Effects Of Antipsychotic Drugs Research Articles

Atypical antipsychotic drugs deregulate the cholesterol metabolism of macrophage-foam cells by activating NOX-ROS-PPARγ-CD36 signaling pathway

BackgroundClinical reports indicate that schizophrenia patients taking atypical antipsychotic drugs suffer from metabolism diseases including atherosclerosis. However, the mechanisms underlying the detrimental effect of atypical antipsychotic drugs on atherosclerosis remain to be explored. MethodsIn this study, we used apolipoprotein E-deficient (apoe−/−) hyperlipidemic mice and apoe−/−cd36−/− mice to investigate the underlying mechanism of atypical antipsychotic drugs on atherosclerosis and macrophage-foam cells. ResultsIn vivo studies showed that genetic deletion of cd36 gene ablated the pro-atherogenic effect of olanzapine in apoe−/− mice. Moreover, in vitro studies revealed that genetic deletion or siRNA-mediated knockdown of cd36 or pharmacological inhibition of CD36 prevented atypical antipsychotic drugs-induced oxLDL accumulation in macrophages. Additionally, olanzapine and clozapine activated NADPH oxidase (NOX) to generate reactive oxygen species (ROS) which upregulated the activity of peroxisome proliferator-activated receptor γ (PPARγ) and subsequently elevated CD36 expression. Inhibition of NOX activity, ROS production or PPARγ activity suppressed CD36 expression and abolished the detrimental effects of olanzapine and clozapine on oxLDL accumulation in macrophages. ConclusionCollectively, our results suggest that atypical antipsychotic drugs exacerbate atherosclerosis and macrophage-foam cell formation by activating the NOX-ROS-PPARγ-CD36 pathway.

Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials

BackgroundAntipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking.MethodsWe will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework.DiscussionThis systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians.Systematic review registrationPROSPERO CRD42020175414

Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia-Relevance for Mental Diseases.

The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor–receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biological principle of forming 5-HT and other heteroreceptor complexes in the brain also help understand the mechanism of action for especially the 5-HT hallucinogens, including putative positive effects of e.g., psilocybin and the indicated prosocial and anti-stress actions of MDMA (ecstasy). The GalR1-GalR2 heterodimer and the putative GalR1-GalR2-5-HT1 heteroreceptor complexes are targets for Galanin N-terminal fragment Gal (1–15), a major modulator of emotional networks in models of mental disease. GPCR-receptor tyrosine kinase (RTK) heteroreceptor complexes can operate through transactivation of FGFR1 via allosteric mechanisms and indirect interactions over GPCR intracellular pathways involving protein kinase Src which produces tyrosine phosphorylation of the RTK. The exciting discovery was made that several antidepressant drugs such as TCAs and SSRIs as well as the fast-acting antidepressant drug ketamine can directly bind to the TrkB receptor and provide a novel mechanism for their antidepressant actions. Understanding the role of astrocytes and their allosteric receptor–receptor interactions in modulating forebrain glutamate synapses with impact on dorsal raphe-forebrain serotonin neurons is also of high relevance for research on major depressive disorder.

Blockade of the orexin 1 receptors in the nucleus accumbens’ shell reversed the reduction effect of olanzapine on motivation for positive reinforcers

Effort-based choice of high reward requires one to decide how much effort to expend for a certain amount of reward. Orexin is a crucial neuropeptide in the physiological aspect especially a variety of affective and cognitive processes. The nucleus accumbens (NAc) is a region of the neural system that serves effort-related high reward choices andthe Orexin 1 receptor (OX1R) is distributed extensively throughout the nucleus accumbens shell (AcbS). Olanzapine (OLZ), a typical antipsychotic drug, has a high affinity to D2 as an antagonist, and also partial agonistic-like action at D2 receptors has been reported. We examined the interaction of OLZ with the orexinergic receptor 1 in AcbS on effort- related high reward choice when two goal arms were different in the amount of accessible reward. The animals had to pass the barrier for receiving a high reward in one arm (HRA) or obtain a low reward in the other arm without any cost. Before surgery, all animals were selecting the HRA on almost every trial.During test days, the rats received local injections of either DMSO 20% /0.5 µl, as vehicle or SB334867 (30, 100, 300 nM/0.5 µl), as selective OX1R antagonist, within the AcbS. Other group received OLZ (32 µM/0.5 µl DMSO20%) / vehicle alone or 5 min after administration of SB334867 (300 nM/0.5 µl). The results showed that administration of OLZ in the AcbS alters rat’s preference for high reward. On the other hand, blocked of the OX1R (300 nM/0.5 µl) in this region could reverse the effect of OLZ, however, administration of the OX1R antagonists alone in the AcbS led to decreasing rat's preference for high reward. This result indicates that the orexin-1 antagonist might affect some effects of antipsychotic drugs.

Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs.

Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system. This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group. In multivariable analysis, clozapine (hazard ratio=0.43), aripiprazole long-acting injectable (LAI) (hazard ratio=0.71), paliperidone LAI (hazard ratio=0.76), antipsychotic polypharmacy (hazard ratio=0.77), and risperidone LAI (hazard ratio=0.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13), and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine. In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.

Safety profile of clozapine: Analysis using national registry data in Japan

Clozapine is the only effective antipsychotic drug used for the treatment of treatment-resistant schizophrenia. Although it has been shown that the frequency of clozapine use is very low in Japan, our previous study revealed that the number of clozapine prescriptions has been increasing in recent years, and that risk factors leading to discontinuation of clozapine were also identified as age ≥40 years, poor tolerability to olanzapine, previous treatment with clozapine, and white blood cell count <6000/mm3. The main cause for discontinuation of clozapine is the occurrence of a wide range of adverse events, including neutropenia/leukopenia and fatal cardiac disorders. In this study, we analyzed the physical details and backgrounds of patients with adverse events that led to clozapine discontinuation using a national registry database of more than 8000 Japanese patients. The physical adverse events that led to discontinuation of clozapine were neutropenia/leukopenia, glucose intolerance, cardiac disorders, gastrointestinal disorders, neuroleptic malignant syndrome, pleurisy, pulmonary embolism, sedation/somnolence, and seizures. Neutropenia/leukopenia had the highest incidence (5.0%). Neutropenia/leukopenia and cardiac disorders tended to occur early in the treatment period, indicating the need for careful monitoring for these adverse events in the early stages of clozapine treatment. Gastrointestinal disorders occurred over a long period of time, suggesting the need for careful observation during the maintenance period. The data obtained in our study will lead to the optimal and safe use of clozapine treatment.

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics.

Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of life.

Amisulpride: What’s Old Can Be New in the United States

Amisulpride: What’s Old Can Be New in the United States

Quantitative Resting State Electroencephalography in Patients with Schizophrenia Spectrum Disorders Treated with Strict Monotherapy Using Atypical Antipsychotics.

ObjectiveThe effect of antipsychotic drugs on quantitative electroencephalography (EEG) has been mainly examined by the administration of a single test dose or among patients using combinations of other psychotropic drugs. We therefore investigated the effects of strict monotherapy with antipsychotic drugs on quantitative EEG among schizophrenia patients.MethodsData from 2,364 medical reports with EEG results from psychiatric patients admitted to the Hokkaido University Hospital were used. We extracted EEG records of patients who were diagnosed with schizophrenia spectrum disorders and who were either undergoing strict antipsychotic monotherapy or were completely free of psychotropic drugs. The spectral power was compared between drug-free patients and patients using antipsychotic drugs. We also performed multiple regression analysis to evaluate the relationship between spectral power and the chlorpromazine equivalent daily dose of antipsychotics in all the patients.ResultsWe included 31 monotherapy and 20 drug-free patients. Compared with drug-free patients, patients receiving antipsychotic drugs demonstrated significant increases in theta, alpha and beta power. When patients taking different types of antipsychotics were compared with drug-free patients, we found no significant change in any spectrum power for the aripiprazole or blonanserin groups. Patients taking risperidone demonstrated significant increases in alpha and beta power. Patients taking clozapine and olanzapine demonstrated significant slow wave increases. Multiple regression analysis revealed that the chlorpromazine equivalent dose was positively associated with theta power.ConclusionUse of any antipsychotic drug by patients was associated with a dose-dependent increase in theta power. However, each type of antipsychotic demonstrated different spectral power changes.

Effects of antipsychotic drugs and potassium channel modulators on spectral properties of local field potentials in mouse hippocampus and pre-frontal cortex

Local field potentials (LFPs) recorded intracranially display a range of location-specific oscillatory spectra which have been related to cognitive processes. Although the mechanisms producing LFPs are not completely understood, it is likely that voltage-gated ion channels which produce action potentials and patterned discharges play a significant role. It is also known that antipsychotic drugs (APDs) affect LFP spectra and a direct inhibitory effect on voltage-gated potassium channels has been reported. Additionally, voltage-gated potassium channels have been implicated in the pathophysiology of schizophrenia, a disorder for which APDs are primary therapies. In this study we sought to: i) better characterise the effects of two APDs on LFPs spectra and connectivity measures and ii) examine the effects of potassium channel modulators on LFPs and potential overlap of effects with APDs. Intracranial electrodes were implanted in hippocampus (HIP) and pre-frontal cortex (PFC) of C57BL/6J mice; power spectra, coherence and phase-amplitude cross-frequency coupling were measured. Drugs tested were APDs haloperidol and clozapine as well as voltage-gated potassium channel modulators (KVMs) 4-aminopyridine (4-AP), tetraethylammonium, retigabine and E−4031. Both APDs and KVMs significantly reduced gamma power except 4-AP, which conversely increased gamma power. Clozapine and retigabine additionally reduced gamma coherence between HIP and PFC, while 4-AP demonstrated the opposite effect. Phase-amplitude coupling between theta and gamma oscillations in HIP was significantly reduced by the administration of haloperidol and retigabine. These results provide previously undescribed effects of APDs on LFP properties and demonstrate novel modulation of LFP characteristics by KVMs that intriguingly overlap with the APD effects.

Effect of antipsychotic drugs and orthostatic hypotension on the risk of falling in schizophrenic patients.

Background: Background: Management of schizophrenia using psychopharmaceuticals requires a long-term treatment. The use of antipsychotic drugs can cause the occurrence of orthostatic hypotension, which leads to the risk of falling in patients. The aim of this study is to determine the effect of the use of antipsychotic drugs and orthostatic hypotension on the risk of falling in schizophrenic patients.Design and Methods: This study used a descriptive design with 53 respondents. Data were analyzed using the contingency coefficient correlation and Spearman Rank test methods.Results: The results of the first study showed no positive effect between the use of antipsychotics on orthostatic hypotension in schizophrenic patients. In addition, a contingency coefficient correlation (C) of 0.199 and p-value of 0.335 (p>0.05) was obtained. The results of the second study showed that there was a significant positive effect between orthostatic hypotension on the risk of falling in schizophrenic patients with a value of r = 0.483 and a pvalue of 0.000 (p0.001).Conclusion: It was suggested that the development of this study’s result is needed for further research in dealing with the incidence of orthostatic hypotension in order to prevent or reduce the risk of falling in schizophrenic patients.Significance for public healthNurses should know how to measure blood pressure in order to determine the incidence of orthostatic hypotension. Nurses have an important role to play in preventing the risk of falling in patients. This is used as an indicator in achieving the quality of patient safety and in determining the quality of services in the hospital. This study describes the effect of the use of antipsychotic drugs and orthostatic hypotension on the risk of falls in schizophrenic patients in Dr. H. Marzoeki Mahdi Hospital Bogor.

A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study)

BackgroundAlthough clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia, it leads to a poor or partial response in 40 to 70% of patients. Augmentation of clozapine with electroconvulsive therapy (ECT) is a highly effective and relatively safe treatment for these clozapine-resistant patients. However, parameters are not yet well specified, such as the optimal number of sessions, their frequency, and the relevance of maintenance ECT. Our objective is to compare the efficacy and tolerance between two protocols of combined ECT and clozapine treatment in patients with ultra-resistant schizophrenia (URS): a 6-month protocol (short protocol with 20 ECT sessions) and a 12-month protocol (long protocol with 40 ECT sessions).MethodsSixty-four patients with schizophrenia with persistent psychotic symptoms despite clozapine treatment will be enrolled in a prospective multicentric assessor-blinded randomized controlled trial. Patients will be randomly assigned to the short or the long protocol. The main outcome is the response rate assessed by the Positive and Negative Symptoms Scale (PANSS) 3 months after the end of the treatment in patients following the long protocol compared to those following the short protocol. The response was defined as a 30% reduction on the PANSS baseline. Clinical assessments (PANSS, BPRS, HAMD-21, YMRS, CGI, GAF, Modified Overt Aggression Scale (MOAS), and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS)) and plasma clozapine concentration will be performed at baseline and at 2, 4, 6, 9, 12, and 15 months. Neuropsychological measures (MMSE, RL/RI-16, Doors test, D2 Test of Attention, Copy of the Rey-Osterrieth complex figure) will be performed at baseline and at 6 and 15 months.DiscussionThe aims of this research are to optimize protocols of combined ECT with clozapine in patients with URS and to offer specific recommendations for these patients’ care.Trial registrationClinicalTrials.gov NCT03542903. Registered on May 31, 2018. Id RCB: 2017-A02657-46

Adenosine and Kynurenic Acid Interactions: Possible Relevance for Schizophrenia Treatment?

Adenosine and Kynurenic Acid Interactions: Possible Relevance for Schizophrenia Treatment?

Modeling Schizophrenia with Glioblastoma Cells: In Vitro Analysis of Risperidone Treatment on Glial Spheroids.

Glioblastoma is the most malicious type of glioma presenting a genetic background via diverse mutations and exhibits differential sensitivity to treatment. Meanwhile, schizophrenia is a heterogeneous disease with a complex etiology. Studies report an elevation in pro-inflammatory cytokines in patients with schizophrenia and changes in biochemical metabolism. In the present study, the tumor spheroid technology is applied to two different glioblastoma lines which resemble schizophrenia manifestation along with the investigation of the potential anti-tumor effect of an atypical antipsychotic drug, risperidone. Our hypothesis built on case reports showing patients with schizophrenia being treated with risperidone that turned out to have glioblastoma in post-mortem evaluation. Risperidone has been suggested to carry therapeutic effects for glioblastoma and elongated lifespan after the diagnosis of cancer. In this current study, 3D models using C6 and U87 glioblastoma cells and monocytes for representing the disease grown as multicellular spheroids were established. Spheroids were treated with the anti-schizophrenic agent risperidone and indicated almost similar results to the clinics suggesting that glioblastoma and schizophrenia share mutual physiological characteristics. U87 and C6 spheroid systems were analyzed molecularly after the treatment of risperidone where U87 spheroid models were found highly resembling the overall behavior of schizophrenia. This present work correlated the stated two diseases in molecular level to encourage the efforts for personalized medicine. The anti-tumor effects of risperidone on glioblastoma is not very well established yet. It should not be missed that a picture of schizophrenia in clinics may be the result of an underlying lesion in a specific brain area. Thus, especially schizophrenia patients who may be at risk for developing brain tumors should be further investigated and treated accordingly.

The Incidence and Economic Burden of Extrapyramidal Symptoms in Patients with Schizophrenia Treated with Atypical Antipsychotics

Extrapyramidal symptoms (EPS), including movement disorders, tremors, and muscle contractions are common side effects of atypical antipsychotic (AAP) drugs in patients with schizophrenia. This study examined the incidence and burden of EPS in patients with schizophrenia initiating AAPs. Patients with schizophrenia initiating AAPs with no prior EPS were identified in the MarketScan Multi-state Medicaid database from 1/1/2012-12/31/2018. Incidence of EPS (identified via ICD-9/ICD-10 diagnoses and medications) was assessed during the 12-months following AAP initiation. Cohorts with and without EPS were defined. Demographics, clinical characteristics, and healthcare resource use and costs over 12 months following the first EPS claim (EPS) or randomly assigned index date (Non-EPS) were assessed. A total of 11,642 patients with schizophrenia were identified; 21.2% developed EPS in the 12-months following AAP initiation. EPS and Non-EPS cohorts included 2,295 (mean age 38, 61% male, CCI 0.6) and 5,607 (mean age 39, 57% male, CCI 0.7) patients, respectively. Over the 12-month post-index period, EPS cohort had significantly higher rates of all-cause (30.2% vs. 24.6%, p<0.001) and schizophrenia-related hospitalizations (22.5% vs. 12.9%, p<0.001) and schizophrenia-related emergency room visits (25.5% vs. 16.7%, p<0.001) compared to Non-EPS cohort. All-cause ($25,911 vs. $21,550, p<0.001) and schizophrenia-related healthcare costs ($12,134 vs. $6,230, p<0.001) were significantly higher in EPS vs. Non-EPS cohort. In the 12 months following AAP initiation, over 20% of schizophrenia patients developed EPS, which was associated with increased healthcare resource utilization and costs. Treatment options that minimize EPS may reduce the economic burden of schizophrenia. Sunovion Pharmaceuticals Inc.

Effect of antipsychotics on breast tumors by analysis of the Japanese Adverse Drug Event Report database and cell-based experiments

BackgroundSince antipsychotics induce hyperprolactinemia via the dopamine D2 receptor, long-term administration may be a risk factor for developing breast tumors, including breast cancer. On the other hand, some antipsychotic drugs have been reported to suppress the growth of breast cancer cells in vitro. Thus, it is not clear whether the use of antipsychotics actually increases the risk of developing or exacerbating breast tumors. The purpose of this study was to clarify the effects of antipsychotic drugs on the onset and progression of breast tumors by analyzing an adverse event spontaneous reporting database and evaluating the proliferation ability of breast cancer cells.MethodsJapanese Adverse Drug Event Report database (JADER) reports from April 2004 to April 2019 were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. Reports of females only were analyzed. Adverse events included in the analysis were hyperprolactinemia and 60 breast tumor-related preferred terms. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) were used to detect signals. Furthermore, MCF-7 cells were treated with haloperidol, risperidone, paliperidone, sulpiride, olanzapine and blonanserin, and cell proliferation was evaluated by WST-8 assay.ResultsIn the JADER analysis, the IC signals of hyperprolactinemia were detected with sulpiride (IC, 3.73; 95% CI: 1.81–5.65), risperidone (IC, 3.69; 95% CI: 1.71–5.61), and paliperidone (IC, 4.54; 95% CI: 2.96–6.12). However, the IC signal of breast tumors was not observed with any antipsychotics. In cell-based experiments, MCF-7 cells were treated with six antipsychotics at concentrations of 2 and 32 μM, and none of the drugs showed any growth-promoting effects on MCF-7 cells. On the other hand, blonanserin markedly suppressed the growth of MCF-7 cells at a concentration of 32 μM, and the effect was concentration dependent.ConclusionsAnalysis of the JADER using the IC did not show breast tumor signals due to antipsychotic drugs. In in vitro experiments, antipsychotics did not promote MCF-7 cell proliferation whereas blonanserin suppressed MCF-7 cell growth. Further research on the effects of blonanserin on the onset and progression of breast tumor is expected.

Assessment of the extrapyramidal side effects among psychosis patients consuming antipsychotic medication with a view to develop an information leaflet on early recognition and management of extrapyramidal side effects in SS selected hospital at Raipur

Introduction: Patients suffering from physical illnesses are given specific treatment because the causes are specific and the signs and symptoms are specific. The doctor generally knows how the treatment works, and the patient co-operates with the doctors, and nurses, in order to get better. In psychiatric hospital the treatment may not be so specific and most patients are given more than one treatment. The nurse has an extremely important role to play in the treatment of the mentally ill. Her actions, attitudes and skills to help him to deal with his problems are themselves an essential part of his treatment. Objectives: The main objective was to assess the extrapyramidal side effects among psychosis patients consuming antipsychotic medication. Secondary objective was to find out the association of extrapyramidal side effects with selected socio-demographic and clinical variables. Methodology: 60 psychosis patients attending outpatient and inpatient department of psychiatry in Dr. Bhim Rao Ambedkar Memorial Hospital, Raipur, Chhattisgarh who receive antipsychotic medications were assessed for extrapyramidal side effect of antipsychotic drugs. The conceptual framework adopted for study was based on Health Belief Model. Modified Simpson Angus Scale (MSAS) was used to assess/measure extrapyramidal side effects. Patients scoring less than 3 were considered ‘normal’. Patients scoring 3 to 5 were considered having ‘minimal movement disorder’. Those scoring 6 to 11 have ‘clinically significant degree of movement disorder’. And those scoring 12 to 17 were present with ‘severe degree of movement disorder’. Result: It was observed that highest number of subjects i.e. 37 (66.66%) were ‘normal’. 11 subjects (18.33%) were with ‘minimal movement disorder’. 7 subjects (11.66%) were with ‘clinically significant extrapyramidal side effects. Only 5 subjects (8.33%) had severe degree of movement disorder. There was significant association of extrapyramidal side effects with duration of illness, duration of antipsychotic use and immediate side effect of antipsychotics at 0.05 level of significance. Conclusion: It was concluded in this study that extrapyramidal side effects may occur among patients consuming antipsychotic medication. Also significant relationship was found between extrapyramidal side effects with duration of illness, duration of antipsychotic use and immediate effect of antipsychotic medication (1-2 days observation).

Association between the glyco-metabolic adverse effects of antipsychotic drugs and their chemical and pharmacological profile: a network meta-analysis and regression.

Glyco-metabolic deteriorations are the most limiting adverse reactions to antipsychotics in the long term. They have been incompletely investigated and the properties of antipsychotics that determine their magnitude are not clarified.To rank antipsychotics by the magnitude of glyco-metabolic alterations and to associate it to their pharmacological and chemical properties, we conducted a network meta-analysis. We searched PubMed, Embase, and Psycinfo on 10 September 2020. We selected studies containing the endpoint-baseline difference or the distinct values of at least one outcome among glucose, HbA1c, insulin, HOMA-IR, triglycerides, total/HDL/LDL cholesterols. Of 2094 articles, 46 were included in network meta-analysis. Study quality was assessed by the RoB 2 and ROBINS-I tools. Mean differences (MD) were obtained by random-effects network meta-analysis; relations between MD and antipsychotic properties were analyzed by linear regressions. Antipsychotic properties investigated were acidic and basic pKa, polar surface area, polarizability, and occupancies of D2, H1, M1, M3, α1A, α2A, 5-HT1A, 5-HT2A, 5-HT2C receptors. We meta-analyzed 46 studies (11 464 patients); on average, studies lasted 15.47 weeks, patients had between 17.68 and 61.06 years of mean age and 61.64% were males. Olanzapine and clozapine associated with greater deteriorations, aripiprazole and ziprasidone with smaller deteriorations. Higher polarizability and 5-HT1A receptor occupancy were associated with smaller deteriorations, H1, M1, and M3 receptor occupancies with larger deteriorations. Drug rankings may guide antipsychotic switching toward metabolically safer drugs. Mechanistic insights may suggest improvements for combination therapies and drug development. More data are required regarding newer antipsychotics.

Stefan Leucht: a (meta)analysis of his life

During our interview, Stefan Leucht describes a seminal moment in his professional life. “During my final year as a medical student, Rolf Engel lectured about meta-analysis and I immediately knew that this was what I wanted to do in research. My university chairman Hans Förstl told me not to, as this would not lead anywhere. But I did not listen to him, and published my first meta-analysis on antipsychotics, which got quoted 1047 times. And now he tells his students ‘do like Dr Leucht and believe in your ideas, irrespective of what other people think!’” This comment highlights not only Leucht's start in his pioneering career in evidence-based psychiatric medicine, but also his self-determination and belief that objective comparisons of psychiatric treatments are the correct thing to do. Second-generation antipsychotic drugs and short-term mortality: a systematic review and meta-analysis of placebo-controlled randomised controlled trialsOverall, and for the main indication of schizophrenia, there is no evidence from randomised trials that antipsychotic drugs increase mortality. However, vulnerable populations (particularly patients with dementia) might be at increased risk. This meta-analysis could only address acute treatment effects leading to death in the short-term, and not long-term effects of antipsychotic drugs on mortality. Full-Text PDF Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysisThere are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences. Full-Text PDF Open Access

Comparative Study of the Effects of Atypical Antipsychotic Drugs on Plasma and Urine Biomarkers of Oxidative Stress in Schizophrenic Patients.

PurposeEvidence that antipsychotic drugs (ADs) can affect oxidative stress estimated with various biomarkers in schizophrenic patients is controversial and limited. Therefore, in the present study, we assessed the ability of six atypical ADs (clozapine, olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone) used in schizophrenia treatment to modulate oxidative damage to different biomolecules such as lipids and proteins.Patients and MethodsWe measured the levels of oxidative stress markers in plasma and urine: total antioxidant capacity by FRAP (according to a modified method of Benzie & Strain), thiobarbituric acid reactive species – TBARS (spectrophotometric method), 4-hydroxy-2-nonenal (4-HNE) (OxiSelect™ HNE Adduct Competitive ELISA Kit), 3-nitrotyrosine (3-NT) (OxiSelect™ Nitrotyrosine ELISA Kit) in plasma, and F2-isoprostanes (BIOXYTECH® Urinary 8-epi-Prostaglandin F2α) in the urine of 60 schizophrenic patients (before and after treatment) and in 30 healthy subjects.ResultsOur results showed that in schizophrenic patients levels of lipid peroxidation markers (TBARS, F2-isoprostanes) were higher than in healthy subjects but FRAP in schizophrenic patients was lower than in healthy controls and increased after 4-week treatment with tested ADs. A 4-week treatment with ADs caused the improvement of psychopathology symptoms estimated by Positive and Negative Syndrome Scale (PANSS) that was accompanied by decreased lipid peroxidation (F2-isoprostanes, TBARS; p=2.9x10−6, p=7.6x10−5, respectively) and an increase in total antioxidative capacity (FRAP) (p=5.16x10−16).ConclusionAtypical antipsychotics especially clozapine, olanzapine and quetiapine demonstrate the effective outcome of antipsychotic treatment, beneficial antioxidative action by reducing lipid peroxidation and increased total plasma antioxidant activity.