect rating scale.Results: During the eight weeks of study; significant improvement was observed in PANSS total and all its subscale scores with both Lurasidone and Risperidone. Mean change in PANSS scores were not significant between the groups (-32.93 vs -35.33 p&gt;0.05). Mean change in SCoRS scores were significantly higher in Lurasidone group as compared to risperidone group (-8.43 vs -2.34, p&lt;0.001). Significant reduction in the IL-6 levels with both the groups but mean change in IL-6 levels were not significant between the group (-10.47 vs -8.31, p&gt;0.05). UKU side effect rating scores were significantly higher with Risperidone as compared to Lurasidone (p&lt;0.001).Conclusions: Lurasidone is as effective as Risperidone in improving psychopathology in patient of schizophrenia. Lurasidone proved more efficacious in improving cognition as compared to Risperidone. Both the treatment modalities are efficacious in lowering IL-6 levels. Lurasidone causes less adverse effects as compared to Risperidone.

M102 - VARIATION IN VOLTAGE-GATED CALCIUM CHANNEL GENES IS ASSOCIATED WITH ANTIPSYCHOTIC TREATMENT RESPONSE IN A SOUTH AFRICAN FIRST EPISODE SCHIZOPHRENIA COHORT

Background Voltage-gated calcium channels have been implicated in schizophrenia aetiology, however little is known about their involvement in antipsychotic treatment response. This study investigated variants within the calcium channel subunit genes for association with antipsychotic treatment response in a first episode schizophrenia cohort. Methods The patient cohort included 103 unrelated South African FES patients (80% South African Coloured, 12% Xhosa and 8% European descent). Treatment response was assessed using the positive and negative syndrome scale (PANSS) over a period of 12 months, with measurements taken biweekly for the first six weeks, and every three months thereafter. Variants within the calcium channel subunit genes (α1, α2δ, β and γ subunits) were mined from available GWAS data produced using the Infinium OmniExpressExome-8 Kit (Illumina, California, USA). In total 1830 variants were identified within 10 CACNA1 genes, four CACNB genes, four CACNA2D genes and eight CACNG genes. Linear mixed-effects models were used to investigate the effect of genetic variants on change in PANSS scores for each domain (positive, negative, general and total) over the twelve-month period, adjusting for age, gender, proportion ancestry, and baseline PANSS scores. Multiple modes of inheritance were considered and the best-fit model was selected for further analysis. Results Twelve regulatory variants were shown to be significantly associated with treatment outcome. Most notably the CACNA1B rs2229949 CC genotype was associated with improved negative symptomology, where the C-allele was predicted to abolish a miRNA-binding site (has-mir-5002-3p), suggesting a possible mechanism of action through which this variant may have an effect. Discussion These results implicate the calcium channel subunits in antipsychotic treatment response and suggest that increased activation of these channels may be explored to enhance or predict antipsychotic treatment outcome.

Effect of Damaging Rare Mutations in Synapse-Related Gene Sets on Response to Short-term Antipsychotic Medication in Chinese Patients With Schizophrenia

The underlying mechanism for individual differences in patient response to antipsychotic medication remains unknown. To discover genes and gene sets harboring rare variants associated with short-term antipsychotic medication efficacy. In this multicenter, open-label, randomized clinical trial conducted between July 6, 2010, and December 31, 2011, 3023 patients recruited in China of Chinese Han descent with schizophrenia with total Positive and Negative Syndrome Scale (PANSS) score ≥ 60 received a 6-week treatment of antipsychotic medications randomly chosen from 5 atypical and 2 typical antipsychotic medications. Whole-exome sequencing (WES) was performed in 316 participants (grouped into those with the best response [n=156] and those who had no response [n=160] to the antipsychotic medication prescribed), according to the total PANSS score reduction rate after 6 weeks of treatment. Validation was performed using targeted sequencing in an independent sample of 1920 patients. Data analyses was performed between March 15, 2016, and March 1, 2017. Drug efficacy at week 6 was assessed according to the change in PANSS scores from baseline. Extremely good and extremely poor responders were selected for an initial WES association study, from which a subset of genes showing putative association was selected for independent replication with a targeted sequencing approach. Of the 3023 patients (1549 [51.24%] female and 1474 [48.8%] male; mean [SD] age, 31.2 [7.9] years), 2336 (77.3%) were eligible for genetic analysis. After quality-control exclusions, 316 patients (10.5%) were included for WES and 1920 (63.5%) were included for replication. In the WES discovery stage, 2 gene sets (reduced NMDA [N-methyl-D-aspartate]-mediated synaptic currents and reduced AMPA [α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid]-mediated synaptic currents) were found to be enriched with rare damaging variants in the nonresponder group, suggesting the involvement of these gene sets in antipsychotic medication efficacy. Reduced NMDA-mediated synaptic currents gene set was further replicated in an independent sample using targeting sequencing. No statistically significant differences in antipsychotic drug response were found among the patients who received different antipsychotic drugs. Genetic variation in glutamatergic or NMDA neurotransmission is implicated in short-term antipsychotic medication efficacy; WES may have utility in the study of rare genetic variation in pharmacogenetics. Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934.

Specificity proteins 1 and 4 in peripheral blood mononuclear cells in postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial

Accumulating evidence suggests that Specificity Protein 1 (SP1) and 4 (SP4) transcription factors are involved in the pathophysiology of schizophrenia. The therapeutic use of selective oestrogen modulators such as raloxifene added to antipsychotic drugs in the treatment of postmenopausal women with schizophrenia has been investigated in a few clinical trials, which reported an improvement in negative, positive, and general psychopathological symptoms. We aimed to investigate the possible association between peripheral SP protein levels and symptom improvement in postmenopausal women with schizophrenia treated with adjuvant raloxifene. In a subgroup of 14 postmenopausal women with schizophrenia from a 24-week, randomized, parallel, double-blind, placebo-controlled clinical trial (NCT015736370), we investigated changes in SP1 and SP4 protein levels in peripheral blood mononuclear cells. Participants were randomized to either 60mg/day adjunctive raloxifene or placebo. Psychopathological symptoms were assessed at baseline and at week 24 with the Positive and Negative Syndrome Scale (PANSS). The expression of SP proteins was evaluated by immunoblot, and changes in PANSS scores and protein levels were compared at baseline and after 24 weeks of treatment. An improvement in symptoms was observed in the intervention group, but not in placebo group. Post-treatment protein levels of SP4, but not SP1, correlated with improvements in general and total PANSS subscales in the raloxifene intervention group. A reduction in SP4 levels was found after raloxifene treatment. These results suggest that SP4 may be involved in raloxifene symptom improvement in postmenopausal women and could be a potential candidate for future studies investigating blood-based biomarkers for raloxifene effectiveness.

S179. PROGNOSTIC UTILITY OF MULTIVARIATE MORPHOMETRY IN SCHIZOPHRENIA

BackgroundGroups of spatially distributed regions show shared variance in morphometric properties (e.g. grey matter volume) among subjects, thus forming independent morphometric ‘sources’ or covariance-based networks. Source based morphometry is a multivariate approach that is based on independent component analysis, and accounts for the inter-relationahsip among different brain regions while filtering out noisy artefactual effects of mass univariate voxel-based approaches. We have previously demonstrated that with multivariate SBM, it is possible to identify the structural basis of subtle psychopathological features such as formal thought disorder, whose anatomical correlates have been hitherto elusive. In the current study, we use multivariate SBM to identify the morphometric sources in drug-naïve first episode subjects that show progressive changes that predict symptom change over 1 year.Methods63 first-episode, drug-naive patients with schizophrenia underwent brain magnetic resonance imaging scans at baseline (T0) and rescanned after 1 year follow-up (T1). Positive and Negative Syndrome Scale (PANSS) was used to assess their psychopathology. Source based morphometry (SBM) was performed to analyze the gray matter volume (GMV), paired T contrasts for loading coefficients of GMV were constructed to detect the components that showed a significant effect of time. The change in PANSS scores between baseline and 1 year was expressed as a ratio of the scores at baseline - adjusted change scores for positive symptoms (POS%), negative symptoms (NEG%) and disorganization symptoms (DISORG%), with each domain score derived using van der Gaag’s 5-factor approach. Multiple regression analysis was conducted to predict the percentage change scores in each domain using the T0 and T1 loading coefficients of components showing time effect with age, gender and cumulative antipsychotic dose as covariates.ResultsOf the 30 spatial components of gray matter identified by SBM, loading coefficients of anterior cingulate cortex (ACC), anterior insula (AI) & inferior frontal gyrus (IFG), superior temporal gyrus (STG), middle temporal gyrus (MTG) and dorsal lateral prefrontal cortex (DLPFC) reduced with time in patients. The lower volume of AI & IFG at baseline and at 1 year related to poor improvement in positive and disorganization symptoms; lower volume of STG & MTG at baseline and 1 year predicted poor improvement in negative symptoms.DiscussionThe baseline distribution of GM in AI & IFG, STG and MTG are predictive of the course of illness. The relationship between GM sources and symptom severity continues even after 1 year of naturalistic exposure to antipsychotic treatment. If judiciously combined with other available predictors of prognosis, source-based morphometric analysis can aid meaningful prognostication in schizophrenia.

Dose-response meta-analysis of differences in means.

BackgroundMeta-analytical methods are frequently used to combine dose-response findings expressed in terms of relative risks. However, no methodology has been established when results are summarized in terms of differences in means of quantitative outcomes.MethodsWe proposed a two-stage approach. A flexible dose-response model is estimated within each study (first stage) taking into account the covariance of the data points (mean differences, standardized mean differences). Parameters describing the study-specific curves are then combined using a multivariate random-effects model (second stage) to address heterogeneity across studies.ResultsThe method is fairly general and can accommodate a variety of parametric functions. Compared to traditional non-linear models (e.g. Emax, logistic), spline models do not assume any pre-specified dose-response curve. Spline models allow inclusion of studies with a small number of dose levels, and almost any shape, even non monotonic ones, can be estimated using only two parameters. We illustrated the method using dose-response data arising from five clinical trials on an antipsychotic drug, aripiprazole, and improvement in symptoms in shizoaffective patients. Using the Positive and Negative Syndrome Scale (PANSS), pooled results indicated a non-linear association with the maximum change in mean PANSS score equal to 10.40 (95 % confidence interval 7.48, 13.30) observed for 19.32 mg/day of aripiprazole. No substantial change in PANSS score was observed above this value. An estimated dose of 10.43 mg/day was found to produce 80 % of the maximum predicted response.ConclusionThe described approach should be adopted to combine correlated differences in means of quantitative outcomes arising from multiple studies. Sensitivity analysis can be a useful tool to assess the robustness of the overall dose-response curve to different modelling strategies. A user-friendly R package has been developed to facilitate applications by practitioners.

Activity groups for people with schizophrenia: a randomized controlled trial

Background: UK guidelines recommend that patients with schizophrenia are offered access to social activities, however, the impact of such interventions have not been examined in a large randomized trial.Aims: To investigate the effect of an activity group intervention on mental health and global functioning 12 months after randomization compared to standard care alone.Methods: Secondary analysis of data from the MATISSE study. Primary outcomes were global functioning, assessed using the Global Assessment of Functioning (GAF), and mental health symptoms measured using the Positive and Negative Syndrome Scale (PANSS).Results: About 140 participants were randomized to activity groups and 137 to standard care alone. Follow-up data were collected from 242 (87%) participants. Mental health improved significantly among those offered activity groups (change in PANSS score = −6.0, 95% CI −2.3 to −9.8) but global functioning did not (change in GAF score = 0.8, 95% CI −1.7 to 3.3). No significant differences were found between treatment arms.Conclusions: Offering activity groups to patients with schizophrenia was not associated with any additional clinical benefits. There was poor uptake and attendance at activity groups. Interventions that aim to improve negative symptoms may be useful in enabling engagement in psychosocial interventions.

The association between weight change and symptom reduction in the CATIE schizophrenia trial

Background Weight gain and changes in metabolic indicators associated with some antipsychotics may be related to symptom improvement and thus an unavoidable correlate of clinical benefit. Methods Data from the CATIE schizophrenia trial comparing the effectiveness of perphenazine, olanzapine, risperidone, quetiapine and ziprasidone in a randomized, double-blind, trial over 18 months were used to evaluate the relationship between percent change in body mass index (BMI) and change in total serum cholesterol and triglycerides with the Positive and Negative Syndrome Scale (PANSS) score. Analysis of covariance for observations at 3 months and a mixed effects model for all observations up to 18 months adjusted for potentially confounding variables were used to examine these associations. Results In both models, there was a significant association ( p = 0.001) between change in PANSS total score and percent change in BMI, equating to a 0.28 and 0.21 point decrease in PANSS total score (range 30–210) per 1% increase in BMI respectively. Change in BMI accounted for 3% or less of variance for change in PANSS scores. There was no evidence that the association of symptoms and weight gain differed across medications in spite of substantial differences in weight gain and other metabolic measures. Neither total serum cholesterol nor triglyceride levels displayed a significant association with change in PANSS. Conclusion The magnitude of the relationship between change in BMI and PANSS was too small to be clinically important, indicating that switching medications to one with less metabolic risk is unlikely to result in meaningful loss of clinical benefit.

Insight: Demographic Differences and Associations with One-Year Outcome in Schizophrenia and Schizoaffective Disorder

Insight is increasingly seen as an important variable for study in psychotic illness, particularly in relation to treatment adherence. This study aims to quantify the association of insight with outcome, sociodemographic variables and diagnosis in a large stable patient sample. Data are from a one-year, open-label, international, multicenter trial (n=670) of long-acting risperidone in adult symptomatically stable patients with schizophrenia or schizoaffective disorder. Psychopathology and insight were quantified using the Positive and Negative Syndrome Scale (PANSS). Patients were assessed at four time points over the year of the study. 31.2% of the sample showed clinically significant deficits in insight at baseline. There were no differences based on sex, but significant differences in age and diagnosis, with oldest patients and schizophrenia patients (cf., schizoaffective disorder) showing more deficits. Baseline insight impairment was correlated with change in PANSS score at one year (r=-0.243, p<0.001). Recursive partitioning showed that, of those whose symptoms improved, those whose insight also improved were more likely to complete the trial. Insight is important above and beyond the effects of symptoms for predicting continuation in drug trials. This may have implications for the design and analysis of such trials, as well as suggesting the importance of targeting insight in treatment to increase likelihood of adherence to treatment. There also appear to be small but significant differences in insight based on age and diagnosis within the schizophrenia spectrum.

Treatment Outcomes of Patients With Tardive Dyskinesia and Chronic Schizophrenia

We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004. Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. clinicaltrials.gov Identifier: NCT00014001.

The —1019 C/G polymorphism of the 5-HT1A receptor gene is associated with negative symptom response to risperidone treatment in schizophrenia patients

The application of pharmacogenetics is currently one of the most promising developments in anti-psychotic treatment and is attracting more and more attention. Although risperidone belongs to the first-line atypical anti-psychotics, there have been relatively few risperidone pharmacogenetic studies, especially in Asian populations. We investigated the relationship between the C825T polymorphism of GBN3 (rs5443) and the -1019 C/G polymorphism of 5-HT(1)A (rs6295) and response to risperidone treatment. One-hundred and thirty schizophrenia patients were recruited. They were treated with risperidone monotherapy for eight weeks. Clinical response was assessed on the Positive and Negative Syndrome Scale (PANSS) on the day of admission and was subsequently assessed after eight weeks following the treatment. Patients were genotyped for two functional polymorphisms: C825T of GBN3 (rs5443) and -1019 C/G of HT(1)A (rs6295). Association tests between genotypes and percentage improvement in total PANSS scores, as well as positive symptom scores and negative symptom scores, were performed using analyses of variance (ANOVA). The -1019 C/G polymorphism of HT(1)A (rs6295) was associated with negative symptom response to treatment. Patients with the CC genotype showed substantial improvement as regards negative symptom response (F = 4.177, df = 2, P = 0.019), compared with the patients with the CG and GG genotypes. No association was observed between C825T of GBN3 (rs5443) and changes in PANSS scores. The results suggest that the -1019 C/G polymorphism (rs6295) in the 5-HT(1)A gene may be a useful predictor of reduction in negative symptoms in schizophrenic patients treated with risperidone.

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The Relationship Between Quality of Life and Clinical Efficacy From a Randomized Trial Comparing Olanzapine and Ziprasidone

To examine treatment-specific changes in health-related quality of life (QOL) among patients with schizophrenia and to assess the association between clinical and QOL improvement. This post hoc analysis used the findings of a 28-week, randomized, multicenter trial of patients with schizophrenia (DSM-IV) treated with olanzapine (10-20 mg/day) or ziprasidone (80-160 mg/day). Data were collected from August 2001 to December 2002. Efficacy was measured using the Positive and Negative Syndrome Scale (PANSS). Quality of life was assessed with the generic health self-administered Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the disease-specific expert-administered Heinrichs-Carpenter Quality of Life Scale (QLS). Mixed-effects-repeated-measures and last-observation-carried-forward approaches were used to assess the effects of treatment on QOL and the association of clinical outcomes to QOL outcomes. Olanzapine- and ziprasidone-treated patients demonstrated similar improvement from baseline to endpoint on the SF-36 and QLS. All correlations between changes in PANSS scores and the SF-36 were significant (p < .001), ranging from -0.159 to -0.400. All correlations between changes in PANSS scores and the QLS were significant (p < .0001), ranging from -0.286 to -0.603. The correlations between the 2 QOL measures were generally significant but small to moderate in magnitude. The results of this study indicate that, in patients with schizophrenia, olanzapine and ziprasidone treatment are associated with significant QOL and clinical improvements. Further, the significant correlation between change scores on the PANSS and QOL measures suggests that treatment-related clinical improvements are associated with improved health-related and disease-specific QOL. ClinicalStudyResults.org identifier 2347.

Switching Female Schizophrenic Patients to Quetiapine from Conventional Antipsychotic Drugs: Effects on Hyperprolactinemia

Conventional antipsychotic medications are associated with elevated prolactin levels, resulting in hyperprolactinemia and a number of unwanted side effects. Several atypical antipsychotics, on the other hand, are less likely to evoke hyperprolactinemia. The aim of this study was to investigate the prevalence of hyperprolactinemia induced by conventional antipsychotic drugs, examine changes in serum prolactin levels and psychiatric symptoms after switching to quetiapine, and identify the relevant characteristics of patients who may be suitable to switch to quetiapine. Sixty-nine of 74 consecutive female patients who had received conventional antipsychotic drugs were initially included in the study. Of these, 49 (71 %) patients suffered from hyperprolactinemia, of which a further 25 were subsequently switched to quetiapine. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS), and serum prolactin levels were measured just before and at 4 and 8 weeks after switching. Eight of the 25 (32 %) "switch" patients dropped out due to psychotic exacerbation during the 8 weeks. In the remaining 17 (68 %) patients, serum prolactin levels were significantly decreased without any significant change in PANSS scores after switching. The 17 patients who completed the switch had previously demonstrated significantly lower positive symptom scores compared to the 8 dropout patients. The present findings suggest that 71 % of female patients receiving conventional antipsychotic drugs may suffer from hyperprolactinemia and that approximately two-thirds of patients can be switched to quetiapine, resulting in an improvement in hyperprolactinemia. The main characteristic of the switched patients may be fewer positive symptoms.