Drug Treatment Of Schizophrenia Research Articles

Association between doxycycline use and long-term functioning in patients with schizophrenia

Importance and objectiveThe brain-penetrant tetracycline antibiotics, minocycline and doxycycline, have been proposed as potential candidate drugs for treatment of schizophrenia, based on preclinical studies and clinical trials. A potential long-term beneficial effect of these antibiotics for schizophrenia patients has not been investigated. This study was designed to determine if redemption of doxycycline prescription in schizophrenia is associated with decreased incidence of disability pension, a proxy for long-term functioning. DesignWe performed a population-based cohort study with data from schizophrenia patients available through the Danish registers. Survival analysis models with time-varying covariates were constructed to assess incidence rate ratios (IRR) of disability pension after exposure to doxycycline or a non-brain penetrant tetracycline, defined as at least one filled prescription. The analysis was adjusted for age, sex, calendar year, parental psychiatric status and educational level. ResultsWe used data from 11,157 individuals with schizophrenia (4,945 female and 6,212 male; average age 22.4 years old, standard deviation (std) 4.50). 718 of these were exposed to brain-penetrant doxycycline, and 1,498 individuals redeemed a prescription of one or more of the non-brain-penetrant tetracyclines. The average years at risk per person in this cohort was 4.9, and 2,901 individuals received disability pension in the follow-up period. There was a significantly lower incidence rate of disability pension in schizophrenia patients who had redeemed doxycycline compared to patients who did not redeem a prescription of any tetracycline antibiotics (Incidence rate ratio (IRR) 0.68; 95 % CI 0.56, 0.83). There was also a significant lower rate of disability pension in schizophrenia patients who redeemed doxycycline compared to individuals who redeemed a prescription of one of the non-brain penetrant tetracycline antibiotics (IRR 0.69 95 % CI 0.55, 0.87). ConclusionsIn this observational study, doxycycline exposure is associated with a reduced incidence of disability pension. These data support further studies on the potential long term neuroprotective effects of doxycycline and level of functioning in schizophrenia patients.

QSPR Analysis of Drugs for Treatment of Schizophrenia Using Topological Indices.

Schizophrenia is a chronic psychotic disorder characterized primarily by cognitive deficits. Drugs and therapies are helpful in managing the symptoms, mostly with long-term compliance. There is a pressing need to design more efficient drugs with fewer adverse effects. Solubility, metabolic stability, toxicity, permeability, and transporter effects are important parameters in the efficacy of drug design, which in turn depend upon different physical and chemical characteristics of drugs. In recent years, there has been growing interest in developing computational tools for the discovery and development of drugs for schizophrenia. Some of these methods use machine learning algorithms to predict the efficacy and side effects of the potential drugs. Other studies have used computer simulations to understand the molecular mechanisms underlying the disease and identify new targets for drug development. Topological indices are numeric quantities linked to the chemical structure of drugs and predict the properties, reactivity, and stability of drugs through the quantitative structure-property relationship (QSPR). This work is aimed at using statistical techniques to link QSPR correlating properties with connectivity indices using linear regression. The QSPR model gives quite a better estimation of the properties of drugs, such as melting point, boiling point, enthalpy, flash point, molar refractivity, refractive index, complexity, molecular weight, and refractivity. Results are validated by comparing actual values to estimated values for the drugs.

Predictors of 6-month follow-up Outcome of Drug Treatment in Schizophrenia in a tertiary hospital of Bangladesh

Background: Schizophrenia may have a better outcome in low- and middle-income countries. In Bangladesh short-term outcome of drug treatment of schizophrenia is also better. It is required to see the predictors of outcome of drug treatment of schizophrenia in Bangladesh.
 Objectives: General objective of this study is to assess the outcome of 6-month follow-up of patients with schizophrenia. Specific objective of this study is to find out the predictors of 6-month follow-up outcome of drug treatment in schizophrenia.
 Methods: Patients with a SCID-1/P diagnosis of schizophrenia (n=42) were assessed prospectively at baseline, at 6-week and at 6-month follow-up. Socio-demographic and relevant variables and questionnaire for family support and previous work record for the study were read in front of the patients and guardians and were filled up by the researcher. Psychopathological measurements were applied at base line by researcher and at 6-week and at 6-month by research assistant for the study population.
 Results: Follow-up data were available for 38 patients at 6-month and among them 86.85% achieved partial remission, 7.89% had not responded and 5.26% had relapsed. In multivariate analysis by General Linear Model Analysis of socio-demographic and relevant variables with the mean BPRS score as outcome in this study we found that age, education, marital status and history of previous work record were significantly associated with the 6-month treatment outcome. Conclusions: Drug treatment outcome of schizophrenia in Bangladesh is better in short-term follow-up. Increase family support and early management by drugs should be a target for intervention.
 Central Medical College Journal Vol 6 No 2 Jauly 2022 Page: 90-96

Schizophrenia and cell senescence candidate genes screening, machine learning, diagnostic models, and drug prediction.

Schizophrenia (SC) is one of the most common psychiatric diseases. Its potential pathogenic genes and effective treatment methods are still unclear. Cell senescence has been confirmed in mental diseases. A link exists between cellular senescence and immunity, and immune-related problems affect suicide rates in individuals suffering from schizophrenia. Therefore, the aims of this study were to identify candidate genes based on cell senescence that can affect the diagnosis and treatment of schizophrenia. Two data sets of schizophrenia were provided by the Gene Expression Omnibus (GEO) database, one was taken as training and the other as a validation group. The genes related to cell senescence were obtained from the CellAge database. DEGs were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). The function enrichment analysis was conducted, followed by machine learning-based identification for least absolute shrinking and selection operators (LASSO) regression. Random Forest were used to identify candidate immune-related central genes and establish artificial neural networks for verification of the candidate genes. The receiver operating characteristic curve (ROC curve) was used for the diagnosis of schizophrenia. Immune cell infiltrates were constructed to study immune cell dysregulation in schizophrenia, and relevant drugs with candidate genes were collected from the DrugBank database. Thirteen co-expression modules were screened for schizophrenia, of which 124 were the most relevant genes.There were 23 intersected genes of schizophrenia (including DEGs and the cellular senescence-related genes), and through machine learning six candidate genes were finally screened out. The diagnostic value was evaluated using the ROC curve data. Based on these results it was confirmed that these candidate genes have high diagnostic value.Two drugs related to candidate genes, Fostamatinib and Ritodine, were collected from the DrugBanks database. Six potential candidate genes (SFN, KDM5B, MYLK, IRF3, IRF7, and ID1) had been identified, all of which had diagnostic significance. Fostamatinib might be a drug choice for patients with schizophrenia to develop immune thrombocytopenic purpura (ITP) after treatment, providing effective evidence for the pathogenesis and drug treatment of schizophrenia.

Prediction of the significance in the improvement of depression symptoms of amisulpride in the treatment of schizophrenia: an 8-week case-control study.

Aminosulpiride is a benzamide used to treat acute or chronic schizophrenia Some researchers believe that early improvement of depression symptoms in patients has a certain predictive effect on the recovery of symptoms after drug treatment for schizophrenia. This study is aimed to explore whether the improvement of depression symptoms is a predictive factor for the amelioration of the schizophrenia symptoms by amisulpride treatment. A total of 383 patients with schizophrenia admitted to 15 hospitals in Fujian and Zhejiang from July 1, 2018 to March 31, 2019 were included in the study. The patients were treated with amisulpride tablets with a dose strategy of 200-1,200 mg/d for 8 weeks. The Positive and Negative Affect Scale (PANAS) was used as the criteria to evaluate the treatment effect, including criterion A and criterion B. After the course of treatment, the improvement of depression symptoms was compared between the remission group and the non-remission group. Logistic regression analysis was used to investigate predictors of symptom relief in schizophrenia patients treated with amisulpride. Of the 383 subjects with schizophrenia, 303 completed the 8-week treatment with amisulpride, and 244 (80.53%) achieved remission of symptoms after the treatment, satisfying criterion A. In 258 patients (85.15%), the symptoms were relieved and satisfied criterion B, while there was no significant difference between the number of patients who met criterion A and those who met criterion B (P>0.05). Both the remission group and the non-remission group had obvious improvement in depression symptoms. Furthermore, the remission group showed a more significant improvement in depression symptoms after the treatment. Logistic regression analysis revealed that the improvement of depression symptoms cannot be used as a predictor of symptomatic relief with amisulpride in the treatment of schizophrenia according to criterion A (B=-0.01, P=0.07). While under the criterion B, the patient's age could be used as a predictive factor of symptom remission from amisulpride in the treatment of schizophrenia (B=-0.08, P=0.03). Amisulpride is effective in the treatment of schizophrenia and improving depression symptoms. The improvement of depression symptoms has no significant predictive effect on the remission of schizophrenia symptoms.

Theories of the pathogenesis of schizophrenia

Introduction: Schizophrenia is one of the most serious and frightening of all mental illnesses. It affects almost 1% of the population worldwide. The main concept and treatment of schizophrenia are based on the dopaminergic hypothesis. However, accumulating evidence has shown that the core pathophysiology of schizophrenia might involve dysfunction in dopaminergic, glutamatergic, serotonergic, and gamma-aminobutyric acid signaling.The aim of the study: The purpose of this systemic review was to collect and analyse current and new information on the pathogenesis of schizophrenia.Material and method: Standard criteria were used to review the literature data. The search of articles in the PubMed database was carried out using the following keywords: schizophrenia, dopamine hypothesis, serotoninergic hypothesis, hypothesis of schizophrenia .Description of the state of knowledge: There are evidence that pathogenesis of schizophrenia include dysfunction in dopaminergic, serotoninergic, GABAergic, glutamatergic systems. The use of drugs that act on any of these systems reduces the symptoms of the disease. Nicotinic receptors may also be the target for drugs in treatment of schizophrenia. Studies about the role of nicotinic receptors in pathogenesis of schizophrenia show that it normalize many of the sensory processing deficits found in schizophrenia.Summary: Despite the fact that current concept and treatment are still based on the dopaminergic hypothesis of the disease, existing theories and each new theory, open up different ways for treating schizophrenia. Considering that schizophrenia is one of the most serious and frightening of all mental illnesses and has major public health implications, more research about pathogenesis and ways of treatment is needed.

Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients\u2014a genome-wide association study adjusting for smoking habits

Clozapine (CLZ) is the superior antipsychotic drug for treatment of schizophrenia, but exhibits an extensive interpatient pharmacokinetic variability. Here, we conducted a genome-wide association study (GWAS) of CLZ serum concentration adjusting for known smoking habits, which is a major nongenetic factor reducing CLZ levels. The study included 484 patients with 10,283 steady-state serum concentrations of CLZ and N-desmethylclozapine, prescribed dosing, co-medications and known smoking habits (n = 422; 9284 serum samples) from a therapeutic drug monitoring (TDM) service. The GWAS analyses were performed with and without smoking habits as covariate, where possible hits were assessed in relation to the target CLZ concentration range applied in the TDM service (300–2500 nmol/L). The smoking-independent analysis of N-desmethylclozapine serum concentration and the CLZ-to-N-desmethylclozapine ratio replicated the previously identified locus on chromosome 4. After adjusting for smoking habits in patients confirmed as ‘smokers’ (61%) or ‘nonsmokers’ (39%), a novel variant (rs28379954; minor T>C allele frequency 4.1%; 7.6% CT carriers in the population) within the gene encoding the nuclear factor 1 B-type (NFIB) was significantly associated with reduced CLZ serum concentration (p = 1.68 × 10−8, beta = −0.376; explained variance 7.63%). There was no significant association between rs28379954 and N-desmethylclozapine concentration in the GWAS analysis (p = 5.63 × 10−5). The fraction of CLZ TDM samples below 300 nmol/L was significantly higher in carriers vs. noncarriers of the rs28379954 minor C allele [12.0% (95% CI: 9.4–14.7) vs. 6.2% (95% CI: 5.7–6.8), p < 0.001]. We identified a novel variant in the NFIB gene associated with reduced CLZ levels and increased risk of subtherapeutic serum concentrations. This warrants testing of clinical relevance of screening for this gene variant, and also experimental studies to investigate the biological mechanisms of NFIB involvement in CLZ pharmacokinetics.

A comparative study of effectiveness, safety and cost effectiveness of olanzapine, risperidone and aripiprazole therapy in schizophrenia

Background: Schizophrenia is the most common psychotic disorder and responsible for approximately half of long-term psychiatric hospitalizations. Antipsychotic medications reduce the psychotic symptoms and prevent relapses. The choice of drug for treatment of schizophrenia depends on many issues, including effectiveness, cost, side-effect burden, availability, and tolerability. Many studies have compared antipsychotic drugs with one another, but no broad consensus has been reached. Our study compares the clinical effectiveness, safety and cost effectiveness of atypical antipsychotics in our setting.Methods: This was an observational, prospective study in which schizophrenia patients receiving either olanzapine, risperidone or aripiprazole were enrolled. Patients were followed up for 3 months. Evaluation of effectiveness was done by analysing mean reduction in PANSS score. Analysis of ADRs was done using WHO causality scale and Hartwig and Siegel severity scale. Cost analysis was done by comparing all three groups in term of cost range of antipsychotic drugs per improvement in PANSS score during the study period.Results: In the present study, the average dose of antipsychotic drugs received by a patient per day was 8.83±2.98 mg in olanzapine group, 4.76±1.12 mg in risperidone group and 20.43±8.5 mg in aripiprazole group. Mean reduction in PANSS score from baseline to 12 weeks was 23.79% in olanzapine group, 25.41% in risperidone group and 24.65% in aripiprazole group. Conclusions: All the groups were equally effective in reduction in PANSS score while risperidone was the most cost effective.

The pharmacoeconomic efficacy of lurasidone in the treatment of schizophrenia

To conduct a comprehensive pharmacoeconomic evaluation of lurasidone for the treatment of patients with schizophrenia under Russian healthcare system conditions and inclusion in EDL (Essential Drugs List) and Medication List for the Certain Categories of Citizens. A retrospective study of lurasidone in the treatment of patients with schizophrenia was performed. Methods of pharmacoeconomic analysis were: cost analysis, budget impact analysis and cost-effectiveness analysis. Use of lurasidone for the treatment of patients with schizophrenia requires 50.04% less costs than the use of paliperidone and 46.69% less costs than the use of sertindole allowing to provide additional therapies to 100.1 and 87.6% of patients, respectively. The cost minimization analysis results are stable when prices fluctuate in the range of ±30%. Considering the current volume of antipsychotic drug supply, replacing 100% of paliperidone with lurasidone from the first year will reduce the cost of antipsychotics for patients who received paliperidone by 39.79 or by 360.81 million rubles over 3 years. Replacing 100% of sertindole with lurasidone from the first year will reduce the cost of antipsychotics for patients who received sertindole by 37.21 or 173.87 million rubles over 3 years. The results of the budget impact analysis are resistant to changes in prices for compared drugs in a wide range. Lurasidone is a more effective drug for treatment of schizophrenia from a pharmacoeconomic point of view in comparison with paliperidone and sertindole. With comparative efficacy with paliperidone and sertindole the use of lurasidone can significantly reduce the burden on budget of state programs of compensation for certain categories of citizens.

Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis

Olanzapine, a representative of antipsychotics, is a first-line drug for treatment of schizophrenia. However, olanzapine-induced liver steatosis limits its clinical utilization. This study is to explore the mechanism of liver steatosis induced by olanzapine based on the regulation of transporters involved in uptake and oxidation of fatty acids. Our results revealed that 12-week oral administration of olanzapine increased hepatic triglyceride(TG), caused liver steatosis. Our further studies showed that the expression of fatty acid transporter 2(FATP2) and fatty acid binding protein 1(FABP1) were up-regulated in liver of female mice after 12-week olanzapine exposure, as well as in primary mouse hepatocytes treated with olanzapine. Olanzapine treatment also reduced hepatic β-hydroxybutyrate level (indicator of fatty acid β-oxidation), meanwhile, the L-carnitine (L-Car) concentration in liver of olanzapine group was significantly lower than that in control group. Further study demonstrated that both mRNA and protein expression of hepatic OCTN2 (carnitine/organic cation transporter 2) were obviously down-regulated in male mice after 12-week olanzapine treatment. Also, olanzapine markedly inhibited L-Car uptake in MDCK-hOCTN2 cells (1.06 μM of IC50), HepG2 cells and primary mouse hepatocytes. Supplementation of L-Car attenuated hepatic TG rise and improved simple steatosis in olanzapine treatment mice. Taken together, up-regulation of FATP2/FABP1 and down-regulation/inhibition of hepatic OCTN2 probably contribute to olanzapine-induced liver steatosis. Supplementation of L-Car is a promising strategy to attenuate olanzapine-induced simple steatosis.

117. Biomarker Assessment of Dose Dependent Target Engagement of mGluR-2,3 Partial Agonist for Schizophrenia Treatment

There is a desperate need for novel drugs for treatment of schizophrenia. Glutamate is a prioritized target for drug development. Attempts to develop mGlu-R partial agonists were unsuccessful. Upon reviewing the data, we concluded that doses to achieve adequate target engagement were tested. This study tested the ability to an mGluR-2,3 partial agonist to inhibit the effects of a pharmacologic model of schizophrenia as reflected by fMRI.

Benzofurazan-based fluorophore for the selective determination of flupentixol dihydrochloride: Application to content uniformity testing.

One of the most commonly used drugs in treatment of schizophrenia is flupentixol dihydrochloride, therefore it is important to develop a simple, low cost and sensitive spectrofluorimetric method for the estimation of flupentixol dihydrochloride. The yellow fluorescent product that is generated from the nucleophilic substitution reaction of the free lone pair of the alcoholic hydroxyl group of the drug and 4-chloro-7-nitrobenzofurazan (NBD-Cl) in Mcllvaine buffer pH7.0 was estimated at 510nm (λex 460nm). The variables that affect the development of the reaction product were explored and optimized. The linear range of this method was 0.5-2.5μgml-1 with a limit of quantitation equal to 0.29μgml-1 . Our method was successfully applied for the assurance of flupentixol in tablet form with average percentage recovery of 99.08±1.01% without obstruction from the basic excipients exhibits. Furthermore, our strategy was extended to study the content uniformity testing of flupentixol in Fluaxnol® tablets.

Genetic evidence for a role of the SREBP transcription system and lipid biosynthesis in schizophrenia and antipsychotic treatment

Schizophrenia is a serious psychotic disorder, with disabling symptoms and markedly reduced life expectancy. The onset is usually in late adolescence or early adulthood, which in time overlaps with the maturation of the brain including the myelination process. Interestingly, there seems to be a link between myelin abnormalities and schizophrenia. The oligodendrocyte-derived myelin membranes in the CNS are highly enriched for lipids (cholesterol, phospholipids and glycosphingolipids), thereby pointing at lipid homeostasis as a relevant target for studying the genetics and pathophysiology of schizophrenia. The biosynthesis of fatty acids and cholesterol is regulated by the sterol regulatory element binding protein (SREBP) transcription factors SREBP1 and SREBP2, which are encoded by the SREBF1 and SREBF2 genes on chromosome 17p11.2 and 22q13.2, respectively. Here we review the evidence for the involvement of SREBF1 and SREBF2 as genetic risk factors in schizophrenia and discuss the role of myelination and SREBP-mediated lipid biosynthesis in the etiology, pathophysiology and drug treatment of schizophrenia.

Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo.

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells.

Case Reports: Treatment-Resistant Schizophrenia with Severe Type 2 Diabetes Mellitus Treated with Clozapine

Objective: Clozapine is regarded as the most effective drug for treatment of schizophrenia but has complex adverse effects associated with hyperglycemia and diabetes mellitus. Method: We report that clozapine was very effective to treat positive, negative, and cognitive symptoms and well tolerated to a treatment-resistant schizophrenia patient with severe type 2 diabetes mellitus (DM) under cautious blood-sugar monitoring. Results: Clozapine itself and discontinuation of other psychotropic and anticholinergic agents after switching may improve cognitive function and adherence to the treatment regimens for schizophrenia and DM. Conclusion: Clozapine can be administered to treatment-resistant schizophrenia patients even with severe DM with caution.

HTR1A Polymorphisms and Clinical Efficacy of Antipsychotic Drug Treatment in Schizophrenia: A Meta-Analysis.

Background:This meta-analysis was conducted to evaluate whether HTR1A gene polymorphisms impact the efficacy of antipsychotic drugs in patients with schizophrenia.Methods:Candidate gene studies that were published in English up to August 6, 2015 were identified by a literature search of PubMed, Web of Science, and Google scholar. Data were pooled from individual clinical trials considering overall symptoms, positive symptoms and negative symptoms, and standard mean differences were calculated by applying a random-effects model.Results:The present meta-analysis included a total of 1281 patients from 10 studies. Three polymorphisms of HTR1A (rs6295, rs878567, and rs1423691) were selected for the analysis. In the pooled data from all studies, none of these HTR1A polymorphisms correlated significantly with either overall symptoms or positive symptoms. However, C allele carriers of the rs6295 polymorphism showed a significantly greater negative symptoms improvement than G allele carriers (P=.04, standardized mean difference =-0.14, 95％CI = 0.01 to 0.28).Conclusions:The results of our present analysis indicate that the HTR1A rs6295 polymorphism may impact negative symptoms improvement but not on either overall symptoms or positive symptoms improvement. However, this meta-analysis was based on a small number of studies and patients, and the effect size on negative symptoms was small. Given this limitation, the results should be confirmed by further investigations.

Association of GRIN1, ABCB1, and DRD4 genes and response to antipsychotic drug treatment in schizophrenia.

Association of GRIN1, ABCB1, and DRD4 genes and response to antipsychotic drug treatment in schizophrenia.

Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

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Sensitivity of individual items of the Positive and Negative Syndrome Scale (PANSS) and items subgroups to differentiate between placebo and drug treatment in schizophrenia

Lack of hard clinical endpoints is an essential problem in schizophrenia research. Disease state and treatment outcomes are measured using rating scales, e.g. Positive and Negative Syndrome Scale (PANSS). However, the PANSS score cannot always differentiate between placebo and drug treatment, even for established antipsychotics. The goal of this study was to identify the individual items of PANSS and subscales of selected items which are most sensitive to differentiate between placebo and drug effect. We analysed data from seven clinical trials of different antipsychotics. “Mini-PANSS” scales consisting of the most sensitive items were created and analysed statistically. The power of these scales to show a significant difference between placebo and drug treatment was compared with the power of total PANSS. Furthermore, pharmacokinetic–pharmacodynamic analysis was performed to determine which of these scales shows the highest drug effect on top of the placebo effect. The results reveal that all 30 items of the PANSS scale show a therapeutic drug effect. The magnitude of placebo effect was not predictive for the power to detect drug effect. Mini-PANSS scales consisting of items with the largest drug treatment response and the scale with the largest mean-to-SD ratio are somewhat better in differentiating between placebo and drug treatment than the total PANSS. However, the difference between these scales and total PANSS is small. Therefore, our analysis does not support replacement of the total PANSS by a reduced scale in the analysis of primary endpoints.