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Sample records for antipsychotic agents

  1. Antipsychotic agents and QT changes.

    OpenAIRE

    Welch, R.; Chue, P

    2000-01-01

    Recently, antipsychotic medications of the novel or atypical classes have received increased attention because of concerns with respect to potential lengthening of the QT interval, yet the currently available and commonly prescribed conventional antipsychotics are significantly more cardiotoxic, particularly agents in the butyrophenone and phenothiazine classes. Lengthening of the QT interval can be associated with a fatal paroxysmal ventricular arrhythmia known as torsades de pointes. The sp...

  2. Antipsychotic agents: efficacy and safety in schizophrenia

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    de Araújo AN

    2012-11-01

    Full Text Available Arão Nogueira de Araújo,1 Eduardo Pondé de Sena,1,2 Irismar Reis de Oliveira,1,3 Mario F Juruena41Postgraduation Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, Brazil; 4Stress and Affective Disorders Program, Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, BrazilAbstract: Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA and third generation antipsychotics (TGA, other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient.Keywords: antipsychotic agents, schizophrenia, pharmacology, safety

  3. Metabolic side effects of antipsychotic agents: a prospective study in a teaching hospital.

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    Ankesh Barnwal

    2012-07-01

    Full Text Available Background: Antipsychotic drugs have propensity to produce side effects like extrapyramidal syndrome, hyperglycemia, lipid abnormalities and weight gain. As data from India related to this aspect are scarce, this study was carried out.Aims and Objectives: To study metabolic effects of antipsychotic drugs using biochemical parameters and to compare metabolic effects of different antipsychotic agents.Materials and methods: This was a prospective study of patients attending the psychiatry outpatient department from September 2007 to May 2008. Each patient enrolled was followed up for 12weeks or less till the antipsychotics were prescribed. Body weight,fasting blood glucose, fasting lipid profile were recorded at baseline and at subsequent visits.Results: Out of 45 patients, 33 completed the study. Bipolar disorder (31% was the most frequent diagnosis followed by brief psychotic disorder (22%, schizophrenia (20% and others.Olanzapine was the most frequently prescribed antipsychotic drug (56% followed by risperidone (24% and haloperidol (20%. 84% received single antipsychotic drug. After 12weeks of therapy all antipsychotics caused significant weight gain (p<0.001, olanzapine caused significant rise in fasting blood glucose (p<0.001 and serum cholesterol (p<0.001. All antipsychotics caused significant rise in serum triglyceride level (p<0.01 Conclusion: All antipsychotics can cause significant abnormalities in carbohydrate and lipid metabolism. Selection of antipsychotics, particularly the newer ones requires consideration of co morbidities like obesity, diabetes mellitus and dyslipidemias. During antipsychotic drug therapy periodic monitoring for metabolic abnormalities is advisable.

  4. Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

    Institute of Scientific and Technical Information of China (English)

    Jaqueline Nascimento PICADA; Viviane Minuzzo PONTES; Patrícia PEREIRA; Bruna de Jesus Neto DOS SANTOS; Franciele CELSO; Jéssica Dias MONTEIRO; Kelly Morais DA ROSA; Leandro Rosa CAMACHO; Luciana Rodrigues VIEIRA; Taís Madelon FREITAS; Tatiana Grasiela DASILVA

    2011-01-01

    Aim:Aripiprazole is an antipsychotic agent to treat schizophrenia,which acts through dopamine D2 partial agonism,serotonin 5-HT1A partial agonism and 5-HT2A antagonism.This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent,as well as its effects on lipoperoxidation.Methods:Open field and inhibitory avoidance tasks were used.Thirty min before performing the behavioral tasks,adult male CF-1 mice were administered aripiprazole (1,3 or 10 mg/kg,ip) once for the acute treatment,or the same doses for 5 d for the subchronic treatment.Genotoxic effects were assessed using comet assay in the blood and brain tissues.Mutagenic effects were evaluated using bone marrow micronucleus test.Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS).Results:Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task.Acute treatment significantly increased the step-down latency for both the short- and long-term memory in the inhibitory avoidance task.Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain.Mutagenic effect was not detected in the acute and subchronic treatments.Nor TBARS levels in the liver were affected.Conclusion:Aripiprazole improved memory,but could impair motor activities in mice.The drug increased DNA damage in blood,but did not show mutagenic effects,suggesting that it might affect long-term genomic stability.

  5. Diabetic ketoacidosis and severe hypertriglyceridaemia as a consequence of an atypical antipsychotic agent.

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    Hepburn, Kirsten; Brzozowska, Malgorzata Monika

    2016-01-01

    The atypical antipsychotic agent clozapine, although an effective treatment for schizophrenia, is linked with metabolic adverse effects. We report a case of diabetic ketoacidosis and very severe hypertriglyceridaemia associated with clozapine use, in a patient with type 2 diabetes mellitus, who was successfully treated with continuous insulin infusion and fluids. As clozapine proved to be the most efficacious in controlling the patient's psychotic symptoms, the patient has been continued on clozapine despite its known metabolic side effects. Importantly the patient has achieved satisfactory long-term lipid and glycaemic control. The current recommendations related to the metabolic care for patients treated with atypical antipsychotic agents as well as the mechanisms behind abnormal glucose and lipid regulation with clozapine therapy are discussed. PMID:27507689

  6. Temporomandibular disorders in patients with schizophrenia using antipsychotic agents: a discussion paper

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    de Araújo AN

    2014-03-01

    Full Text Available Arão Nogueira de Araújo,1 Marion Alves do Nascimento,1 Eduardo Pondé de Sena,1,2 Abrahão Fontes Baptista3,4 1Postgraduate Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Biomorphology, Institute of Health Sciences, 4Postgraduate Program in Medicine and Health, Federal University of Bahia, Salvador, Brazil Abstract: Patients with psychiatric problems show a tendency to develop temporomandibular disorders (TMD. Particularly, patients with schizophrenia are quite likely to have signs and symptoms of TMD due to the impairment of their oral health, the use of antipsychotic drugs, and other general health problems. In nonschizophrenic populations, TMD have been considered as the main cause of nondental pain in the orofacial region, involving mechanisms associated with changes in masticatory activity at the cortical and neuromuscular levels. Individuals with schizophrenia do not usually complain of pain, and TMD is misdiagnosed in this population. In this paper, we aimed to review the clinical aspects of TMD in people with schizophrenia on antipsychotic drug therapy. Keywords: schizophrenia, temporomandibular joint, pain, antipsychotic agents

  7. Pharmacoeconomic comparison of ziprasidone with other atypical oral antipsychotic agents in schizophrenia

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    Andrea Fagiolini

    2011-03-01

    Full Text Available Objective: to comparatively investigate – by means of computer simulations – the economic cost and clinical outcomes of five atypical oral antipsychotic agents (ziprasidone, olanzapina, risperidone, paliperidone and aripiprazolo.Methods: a cyclical stochastic model representing patient evolution, taking into account main adverse reactions (akathisia, weight gain and extra-pyramidal ARs, drug efficacy on psychosis stabilization and probability of relapse, was developed. Ten different scenarios were compared, each starting with one of the considered antipsychotics, prescribed either at home or in a hospital setting. Switching to another medication was allowed until no untried drugs were available, in which case clozapine treatment or admission to a Psychiatric Therapeutic Rehabilitation Center were irreversibly assigned. Model inputs were probabilities of ARs, probabilities of stabilization and probabilities of destabilization (assumed equal for all; as well as costs attributable to drugs, hospitalization, outpatient care and costs adverse reactions in terms of concomitant medications. Sources for the inputs were the trials reported in the most recent literature (from the year 2000, selected based on the homogeneity of the observational period and antipsychotic dosage used.Results: in each scenario, the hospitalization cost represented the highest component of the overall cost (approximately 67%. Assuming equal drug effectiveness, ziprasidone fared better than all other considered competitors, showing the lowest average annual costs per patient (and also the lowest average annual hospitalization costs as well as the largest numbers of controlled months without adverse reactions, independently of the initial setting. Conclusions: the most important determinant of total cost appears to be hospitalization, whose cost is about 600% higher than the medications cost. Medication effectiveness and tolerability remain however of utmost importance for

  8. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy.

    Science.gov (United States)

    Wu, Chia-Hsien; Bai, Li-Yuan; Tsai, Ming-Hsui; Chu, Po-Chen; Chiu, Chang-Fang; Chen, Michael Yuanchien; Chiu, Shih-Jiuan; Chiang, Jo-Hua; Weng, Jing-Ru

    2016-01-01

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38, and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5, and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy. PMID:27277973

  9. Research progress of atypical antipsychotic agent%非典型抗精神病新药研究进展

    Institute of Scientific and Technical Information of China (English)

    张邦禹; 董文心

    2012-01-01

    The etiology of schizophrenia is complicated and remains unclear. To improve the symptoms currently is the major goal of the antipsychotics. This article reviews clinical efficacy of atypical antipsychotic agents approved by FDA from 2007 in the treatment of schizophrenia in adults to provide reference for drug therapy in clinical practice.%精神分裂症发病机制复杂,治疗药物多以缓解症状为主要目的,临床尚无能有效治愈精神分裂症的药物.本文回顾了2007年以来美国食品药品管理局批准上市的治疗成人精神分裂症的非典型抗精神病药物,以期对精神分裂症的治疗提供参考.

  10. Genetic determinants of antipsychotic drug response

    NARCIS (Netherlands)

    Gregoor, J.G.

    2012-01-01

    Since their introduction, the use of antipsychotic drugs has been complicated by adverse effects. While the first generation of antipsychotic agents mainly caused motor side effects, the newer antipsychotic drugs are also associated with metabolic disturbance such as diabetes and obesity. The introd

  11. Antipsychotics as antidepressants.

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    Roberts, Rona Jeannie; Lohano, Kavita K; El-Mallakh, Rif S

    2016-09-01

    Three second-generation antipsychotic (SGA) agents have received FDA approval for adjunctive treatment, to antidepressant, of major depressive disorder: quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone have been approved for the treatment of bipolar depression. There are data suggesting that quetiapine is effective for major depressive disorder as monotherapy. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all SGA will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e., produce a depression-like clinical picture). The antidepressant effect appears to be unique to some agents, with direct evidence of insignificant antidepressant action for ziprasidone. Three general principles can guide the use of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects; (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic doses are to be used; and (iii) SGAs do not have a general antidepressant effect, rather, this appears to be unique to quetiapine and aripiprazole, and possibly lurasidone. PMID:25963405

  12. A TYPICAL ANTIPSYCHOTIC: A REVIEW

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    Mukesh Ratnaparkhi

    2010-12-01

    Full Text Available Recent advances in understanding the pathophysiology of underlying psychotic disorder and subsequent development of new antipsychotic drugs to treat these diseases have altered clinicians? pharmacological approach. It has also helped researcher to produce a new generation antipsychotic agents (NGA which could show better clinical results. However methodical approach as well as in-depth research in this area has provided several potent atypical antipsychotic agents. Now days all the atypical antipsychotics agents are FDA approved and being frequently used for pharmacotherapy of schizophrenia, acute mania, bipolar mania, psychotic agitation, bipolar maintenance, and other indications. Atypical antipsychotics are associated with the numbers of clinical benefits such as higher rate of responders, efficiency in patients with refractory disease, lower risk of suicides, better functional capacity and an improved quality of life and thus, have showed their efficacy against previous modes of treatment. The present review highlights the advantages, disadvantages as well as risk factors associated with novel antipsychotic agent with a view to outline their future scope.

  13. Affinity Chromatography Method for Determination of Binding of Drugs to Melanin and Evaluation of Side Effect Potential of Antipsychotic Agents

    OpenAIRE

    Marszałł, Michał Piotr; Proszowska, Anna; Buciński, Adam; Kaliszan, Roman

    2014-01-01

    The extrapyramidal side effect parameters of typical and atypical antypsychotics were correlated with affinity chromatographic data determined on the melanin-based column. The chromatographic study was performed according to the hypothesis that extrapyramidal symptoms (EPS) as side effects of the use of antipsychotic drugs at clinically effective doses are correlated to the affinity of these drugs to neuromelanin. For that aim the polymerization product of L-DOPA (melanin) was immobilized ont...

  14. Pyrrolo[1,3]benzothiazepine-based serotonin and dopamine receptor antagonists. Molecular modeling, further structure-activity relationship studies, and identification of novel atypical antipsychotic agents.

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    Campiani, Giuseppe; Butini, Stefania; Fattorusso, Caterina; Catalanotti, Bruno; Gemma, Sandra; Nacci, Vito; Morelli, Elena; Cagnotto, Alfredo; Mereghetti, Ilario; Mennini, Tiziana; Carli, Miriana; Minetti, Patrizia; Di Cesare, M Assunta; Mastroianni, Domenico; Scafetta, Nazzareno; Galletti, Bruno; Stasi, M Antonietta; Castorina, Massimo; Pacifici, Licia; Vertechy, Mario; Di Serio, Stefano; Ghirardi, Orlando; Tinti, Ornella; Carminati, Paolo

    2004-01-01

    Recently we reported the pharmacological characterization of the 9,10-dihydropyrrolo[1,3]benzothiazepine derivative (S)-(+)-8 as a novel atypical antipsychotic agent. This compound had an optimum pK(i) 5-HT(2A)/D(2) ratio of 1.21 (pK(i) 5-HT(2A) = 8.83; pK(i) D(2) = 7.79). The lower D(2) receptor affinity of (S)-(+)-8 compared to its enantiomer was explained by the difficulty in reaching the conformation required to optimally fulfill the D(2) pharmacophore. With the aim of finding novel atypical antipsychotics we further investigated the core structure of (S)-(+)-8, synthesizing analogues with specific substituents; the structure-activity relationship (SAR) study was also expanded with the design and synthesis of other analogues characterized by a pyrrolo[2,1-b][1,3]benzothiazepine skeleton, substituted on the benzo-fused ring or on the pyrrole system. On the 9,10-dihydro analogues the substituents introduced on the pyrrole ring were detrimental to affinity for dopamine and for 5-HT(2A) receptors, but the introduction of a double bond at C-9/10 on the structure of (S)-(+)-8 led to a potent D(2)/5-HT(2A) receptor ligand with a typical binding profile (9f, pK(i) 5-HT(2A)/D(2) ratio of 1.01, log Y = 8.43). Then, to reduce D(2) receptor affinity and restore atypicality on unsaturated analogues, we exploited the effect of specific substitutions on the tricyclic system of 9f. Through a molecular modeling approach we generated a novel series of potential atypical antipsychotic agents, with optimized 5HT(2A)/D(2) receptor affinity ratios and that were easier to synthesize and purify than the reference compound (S)-(+)-8. A number of SAR trends were identified, and among the analogues synthesized and tested in binding assays, 9d and 9m were identified as the most interesting, giving atypical log Y scores respectively 4.98 and 3.18 (pK(i) 5-HT(2A)/D(2) ratios of 1.20 and 1.30, respectively). They had a multireceptor affinity profile and could be promising atypical agents

  15. Pyrrolo[1,3]benzothiazepine-based atypical antipsychotic agents. Synthesis, structure-activity relationship, molecular modeling, and biological studies.

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    Campiani, Giuseppe; Butini, Stefania; Gemma, Sandra; Nacci, Vito; Fattorusso, Caterina; Catalanotti, Bruno; Giorgi, Gianluca; Cagnotto, Alfredo; Goegan, Mara; Mennini, Tiziana; Minetti, Patrizia; Di Cesare, M Assunta; Mastroianni, Domenico; Scafetta, Nazzareno; Galletti, Bruno; Stasi, M Antonietta; Castorina, Massimo; Pacifici, Licia; Ghirardi, Orlando; Tinti, Ornella; Carminati, Paolo

    2002-01-17

    The prototypical dopamine and serotonin antagonist (+/-)-7-chloro-9-(4-methylpiperazin-1-yl)-9,10-dihydropyrrolo[2,1-b][1,3]benzothiazepine (5) was resolved into its R and S enantiomers via crystallization of the diastereomeric tartaric acid salts. Binding studies confirmed that the (R)-(-)-enantiomer is a more potent D(2) receptor antagonist than the (S)-(+)-enantiomer, with almost identical affinity at the 5-HT(2) receptor ((S)-(+)-5, log Y = 4.7; (R)-(-)-5, log Y = 7.4). These data demonstrated a significant stereoselective interaction of 5 at D(2) receptors. Furthermore, enantiomer (S)-(+)-5 (ST1460) was tested on a panel of receptors; this compound showed an intriguing binding profile characterized by high affinity for H(1) and the alpha(1) receptor, a moderate affinity for alpha(2) and D(3) receptors, and low affinity for muscarinic receptors. Pharmacological and biochemical investigation confirmed an atypical pharmacological profile for (S)-(+)-5. This atypical antipsychotic lead has low propensity to induce catalepsy in rat. It has minimal effect on serum prolactin levels, and it has been selected for further pharmacological studies. (S)-(+)-5 increases the extracellular levels of dopamine in the rat striatum after subcutaneous administration. By use of 5 as the lead compound, a novel series of potential atypical antipsychotics has been developed, some of them being characterized by a stereoselective interaction at D(2) receptors. A number of structure-activity relationships trends have been identified, and a possible explanation is advanced in order to account for the observed stereoselectivity of the enantiomer of (+/-)-5 for D(2) receptors. The molecular structure determination of the enantiomers of 5 by X-ray diffraction and molecular modeling is reported. PMID:11784139

  16. Regulation of P-glycoprotein expression in brain capillaries in Huntington's disease and its impact on brain availability of antipsychotic agents risperidone and paliperidone.

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    Kao, Yu-Han; Chern, Yijuang; Yang, Hui-Ting; Chen, Hui-Mei; Lin, Chun-Jung

    2016-08-01

    Huntington's disease (HD) is a neurodegenerative disease marked by an expanded polyglutamine (polyQ) tract on the huntingtin (HTT) protein that may cause transcriptional dysfunction. This study aimed to investigate the regulation and function of P-glycoprotein, an important efflux transporter, in brain capillaries in HD. The results showed that, compared with the littermate controls, R6/2 HD transgenic mice with the human mutant HTT gene had higher levels of P-glycoprotein mRNA and protein and enhanced NF-κB activity in their brain capillaries. Higher P-glycoprotein expression was also observed in the brain capillaries of human HD patients. Consistent with this enhanced P-glycoprotein expression, brain extracellular levels and brain-to-plasma ratios of the antipsychotic agents risperidone and paliperidone were significantly lower in R6/2 mice than in their littermate controls. Exogenous expression of human mutant HTT protein with expanded polyQ (mHTT-109Q) in HEK293T cells enhanced the levels of P-glycoprotein transcripts and NF-κB activity compared with cells expressing normal HTT-25Q. Treatment with the IKK inhibitor, BMS-345541, decreased P-glycoprotein mRNA level in cells transfected with mHTT-109Q or normal HTT-25Q In conclusion, mutant HTT altered the expression of P-glycoprotein through the NF-κB pathway in brain capillaries in HD and markedly affected the availability of P-glycoprotein substrates in the brain.

  17. 18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models.

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    Wang, Di; Zhang, Yongfeng; Wang, Chunyue; Jia, Dongxu; Cai, Guangsheng; Lu, Jiahui; Wang, Di; Zhang, Zhang-Jin

    2016-09-01

    The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.

  18. Regulation of P-glycoprotein expression in brain capillaries in Huntington's disease and its impact on brain availability of antipsychotic agents risperidone and paliperidone.

    Science.gov (United States)

    Kao, Yu-Han; Chern, Yijuang; Yang, Hui-Ting; Chen, Hui-Mei; Lin, Chun-Jung

    2016-08-01

    Huntington's disease (HD) is a neurodegenerative disease marked by an expanded polyglutamine (polyQ) tract on the huntingtin (HTT) protein that may cause transcriptional dysfunction. This study aimed to investigate the regulation and function of P-glycoprotein, an important efflux transporter, in brain capillaries in HD. The results showed that, compared with the littermate controls, R6/2 HD transgenic mice with the human mutant HTT gene had higher levels of P-glycoprotein mRNA and protein and enhanced NF-κB activity in their brain capillaries. Higher P-glycoprotein expression was also observed in the brain capillaries of human HD patients. Consistent with this enhanced P-glycoprotein expression, brain extracellular levels and brain-to-plasma ratios of the antipsychotic agents risperidone and paliperidone were significantly lower in R6/2 mice than in their littermate controls. Exogenous expression of human mutant HTT protein with expanded polyQ (mHTT-109Q) in HEK293T cells enhanced the levels of P-glycoprotein transcripts and NF-κB activity compared with cells expressing normal HTT-25Q. Treatment with the IKK inhibitor, BMS-345541, decreased P-glycoprotein mRNA level in cells transfected with mHTT-109Q or normal HTT-25Q In conclusion, mutant HTT altered the expression of P-glycoprotein through the NF-κB pathway in brain capillaries in HD and markedly affected the availability of P-glycoprotein substrates in the brain. PMID:26661162

  19. Antipsychotic treatments; Focus on lurasidone

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    Tomiki eSumiyoshi

    2013-08-01

    Full Text Available The introduction of atypical antipsychotic drugs (AAPDs, or second-generation antipsychotics, with clozapine as the prototype, has largely changed the clinicians’ attitudes towards the treatment of mental illnesses including, but not limited to schizophrenia. Initially, there was optimism that AAPDs would be superior over typical antipsychotic drugs (TAPDs, or first-generation antipsychotic drugs, in terms of efficacy for various phenomenological aspects, including cognitive impairment, and less likelihood of causing adverse events. However, these views have been partly challenged by results from recent meta-analysis studies. Specifically, cardio-metabolic side effects of AAPDs, in spite of a relative paucity of extrapyramidal symptoms, may sometimes limit the use of these agents. Accordingly, attempts have been made to develop newer compounds, e.g. lurasidone, with the aim of increasing efficacy and tolerability. Further investigations are warranted to determine if a larger proportion of patients will be benefitted by treatment with AAPDs compared to TAPDs in terms of remission and recovery.

  20. Antipsychotic treatment of schizophrenia: an update.

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    Bruijnzeel, Dawn; Suryadevara, Uma; Tandon, Rajiv

    2014-10-01

    The primary objectives in the treatment of schizophrenia are to reduce the frequency and severity of psychotic exacerbation, ameliorate a broad range of symptoms, and improve functional capacity and quality of life. Treatment includes pharmacotherapy and a range of psychosocial interventions. Antipsychotics are the cornerstone of pharmacological treatment for schizophrenia. The sixty-five antipsychotics available in the world are classified into two major groups: first-generation (conventional) agents (FGAs) and second-generation (atypical) agents (SGAs). Whereas clozapine is found to be more efficacious than other agents among otherwise treatment-refractory schizophrenia patients, other differences in efficacy between antipsychotic agents are minor. There are, however, pronounced differences in adverse effect profiles among the 65 antipsychotic medications. Although the 14 SGAs differ "on average" from the 51 FGAs in terms of being associated with a lower risk of EPS and greater risk of metabolic side-effects, substantial variation within the two classes with regard to both risks and other relevant clinical properties undermines the categorical distinction between SGAs and FGAs. Choice of antipsychotic medication should be based on prior treatment response, individual preference, medical history and individual patient vulnerabilities. An individualized treatment approach with ongoing risk-benefit monitoring and collaborative decision-making is outlined. Even as rapid neuroscience advances promise revolutionary improvements in the future, a thoughtful and disciplined approach can provide enhanced outcomes for all schizophrenia patients today.

  1. Application of atypical antipsychotic agents in the treatment of bipolar disorder%非典型抗精神病药物在双相情感障碍治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    蔡亦蕴; 徐理; 吴彦

    2014-01-01

    Atypical antipsychotic agents in the treatment of bipolar disorder remain a hot issue in clinic. Their efifcacy in acute manic and depression episodes has been veriifed. However, the long-term preventive efifcacy has not yet been demonstrated. This paper reviews the application of atypical antipsychotic agents in the treatment of bipolar disorder so as to provide a guideline for pharmacotherapy in clinic.%非典型抗精神病药物在双相情感障碍治疗中的应用备受关注。非典型抗精神病药物用于双相情感障碍躁狂相和抑郁相的急性发作期治疗有较为肯定的疗效,但用于稳定期维持治疗的疗效不确定。本文介绍非典型抗精神病药物在双相情感障碍治疗中的应用,为临床合理用药提供参考。

  2. Hematological Side Effects of Atypical Antipsychotic Drugs

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    Serap Erdogan

    2009-10-01

    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  3. Incident users of antipsychotics

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kruse, Marie

    2016-01-01

    PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to exami....... As a consequence of the range of adverse effects associated with antipsychotic drug use, the documented widespread off-label prescribing practices warrant careful monitoring for adverse effects and prompt discontinuation in case of an unfavorable risk-benefit ratio.......PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine...

  4. Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management.

    Science.gov (United States)

    Fang, Fang; Sun, Hongwei; Wang, Zuowei; Ren, Ming; Calabrese, Joseph R; Gao, Keming

    2016-09-01

    Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to

  5. Antipsychotic-induced Hyperprolactinemia

    Directory of Open Access Journals (Sweden)

    Suheyla Dogan Bulut

    2015-06-01

    Full Text Available Prolactin provides the growth of the mammary gland during pregnancy and synthesis and preparation of breast milk for lactation. Antipsychotics and antidepressants that are frequently used in psychiatry, cause hyperprolactinemia. The prevalent opinion is that especially typical antipsychotics increase prolactin levels primarily by blocking D2 receptors in the anterior pituitary. The effects of atypical antipsychotics on hyperprolactinemia vary. Hyperprolactinemia causes galactorrhea, gynecomastia, sexual dysfunction, infertility, acne, hirsutism in women, weight gain, obesity and mood changes in addition to menstrual irregularities such as oligomenorrhea, polymenorrhea and amenorrhea. In the long term, hyperprolactinemia may cause reduction in bone density and osteoporosis. Hyperprolactinemia as a side effect of antipsychotics drugs and its treatment will be reviewed in this article. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 109-124

  6. Depot Typical Antipsychotics versus Oral Atypical Antipsychotics in Relapse Rate Among Patients with Schizophrenia: A Five -Year Historical Cohort Study

    OpenAIRE

    Ahmadkhaniha, Hamid-Reza; Bani-Hashem, Shahab; Ahmadzad-Asl, Masoud

    2014-01-01

    Objective: The present study aimed to review the relapse rate in patients with schizophrenia treated with orally taken atypical agents (serotonin dopamine antagonists, SDAs) and depot preparation of conventional (typical) antipsychotics. Methods: In this historical cohort study, mean relapse per month (MRM) index, duration between initiation of antipsychotic treatment and the first relapse episode, and the time gap between successive relapses were compared between 84 patients on SDAs-except c...

  7. O papel dos antipsicóticos atípicos no tratamento do transtorno bipolar: revisão da literatura The role of atypical antipsychotic agents in the treatment of bipolar disorder: a literature review

    Directory of Open Access Journals (Sweden)

    Acioly LT Lacerda

    2002-03-01

    Full Text Available Estudos recentes têm demonstrado que a eficácia do lítio é significativamente inferior à descrita pelos primeiros trabalhos, embora ainda seja a medicação de referência no tratamento do transtorno afetivo bipolar. Apesar de um perfil de segurança desfavorável, os antipsicóticos clássicos sempre apresentaram um papel importante no tratamento desse transtorno psiquiátrico, especialmente como coadjuvante em sua fase maníaca aguda. Os autores, utilizando informação obtida no Medline, fizeram uma revisão acerca do papel dos antipsicóticos atípicos no tratamento dos pacientes bipolares. Baseado nos dados da literatura, a olanzapina mostrou-se bastante eficaz no manejo da mania aguda, quando uma média de 63,5% dos pacientes apresentaram melhora significativa em estudos duplo-cego controlados, apresentando ganho de peso como único efeito colateral relevante. A clozapina e, mais ainda, a risperidona apresentaram dados menos consistentes, grande parte em função de deficiências metodológicas dos poucos estudos conduzidos até o presente estudo. Os dados preliminares relativos à eficácia desse grupo farmacológico nos quadros refratários e nos sintomas depressivos são promissores, mas ainda não definitivos. Em relação a seus efeitos potenciais como estabilizadores do humor, não existem evidências conclusivas oriundas de estudos controlados, mas há interesse considerável para realização de investigações em pacientes bipolares tratados com antipsicóticos atípicos por períodos de tempo mais prolongados. Pesquisas futuras poderão tornar mais claras essas possíveis características terapêuticas.Even though lithium is still the choice drug in the treatment of bipolar disorder, recent studies have shown that it has a significant lower efficacy than previously described in earlier studies. Despite its adverse side effects, typical antipsychotic agents have often had a prominent role in the treatment of this psychiatric

  8. Antipsychotic Potentials of Ocimum sanctum Leaves

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    Renu Kadian

    2015-01-01

    Full Text Available The present study was undertaken to evaluate the antipsychotic potential of Ocimum sanctum in experimental animal models. Male Wistar rats (180-220 g and albino mice (25-30 g were used for the study. The antipsychotic effect of the Ocimum sanctum was evaluated on haloperidol induced catalepsy, cooks pole climbing apparatus, locomotor activity on actophotometer, ketamine induced stereotype behavior. Different groups of rats were fed orally with a specially prepared diet containing various concentrations (2% w/w, 4% w/w and 8% w/w of Ocimum sanctum leaves paste (OCLP for 15 consecutive days. Further, the biochemical estimations were done by estimating brain dopamine levels. The OCLP produced significant dose dependent potentiation of haloperidol (1mg/kg, i.p. induced catalepsy in rats, significantly increased the time taken by the rat to climb the pole in dose dependent manner, significantly decreased the locomotor activity. The OCLP significantly decreased ketamine (50 mg/kg, i.p. induced stereotyped behavior in a dose dependent manner. Ocimum sanctum leaves paste (OCLP significantly decreased the brain dopamine levels. The results suggest that OCLP posse’s antipsychotic activity. Further neurochemical investigation can explore the mechanism of action of the plant drug with respect to anti-dopaminergic functions and help to establish the plant as an antipsychotic agent.

  9. New users of antipsychotic medication

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services. RESULTS: The majority of new antipsychotic users...... regimen. CONCLUSIONS: Antipsychotic treatment, especially in combination with other antipsychotics or other psychotropic drugs, could serve as a marker of subjects with increased need for support to maintain the labor market affiliation. However, causality cannot be inferred from an observational study...

  10. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

    Directory of Open Access Journals (Sweden)

    Izchak Kohen

    2010-03-01

    Full Text Available Izchak Kohen1, Paula E Lester2, Sum Lam31Division of Geriatric Psychiatry, Zucker-Hillside Hospital, Glen Oaks, NY, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, NY, USA; 3Division of Pharmacy and Geriatrics, St. John’s University College of Pharmacy and Allied Health Professions, Queens, NY, USAAbstract: Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient’s previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence.Keywords: aripiprazole, antipsychotics, elderly, adverse drug reaction

  11. O impacto dos agentes antipsicóticos na densidade mineral óssea de pacientes esquizofrênicos Impact of antipsychotic agents in bone mineral density of schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Lísia Rejane Guimarães

    2006-12-01

    Full Text Available Estudos têm evidenciado o alto risco de osteoporose em pacientes esquizofrênicos. Alguns estudos têm demonstrado que os neurolépticos típicos e a risperidona podem induzir a osteoporose ou reduzir a densidade mineral óssea. Isso pode ser atribuído ao fato de estas drogas, em uso prolongado, induzirem a hiperprolactinemia a níveis acima do normal, em ambos os sexos, e a baixa dos níveis de estrogênio e de testosterona, aumentando o risco para osteopenia/osteoporose. Neste relato, será apresentado um caso de osteopenia em uma paciente mulher de 53 anos, em uso de antipsicóticos há 30 anos, sendo comentados os procedimentos recomendados para detecção dessa ocorrência e as diretrizes existentes para seu manejo.Studies have shown a high risk of osteoporosis in schizophrenic patients. Some studies have demonstrated that typical neuroleptics and risperidone may induce osteoporosis or reduce bone mineral density. This can be due to the fact that prolonged use of those drugs induces hyperprolactinemia to levels above normal in both genders, and reduces the levels of estrogen and testosterone, thus increasing the risk of osteopenia/osteoporosis. We report on a case of osteopenia in a 53-year-old female patient using antipsychotics for 30 years. We comment on the recommended procedures to detect osteopenia and on the existing guidelines for its management.

  12. Safety and tolerability of antipsychotics: focus on amisulpride

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    Mario F Juruena

    2010-10-01

    Full Text Available Mario F Juruena1, Eduardo Pondé de Sena2, Irismar Reis de Oliveira31Stress and Affective Disorders Programme, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil; 2Department of Pharmacology, Institute of Health Sciences, Federal University of Bahia, Salvador; 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, BA, BrazilAbstract: The introduction of the atypical antipsychotic drugs represents an important advance in the treatment of schizophrenia, because the therapeutic efficacy, tolerability, and safety profiles of these agents seem to be superior to that of the classical neuroleptics. As would be predicted from the pharmacologic profile of a pure D2/D3 receptor blocker, amisulpride is an atypical antipsychotic agent, effective for positive and negative symptoms, which can bring about additional improvement in the social functioning and quality of life of patients with schizophrenia. Amisulpride is effective in acute schizophrenia as determined by Clinical Global Impression scores. The major concern regarding the safety of the atypical antipsychotics is related to their propensity to induce weight gain and alter glucose and lipid metabolism. Amisulpride has one of the lowest potentials for weight gain of all the antipsychotic agents, and is associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. Amisulpride is well tolerated with regard to anxiety and insomnia, and not notably different from placebo. Amisulpride has a pronounced prolactin-elevating effect which appears to be independent of dosage and duration of administration. Hyperprolactinemia rapidly reverses following amisulpride discontinuation. Amisulpride benefits patients with negative symptoms, and is the only antipsychotic to demonstrate efficacy in patients with

  13. Antipsychotic drug use and community-acquired pneumonia

    NARCIS (Netherlands)

    G. Trifirò (Gianluca)

    2011-01-01

    textabstractAntipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psychiatric disorders. In April 2005, the US Food and Drug Administration issued a warning about the increased risk of all-cause mortal

  14. Depression: Should You Consider Antipsychotics?

    Science.gov (United States)

    ... Ask for other treatments, such as talk therapy (psychotherapy). • If you try an antipsychotic, ask for a ... the marketing of the prescription drug Neurontin. This brief should not be viewed as a substitute for ...

  15. Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior

    DEFF Research Database (Denmark)

    Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe;

    2009-01-01

    Dopamine D(3) antagonism combined with serotonin 5-HT(1A) and 5-HT(2A) receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacological features of 5i are a high affinity for dopamine D(3), serotonin 5-HT(1A) and 5-HT(2A) receptors, together w...

  16. Antipsychotic efficacy: relationship to optimal D2-receptor occupancy.

    Science.gov (United States)

    Pani, Luca; Pira, Luigi; Marchese, Giorgio

    2007-07-01

    Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords 'antipsychotic or neuroleptic', 'receptor' and 'occupancy' and 'dopamine' and 'D2' supplemented by the authors' knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a 'therapeutic window' between approximately 65 and approximately 80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia. PMID:17419008

  17. Antipsychotics dosage and antiparkinsonian prescriptions

    Directory of Open Access Journals (Sweden)

    Gasquet Isabelle

    2007-09-01

    Full Text Available Abstract Background To study the link between the dosage of several antipsychotics and the prescription of antiparkinsonians in an observational study. Methods In the context of a national naturalistic prospective observational study, a database containing all the prescriptions from 100 French psychiatrists during the year 2002 was analysed. The inclusion criteria were a diagnosis of schizophrenia or schizoaffective disorder and age over 18. The mean dosage of antipsychotics with and without antiparkinsonians was compared. Since there were multiple prescriptions for a given subject, generalised mixed linear models were also used to study the link between antiparkinsonian prescription and antipsychotic dosage. Results antiparkinsonians were prescribed to 32,9% of the patients. Two groups of antipsychotics were observed relating to differences in dosage when an antiparkinsonian was co prescribed or not : a first group, where the mean dosage was higher with antiparkinsonians (risperidone, amisulpride and haloperidol and a second group (clozapine, olanzapine, in which antiparkinsonian co prescription was not related to the dosage of antipsychotics. Conclusion As a conclusion, it can be said that it is important to consider the dosage and the type of antipsychotic in the treatment of patients suffering of schizophrenia, because neurological side effects are frequent and can impair quality of life. Moreover the prescription of antiparkinsonians can lead to different side effects such anticholinergic effects.

  18. Antipsychotic discontinuation syndrome following risperidone withdrawal: a case report from rural India

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    Sravanti L. Sanivarapu

    2014-02-01

    Full Text Available Risperidone is an atypical antipsychotic agent used primarily to treat schizophrenia. It is a dopamine antagonist with antiserotonergic, antihistaminergic and antiadrenergic properties. Antipsychotic discontinuation symptoms have been described in the literature following abrupt or rapid reduction in the dose. This unusual case demonstrates that sudden withdrawal of even a modest dose of risperidone may cause significant discontinuation symptoms in susceptible individuals. Hence, there is a need for caution while taking a patient off antipsychotic medications in view of the vulnerable subgroup. [Int J Basic Clin Pharmacol 2014; 3(1.000: 233-234

  19. Antipsychotic discontinuation syndrome following risperidone withdrawal: a case report from rural India

    OpenAIRE

    Sanivarapu, Sravanti L.; Krishnamurthy CN

    2014-01-01

    Risperidone is an atypical antipsychotic agent used primarily to treat schizophrenia. It is a dopamine antagonist with antiserotonergic, antihistaminergic and antiadrenergic properties. Antipsychotic discontinuation symptoms have been described in the literature following abrupt or rapid reduction in the dose. This unusual case demonstrates that sudden withdrawal of even a modest dose of risperidone may cause significant discontinuation symptoms in susceptible individuals. Hence, there is a n...

  20. Off-label indications for atypical antipsychotics: A systematic review

    OpenAIRE

    Fountoulakis, Konstantinos N; Nimatoudis, Ioannis; Iacovides, Apostolos; Kaprinis, George

    2004-01-01

    Introduction With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. Material and method MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory d...

  1. [Metabolic disorders under antipsychotic treatment].

    Science.gov (United States)

    Steffenhagen, N; Rummel-Kluge, C; Himmerich, H

    2012-03-01

    Patients with severe mental illness, such as schizophrenia, depression or bipolar disorder, are more likely to be overweight and to suffer from dyslipidaemia, diabetes or cardiovascular disease. Unhealthy lifestyles, including poor diet and sedentary behaviour, but also pharmacotherapy contribute to the adverse risk profile. This article reviews the epidemiology and pharmacodynamics of metabolic abnormalities in psychiatric patients treated with antipsychotics, focusing on substance-specific differences. PMID:21206997

  2. Previous hospital admissions and disease severity predict the use of antipsychotic combination treatment in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Agartz Ingrid

    2011-08-01

    Full Text Available Abstract Background Although not recommended in treatment guidelines, previous studies have shown a frequent use of more than one antipsychotic agent among patients with schizophrenia. The main aims of the present study were to explore the antipsychotic treatment regimen among patients with schizophrenia in a catchment area-based sample and to investigate clinical characteristics associated with antipsychotic combination treatment. Methods The study included 329 patients diagnosed with schizophrenia using antipsychotic medication. Patients were recruited from all psychiatric hospitals in Oslo. Diagnoses were obtained by use of the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I. Additionally, Global Assessment of Functioning (GAF, Positive and Negative Syndrome Scale (PANSS and number of hospitalisations and pharmacological treatment were assessed. Results Multiple hospital admissions, low GAF scores and high PANSS scores, were significantly associated with the prescription of combination treatment with two or more antipsychotics. The use of combination treatment increased significantly from the second hospital admission. Combination therapy was not significantly associated with age or gender. Regression models confirmed that an increasing number of hospital admission was the strongest predictor of the use of two or more antipsychotics. Conclusions Previous hospital admissions and disease severity measured by high PANSS scores and low GAF scores, predict the use of antipsychotic combination treatment in patients with schizophrenia. Future studies should further explore the use of antipsychotic drug treatment in clinical practice and partly based on such data establish more robust treatment guidelines for patients with persistently high symptom load.

  3. Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes.

    Science.gov (United States)

    Mojtabai, Ramin; Lavelle, Janet; Gibson, P Joseph; Bromet, Evelyn J

    2003-01-01

    This study compares the effects of atypical and conventional antipsychotic medications on treatment continuation and outcomes in a first admission sample of patients with schizophrenia treated in usual practice settings. In a sample of 189 participants with a research diagnosis of DSM-IV schizophrenia drawn from the Suffolk County Mental Health Project, we compared the effects of atypical and conventional agents on change of medication, medication gaps, and rehospitalization. For these analyses we used the method of survival analysis for recurrent events, in which the episodes of treatment rather than individual subjects are the units of analysis. In addition, we compared improvement in positive and negative symptoms from intake to 24- or 48-month followups for subjects who stayed on one type of medication or changed to atypicals from conventional antipsychotics. Atypical agents were associated with lower risk of medication change, medication gaps, and rehospitalization. Both conventional and atypical agents were associated with improvement of positive symptoms at followup, but only subjects on atypical agents at followup experienced a significant improvement in negative symptoms. We conclude that in usual practice settings, as in randomized clinical trials, atypical agents are associated with improved treatment continuation and outcomes.

  4. Effects of Antipsychotics on Bone Mineral Density in Patients with Schizophrenia: Gender Differences

    Science.gov (United States)

    Chen, Chien-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2016-01-01

    Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed. PMID:27489377

  5. Effects of Antipsychotics on Bone Mineral Density in Patients with Schizophrenia: Gender Differences.

    Science.gov (United States)

    Chen, Chien-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2016-08-31

    Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed. PMID:27489377

  6. Schizophrenia, antipsychotics and risk of hip fracture

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Jensen, Signe O W; Nielsen, Jimmi

    2013-01-01

    In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co-morb....... Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics....... (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics...

  7. Association between LEP and LEPR gene polymorphisms and dyslipidemia in patients using atypical antipsychotic medication

    NARCIS (Netherlands)

    Gregoor, Jochem G.; van der Weide, Jan; Loovers, Harriet M.; van Megen, Harold J.; Egberts, Toine C.; Heerdink, Eibert R.

    2010-01-01

    Background Treatment with atypical antipsychotic agents is often complicated by dyslipidemia, which is a risk factor for cardiovascular disease. Objectives To determine whether the LEPR Q223R, the LEP -2548G/A, and the HTR2C -759C/T polymorphisms are associated with dyslipidemia in patients using at

  8. Polymorphisms of the LEP- and LEPR Gene and Obesity in Patients Using Antipsychotic Medication

    NARCIS (Netherlands)

    Gregoor, Jochem G.; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J. G. M.; Egberts, Antoine C. G.; Heerdink, Eibert R.

    2009-01-01

    Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/ A polymorphism are associated with

  9. Use of antipsychotics and risk of venous thromboembolism in postmenopausal women. A population-based nested case-control study.

    Science.gov (United States)

    Wang, Meng-Ting; Liou, Jun-Ting; Huang, Yun-Wen; Lin, Chen Wei; Wu, Gwo-Jang; Chu, Che-Li; Yeh, Chin-Bin; Wang, Yun-Han

    2016-06-01

    Despite continued uncertainty of venous thromboembolism (VTE) caused from antipsychotic agents, this safety issue has not been examined in postmenopausal women, a population with high usages of antipsychotics and at high risk for VTE. We assessed whether antipsychotic use was associated with an increased VTE risk in women after menopause. We conducted a nested case-control study of all Taiwanese women aged ≥ 50 years (n = 316,132) using a nationwide healthcare claims database between 2000 and 2011. All newly diagnosed VTE patients treated with an anticoagulant or thrombectomy surgery were identified as cases (n = 2,520) and individually matched to select controls (n = 24,223) by cohort entry date, age, cancer diagnosis and major surgery procedure. The odds ratios (ORs) and 95 % confidence interval (CI) of VTE associated with antipsychotics were estimated by multivariate conditional logistic regressions. Current use of antipsychotics was associated with a 1.90-fold (95 % CI = 1.64-2.19) increased VTE risk compared with nonuse in postmenopausal women. The VTE risk existed in a dose-dependent fashion (test for trend, p 30 days. In conclusion, current use of antipsychotics is significantly associated with a dose-dependent increased risk of VTE in postmenopausal women, especially for those currently taking high-dose or receiving parenteral antipsychotics. PMID:26941052

  10. Atypical Antipsychotics and Other Therapeutic Options for Treatment of Resistant Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Allan H. Young

    2010-12-01

    Full Text Available Antidepressant therapies, such as selective serotonin reuptake inhibitors (SSRIs, are current first-line treatments for Major Depressive Disorder. However, over 50% of treated patients show an inadequate response to initial antidepressant therapy. If the therapeutic outcomes from two antidepressant therapies are suboptimal, potentially resulting in Treatment Resistant Depression, subsequent strategies include switching to another antidepressant or augmenting treatment by combining with other agents. When combined with SSRIs, atypical antipsychotics have supplementary action on dopaminergic and noradrenergic systems. Studies on combined treatment with atypical antipsychotics have shown significantly increased remission rates, shortened response times, and favorable side effects. Augmentation of antidepressants with atypical antipsychotics is now an acceptable treatment strategy which leads to increased remission rates and better outcomes for patients.

  11. Second Generation Antipsychotics Improve Sexual Dysfunction in Schizophrenia: A Randomised Controlled Trial

    Directory of Open Access Journals (Sweden)

    Ahmed Mahmoud

    2011-01-01

    Full Text Available The impact of antipsychotic drug treatment on sexual function was investigated during a randomised trial comparing first generation antipsychotics (FGAs to (nonclozapine second generation antipsychotics (SGAs. Sexual function and quality of life were (rater-blind assessed in 42 patients with DSM-IV schizophrenia (aged 18–65 using the self-report version of the Derogatis Interview for Sexual Function (DISF-SR and the Heinrichs Quality of Life Scale (QLS, prior to, and 12 weeks following, a change in medication from an FGA drug to either an FGA or SGA drug. SGAs significantly improved sexual function compared to FGAs. Change in sexual function was associated with change in quality of life. Where impaired sexual functioning is a distressing adverse effect of treatment with an FGA agent, consideration should be given to switching to an SGA.

  12. Developments in antipsychotic drugs - an update.

    Science.gov (United States)

    Reynolds, G P

    1998-02-01

    Antipsychotic drug research has recently made much progress. Over the past two years several new drugs have been introduced for the treatment of schizophrenia and more compounds are shortly to be released. Pharmacological studies, improved behavioural models and modern imaging techniques have all contributed to a better understanding of the mechanisms of antipsychotic drug action. Some of the developments that have been made over the past year are reviewed here. PMID:15991957

  13. Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study

    DEFF Research Database (Denmark)

    Baandrup, Lone; Gasse, Christiane; Jensen, Vibeke;

    2010-01-01

    OBJECTIVE: Concomitant prescription of more than 1 antipsychotic agent (antipsychotic polypharmacy) in the treatment of schizophrenia is prevalent, although monotherapy is generally recommended. Mortality from natural causes is markedly increased in schizophrenia, and the role of polypharmacy...... remains controversial. The objective was to investigate if antipsychotic polypharmacy is associated with the excess mortality from natural causes among patients with schizophrenia. METHOD: A population-based nested case-control study was conducted using patient data from January 1, 1996, to December 31...... hours) was associated with increased risk of natural death in patients with schizophrenia treated with antipsychotics (OR = 1.78 [95% CI, 1.25-2.52]). CONCLUSIONS: Antipsychotic polypharmacy did not contribute to the excess mortality from natural causes in middle-aged patients with schizophrenia. The...

  14. Newer antipsychotics and the rabbit syndrome

    Directory of Open Access Journals (Sweden)

    Masalehdan Azadeh

    2007-06-01

    Full Text Available Abstract Background Rabbit syndrome is a movement disorder that is associated with long-term exposure to neuroleptic medications. Of particular interest and importance is the risk of rabbit syndrome with exposure to the newer atypical antipsychotics. Our recent experience with such a case brought to light the importance of exploring this risk. Methods MEDLINE and PubMed (1972–2006 databases were searched for English language articles using the keywords rabbit syndrome, tardive dyskinesia, antipsychotic, extrapyramidal symptoms and side effects. A recent case study is used to expand upon the literature available on newer antipsychotics and rabbit syndrome. Results We reviewed papers that addressed the following aspects of rabbit syndrome 1 the clinical manifestations 2 prevalence and risk factors, 3 etiopathogenesis 4 older antipsychotics and rabbit syndrome 5 newer antipsychotics, 6 treatment options. Moreover, we report a case of RS in a 50 year old white female, diagnosed with bipolar I disorder, that, after the discontinuation of risperidone, developed involuntary movements of the mouth that were fine, rhythmic and rapid, along the vertical axis, and without involvement of the tongue. After the re-introduction of risperidone, the symptoms decreased in a few hours and disappeared after 3 days. Conclusion Eleven cases of rabbit syndrome have been documented since the implementation of newer antipsychotics. Future research is needed to better understand the etiopathogenesis of rabbit syndrome in psychiatric populations treated with the atypical antipsychotics. Understanding the differences and similarities of rabbit syndrome and tardive dyskinesia is crucial to the creation of a successful treatment paradigm.

  15. Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Correll Christoph

    2005-05-01

    Full Text Available Abstract Background Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. Methods Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796 who were initiated during the study on olanzapine (N = 405, quetiapine (N = 115, or risperidone (N = 276. The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. Results During the 1-year period, only a third (35.7% of the patients were treated predominately with monotherapy (>300 days. Most patients (57.7% had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days. Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043 or quetiapine (p = .002. The number of monotherapy days was significantly greater for olanzapine than quetiapine (p Conclusion Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic

  16. Antipsychotic drug-induced hematologic disorders

    Directory of Open Access Journals (Sweden)

    Theocharis Kyziridis

    2014-01-01

    Full Text Available Over half a century after the discovery of chlorpromazine and haloperidol, antipsychotic drugs showed a true evolutionary revolution. The knowledge of their adverse effects is of outmost importance as it may contribute to the prevention of unwanted sequelae, to the decrease of the duration and cost of hospitalization, it may improve the quality of life of patients, minimize the problems and maximize the therapeutic gain. Aim: The aim of this review was the presentation of the hematologic side-effects of antipsychotic drugs, and most particularly their frequency and association with the different classes of these drugs, their clinical picture and their pathophysiologic mechanisms. Material-method: This paper is a review of the literature (mainly articles from journals, PubMed, as well as books and monographs of the period 1978-2012. Key-words used included antipsychotics, hematologic adverse effects, drug-induced adverse effects. Results: Antipsychotic-drug induced hematologic side-effects are not particularly highly prevalent, while many of them are found in case reports. For this reason they have not drawn much of attention. These hematologic dyscrasias may concern all the blood cell series as well as the coagulation mechanism. Excluded from this rule is the case of clozapine-induced agranulocytosis, which demands increased clinical vigilance. In fact, agranulocytosis was the reason why the drug was drawn away from circulation approximately 35 years ago. Conclusions: In any case the appearance of a hematologic disorder in a patient receiving antipsychotic medications should prompt careful evaluation.

  17. Diabetic ketoacidosis in patients exposed to antipsychotics

    DEFF Research Database (Denmark)

    Polcwiartek, Christoffer; Vang, Torkel; Bruhn, Christina Hedegård;

    2016-01-01

    RATIONALE: Patients exposed to second-generation antipsychotics (SGAs) have approximately 10 times increased risk of diabetic ketoacidosis (DKA) compared with the general population. However, as DKA is a rare complication of type 2 diabetes mellitus, and susceptible patients exposed...... to antipsychotics may rapidly develop DKA independently of treatment duration and weight gain, this is rather suggestive of type 1 diabetes mellitus (T1DM) or latent autoimmune diabetes in adults. OBJECTIVES: We performed a systematic review of current studies regarding antipsychotic-associated DKA with type 1...... etiology and analyzed Danish adverse drug event (ADE) reports (previously unpublished cases). METHODS: PubMed, Embase, and the Cochrane Library were searched for all relevant studies, and the Danish Medicines Agency retrieved ADE reports using the Danish ADE database (up to date as of June 28, 2016...

  18. 'Rapid tranquillisation': an historical perspective on its emergence in the context of the development of antipsychotic medications.

    Science.gov (United States)

    Allison, Laura; Moncrieff, Joanna

    2014-03-01

    This paper examines factors involved in the theory and practice of emergency sedation for behavioural disturbance in psychiatry in the mid-twentieth century, and the emergence of the concept of 'rapid tranquillisation'. The practice received little attention until the arrival of antipsychotic drugs, which replaced older sedatives and became the agents most strongly associated with the treatment of aggression and challenging behaviour. Emergency sedation was subsequently portrayed in psychiatric literature and advertising as a therapeutic and diagnosis-driven endeavour, and the concept of rapid tranquillisation emerged in this context in the 1970s. Use of non-antipsychotic sedatives, like the benzodiazepines, is barely visible in contemporary sources, and the research suggests that antipsychotics became the mainstay of rapid tranquillisation strategies because of beliefs about their specific therapeutic properties in psychosis and schizophrenia, and not because of demonstrated superiority over other agents.

  19. Antipsychotic-Like Effect of Trimetazidine in a Rodent Model

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    Oytun Erbaş

    2013-01-01

    Full Text Available Trimetazidine (TMZ has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat ( were administrated with TMZ (10 and 20 mg/kg, i.p., chlorpromazine (1 mg/kg, i.p., or isotonic saline. One hour later, apomorphine (2 mg/kg, s.c. was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug.

  20. Long-Acting Injectable Antipsychotics for Prevention of Relapse in Bipolar Disorder: A Systematic Review and Meta-Analyses of Randomized Controlled Trials

    Science.gov (United States)

    Oya, Kazuto; Iwata, Nakao

    2016-01-01

    Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n=1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials)=449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents=283]; and placebo=284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio=0.63, P<.0001), relapse of manic symptoms (risk ratio=0.42, P<.00001), and all-cause discontinuation (risk ratio=0.75, P=.007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio=4.82, P=.001) and weight gain (risk ratio=3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2=74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2=0%, RR=0.58, P=.0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, long-acting injectable antipsychotics did not outperform second

  1. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads;

    2003-01-01

    Several clinical reports have demonstrated that most antipsychotics of the new generation, but not the typical antipsychotic haloperidol, induce weight gain in schizophrenic patients. Since weight gain induces serious health complications in humans, it is crucial to test upcoming antipsychotic co...

  2. Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior

    Science.gov (United States)

    Tang, Yan; Chang, Chung-Chou H.; Lave, Judith R.; Gellad, Walid F.; Huskamp, Haiden A.; Donohue, Julie M.

    2016-01-01

    prescribing behavior and indicate that even among specialties regularly prescribing a therapeutic category, some physicians rely heavily on a small number of agents. Implications for Health Policies, Health Care Provision and Use Health systems may need to offer educational interventions to clinicians in order to improve their ability to tailor treatment decisions to the needs of individual patients. Implications for Future Research Future studies should examine the impact of the diversity of antipsychotic prescribing to determine whether more diversified prescribing improves patient adherence and outcomes. PMID:27084793

  3. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

    Directory of Open Access Journals (Sweden)

    Caccia S

    2013-08-01

    Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

  4. Association study between G-protein β3 subunit gene polymorphism and antipsychotic agent-induced obesity%G蛋白β3亚单位基因多态性与抗精神病药源性肥胖的相关性

    Institute of Scientific and Technical Information of China (English)

    张文跃; 祁小飞; 杨忠; 王梅芬; 顾凤华; 宣春明; 韩晓东

    2011-01-01

    目的 探讨G蛋白β3亚单位(GNB3)基因C825T多态性与抗精神病药源性肥胖的关系.方法 收集126例长期应用抗精神病药的精神分裂症患者,按体重指数(BMI)分成肥胖组(62例)和非肥胖组(64例);采用聚合酶链式反应(PCR)和DNA测序技术测定GNB3基因C825T多态性;常规检测空腹血糖(FBG)、餐后2h血糖(2hPBG)、血脂、血尿酸(UA)水平.结果 (1)肥胖组与非肥胖组均发现GNB3基因C825T多态性,并符合Hardy-Weinberg平衡率;(2)肥胖组基因型频率(CC 17.75%,CT 58.06%,TT24.19%)与非肥胖组(CC 18.75%,CT 62.50%,TT 18.75%)比较差异无统计学意义(x2=0.59,P>0.05),肥胖组等位基因频率(C 46.77%,T 53.23%)与非肥胖组(C 50%,T 50%)比较差异也无统计学意义(x2=0.26,P>0.05);(3)不同基因型之间BMI、FBG、2hPBG、血脂、UA水平差异无统计学意义(均P>0.05),携T等位基因(CT型+TT型)与非携T等位基因者(CC型)之间BMI、FBG、2hPBG、血脂、UA水平差异也无统计学意义(均P>0.05).结论 GNB3基因C825T多态性可能不是抗精神病药源性肥胖的基因危险因素.%Objective To explore the relationship between G-protein β3 subunit (GNB3) gene C825T polymorphism and antipsychotic agent-induced obesity.Methods 126 schizophrenic inpatients with long-term antipsychotics treatment were collected.According to body mass index ( BMI),patients were divided into obesity group ( n =62) and non-obesity group ( n =64).The GNB3 gene C825T polymorphism was detected by polymerase chain reaction and DNA sequencing technique.Levels of fasting blood glucose,2-hour postprandial blood glucose,blood lipids and blood uric acid of all patients were routinely measured.Results (1)The GNB3 gene C825T polymorphism were found in obesity group and non-obesity group respectively,and the distribution of genotypes in two groups were both consistent with Hardy-Weinberg equilibrium.(2)There was no significant difference in genotype

  5. [Therapy of dementia with antipsychotics and antidepressives].

    Science.gov (United States)

    Frölich, L; Hausner, L

    2015-04-01

    In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia. PMID:25787724

  6. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents–A drug repurposing strategy

    OpenAIRE

    Chia-Hsien Wu; Li-Yuan Bai; Ming-Hsui Tsai; Po-Chen Chu; Chang-Fang Chiu; Michael Yuanchien Chen; Shih-Jiuan Chiu; Jo-Hua Chiang; Jing-Ru Weng

    2016-01-01

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the pa...

  7. Long-Acting Injectable Antipsychotics for Prevention of Relapse in Bipolar Disorder: A Systematic Review and Meta-Analyses of Randomized Controlled Trials

    Science.gov (United States)

    Oya, Kazuto; Iwata, Nakao

    2016-01-01

    Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n=1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials)=449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents=283]; and placebo=284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio=0.63, Psymptoms (risk ratio=0.42, Pprevention in patients with rapid cycling. Furthermore, randomized controlled trials comparing long-acting injectable antipsychotics and oral second-generation antipsychotic using larger samples of rapid cycling patients are warranted. PMID:27207910

  8. Polymorphisms of the LEP- and LEPR gene and obesity in patients using antipsychotic medication.

    Science.gov (United States)

    Gregoor, Jochem G; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J G M; Egberts, Antoine C G; Heerdink, Eibert R

    2009-02-01

    Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications. PMID:19142102

  9. Repurposing the Antipsychotic Trifluoperazine as an Antimetastasis Agent

    OpenAIRE

    Pulkoski-Gross, Ashleigh; Li, Jian; Zheng, Carolina; Li, Yiyi; Ouyang, Nengtai; Rigas, Basil; Zucker, Stanley; Cao, Jian

    2015-01-01

    Because cancer cell invasion is a critical determinant of metastasis, targeting invasion is a viable approach to prevent metastasis. Utilizing a novel three-dimensional high-throughput invasion assay, we screened a National Cancer Institute compound library and discovered compounds demonstrating inhibitory effects on cancer cell invasion. One hit, trifluoperazine, suppresses invasion of human cancer cell lines while displaying a limited cytotoxicity profile. This inhibition is due to the inte...

  10. Schizophrenia Gene Expression Profile Reverted to Normal Levels by Antipsychotics

    OpenAIRE

    Crespo Facorro, Benedicto; Prieto Sánchez, Carlos; Sainz Maza, Jesús Vicente

    2015-01-01

    BACKGROUND: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. METHODS: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. RESULTS: We found that 17 genes, among the 21 495 genes analyz...

  11. Serum prolactin levels and sexual dysfunctions in antipsychotic medication, such as risperidone : a review

    NARCIS (Netherlands)

    Knegtering, H; Lambers, PA; Prakken, G; ten Brink, C

    2000-01-01

    Classical antipsychotic drugs increase the level of serum prolactin. The atypical antipsychotic clozapine barely increases prolactin levels. An open naturalistic study in the University Hospital of Groningen suggests that treatment with risperidone in comparison to classical antipsychotics seems to

  12. Antipsychotics and Sexual Dysfunction: Sexual Dysfunction - Part III

    Directory of Open Access Journals (Sweden)

    Anil Kumar Mysore Nagaraj

    2009-11-01

    Full Text Available Satisfying sexual experience is an essential part of a healthy and enjoyable life for most people. Antipsychotic drugs are among the various factors that affect optimal sexual functioning. Both conventional and novel antipsychotics are associated with significant sexual side effects. This review has presented various studies comparing different antipsychotic drugs. Dopamine antagonism, increased serum prolactin, serotonergic, adrenergic and cholinergic mechanisms are all proposed to be the mechanisms for sexual dysfunction. Drug treatment for this has not given satisfactory long-term results. Knowledge of the receptor pharmacology of an individual antipsychotic will help to determine whether it is more or less likely to cause sexual side effects and its management.

  13. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne;

    2012-01-01

    with the antipsychotic compound amisulpride. Controls were followed up without treatment. MAIN OUTCOME MEASURES Task-related blood oxygen level-dependent activations as measured by functional magnetic resonance imaging before and after antipsychotic treatment. RESULTS At baseline, patients, as compared with controls...

  14. Can antipsychotic treatment contribute to drug addiction in schizophrenia?

    Science.gov (United States)

    Samaha, Anne-Noël

    2014-07-01

    Individuals with schizophrenia are at very high risk for drug abuse and addiction. Patients with a coexisting drug problem fare worse than patients who do not use drugs, and are also more difficult to treat. Current hypotheses cannot adequately account for why patients with schizophrenia so often have a co-morbid drug problem. I present here a complementary hypothesis based on evidence showing that chronic exposure to antipsychotic medications can induce supersensitivity within the brain's dopamine systems, and that this in turn can enhance the rewarding and incentive motivational effects of drugs and reward cues. At the neurobiological level, these effects of antipsychotics are potentially linked to antipsychotic-induced increases in the striatal levels of dopamine D2 receptors and D2 receptors in a high-affinity state for dopamine, particularly at postsynaptic sites. Antipsychotic-induced dopamine supersensitivity and enhanced reward function are not inevitable consequences of prolonged antipsychotic treatment. At least two parameters appear to promote these effects; the use of antipsychotics of the typical class, and continuous rather than intermittent antipsychotic exposure, such that silencing of dopaminergic neurotransmission via D2/3 receptors is unremitting. Thus, by inducing forms of neural plasticity that facilitate the ability of drugs and reward cues to gain control over behaviour, some currently used treatment strategies with typical antipsychotics might contribute to compulsive drug seeking and drug taking behaviours in vulnerable schizophrenia patients. PMID:23793001

  15. Antipsychotic medication prescribing trends in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Riyaz Ahmed Siddiqui

    2016-08-01

    Conclusions: Atypical antipsychotics are more commonly used as compared to the typical ones. Atypical antipsychotics like olanzapine, resperidone and quetiapine are preferred because of their lesser propensity to cause extrapyramidal adverse effects and they also helps in improving negative symptoms of schizophrenia. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1417-1420

  16. Corrected QT changes during antipsychotic treatment of children and adolescents

    DEFF Research Database (Denmark)

    Jensen, Karsten Gjessing; Juul, Klaus; Fink-Jensen, Anders;

    2015-01-01

    OBJECTIVE: To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth. METHOD: We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) for randomized or open clinical trials of antipsychotics in youth <18 years with QTc data, meta-analyzing the results. Meta-regression a...

  17. Use of antipsychotics in the treatment of depressive disorders

    Institute of Scientific and Technical Information of China (English)

    Ping WANG; Tianmei SI

    2013-01-01

    There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.

  18. Patient perspectives on antipsychotic treatments and their association with clinical outcomes

    Directory of Open Access Journals (Sweden)

    Hong Liu-Seifert

    2010-09-01

    Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

  19. Pharmacogenetics of second-generation antipsychotics.

    Science.gov (United States)

    Brennan, Mark D

    2014-04-01

    This review considers pharmacogenetics of the so called 'second-generation' antipsychotics. Findings for polymorphisms replicating in more than one study are emphasized and compared and contrasted with larger-scale candidate gene studies and genome-wide association study analyses. Variants in three types of genes are discussed: pharmacokinetic genes associated with drug metabolism and disposition, pharmacodynamic genes encoding drug targets, and pharmacotypic genes impacting disease presentation and subtype. Among pharmacokinetic markers, CYP2D6 metabolizer phenotype has clear clinical significance, as it impacts dosing considerations for aripiprazole, iloperidone and risperidone, and variants of the ABCB1 gene hold promise as biomarkers for dosing for olanzapine and clozapine. Among pharmacodynamic variants, the TaqIA1 allele of the DRD2 gene, the DRD3 (Ser9Gly) polymorphism, and the HTR2C -759C/T polymorphism have emerged as potential biomarkers for response and/or side effects. However, large-scale candidate gene studies and genome-wide association studies indicate that pharmacotypic genes may ultimately prove to be the richest source of biomarkers for response and side effect profiles for second-generation antipsychotics.

  20. Successful Use of Add - On Topiramate for Antipsychotic - Induced Weight Gain

    Directory of Open Access Journals (Sweden)

    Venkataram Shivakumar

    2012-01-01

    Full Text Available Antipsychotic induced weight gain is the most common and distressing side effect. This also affects the compliance toward the treatment and hence the prognosis. Non - pharmacological interventions such as exercise and diet modifications alone might not be sufficient most of the times; also ensuring compliance toward this is difficult in patients with psychiatric illness. So, the role of weight - reducing drugs become important. In this case report, we describe the use of low - dose topiramate as a weight - reducing agent, in a patient with a bipolar affective disorder - mania with psychotic symptoms, who had significant risperidone - induced weight gain.

  1. Antipsychotic Management of Schizoaffective Disorder: A Review.

    Science.gov (United States)

    Lindenmayer, Jean-Pierre; Kaur, Amandeep

    2016-04-01

    Schizoaffective disorder (SAD) is an incapacitating illness that presents clinicians with challenges in terms of both its diagnosis and its psychopharmacological management. Most studies conducted on the psychopharmacological treatment of SAD also include patients with schizophrenia or other psychotic illnesses, thereby providing an unspecific view to the clinician as to the best way of treating patients with SAD. The objective of this article is to review studies on evidence-based treatment of patients with SAD. We conducted a systematic literature search in MEDLINE/PubMed for full-text studies in the English language using the terms 'Schizoaffective and treatment' or 'antipsychotic schizoaffective'. Our review found relatively few studies with either an active comparator or placebo that examined the efficacy of antipsychotics for patients with SAD without an admixture of patients with schizophrenia. Only oral paliperidone extended release (ER), paliperidone long-acting injection (LAI), and risperidone have been shown to be effective and safe in reducing psychotic as well as affective components in acutely ill SAD patients in controlled studies. Paliperidone ER and LAI have also been shown to be efficacious in the maintenance treatment phase of SAD patients. While no supportive data exist, it is possible that other atypical antipsychotics may have similar efficacy to the two mentioned above. We conclude with a number of research recommendations for the study of treatment options for patients with SAD. First, there is a need for studies with patients specifically diagnosed with SAD for both the acute and the maintenance phase. The sample size needs to be adequate to allow a primary analysis of efficacy and to allow for analysis of the SAD subtypes: depressed and bipolar. Another recommendation is the need for studies of patients with SAD stratified into patients with and without mood stabilizers or antidepressants to allow the examination of the adjunctive role of

  2. Time trends in antipsychotic drug use in patients with dementia

    DEFF Research Database (Denmark)

    Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane;

    2016-01-01

    . The decreasing use of antipsychotics was accompanied by decreasing use of anxiolytics and hypnotics/sedatives, but an increase in the use of antidepressants from 43.3% in 2000 to 53.8% in 2012. These changes were significant across almost all age groups. Treatment intensity among patients using antipsychotics...... increased as the annual median number of defined daily doses (DDD) increased from 33.3 to 42.0 DDD. CONCLUSIONS: The changing patterns of psychotropic drug use may be caused by warnings against use of antipsychotics. Further research is needed to explore the implications for patient safety....

  3. [Effect of antipsychotic amisulpride on immune reactivity].

    Science.gov (United States)

    Idova, G V; Al'perina, E L; Lobacheva, O A; Zhukova, E N; Cheĭdo, M A; Meniavtseva, T A; Vetlugina, T P

    2013-01-01

    The effect of atypical antipsychotic solian (amisulpride), binding predominantly to dopamine D2/D3-receptors, on the immune reactivity has been studied in mice of the CBA strain with different psychoemotional states (aggressive and submissive behavior). In addition, the effect of solian on the expression of various CD-markers of lymphocytes in has been analyzed in vitro for patients with schizophrenia diagnosis. Chronic (10 days) administration of solian in mice at a dose of 5.0 mg/kg resulted in a significant suppression of the immune response to T-dependent antigen (sheep red blood cells). This effect was manifested in animals with both psychoemotional states, but was more expressed in aggressive animals. In the in vitro system, solian produced opposite effects on the expression of surface CD receptors in lymphocytes of patients with schizophrenia. It is suggested that solian does not only affects immune function through D2 receptors of the brain, but also directly influences immunocompetent cells.

  4. Switching antipsychotics: Imaging the differential effect on the topography of postsynaptic density transcripts in antipsychotic-naïve vs. antipsychotic-exposed rats.

    Science.gov (United States)

    de Bartolomeis, Andrea; Marmo, Federica; Buonaguro, Elisabetta F; Latte, Gianmarco; Tomasetti, Carmine; Iasevoli, Felice

    2016-10-01

    The postsynaptic density (PSD) has been regarded as a functional switchboard at the crossroads of a dopamine-glutamate interaction, and it is putatively involved in the pathophysiology of psychosis. Indeed, it has been demonstrated that antipsychotics may modulate several PSD transcripts, such as PSD-95, Shank, and Homer. Despite switching antipsychotics is a frequent strategy to counteract lack of efficacy and/or side effect onset in clinical practice, no information is available on the effects of sequential treatments with different antipsychotics on PSD molecules. The aim of this study was to evaluate whether a previous exposure to a typical antipsychotic and a switch to an atypical one may affect the expression of PSD transcripts, in order to evaluate potential neurobiological correlates of this common clinical practice, with specific regards to putative synaptic plasticity processes. We treated male Sprague-Dawley rats intraperitoneally for 15days with haloperidol or vehicle, then from the sixteenth day we switched the animals to amisulpride or continued to treat them with vehicle or haloperidol for 15 additional days. In this way we got six first treatment/second treatment groups: vehicle/vehicle, vehicle/haloperidol, vehicle/amisulpride, haloperidol/vehicle, haloperidol/haloperidol, haloperidol/amisulpride. In this paradigm, we evaluated the expression of brain transcripts belonging to relevant and interacting PSD proteins, both of the Immediate-Early Gene (Homer1a, Arc) and the constitutive classes (Homer1b/c and PSD-95). The major finding was the differential effect of amisulpride on gene transcripts when administered in naïve vs. antipsychotic-pretreated rats, with modifications of the ratio between Homer1a/Homer1b transcripts and differential effects in cortex and striatum. These results suggest that the neurobiological effects on PSD transcripts of amisulpride, and possibly of other antipsychotics, may be greatly affected by prior antipsychotic

  5. Antipsychotic Medications and Risk of Acute Coronary Syndrome in Schizophrenia: A Nested Case-Control Study

    Science.gov (United States)

    Liu, Hsing-Cheng; Yang, Shu-Yu; Liao, Ya-Tang; Chen, Chiao-Chicy; Kuo, Chian-Jue

    2016-01-01

    Background This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients. Methods A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147) were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association. Results We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27–10.64, p<0.05) and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40–6.24, p<0.001) were associated with a dose-dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20–3.44, p<0.01), there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis. Conclusions Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy. PMID:27657540

  6. First-generation antipsychotics: not gone but forgotten

    OpenAIRE

    Dibben, Claire R. M.; Khandaker, Golam M.; Underwood, Benjamin R.; O'Loughlin, Christopher; Keep, Catherine; Mann, Louisa; Jones, Peter B.

    2016-01-01

    Aims and method To identify training needs of the next generation of psychiatrists and barriers in prescribing first-generation antipsychotics (FGAs). We have surveyed psychiatry trainees in East Anglia with regard to their training experience, knowledge and attitudes to the use of oral FGAs as regular medication. Results Two-thirds of trainees were aware that first- and second-generation antipsychotics (SGAs) have similar efficacy, and a similar proportion perceived the older drugs to have m...

  7. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    OpenAIRE

    Rosenbloom, Arlan L.

    2010-01-01

    There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-ge...

  8. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    OpenAIRE

    Rosenbloom ArlanL

    2010-01-01

    There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-g...

  9. The personal, societal, and economic burden of schizophrenia in the People's Republic of China: implications for antipsychotic therapy

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2013-08-01

    antipsychotic medication appears common and is a strong predictor of relapse. Cost-effectiveness research in the People's Republic of China is needed to examine the potential gains from improved outpatient antipsychotic treatment.Conclusion: Schizophrenia is a very costly mental illness in terms of personal, economic, and societal burden, both in the People's Republic of China and globally. When treated effectively, patients tend to persist longer with antipsychotic treatment, have fewer costly relapses, and have improved functioning. Further research examining the long-term effects of reducing barriers to effective treatments on the societal burden of schizophrenia in the People's Republic of China is needed.Keywords: People's Republic of China, schizophrenia, relapse, review, health care costs, antipsychotic agents

  10. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Zuardi A.W.

    2006-01-01

    Full Text Available A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD, a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.

  11. Antipsychotic Prescriptions for Children Aged 5 Years or Younger

    Directory of Open Access Journals (Sweden)

    Ana Lòpez-De Fede

    2014-10-01

    Full Text Available The use of antipsychotics in very young children is of concern given the lack of empirical evidence in their efficacy and long-term impact on children’s health. This study examined the prescription of antipsychotics among children aged ≤5 years enrolled in a state Medicaid program. Secondary data analysis was conducted using the Medicaid administrative data of a southeastern state. Using SAS 9.3, descriptive statistics were performed to examine socio-demographic characteristics, psychiatric diagnoses, off-label use, receipt of medications from multiple psychotropic drug classes, and receipt of non-pharmacologic psychiatric services among children aged ≤5 years who received antipsychotic prescriptions in calendar year (CY 2011. A total of 112 children in the target age group received antipsychotics in CY 2011, the most common prescription being risperidone. The most common listed psychiatric diagnosis was attention deficit hyperactivity disorder. Two in five children received antipsychotics for off-label use. Three in four children also received medications from at least one other psychotropic drug class. More than half did not receive adjunct psychiatric services. State-level policies offering specific guidance and recommendations for antipsychotic use among very young children are urgently needed. Future research is warranted to examine long-term impact of such practices on children’s growth and development.

  12. Priapism in Antipsychotic Drug Use: A Rare but Important Side Effect

    Directory of Open Access Journals (Sweden)

    Igne Sinkeviciute

    2012-01-01

    Full Text Available Priapism is a rare but important side effect of antipsychotic drugs which may evolve into a urological emergency. Most antipsychotic drugs are alpha-1 adrenergic antagonists, which is thought to be the principal mechanism involved in antipsychotic-induced priapism. Other aetiologies exist, however. A case is presented with multiple episodes of priapism during the use of several different antipsychotic drugs. The case is representative of many patients treated with antipsychotic drugs, as there were hyperprolactinemia, and illicit drug use, which are known causes of priapism. Moreover, the patient used combinations of antipsychotic drugs. The case thus illustrates the etiological complexity which could delay a diagnosis of antipsychotic-induced priapism, and the problem of establishing a link between priapism and one particular ingredient of a drug combination. The case presents how a treatment regimen was finally established balancing antipsychotic efficacy to acceptable side effects and offers guidance to physicians regarding how antipsychotic-induced priapism may be resolved.

  13. Dislipidemias e antipsicóticos atípicos Dyslipidemias and atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Edilberto Amorim de Cerqueira Filho

    2006-01-01

    Full Text Available OBJETIVO: Um progressivo número de evidências surge associando o uso de antipsicóticos atípicos a dislipidemias, situação pouco atentada por considerável número de psiquiatras e preditora importante de doenças cardiovasculares (DCVs e de morbimortalidade. O propósito deste estudo é revisar a associação entre o uso de antipsicóticos atípicos e o desenvolvimento de dislipidemias em pacientes com esquizofrenia. MÉTODOS: A pesquisa bibliográfica utilizou os bancos de dados MEDLINE e Scientific Electronic Library Online (SciELO, com os descritores: schizophrenia, dyslipidemia, hyperlipidemia e lipids, para identificar artigos originais publicados no período de 1997 a setembro de 2006. RESULTADOS: Os artigos foram agrupados segundo cada agente terapêutico, de acordo com o seu impacto sobre o perfil lipídico. CONCLUSÃO: Observa-se maior risco de desenvolvimento de dislipidemias em pacientes com esquizofrenia em uso de alguns antipsicóticos atípicos. Intervenções comportamentais e farmacológicas devem ser associadas nos indivíduos com esquizofrenia em tratamento antipsicótico e que desenvolvem dislipidemias.OBJECTIVE: Pieces of evidence appear associating the use of atypical antipsychotics to dyslipidemias, situation that is of little attention by considerable number of psychiatrists and important predictor of cardiovascular illnesses and morbi-mortality. The intention of this study is to review the association between the atypical antipsychotic use and the development of dyslipidemias in patients with schizophrenia. METHODS: The bibliographical research used databases MEDLINE and SciELO, for the key words: schizophrenia, dyslipidemia, hyperlipidemia and lipids, with the objective to identify original articles published in the period of 1997 to September 2006. RESULTS: The articles were distributed according to each therapeutic agent and their impact on lipidic profile. CONCLUSION: Higher risk of development of dyslipidemias

  14. Antipsychotic medication and prefrontal cortex activation : A review of neuroimaging findings

    NARCIS (Netherlands)

    Liemburg, Edith J.; Knegtering, Henderikus; Klein, Hans C.; Kortekaas, Rudie; Aleman, Andre

    2012-01-01

    Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which sha

  15. Association of antipsychotic polypharmacy with health service cost: a register-based cost analysis

    DEFF Research Database (Denmark)

    Baandrup, Lone; Lublin, Henrik Kai Francis; Nordentoft, Merete;

    2012-01-01

    OBJECTIVE: To investigate the association of antipsychotic polypharmacy in schizophrenia with cost of primary and secondary health service use. METHOD: Comparative analysis of health service cost for patients prescribed antipsychotic polypharmacy versus antipsychotic monotherapy. Resource......, disease duration, psychiatric inpatient admissions, and treatment site as covariates. RESULTS: The sample consisted of 736 outpatients with a diagnosis in the schizophrenia spectrum. Antipsychotic polypharmacy was associated with significantly higher total health service costs compared with monotherapy...

  16. Attitudes Towards Antipsychotics Among Patients with Schizophrenia on First- or Second-Generation Medications

    OpenAIRE

    Karthik, M. S.; Nisha Warikoo; Subho Chakrabarti; Sandeep Grover; Parmanand Kulhara

    2014-01-01

    Background: Given the paucity of research in this area, this study attempted to assess attitudes toward antipsychotic medications and its correlates among patients with schizophrenia, either on first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs) medications. Materials and Methods: Structured assessments of attitudes to antipsychotics, psychopathology, insight and side-effects were carried out in 120 patients with DSM-IV schizophrenia; 89 of these were on SGAs and...

  17. Type 2 diabetes in children and adolescents on atypical antipsychotics.

    Science.gov (United States)

    Pramyothin, Pornpoj; Khaodhiar, Lalita

    2015-08-01

    Youth receiving treatment with antipsychotics are particularly susceptible to weight gain, type 2 diabetes (T2D), and associated metabolic disorders, which is directly associated with excess morbidity and mortality in this vulnerable population. The risk of T2D is 2- to 3-fold that of the general population, starts early in the course of treatment, and reflects the effects of weight gain in conjunction with direct effects of antipsychotics on the hypothalamus, pancreatic beta cells, and insulin-sensitive peripheral tissues. Close monitoring with early intervention through lifestyle intervention, switching away from antipsychotics with deleterious metabolic effects, and adjunctive treatment with metformin are modalities available to mitigate weight gain and improve cardiometabolic health in these patients. Despite rapidly advancing knowledge in the field, patient's access to metabolic screening and quality care remains limited. Efforts must be made to broaden reach of early cardiometabolic intervention among these patients in order to avert serious cardiovascular disease burden in the future.

  18. Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges

    Science.gov (United States)

    LEE, JIN-KU; NAM, DO-HYUN; LEE, JEONGWU

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor, with tragically little therapeutic progress over the last 30 years. Surgery provides a modest benefit, and GBM cells are resistant to radiation and chemotherapy. Despite significant development of the molecularly targeting strategies, the clinical outcome of GBM patients remains dismal. The challenges inherent in developing effective GBM treatments have become increasingly clear, and include resistance to standard treatments, the blood-brain barrier, resistance of GBM stem-like cells, and the genetic complexity and molecular adaptability of GBM. Recent studies have collectively suggested that certain antipsychotics harbor antitumor effects and have potential utilities as anti-GBM therapeutics. In the present review, the anti-tumorigenic effects and putative mechanisms of antipsychotics, and the challenges for the potential use of antipsychotic drugs as anti-GBM therapeutics are reviewed. PMID:26893731

  19. How antipsychotics work-from receptors to reality.

    Science.gov (United States)

    Kapur, Shitij; Agid, Ofer; Mizrahi, Romina; Li, Ming

    2006-01-01

    How does a small molecule blocking a few receptors change a patients' passionately held paranoid belief that the FBI is out to get him? To address this central puzzle of antipsychotic action, we review a framework linking dopamine neurochemistry to psychosis, and then link this framework to the mechanism of action of antipsychotics. Normal dopamine transmission has a role in predicting novel rewards and in marking and responding to motivationally salient stimuli. Abnormal dopamine transmission alters these processes and results in an aberrant sense of novelty and inappropriate assignment of salience leading to the experience of psychosis. Antipsychotics improve psychosis by diminishing this abnormal transmission by blocking the dopamine D2/3 receptor (not D1 or D4), and although several brain regions may be involved, it is suggested that the ventral striatal regions (analog of the nucleus accumbens in animals) may have a particularly critical role. Contrary to popular belief, the antipsychotic effect is not delayed in its onset, but starts within the first few days. There is more improvement in the first 2 weeks, than in any subsequent 2-week period thereafter. However, a simple organic molecule cannot target the complex phenomenology of the individual psychotic experience. Antipsychotics diminish dopamine transmission and thereby dampen the salience of the pre-occupying symptoms. Therefore, in the initial stage of an antipsychotic response, the patients experience a detachment from symptoms, a relegation of the delusions and hallucinations to the back of their minds, rather than a complete erasure of the symptoms. Only with time, and only in some, via the mediation of new learning and plasticity, is there a complete resolution of symptoms. The implications of these findings for clinical care, animal models, future target discovery and drug development are discussed. PMID:16490410

  20. Chlorpromazine equivalents versus defined daily doses : How to compare antipsychotic drug doses?

    NARCIS (Netherlands)

    Rijcken, CAW; Monster, TBM; Brouwers, JRBJ; de Jong-van den Berg, LTW

    2003-01-01

    Classic chlorpromazine (CPZ) equivalents can be used to chart relative antipsychotic potencies of antipsychotic drugs. Values of CPZ equivalents per drug are ambiguous in literature. In drug use evaluation studies, antipsychotic doses are frequently compared by use of the defined daily dose (DDD). T

  1. Trends in Scientific Literature on Atypical Antipsychotics in South Korea: A Bibliometric Study

    OpenAIRE

    López-Muñoz, Francisco; Shen, Winston W.; Pae, Chi-un; Moreno, Raquel; Rubio, Gabriel; Molina, Juan D.; Noriega, Concha; Pérez-Nieto, Miguel A.; Huelves, Lorena; Álamo, Cecilio

    2013-01-01

    Objective We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. Methods With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine...

  2. Antipsychotic pathway genes with expression altered in opposite direction by antipsychotics and amphetamine.

    Science.gov (United States)

    Ko, Françoise; Tallerico, Teresa; Seeman, Philip

    2006-08-01

    To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia.

  3. Current Trends on Antipsychotics: Focus on Asenapine.

    Science.gov (United States)

    Marazziti, Donatella; Piccinni, Armando; Baroni, Stefano; Mungai, Francesco; Presta, Silvio; Mucci, Federico; Dell'Osso, Liliana

    2016-01-01

    Over the years, both first- (FGAs) and second-generation antipsychotics (SGAs), continue to gain increasing evidence of being effective in the treatment of psychotic symptoms. Currently, they represent the first-line treatment of schizophrenia and bipolar disorder, although they are widely used in psychotic depression and other clinical conditions, such as agitation and/or behavioural disturbances. Despite representing an indispensable tool for the treatment of severe psychotic disorders, they are widely known to have a number of unwanted side effects that the clinician must be aware of, and handle carefully to provide the patient the best available treatment in the short and long-term. However, even with respect to the long-term use of some of the most effective SGAs, it is imperative for clinicians not to overlook the risk linked to the onset of potentially severe metabolic side effects such as weight gain, dyslipidaemia, insulinresistance and type II diabetes. Asenapine is one of the newest SGAs licenced in Europe for the treatment of manic episodes and in the US for schizophrenia. It belongs to the same class of clozapine, olanzapine and quetiapine, sharing with them a rather complex pharmacological binding profile. In fact, asenapine shows a high affinity for the serotonin (5HT) receptor of the type 2A (5HT2A) and to a lesser extent for the dopamine receptor of the type 2 (D2), similar to other SGAs. Asenapine behaves also as an antagonist at the level of 5HT2C, H1 and α2-receptors. Asenapine has been reported to be effective either in monotherapy or in combination with mood stabilers (lithium and valproate) in the treatment of manic or mixed episodes, with a lower propensity to induce, or being followed by, depressive symptoms, when compared to other SGAs. These unique properties may explain the increasing interest towards the use of this drug in mixed states, besides schizophrenia and acute mania. The aim of this paper was at reviewing current data on

  4. Development of a Patient-Centered Antipsychotic Medication Adherence Intervention

    Science.gov (United States)

    Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia

    2014-01-01

    Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…

  5. Antipsychotic-like effects of zolpidem in Wistar rats.

    Science.gov (United States)

    Mierzejewski, Pawel; Kolaczkowski, Marcin; Marcinkowska, Monika; Wesolowska, Anna; Samochowiec, Jerzy; Pawlowski, Maciej; Bienkowski, Przemyslaw

    2016-02-15

    Aside from their use in the treatment of anxiety disorders and insomnia, benzodiazepines and other GABAA receptor positive modulators are widely used as add-on treatments in schizophrenic and non-schizophrenic psychoses. However, there is relatively little direct clinical or pre-clinical evidence for antipsychotic effects of GABAergic medications. Previous studies have indicated that zolpidem, a GABAergic drug acting preferentially at α1-containing GABAA receptors, may produce catalepsy through interactions with dopaminergic neurotransmission. The aim of the present study was to investigate effects of zolpidem in experimental models of antipsychotic activity and extrapyramidal side effects in Wistar rats. Effects of zolpidem were compared with that of a classic benzodiazepine drug, diazepam and a second-generation antipsychotic medication, risperidone. High doses of risperidone (10.0mg/kg, i.p.) and zolpidem (10.0mg/kg, i.p.), but not diazepam, induced relatively short-lasting cataleptic responses in the bar test. Zolpidem and risperidone, but not diazepam, produced some antipsychotic-like effects at doses, which produced no catalepsy and did not inhibit spontaneous locomotor activity and apomorphine-induced stereotypies. The present results tend to indicate that zolpidem exerts some neuroleptic-like effects at doses, which do not produce motor side effects. Our findings may provide further rationale for the development of new subtype-selective GABAA receptor modulators for the treatment of psychotic symptoms. PMID:26825544

  6. Beyond Dopamine: Glutamate as a Target for Future Antipsychotics

    OpenAIRE

    Kyra-Verena Sendt; Giovanni Giaroli; Tracy, Derek K.

    2012-01-01

    The dopamine hypothesis of schizophrenia remains the primary theoretical framework for the pharmacological treatment of the disorder. Despite various lines of evidence of dopaminergic abnormalities and reasonable efficacy of current antipsychotic medication, a significant proportion of patients show suboptimal treatment responses, poor tolerability, and a subsequent lack of treatment concordance. In recent decades, intriguing evidence for the critical involvement of other neurotransmitter sys...

  7. Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update

    Science.gov (United States)

    Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Jun, Tae-Youn; Patkar, Ashwin A; Masand, Prakash S

    2016-01-01

    Less than one third of patients who suffer from major depressive disorder (MDD) report remission following antidepressant treatments requiring more diverse treatment approaches. Augmentation of second generation antipsychotics (SGAs) has been increasingly recognized as an important treatment option. The authors have previously provided a comprehensive review of SGAs for the treatment of MDD in 2013. Since then, numerous additional clinical trials have been conducted to investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new SGA, brexpiprazole, was recently approved by the Food and Drug Administration in July 2015 for the treatment of MDD as an augmentation agent to antidepressants. Thus, the aim of this study was to provide a concise update of all the available SGAs for the treatment of MDD, in particular on the additional clinical trials which have been published since 2013.

  8. Torsadogenic risk of antipsychotics: combining adverse event reports with drug utilization data across Europe.

    Directory of Open Access Journals (Sweden)

    Emanuel Raschi

    Full Text Available BACKGROUND: Antipsychotics (APs have been associated with risk of torsade de Pointes (TdP. This has important public health implications. Therefore, (a we exploited the public FDA Adverse Event Reporting System (FAERS to characterize their torsadogenic profile; (b we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. METHODS: FAERS data (2004-2010 were analyzed based on the following criteria: (1 ≥ 4 cases of TdP/QT abnormalities; (2 Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers; (3 ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD; (4 Significant ROR for VA/SCD; (5 Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled to group E (unclear/uncertain signal: only 2/5 criteria. Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID. RESULTS: Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone. In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia to 13.99 (France, 2009. Considerable increment of Group A agents was found in several Countries (+3.47 in France: the exposure to olanzapine increased across all Countries (+1.84 in France and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009. Among Group B drugs, levomepromazine peaked 3.78 (Serbia; fluphenazine 1.61 (Slovenia. CONCLUSIONS: This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  9. Antipsychotic polypharmacy in clozapine resistant schizophrenia: a randomized controlled trial of tapering antipsychotic co-treatment

    Directory of Open Access Journals (Sweden)

    Jari Tiihonen

    2012-01-01

    Full Text Available There is a considerable disparity between clinical practice and recommendations based on meta-analyses of antipsychotic polypharmacy in clozapine resistant schizophrenia. For this reason, we investigated the clinical response to reducing the use olanzapine that had been previously added on clozapine treatment among seriously ill hospitalized patients. In a randomized controlled trial with crossover design, we studied volunteer patients (N = 15 who had olanzapine added on to clozapine in a state mental hospital. Clozapine monotherapy was just as effective as clozapine-olanzapine therapy, according to results from Clinical Global Impression Scale and Global Assessment of Functioning as primary outcome measures. Polypharmacy is widely used in treating schizophrenia, and usually, add-on medications are started because of worsening of the clinical state. A major confounding feature of these add-ons is whether observed improvements are caused by the medication or explained by the natural fluctuating course of the disorder. The present study, in spite of its small size, indicates the necessity of reconsidering the value of polypharmacy in treating schizophrenia.

  10. Brain Connectivity Studies in Schizophrenia: Unravelling the Effects of Antipsychotics

    DEFF Research Database (Denmark)

    Nejad, A.B.; Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte Yding;

    2012-01-01

    Impaired brain connectivity is a hallmark of schizophrenia brain dysfunction. However, the effect of drug treatment and challenges on the dysconnectivity of functional networks in schizophrenia is an understudied area. In this review, we provide an overview of functional magnetic resonance imaging...... studies examining dysconnectivity in schizophrenia and discuss the few studies which have also attempted to probe connectivity changes with antipsychotic drug treatment. We conclude with a discussion of possible avenues for further investigation....

  11. Antipsychotic-like effect of minocycline in a rat model

    OpenAIRE

    Dokuyucu, Recep; Kokacya, Hanifi; Inanir, Sema; Copoglu, Umit Sertan; Erbas, Oytun

    2014-01-01

    Objectives: Tetracycline antibiotic drug minocycline has strongly neuroprotective and anti-inflammatory effects. Minocycline has also remarkable brain tissue penetration, is clinically entirely tolerated and properly absorbed when taken orally. In our study, we class with the effects of minocycline and chlorpromazine, a conventional antipsychotic drug, by evaluating the novelty-induced rearing, apomorphine-induced stereotypic behavior, and brain MDA levels in rats. Materials and Methods: Four...

  12. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug

    OpenAIRE

    Zuardi A.W.; Crippa J.A.S.; Hallak J.E.C.; Moreira F.A.; Guimarães F.S.

    2006-01-01

    A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis) component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD), a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxi...

  13. VALID GROUNDS FOR THE SWITCH OF ORIGINAL ANTIPSYCHOTICS WITH GENERICS

    OpenAIRE

    Ružić, Klementina; Dadić-Hero, Elizabeta; Knez, Rajna; Medved, Paola; Graovac, Mirjana

    2010-01-01

    Patients' non-compliance in treatments, such as irregular taking of medication, represents an enormous problem with psychiatric patients in general. This difficulty occurs especially in patients suffering from chronic mental illnesses such as schizophrenia. There are not any significant differences in the efficacy of reducing the positive symptoms in schizophrenia between the conventional and the atypical antipsychotics. However, the effects which are manifested in negative schizophr...

  14. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    OpenAIRE

    JP Lindenmayer

    2010-01-01

    JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identifi...

  15. Pharmacological and clinical profile of recently approved second-generation antipsychotics: implications for treatment of schizophrenia in older patients.

    Science.gov (United States)

    Rado, Jeffrey; Janicak, Philip G

    2012-10-01

    Antipsychotics are frequently used in elderly patients to treat a variety of conditions, including schizophrenia. While extensively studied for their impact in younger populations, there is comparatively limited evidence about the effectiveness of these agents in older patients. Further complicating this situation are the high comorbidity rates (both psychiatric and medical) in the elderly; age-related changes in pharmacokinetics that lead to a heightened proclivity for adverse effects; and the potential for multiple, clinically relevant drug interactions. With this background in mind, we review diagnostic and treatment-related issues specific to elderly patients suffering from schizophrenia. We then focus on the potential role of the most recently approved second-generation antipsychotics, paliperidone (both the extended-release oral formulation and the long-acting injectable formulation), iloperidone, asenapine and lurasidone, given the limited clinical experience with these agents in the elderly. While there is limited data to support their safety, tolerability and efficacy in older patients with schizophrenia, each has unique characteristics that should be considered when used in this population.

  16. Antipsychotic drug treatment for patients with schizophrenia: theoretical background, clinical considerations and patients preferences

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Nielsen, Jimmi

    2009-01-01

    -effects have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during......  The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ...

  17. Thalamic shape abnormalities in antipsychotic naïve schizophrenia

    Directory of Open Access Journals (Sweden)

    Vijay Danivas

    2013-01-01

    Full Text Available Background: Neurodevelopmental hypothesis of schizophrenia states abnormal pruning as one of the pathogenetic mechanism in schizophrenia. Though thalamic volume abnormalities have been documented, the shape differences of thalamus in antipsychotic-free schizophrenia in comparison with age- and sex-matched healthy volunteers need validation. Materials and Methods: We examined antipsychotic naïve schizophrenia patients ( n=60 and age- and sex-matched healthy volunteers ( n=44. The thalamic shape abnormalities were analyzed from their coded structural magnetic resonance imaging (MRI data using three-dimensional automated image analysis software, FMRIB′s (Oxford Center for the functional MRI of the brain tools-FIRST (FMRIB′s Integrated Registration and Segmentation Tool by creating deformable mesh model. Correlation with the psychopathology scores was carried out using F-statistics. Results: Patients with schizophrenia showed significant inward deformations in the regions corresponding to anterior, ventromedial, mediodorsal, and pulvinar nuclei. There was a direct correlation between negative syndrome score and the deformation in the right mediodorsal and right pulvinar nuclei. Conclusion: The inward deformations of thalamus in antipsychotic naive schizophrenia patients correspond to those nuclei which have reciprocal connections with frontal, superior temporal, and anterior cingulate regions and support the neurodevelopmental hypothesis of schizophrenia.

  18. Could cannabidiol be used as an alternative to antipsychotics?

    Science.gov (United States)

    Fakhoury, Marc

    2016-09-01

    Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects. Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes. Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD. PMID:27267317

  19. Adjunctive metformin for antipsychotic-induced hyperprolactinemia: A systematic review.

    Science.gov (United States)

    Bo, Qi-Jing; Wang, Zhi-Min; Li, Xian-Bin; Ma, Xin; Wang, Chuan-Yue; de Leon, Jose

    2016-03-30

    This systematic review examines adjunctive metformin therapy for the treatment of antipsychotic-induced hyperprolactinemia. A computerized search of databases in Chinese and the international databases in English provided three trials with a total of 325 patients including one randomized clinical trial (RCT) and two observational studies (single-group, before-after design). A meta-analysis could not be conducted. The quality of evidence ranged from "very low" to "moderate". Metformin patients had a significant decrease in serum prolactin level with a mean of 54.6μg/l in the three trials. In the RCT, menstruation restarted in 67% of those with menstrual disturbances versus 5% in placebo. In one observational study, 91% of patients no longer had signs or symptoms of galactorrhea. In the RCT, adverse drug reactions (ADRs) occurred at similar incidence rates among metformin and placebo patients, except that no significant increases in nausea, insomnia and agitation occurred which were not associated with discontinuations. Our systematic review indicated that adjunctive metformin significantly lowered prolactin level and relieved prolactin-related symptoms in patients with antipsychotic-induced hyperprolactinemia. Future higher quality RCTs need to verify the currently available limited evidence based on three trials which suggest that adjunctive metformin may be used effectively and safely for antipsychotic-induced hyperprolactinemia. PMID:26822064

  20. Trends in the use of antipsychotics in the Israeli inpatient population, 2004–2013

    OpenAIRE

    Ponizovsky, Alexander M.; Marom, Eli; Ben-Laish, Michal; Barash, Igor; Weizman, Abraham; Schwartzberg, Eyal

    2016-01-01

    Background Although serious mental illneses are treated with both typical and atypical antipsychotic grugs, trends in their use in psychiatric inpatient population in Israel are unrecognized. The aim of this study was to detect trends in the use of typical and atypical antipsychotic drugs in the Israeli inpatient psychiatric population throughout the last decade. Methods Data regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the ele...

  1. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    Science.gov (United States)

    Boonlue, Tuanthon; Subongkot, Suphat; Dilokthornsakul, Piyameth; Kongsakon, Ronnachai; Pattanaprateep, Oraluck; Suanchang, Orabhorn; Chaiyakunapruk, Nathorn

    2016-01-01

    Background Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual atypical antipsychotics therapy. Outcomes were schizophrenia-related hospitalization and total health care cost. Logistic and Poisson regression were used to evaluate the risk of hospitalization, and generalized linear model with gamma distribution was used to determine the health care cost. All analyses were adjusted by employing propensity score and multivariable analyses. All cost estimates were adjusted according to 2013 consumer price index and converted to US$ at an exchange rate of 32.85 Thai bahts/US$. Results A total of 2,354 patients were included. Of them, 166 (7.1%) patients switched to typical antipsychotics. The adjusted odds ratio for schizophrenia-related hospitalization in atypical antipsychotic switching group was 1.87 (95% confidence interval [CI] 1.23–2.83). The adjusted incidence rate ratio was 2.44 (95% CI 1.57–3.79) for schizophrenia-related hospitalizations. The average total health care cost was lower in patients with antipsychotic switching (−$64; 95% CI −$459 to $332). Conclusion Switching from atypical to typical antipsychotics is associated with an increased risk of schizophrenia-related hospitalization

  2. A pharmacy led program to review anti-psychotic prescribing for people with dementia

    Directory of Open Access Journals (Sweden)

    Child Anne

    2012-09-01

    Full Text Available Abstract Background Anti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics. Methods This project was conducted within primary care in Medway Primary Care Trust (PCT in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search. Results Data were collected from 59 practices. One hundred and sixty-one (15.3% of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462 vs. 7.3% of people living at home (43/589] than people living in their own homes (p  Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4% following the pharmacy-led medication review. Conclusions In total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to people with dementia.

  3. Healthcare Costs of Atypical Antipsychotic Use for Patients with Bipolar Disorder in a Medicaid Programme

    OpenAIRE

    Ying Qiu; Fu, Alex Z; Gordon G. Liu; Christensen, Dale B.

    2010-01-01

    Background: A large body of clinical studies have demonstrated the efficacy of atypical antipsychotic use in the treatment of bipolar disorder. Facing increasing budget pressure, third-party payers, such as state Medicaid programmes in the US, are demanding better understanding of the medical costs beyond atypical antipsychotic drug costs alone in treating bipolar disorder. Objective: To examine healthcare costs associated with the atypical antipsychotic treatments for bipolar disorder from a...

  4. Progress in studies on hyperprolactinemia induced by antipsychotic drugs%抗精神病药物所致高催乳素血症的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙振晓; 于相芬

    2012-01-01

    Hyperprolactinemia is a common adverse effect of antipsychotic drugs. The clinical presentations of hyperprolactinemia are gynecomastia in men, and breast distending pain, galactorrhea, menstrual disturbance, sexual dysfunction, osteoporosis, and metabolic disturbance in women. The incidence of hyperprolactinemia is 25%-89%. The factors related to antipsychotic-induced hyperprolactinemia are gender, age, the type of antipsychotic drugs and dosage. The mechanism of antipsychotic-induced hyperprolactinemia may be related to blockade of dopamine D2 receptors on the anterior pituitary by antipsychotic drugs and reduction of dopamine inhibitory effect on prolactin secretion of prolactin cells, leading to prolactin elevation. Antipsychotic-induced hyperprolactinemia should be distinguished from hyperprolactinemia due to severe stress, depressive state, pregnancy, hypothyroidism, renal failure, pituitary tumor and ovarian disease. The treatment of antipsychotic-induced hyperprolactinemia includes discontinuing antipsychotic drugs, reducing antipsychotic drugs dosage, switching to a prolactin-sparing agent, prescribing a dopamine receptor agonist or Chinese herbal medicines, and using low-frequency repetitive transcranial magnetic stimulation.%催乳素升高是抗精神病药物常见的不良反应,临床表现为男性乳房女性化、女性乳房胀痛、溢乳、月经失调症状、性功能障碍、骨质疏松及代谢障碍等,发生率为25%~89%.抗精神病药物所致高催乳素血症(HPRL)的发生与性别、年龄、药物种类及剂量等相关.发病机制可能是抗精神病药物阻断垂体前叶D2受体而减弱多巴胺抑制泌乳素细胞分泌的作用,导致催乳素水平升高.抗精神病药物所致HPRL须与严重应激或抑郁状态、妊娠、甲状腺功能减退症、肾衰竭、垂体肿瘤及卵巢病变等进行鉴别诊断.抗精神病药物所致HPRL的治疗包括停用致病药物,降低药物剂量,换

  5. The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.

    Science.gov (United States)

    Riga, Maurizio S; Soria, Guadalupe; Tudela, Raúl; Artigas, Francesc; Celada, Pau

    2014-08-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

  6. Antipsychotic polypharmacy in a regional health service: a population-based study

    Directory of Open Access Journals (Sweden)

    Bernardo Miguel

    2012-05-01

    Full Text Available Abstract Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain, focusing on the use of clozapine and long-acting injections (LAI. Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA from the Anatomical Therapeutic Chemical classification (ATC code N05A (except lithium were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9% corresponded to an antipsychotic combination, 47,386 (66.7% to monotherapy and 13,763 (19.4% to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1% and oral risperidone (36.4% were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8% revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%. Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%. A total of 3.800 patients (5.4% were given LAI antipsychotics, and 2.662 of these (70.1% were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine.

  7. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    Science.gov (United States)

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology.

  8. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    Science.gov (United States)

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology. PMID:14642968

  9. Use of antipsychotic drugs in individuals with intellectual disability (ID) in the Netherlands : prevalence and reasons for prescription

    NARCIS (Netherlands)

    de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

    2010-01-01

    Background We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods A cross-sectional study of medical and pharmaceutical re

  10. Arterial Stiffness in Patients Taking Second-generation Antipsychotics

    Science.gov (United States)

    Fındıklı, Ebru; Gökçe, Mustafa; Nacitarhan, Vedat; Camkurt, Mehmet Akif; Fındıklı, Hüseyin Avni; Kardaş, Selçuk; Şahin, Merve Coşgun; Karaaslan, Mehmet Fatih

    2016-01-01

    Objective That treatment with second-generation antipsychotics (SGAs) causes metabolic side effects and atherosclerosis in patients with schizophrenia and bipolar disorder (BD) is well-known. Increased arterial stiffness is an important marker of arteriosclerosis and has been identified as an independent risk factor for cardiovascular diseases. We measured pulse wave velocity (PWV) as a marker of arteriosclerosis in patients with schizophrenia and BD who use SGAs. Methods Patients and controls were collected from our psychiatry outpatient clinics or family medicine. Mental illness was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Mean age, gender, systolic and diastolic blood pressure, body mass index, Framingham risk score (FRS), etc. were determined. Simultaneous electrocardiography and pulse wave were recorded with an electromyography device. The photo-plethysmographic method was used to record the pulse wave. Inclusion criteria included use of SGAs for at least the last six months. Patients with diseases that are known to cause stiffness and the use of typical antipsychotics were excluded. Results Ninety-six subject (56 patients, 40 controls) were included in our study. There were 49 females, 47 males. Patients had schizophrenia (n=17) and BD (n=39). Their treatments were quetiapine (n=15), risperidone (n=13), olanzapine (n=15), and aripiprazole (n=13). Although differences in mean age, gender, and FRS in the patient and control groups were not statistically significant (p=1), PWV was greater in patients in the antipsychotic group (p=0.048). Conclusion This study supported the liability to stiffness in patients with schizophrenia and BD. Using SGAs may contribute to arterial stiffness in these patients. PMID:27776389

  11. Impact of antipsychotic medication on physical activity and physical fitness in adolescents: An exploratory study.

    Science.gov (United States)

    Vancampfort, Davy; Probst, Michel; Daenen, Anne; Damme, Tine Van; De Hert, Marc; Rosenbaum, Simon; Bruyninckx, David

    2016-08-30

    Antipsychotics are used increasingly in adolescents for a range of psychiatric disorders. The aim of the current study was to investigate whether physical activity levels and physical fitness of adolescent inpatients treated with antipsychotic medication, differs from either (i) antipsychotic naïve adolescents with mental health problems and, (ii) healthy controls. All participants completed the Physical Activity Questionnaire for Adolescents, the Positive-and-Negative-Affect-Schedule and performed the Eurofit test battery. Adolescents with mental health problems (irrespective of antipsychotic medication) were significantly (Prunning speed and cardiovascular endurance compared to healthy controls (n=15, 8♂, 15.9±1.3 years). Adolescents treated with antipsychotic medication (n=15, 8♂, 15.5±1.3 years) were less physically active and had an impaired whole body balance compared with antipsychotic naïve adolescents (n=15, 8♂, 15.7±1.4 years). Given the overwhelming deleterious impact of physical inactivity and low physical fitness on physical and mental health outcomes, interventions specifically targeting physical activity and physical fitness among adolescents experiencing mental illness, both treated with, and not treated with antipsychotic medication are warranted as a priority. Antipsychotic medication should be considered as a risk factor for physical inactivity and poor physical fitness. PMID:27288738

  12. Improving physical health for people taking antipsychotic medication in the Community Learning Disabilities Service

    OpenAIRE

    Hall, Ian; Shah, Amar

    2016-01-01

    Adherence with antipsychotic monitoring guidelines is notoriously low nationally. Without active monitoring and measures to improve metabolic abnormalities, more patients may develop related morbidity and mortality. An audit highlighted antipsychotic monitoring in this learning disability service in London did not match guideline recommendations. People with intellectual disability also experience health inequalities. Psychiatrists are well placed to provide advice and assistance that is suit...

  13. Loxapine for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review

    Science.gov (United States)

    Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.

    2016-01-01

    Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…

  14. Antipsychotic Polypharmacy in a Treatment-Refractory Schizophrenia Population Receiving Adjunctive Treatment With Electroconvulsive Therapy

    DEFF Research Database (Denmark)

    Kristensen, Diana; Hageman, Ida; Bauer, Jeanett;

    2013-01-01

    Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT).......Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT)....

  15. Exploring regional variation in antipsychotic coprescribing practice: a Danish questionnaire survey

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter N.; Nordentoft, Merete;

    2010-01-01

    The pharmacologic treatment of schizophrenia is characterized by excessive use of antipsychotic polypharmacy, which reflects a gap between evidence and practice. The aim of the present study was to investigate regional differences in treatment setting characteristics and in physician and nurse...... attitudes toward antipsychotic polypharmacy and clinical guidelines....

  16. Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

    Science.gov (United States)

    Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2016-01-30

    Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia.

  17. Assessing QT interval prolongation and its associated risks with antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.;

    2011-01-01

    heart, illustrated as a prolongation of the QT interval on a surface ECG. SCD in individuals receiving antipsychotics has an incidence of approximately 15 cases per 10,000 years of drug exposure but the exact association with TdP remains unknown because the diagnosis of TdP is uncertain. Most patients...... other surrogate markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a...

  18. Does a GLP-1 receptor agonist change glucose tolerance in patients treated with antipsychotic medications?

    DEFF Research Database (Denmark)

    Larsen, Julie Rask; Vedtofte, Louise; Holst, Jens Juul;

    2014-01-01

    BACKGROUND: Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances. Addition......BACKGROUND: Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances....... Additionally, patients with schizophrenia-spectrum disorders not infrequently consume alcohol. Glucagon-like peptide-1 (GLP-1) has shown to improve glycaemic control and reduce alcohol intake among patients with type 2 diabetes. OBJECTIVES: To investigate whether the beneficial effects of GLP-1 analogues...... on glycaemic control and alcohol intake, in patients with type 2 diabetes, can be extended to a population of pre-diabetic psychiatric patients receiving antipsychotic treatment. METHODS AND ANALYSIS: Trial design, intervention and participants: The study is a 16-week, double-blinded, randomised, parallel...

  19. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu

    2011-03-01

    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  20. 5-HT2 receptors modulate the expression of antipsychotic-induced dopamine supersensitivity.

    Science.gov (United States)

    Charron, Alexandra; Hage, Cynthia El; Servonnet, Alice; Samaha, Anne-Noël

    2015-12-01

    Antipsychotic treatment can produce supersensitivity to dopamine receptor stimulation. This compromises the efficacy of ongoing treatment and increases the risk of relapse to psychosis upon treatment cessation. Serotonin 5-HT2 receptors modulate dopamine function and thereby influence dopamine-dependent responses. Here we evaluated the hypothesis that 5-HT2 receptors modulate the behavioural expression of antipsychotic-induced dopamine supersensitivity. To this end, we first treated rats with the antipsychotic haloperidol using a clinically relevant treatment regimen. We then assessed the effects of a 5-HT2 receptor antagonist (ritanserin; 0.01 and 0.1mg/kg) and of a 5-HT2A receptor antagonist (MDL100,907; 0.025-0.1mg/kg) on amphetamine-induced psychomotor activity. Antipsychotic-treated rats showed increased amphetamine-induced locomotion relative to antipsychotic-naïve rats, indicating a dopamine supersensitive state. At the highest dose tested (0.1mg/kg for both antagonists), both ritanserin and MDL100,907 suppressed amphetamine-induced locomotion in antipsychotic-treated rats, while having no effect on this behaviour in control rats. In parallel, antipsychotic treatment decreased 5-HT2A receptor density in the prelimbic cortex and nucleus accumbens core and increased 5-HT2A receptor density in the caudate-putamen. Thus, activation of either 5-HT2 receptors or of 5-HT2A receptors selectively is required for the full expression of antipsychotic-induced dopamine supersensitivity. In addition, antipsychotic-induced dopamine supersensitivity enhances the ability of 5-HT2/5-HT2A receptors to modulate dopamine-dependent behaviours. These effects are potentially linked to changes in 5-HT2A receptor density in the prefrontal cortex and the striatum. These observations raise the possibility that blockade of 5-HT2A receptors might overcome some of the behavioural manifestations of antipsychotic-induced dopamine supersensitivity. PMID:26508706

  1. Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Swartz Marvin

    2006-02-01

    Full Text Available Abstract Background There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia. Methods We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone or oral typical antipsychotics (low, medium, or high potency were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods. To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a only 1 medication episode for each patient, the one with which the patient was treated first, and (b all medication episodes, including those simultaneously initiated on more than 1 antipsychotic. Results Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days compared to typical antipsychotics (N = 534, 197.2 days; p Conclusion In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium

  2. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

    Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

  3. The therapeutic relationship and adherence to antipsychotic medication in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Rosemarie McCabe

    Full Text Available OBJECTIVE: Previous research has shown that a better therapeutic relationship (TR predicts more positive attitudes towards antipsychotic medication, but did not address whether it is also linked with actual adherence. This study investigated whether the TR is associated with adherence to antipsychotics in patients with schizophrenia. METHODS: 134 clinicians and 507 of their patients with schizophrenia or a related psychotic disorder participated in a European multi-centre study. A logistic regression model examined how the TR as rated by patients and by clinicians is associated with medication adherence, adjusting for clinician clustering and symptom severity. RESULTS: Patient and clinician ratings of the TR were weakly inter-correlated (r(s = 0.13, p = 0.004, but each was independently linked with better adherence. After adjusting for patient rated TR and symptom severity, each unit increase in clinician rated TR was associated with an increase of the odds ratio of good compliance by 65.9% (95% CI: 34.6% to 104.5%. After adjusting for clinician rated TR and symptom severity, for each unit increase in patient rated TR the odds ratio of good compliance was increased by 20.8% (95% CI: 4.4% to 39.8%. CONCLUSIONS: A better TR is associated with better adherence to medication among patients with schizophrenia. Patients' and clinicians' perspectives of the TR are both important, but may reflect distinct aspects.

  4. Current status of atypical antipsychotics for the treatment of fibromyalgia.

    Science.gov (United States)

    Rico-Villademoros, F; Calandre, E P; Slim, M

    2014-06-01

    The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

  5. The pharmacogenetics of symptom response to antipsychotic drugs.

    Science.gov (United States)

    Reynolds, Gavin P

    2012-03-01

    Antipsychotic drugs are limited in their efficacy by the relatively poor response of negative and cognitive symptoms of schizophrenia as well as by the substantial variability in response between patients. Pharmacogenetic studies have sought to identify the genetic factors that underlie the individual variability in response to treatment, with a past emphasis on dopamine and serotonin receptors as candidate genes. Few studies have separated effects on positive and negative symptoms, despite the established differences in response to drug treatment between these syndromes. Where this has been done most findings are consistent with the conclusion that dopamine receptor polymorphisms relate to positive symptom response, while negative symptom improvement is influenced by polymorphisms of genes involved in 5-HT neurotransmission. A wide range of polymorphisms in other candidate genes have been investigated, with some positive findings in those genes associated with glutamatergic transmission and/or risk factors for schizophrenia. However, there remains a lack of good replicated findings; furthermore there is little evidence to support drug-specific genetic associations with treatment response. While most past studies focused on single candidate genes, technology now permits genome-wide association studies with response to antipsychotics. Although not without major limitations, these "hypothesis-free" approaches are beginning to identify further important risk factors for treatment response. Again there is little consistency between various studies, although some of the polymorphisms identified are in genes involved in neurodevelopment, which is increasingly being recognized as important in the pathophysiology of schizophrenia. PMID:22396678

  6. The effect of atypical antipsychotics on brain N-acetylaspartate levels in antipsychotic-naïve first-episode patients with schizophrenia: a preliminary study

    Directory of Open Access Journals (Sweden)

    Grošić V

    2014-07-01

    Full Text Available Vladimir Grošić,1 Petra Folnegovic Grošić,2 Petra Kalember,3,4 Maja Bajs Janović,2 Marko Radoš,3,4 Mate Mihanović,1 Neven Henigsberg3,51Psychiatric Hospital Sveti Ivan, Zagreb, 2University Hospital Center Zagreb, University of Zagreb, Zagreb, 3Polyclinic Neuron, Croatian Institute for Brain Research, Zagreb, 4Department of Neuropharmacology and Behavioral Pharmacology, Croatian Institute for Brain Research, University of Zagreb, Zagreb, 5Vrapče University Hospital, University of Zagreb, Zagreb, CroatiaPurpose: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics.Patients and methods: Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using 1H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London – Drexel University, Letter–Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced.Results: After 12 study months, the N-acetylaspartate/creatine (NAA/Cr level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008 and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005. On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months.Conclusion: One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn’t result

  7. Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

    Science.gov (United States)

    Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

    2014-03-01

    Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

  8. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents–A drug repurposing strategy

    Science.gov (United States)

    Wu, Chia-Hsien; Bai, Li-Yuan; Tsai, Ming-Hsui; Chu, Po-Chen; Chiu, Chang-Fang; Chen, Michael Yuanchien; Chiu, Shih-Jiuan; Chiang, Jo-Hua; Weng, Jing-Ru

    2016-01-01

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38, and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5, and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy. PMID:27277973

  9. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies

    Directory of Open Access Journals (Sweden)

    Haddad PM

    2014-06-01

    Full Text Available Peter M Haddad,1,2 Cecilia Brain,3,4 Jan Scott5,6 1Neuroscience and Psychiatry Unit, University of Manchester, Manchester, 2Greater Manchester West Mental Health NHS Foundation Trust, Salford, UK; 3Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, 4Nå Ut-teamet, Psychosis Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Academic Psychiatry, Institute of Neuroscience, Newcastle University, 6Centre for Affective Disorders, Institute of Psychiatry, London, UK Abstract: Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders

  10. Antipsychotics and Associated Risk of Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Weeke, Peter; Jensen, Aksel; Folke, Fredrik;

    2014-01-01

    use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of event. Overall treatment with any antipsychotic was associated with OHCA (odds ratio [OR]= 1.53, 95.......20-4.93) and levomepromazine (OR= 2.05, CI: 1.18-3.56) as was one atypical antipsychotic, quetiapine (OR= 3.64, CI: 1.59-8.30).Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 24 June 2014; doi:10.1038/clpt.2014.139....

  11. Prescribing pattern of antipsychotic medications in patients with schizophrenia in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    H. K. Sushma

    2015-02-01

    Conclusions: Schizophrenia is mostly seen in males, middle age group and unemployed people. The present study showed that combination therapy is preferred for the treatment of Schizophrenia. Despite several side-effects, typical antipsychotics, especially trifluoperazine was the most commonly used drug, followed by chlorpromazine either alone or in combination. Among atypical antipsychotics, risperidone was commonly used followed by quetiapine and asenapine. Most of the patients received trihexyphenidyl, an anticholinergic drug along with antipsychotics to reduce extra pyramidal side-effects. [Int J Basic Clin Pharmacol 2015; 4(1.000: 134-138

  12. Volumetric changes in the Basal Ganglia after antipsychotic monotherapy

    DEFF Research Database (Denmark)

    Ebdrup, B H; Nørbak, H; Borgwardt, S;

    2013-01-01

    monotherapy. Material and Methods: We systematically searched PubMed for longitudinal MRI studies of patients with schizophrenia or non-affective psychosis who had undergone a period of antipsychotic monotherapy. We used specific, predefined search terms and extracted studies were hand searched for additional...... studies. Results: We identified 13 studies published in the period from 1996 to 2011. Overall six compounds (two classified as FGAs and four as SGAs) have been investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine, and quetiapine. The follow-up period ranged from 3-24 months....... Unexpectedly, no studies found that specific FGAs induce significant BG volume increases. Conversely, both volumetric increases and decreases in the BG have been associated with SGA monotherapy. Discussion: Induction of striatal volume increases is not a specific feature of FGAs. Except for clozapine treatment...

  13. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

    Science.gov (United States)

    Cai, H L; Tan, Q Y; Jiang, P; Dang, R L; Xue, Y; Tang, M M; Xu, P; Deng, Y; Li, H D; Yao, J K

    2015-10-20

    Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.

  14. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies.

    Science.gov (United States)

    Haddad, Peter M; Brain, Cecilia; Scott, Jan

    2014-01-01

    Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive

  15. Development of antipsychotic medications with novel mechanisms of action based on computational modeling of hippocampal neuropathology.

    Directory of Open Access Journals (Sweden)

    Peter J Siekmeier

    Full Text Available A large number of cellular level abnormalities have been identified in the hippocampus of schizophrenic subjects. Nonetheless, it remains uncertain how these pathologies interact at a system level to create clinical symptoms, and this has hindered the development of more effective antipsychotic medications. Using a 72-processor supercomputer, we created a tissue level hippocampal simulation, featuring multicompartmental neuron models with multiple ion channel subtypes and synaptic channels with realistic temporal dynamics. As an index of the schizophrenic phenotype, we used the specific inability of the model to attune to 40 Hz (gamma band stimulation, a well-characterized abnormality in schizophrenia. We examined several possible combinations of putatively schizophrenogenic cellular lesions by systematically varying model parameters representing NMDA channel function, dendritic spine density, and GABA system integrity, conducting 910 trials in total. Two discrete "clusters" of neuropathological changes were identified. The most robust was characterized by co-occurring modest reductions in NMDA system function (-30% and dendritic spine density (-30%. Another set of lesions had greater NMDA hypofunction along with low level GABA system dysregulation. To the schizophrenic model, we applied the effects of 1,500 virtual medications, which were implemented by varying five model parameters, independently, in a graded manner; the effects of known drugs were also applied. The simulation accurately distinguished agents that are known to lack clinical efficacy, and identified novel mechanisms (e.g., decrease in AMPA conductance decay time constant, increase in projection strength of calretinin-positive interneurons and combinations of mechanisms that could re-equilibrate model behavior. These findings shed light on the mechanistic links between schizophrenic neuropathology and the gamma band oscillatory abnormalities observed in the illness. As such, they

  16. Cardiovascular risk factors in chronic treatment with antipsychotic agents used in primary care.

    Science.gov (United States)

    Mundet-Tudurí, Xavier; Iglesias-Rodal, Manuel; Olmos-Domínguez, Carmen; Bernard-Antoranz, M Lluïsa; Fernández-San Martín, M Isabel; Amado-Guirado, Ester

    2013-12-01

    Objetivo. Comparar la prevalencia de factores de riesgo cardiovascular (FRCV) y eventos vasculares en pacientes tratados con antipsicoticos, comparandolos con los no tratados. Sujetos y metodos. Estudio descriptivo transversal de pacientes atendidos en atencion primaria de la ciudad de Barcelona y tratados con antipsicoticos entre el 2008 y el 2010, comparandolos con una poblacion no tratada. Se registraron las variables antropometricas y clinicas y los FRCV. Se estudio por separado a pacientes adultos y ancianos, y a los tratados con antipsicoticos tipicos y atipicos. Resultados. Un total de 14.087 pacientes habian sido tratados con antipsicoticos (63,4% atipicos). El mas prescrito fue la risperidona. Se aparejaron 13.724 pacientes de la misma edad y genero, pero no tratados (n total = 27.811). Los tratados con antipsicoticos presentaron una prevalencia superior de obesidad (16,9% frente a 10,6%), tabaquismo (22,2% frente a 11,1%), diabetes mellitus (16% frente a 11,9%) y dislipemia (32,8% frente a 25,8%) (p tabaquismo). La presencia de ictus fue superior entre los tratados con antipsicoticos. No se detectaron diferencias importantes entre los pacientes tratados con antipsicoticos tipicos y atipicos.

  17. Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons

    DEFF Research Database (Denmark)

    Sahlberg, Marie; Holm, Ellen; Gislason, Gunnar H;

    2015-01-01

    aged ≥70 years that initiated treatment with APs for the first time between 1997 and 2011 (n=91 774, mean age 82±7 years, 35 474 [39%] were men). Incidence rate ratios associated with use of different APs were assessed by multivariable time-dependent Poisson regression models. For the first 30 days...... of treatment, compared with risperidone, incidence rate ratios of major adverse cardiovascular events were higher with use of levomepromazine (3.80, 95% CI 3.43 to 4.21) and haloperidol (1.85, 95% CI 1.67 to 2.05) and lower for treatment with flupentixol (0.54, 95% CI 0.45 to 0.66), ziprasidone (0.31, 95% CI 0...... events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. METHODS AND RESULTS: We followed all treatment-naïve Danish citizens...

  18. Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Knop, Filip K; Madsen, Anna;

    2014-01-01

    OBJECTIVE: Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear. METHOD: Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients.......3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones...... signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic...

  19. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

    Directory of Open Access Journals (Sweden)

    Maurizio Pompili

    2016-10-01

    Full Text Available Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia. We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior.

  20. Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

    DEFF Research Database (Denmark)

    Fink-Jensen, Anders; Schmidt, Lene S; Dencker, Ditte;

    2011-01-01

    A delicate balance exists between the central dopaminergic and cholinergic neurotransmitter systems with respect to motor function. An imbalance can result in motor dysfunction as observed in Parkinson's disease patients and in patients treated with antipsychotic compounds. Cholinergic receptor a...

  1. Antipsychotic drugs a last resort for these 5 conditions (ADHD, Anxiety, Depression, Insomnia and PTSD)

    Science.gov (United States)

    ... neurological events, and sedation. Studies in people with schizophrenia found that risperidone is the most likely of the newer antipsychotic drugs to increase a hormone called prolactin, which can result in women missing ...

  2. Determinants of physical health parameters in individuals with intellectual disability who use long-term antipsychotics

    NARCIS (Netherlands)

    de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Scholte, Frans; Visser, Frank; Hoekstra, Pieter J.

    2013-01-01

    Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which

  3. Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry

    DEFF Research Database (Denmark)

    Kiss, A; Bundzikova, J; Pirnik, Z;

    2010-01-01

    in autonomic, neuroendocrine, and behavioral processes. This study was focused to reveal the responsiveness of hypothalamic OXY- and AVP- producing magnocellular neurons, in terms of quantitative and topographical distinctions, to antipsychotics displaying different pharmacological profiles. Naive male Wistar...

  4. 抗精神病药引起体重增加的药物基因组学研究进展%Pharmacogenomics of antipsychotics induced weight gain

    Institute of Scientific and Technical Information of China (English)

    伍海姗; 赵丽萍; 赵靖平; 陈晋东

    2013-01-01

    Weight gain is a common adverse reaction of antipsychotic treatment,and the mechanism of weight gain induced by antipsychotics is complex and uncertain,in which individual differences in genetic polymorphisms may play an important role.This paper reviewed the related genes of antipsychotics-induced weight gain.HTR2C and leptin gene are considered to be the highest risk of weight gain.Recent studies showed a growing number of genes were related to antipsychotics-induced weight gain.The paper analyzed the relationship between antipsychotic agents and weight gain from the point of pharmacogenomics research,designed to provide a theoretical basis for future clinical personalized medication.%体重增加是抗精神病药治疗中常见的不良反应,抗精神病药引起体重增加的机制复杂且不确定,个体差异与遗传多态性可能在其中发挥了重要的作用.本文综述了与抗精神病药源性体重增加的相关基因研究进展,其中HTR2C和瘦素基因被认为是引起体重增加风险最高的基因,新近的研究显示越来越多的基因被发现与抗精神病药物引起的体重增加相关.本文主要从药物基因组学的研究角度分析抗精神病药与体重增加的关系,旨在为以后临床个体化用药提供理论依据.

  5. Role of 5-HT2C receptor gene variants in antipsychotic-induced weight gain

    Directory of Open Access Journals (Sweden)

    Brandl EJ

    2011-08-01

    Full Text Available Tessa JM Wallace, Clement C Zai, Eva J Brandl, Daniel J MüllerNeurogenetics Section, Center for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, CanadaAbstract: Antipsychotic-induced weight gain is a serious side effect of antipsychotic medication that can lead to increased morbidity, mortality, and non-compliance in patients. Numerous single nucleotide polymorphisms have been studied for association with antipsychotic-induced weight gain in an attempt to find genetic predictors of this side effect. An ability to predict this side effect could lead to personalized treatment plans for predisposed individuals, which could significantly decrease the prevalence and severity of weight gain. Variations in the serotonin receptor 2c gene (HTR2C have emerged as promising candidates for prediction of antipsychotic-induced weight gain. Specifically, the well-studied -759C/T promoter polymorphism has been associated with weight gain in diverse populations, although some studies have reported no association. This discrepancy is likely due to heterogeneity in study design with respect to ethnicity, treatment duration, and other variables. Notably, the association between HTR2C and antipsychotic-induced weight gain appears strongest in short-term studies on patients with limited or no previous antipsychotic treatment. Other, less extensively studied promoter polymorphisms (-697C/G, -997G/A, and -1165A/G have also emerged as potential predictors of antipsychotic-induced weight gain. Conversely, the well-studied intronic polymorphism Cys23Ser does not appear to be associated. With further research on both HTR2C and other genetic and environmental predictors of antipsychotic-induced weight gain, a predictive test could one day be created to screen patients and provide preventative or alternative treatment for those who are predisposed to this serious side effect.Keywords: HTR2C, pharmacogenomics, promoter polymorphism

  6. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    International Nuclear Information System (INIS)

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  7. Principles of antipsychotic drugs administration and the problem of compliance of the patients

    OpenAIRE

    Theocharis Kyziridis

    2010-01-01

    The introduction of antipsychotic medications in the clinical practice of psychiatric pharmacotherapy that took place half a century ago was a real revolution. Antipsychotic medications reorientated the organic basis of mental disease and gave a clear therapeutic choice in the treatment of psychotic patients. The gradual application of their use made possible the de-institutionalization of patients as well as the 4th revolution of psychiatry, that is community and social psychiatry.Αntipsycho...

  8. Second-Generation Antipsychotics and Neuroleptic Malignant Syndrome: Systematic Review and Case Report Analysis

    OpenAIRE

    Belvederi Murri, Martino; Guaglianone, Argentina; Bugliani, Michele; Calcagno, Pietro; Respino, Matteo; Serafini, Gianluca; Innamorati, Marco; Pompili, Maurizio; Amore, Mario

    2015-01-01

    Background Neuroleptic malignant syndrome (NMS) is a rare, severe, idiosyncratic adverse reaction to antipsychotics. Second-generation antipsychotics (SGAs) were originally assumed to be free from the risk of causing NMS, however several cases of NMS induced by SGAs (SGA-NMS) have been reported. Objectives The aim of this study was to systematically review available studies and case reports on SGA-NMS and compare the presentation of NMS induced by different SGAs. Data Sources Citations were r...

  9. CHALLENGE WITH ATYPICAL ANTIPSYCHOTIC DRUGS IN RISPERIDONE INDUCED NEUROLEPTIC MALIGNANT SYNDROME: A CASE REPORT

    OpenAIRE

    Mendhekar, D.N.; Jiloha, R.C.; M M Mehndiratta; War, L.

    2002-01-01

    There are several reports available on neuroleptic malignant syndrome (NMS) associated with risperidone but when a more stringent criterion is applied there are only a few. Report on challenge and rechallenge with various atypical antipsychotic drugs in re-emergence of post NMS psychosis is scanty. Our aim of presenting this is to highlight the differential response of various atypical antipsychotic drugs in the treatment of post NMS psychosis. This paper reports a young male with mild mental...

  10. A Case of Catatonia and Neuroleptic Malignant Syndrome Probably Associated with Antipsychotic in Korea

    OpenAIRE

    Choi, Ho-Dong; Kim, Kyoung-Keun; Koo, Bon-Hoon

    2011-01-01

    Several studies have reported on catatonia caused by the use of antipsychotic drugs and on the association between catatonia and neuroleptic malignant syndrome (NMS), but none has reported such a case in Korea. Here, we report the case of a 20-year-old woman whose catatonia and NMS appeared associated with the administration of an atypical antipsychotic drug. We discuss the association between NMS and catatonia due to neuroleptic use.

  11. Prevalence of the metabolic syndrome in Danish psychiatric outpatients treated with antipsychotics

    DEFF Research Database (Denmark)

    Krane-Gartiser, Karoline; Breum, Leif; Glümrr, Charlotte;

    2011-01-01

    The incidence of the metabolic syndrome, a major risk factor for diabetes and cardiovascular disease, is increasing worldwide and is suggested to be higher among psychiatric patients, especially those on antipsychotic treatment.......The incidence of the metabolic syndrome, a major risk factor for diabetes and cardiovascular disease, is increasing worldwide and is suggested to be higher among psychiatric patients, especially those on antipsychotic treatment....

  12. Pattern of adverse reactions of antipsychotics in a tertiary care hospital

    OpenAIRE

    Meenakshy T. Viswanathan; Asha Sisupalan; Vidhukumar Karunakaran

    2016-01-01

    Background: This study was undertaken to analyse the pattern of adverse drug reactions (ADR) of antipsychotics among patients attending the psychiatry outpatient department of a tertiary care centre. Methods: Patients attending the psychiatry outpatient department who have been on treatment with one or more antipsychotics for more than 6 weeks were included in the study. Details about the prescription given in the previous appointment were collected. Various adverse effects associated with...

  13. A pharmacy led program to review anti-psychotic prescribing for people with dementia

    OpenAIRE

    Child Anne; Clarke Amy; Fox Chris; Maidment Ian

    2012-01-01

    Abstract Background Anti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics. Methods This project was conducted within primary care in Medway Primary Care Trust (PCT) in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people ...

  14. Both typical and atypical long-acting injectable antipsychotics in bipolar disorder: a retrospective chart review

    OpenAIRE

    Alpak, Gokay; Demir, Bahadir; Aksoy, Ihsan; Kaya, Hilal; Unal, Ahmet; Bulbul, Feridun; Savas, Haluk A.

    2014-01-01

    Objective: Bipolar disorder (BD) is a chronic psychiatric disorder which shows difficulties in the process of diagnosis and treatment. One of the biggest problems in BD maintenance therapy is to ensure medication compliance. Long-acting injectable (LAI) antipsychotic medications have important advantages in such cases. In this study we aimed to include both LAI atypical and typical antipsychotics and to compare the clinical status, number of hospitalization, and side effects of pre and post-t...

  15. ANTIPSYCHOTIC SIDE-EFFECT – POTENTIAL RISK OF PATIENTS REJECTING THEIR TREATMENTS

    OpenAIRE

    Dadić-Hero, Elizabeta; Ružić, Klementina; Medved, Paola; Tatalović-Vorkapić, Sanja; Graovac, Mirjana

    2010-01-01

    Antipsychotics side-effects pose an enormous problem in psychiatric treatment. The choice of antipsychotics is a crucial issue in the treatment as both patients' cooperation and compliance often depend upon it. Severe side-effects might sometimes cause the treatment interruption, to which each patient is entitled. Schizotypal personality disorder (SPD) features include social and interpersonal deficits, discomfort with close relationships, as well as cognitive and perceptual distorti...

  16. Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

    OpenAIRE

    Fink-Jensen, Anders; Schmidt, Lene S.; Dencker, Ditte; Schülein, Christina; Wess, Jürgen; Wörtwein, Gitta; Woldbye, David P.D.

    2011-01-01

    A delicate balance exists between the central dopaminergic and cholinergic neurotransmitter systems with respect to motor function. An imbalance can result in motor dysfunction as observed in Parkinson’s disease patients and in patients treated with antipsychotic compounds. Cholinergic receptor antagonists can alleviate extrapyramidal symptoms in Parkinson’s disease and motor side effects induced by antipsychotics. The effects of anticholinergics are mediated by muscarinic receptors of which ...

  17. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: jzvereb@gmail.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: ipuray@mdanderson.org [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: fesus@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences (Hungary); Balajthy, Zoltán, E-mail: balajthy@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

    2014-08-08

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  18. A translational research approach to poor treatment response in patients with schizophrenia: clozapine–antipsychotic polypharmacy

    OpenAIRE

    Honer, William G.; Procyshyn, Ric M.; Eric Y. H. Chen; MacEwan, G. William; Barr, Alasdair M.

    2009-01-01

    Poor treatment response in patients with schizophrenia is an important clinical problem, and one possible strategy is concurrent treatment with more than one antipsychotic (polypharmacy). We analyzed the evidence base for this strategy using a translational research model focused on clozapine-antipsychotic polypharmacy (CAP). We considered 3 aspects of the existing knowledge base and translational research: the link between basic science and clinical studies of efficacy, the evidence for effe...

  19. Bone Density in Chronic Schizophrenia with Long-Term Antipsychotic Treatment: Preliminary Study

    OpenAIRE

    Lee, Tae-Young; Chung, Moon-Yong; Chung, Hae-Kyung; Choi, Jin-Hee; Kim, Tae-Yong; So, Hyung-Seok

    2010-01-01

    Objective Decreased bone mineral density has been found in the chronic schizophrenic patients who have been given a long-term administration of antipsychotics. Hyperprolactinemia from the antipsychotics and the negative symptom of schizophrenia were considered as the causes for this finding. In this study, the effect of hyperprolactinemia and the negative symptom of schizophrenia on bone mineral density was investigated on male schizophrenic patients. Methods The cross-sectional study was car...

  20. Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers

    Directory of Open Access Journals (Sweden)

    Ishioka M

    2015-02-01

    Full Text Available Masamichi Ishioka, Norio Yasui-Furukori, Norio Sugawara, Hanako Furukori, Shuhei Kudo, Kazuhiko Nakamura Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan Objective: The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation.Method: The participants included 182 patients with schizophrenia (male =89, female =93 who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex and serum prolactin concentrations were measured.Results: Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002 and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026 but not of the thrombin–antithrombin complex level (r=0.117, ns among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion: The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. Keywords: prolactin, antipsychotics, venous thromboembolism

  1. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    Directory of Open Access Journals (Sweden)

    Boonlue T

    2016-04-01

    Full Text Available Tuanthon Boonlue,1,2 Suphat Subongkot,1,2 Piyameth Dilokthornsakul,3,4 Ronnachai Kongsakon,5 Oraluck Pattanaprateep,6 Orabhorn Suanchang,7 Nathorn Chaiyakunapruk3,8–10 1Clinical Pharmacy Division, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand; 2The College of Pharmacotherapy of Thailand, Nonthaburi, Thailand; 3Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 4Center for Pharmaceutical Outcomes Research, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA; 5Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Department of Health Informatics, Ramathibodi Hospital, Mahidol University, 7Department of Pharmacy, Somdet Chaopraya Institute of Psychiatry, Bangkok, Thailand; 8School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 9School of Population Health, University of Queensland, Brisbane, Australia; 10School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA Background: Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective: This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods: From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual

  2. Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar Anticonvulsants and antipsychotics in the treatment of Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Ricardo Alberto Moreno

    2004-10-01

    effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics.

  3. The use of antipsychotic medication in child and adolescent psychiatric treatment in Denmark. A cross-sectional survey

    DEFF Research Database (Denmark)

    Deurell, Maria; Weischer, Merete; Pagsberg, Anne Katrine;

    2008-01-01

    for patients in antipsychotic treatment were: schizophrenia, schizotypal disorder, autism spectrum disorders and personality disorders. Monotherapy was used in 87% of cases. Sixty-four per cent of patients treated with antipsychotics, received a second-generation antipsychotic as the main treatment. All 244......The number of children and adolescents with psychiatric disorders being treated with antipsychotic medication is increasing significantly; however, only a limited evidence-base is available on this topic, especially when children are concerned. This study reports and discusses the use...... patients received one or more additional treatment modalities other than medication. Antipsychotic medication has a definite role in the treatment of children and adolescents with psychiatric disorders. Second-generation antipsychotics used as monotherapy prevail....

  4. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    Directory of Open Access Journals (Sweden)

    JP Lindenmayer

    2010-05-01

    Full Text Available JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS. While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of

  5. Imaging brain gene expression profiles by antipsychotics: region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol.

    Science.gov (United States)

    de Bartolomeis, Andrea; Marmo, Federica; Buonaguro, Elisabetta Filomena; Rossi, Rodolfo; Tomasetti, Carmine; Iasevoli, Felice

    2013-11-01

    Induction of motor disorders is considered the clinical landmark differentiating typical from atypical antipsychotics, and has been mainly correlated to dopamine D2 receptors blockade in striatum. This view is challenged by benzamides, such as amisulpride, which display low liability for motor side effects despite being D2/D3 receptors high-affinity blocking agents. These effects have been explained with the prominent presynaptic action of amisulpride or with the fast dissociation at D2 receptors, but there is scarce information on the effects of amisulpride on postsynaptic signaling. We carried out a molecular imaging study of gene expression after acute administration of haloperidol (0.8 mg/kg), amisulpride (10 or 35 mg/kg), or vehicle, focusing on postsynaptic genes that are key regulators of synaptic plasticity, such as Arc, c-fos, Zif-268, Norbin, Homer. The last one has been associated to schizophrenia both in clinical and preclinical studies, and is differentially induced by antipsychotics with different D2 receptors affinity. Topography of gene expression revealed that amisulpride, unlike haloperidol, triggers transcripts expression peak in medial striatal regions. Correlation analysis of gene expression revealed a prevalent correlated gene induction within motor corticostriatal regions by haloperidol and a more balanced gene induction within limbic and motor corticostriatal regions by amisulpride. Despite the selective dopaminergic profile of both compounds, our results demonstrated a differential modulation of postsynaptic molecules by amisulpride and haloperidol, the former impacting preferentially medial regions of striatum whereas the latter inducing strong gene expression in lateral regions. Thus, we provided a possible molecular profile of amisulpride, putatively explaining its "atypical atypicality".

  6. Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy

    Directory of Open Access Journals (Sweden)

    Stanković Žana

    2013-01-01

    Full Text Available Background/Aim. There is a high rate of schizophrenic patients who do not adhere to their prescribed therapy, despite the implementation of antipsychotic long-acting injections and the introduction of atypical antipsychotics. The aim of this study was to investigate the differences in sociodemographic, clinical and medication adherence variables between the two groups of schizophrenic patients on maintenance therapy with depot antipsychotic fluphenazine decanoate and oral antipsychotics only as well as a correlation between the medication adherence and other examined variables. Methods. A total of 56 patients of both genders, aged < 60 years, with the diagnosis of schizophrenia (F20 (ICD-10, 1992 clinically stable for at least 6 months were introduced in this cross-sectional study. The patients from the depot group (n = 19 were on classical depot antipsychotic fluphenazine decanoate administering intramuscularly every 4 weeks (with or without oral antipsychotic augmentation and the patients from the oral group (n = 37 were on oral therapy alone with classical or atypical antipsychotics, either as monotherapy or combined. The Positive and Negative Syndrome Scale (PANSS was used to assess symptom severity. Item G12 of the PANSS was used to assess insight into the illness. The patients completed the Medical Adherence Rating Scale (MARS was used to assess adherence to the therapy. A higher MARS score indicates behavior [Medical Adherence Questionnaire (MAQ subscale] and attitudes toward medication [Drug Attitude Inventory (DAI subscale] that are more consistent with treatment adherence. The exclusion criteria were determined. The Pearson's χ2 test was used to compare categorical variables, Student's t-test to compare continuous variables and Pearson's correlation to test the correlation significance; p = 0.05. Results. Significant betweengroup differences in age, illness duration, chlorpromazine equivalents, PANSS score and DAI subscore were found

  7. The Impact of Open Access to Atypical Antipsychotics on Treatment Costs for Medi-Cal Patients with Bipolar Disorder

    OpenAIRE

    Sangeeta Narayan; Kimberly L. Sterling; McCombs, Jeffrey S.

    2006-01-01

    Background: The California Medicaid Program (Medi-Cal) provided open access to atypical antipsychotics in October 1997. This study investigated the impact of open access to atypical antipsychotics on the costs and duration of therapy for patients with bipolar disorders. Methods: Paid claims data from Medi-Cal were used to identify episodes of treatment using antipsychotics, antidepressants, mood stabilizers, or selected anticonvulsants initiated by patients with bipolar disorders. Episodes of...

  8. Venous thromboembolism as an adverse effect of antipsychotic treatment

    Directory of Open Access Journals (Sweden)

    Bałkowiec-Iskra, Ewa

    2014-10-01

    Full Text Available Many studies suggest an association between the use of antipsychotics (APs and occurrence of venous thromboembolism (VTE. Thromboembolism is often related to a significant risk of disability or death. Despite many years of investigating the interrelations between use of APs and VTE, they have not been specified yet. This paper aims to summarize reports on the VTE risk factors in patients using APs. Based on the analyzed clinical studies, meta-analyses and data published by European Medicines Agency, it has been determined, that the main risk factors for VTE are duration of treatment and patient-related factors, such as gender, age, body mass, and physical activity. Current data do not allow to identify the prothrombotic potential for individual APs or indicate a higher risk for developing VTE in patients treated with newer atypical APs. Due to the complex pathogenesis of VTE it would be necessary to perform large, comparative studies, allowing to identify precisely differences in prothrombotic potential of individual APs. It is necessary to specify products with the lowest VTE risk, what would be useful in the treatment of high-risk patients. All patients treated with APs should be assessed with the risk of VTE and, if needed, appropriate prevention methods (including most of all the elimination of modifiable risk factors should be implemented. Moreover, patients should be educated in scope of VTE prodromal symptoms. All patients with the higher VTE risk should be diagnosed as soon as possible and adequate treatment should be implemented.

  9. Adherence to Antipsychotic Medication in Bipolar Disorder and Schizophrenic Patients

    Science.gov (United States)

    García, Saínza; Martínez-Cengotitabengoa, Mónica; López-Zurbano, Saioa; Zorrilla, Iñaki; López, Purificación; Vieta, Eduard; González-Pinto, Ana

    2016-01-01

    Abstract Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients. PMID:27307187

  10. [Antipsychotics for schizophrenia: the paradigm of psychiatric drugs].

    Science.gov (United States)

    Pol Yanguas, Emilio

    2015-03-01

    Antipsychotic drugs do not appear to reverse the causes of schizophrenia, and although they can relieve symptoms in the short to medium term, in the long term they may not be beneficial and could even be counterproductive. Their use should be limited to acute situations in which agitation and tension is disabling. The drugs have significant adverse effects, and given the refusal of a person to continue taking them, a harm reduction strategy to support and monitor the withdrawal may be preferable to coercion. There are alternatives to neuroleptics. Prescribers should be more vigilant and consider the assessments of users regarding the drugs' effects. Adherence to treatment guidelines is low, probably because the guidelines are based on clinical trials of deficient quality which consequently should be improved and extended over a greater period of time. The root of the problem is likely the tautology on the etiology and biological nature of what is known as schizophrenia, which in fact does not seem to be more than a commercial and ideological construct.

  11. Analysis of adverse drug reactions of atypical antipsychotic drugs in psychiatry OPD

    Directory of Open Access Journals (Sweden)

    Kiran G Piparva

    2011-01-01

    Full Text Available Background: Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS. However, these drugs have separate set of adverse drug reactions (ADRs. Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment. Materials and Methods: A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex, who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients′ responses were recorded in the case record form. Results: Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93 were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4-6 mg/day and olanzepine (at 10-15 mg/day, gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2-3 months after treatment course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3-9 months use. Conclusion: The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized.

  12. Attitudes towards antipsychotics among patients with schizophrenia on first- or second-generation medications

    Directory of Open Access Journals (Sweden)

    M S Karthik

    2014-01-01

    Full Text Available Background: Given the paucity of research in this area, this study attempted to assess attitudes toward antipsychotic medications and its correlates among patients with schizophrenia, either on first-generation antipsychotics (FGAs or second-generation antipsychotics (SGAs medications. Materials and Methods: Structured assessments of attitudes to antipsychotics, psychopathology, insight and side-effects were carried out in 120 patients with DSM-IV schizophrenia; 89 of these were on SGAs and 31 on FGAs. Results: Patients had predominantly positive attitudes toward antipsychotics. Severity of side-effects was the principal correlate of attitudes, explaining 19.5% of the variance, followed by greater insight (4.2% of the variance. Other factors such as younger age, male gender, employment, higher family income, urban residence and lower symptom-severity explained only a negligible proportion of the variance (0.2% in attitudes. Patients on SGAs had more positive views of their medications than those on FGAs. They felt more normal on their medications, believed that their thoughts were clearer on medications, felt that good things about their medications outweighed the bad and believed that their medications helped them from falling ill again. In addition, they did not feel as tired and sluggish on their medications and did not believe that medications were unnatural or controlled their bodies. Conclusions: Positive attitudes toward antipsychotics were common among patients with schizophrenia. Attitudes were principally determined by severity of side-effects and insight levels. Patients on SGAs had better attitudes, possibly because of less severe side-effects and greater insight among them. The importance of exploring patients′ attitudes toward their antipsychotics is highlighted by this study.

  13. Antipsychotics--history of development and field of indication, new wine--old glassess.

    Science.gov (United States)

    Jašović-Gašić, Miroslava; Vuković, Olivera; Pantović, Maja; Cvetić, Tijana; Marić-Bojović, Nadja

    2012-10-01

    More than half a century ago, Delay and colleagues have discovered, quite accidentally, that antihistamine (chlorpromazine) relieves psychotic symptoms. This discovery prompted further investigation through a series of performed experiments aimed to elucidate the antipsychotic mechanism of action. Initial results have shown that antipsychotic drugs in experimental animals lead to "neuroleptic effect" (indifference). However, not until the end of 1960s, it becomes clear that all previously known antipsychotics block dopamine receptors, particularly postsynaptic D2 receptors. The next three decades marked the development and application of these so-called classic neuroleptics in the treatment of psychotic patients. During the nineteen nineties, as a result of ongoing efforts to achieve greater efficiency and reduce the scope of side effects, novel antipsychotics were synthesized (second generation antipsychotics--SGA). As a result the notion of serotonin-dopamine antagonist (SDA) was formulated. According to one of the hypothesis, "new", so called atypical antipsychotic drugs strongly block the serotonin (5-HT2), and weakly block the dopamine (D2) receptors. Yet, there is still a debate as to the molecular basis of atypicality, whether it is in dopaminergic and serotonergic antagonism of neurotransmission or it lays exclusively in the modulation of dopaminergic system and dissociation rate at the level of D2 receptors in specific brain regions. Although the synthesis and use of antipsychotics in clinical practice have radically changed not only the basic approach to the patient, but also the quality of life of millions of people, the question remains whether this is just "old wine in new glasses".

  14. Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

    Science.gov (United States)

    Schirmbeck, Frederike; Mier, Daniela; Esslinger, Christine; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

    2015-01-01

    Background Patients with schizophrenia have an approximately 10-fold higher risk for obsessive–compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. Methods To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. Results We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. Limitations The main limitation of this study is its cross-sectional design. Conclusion To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations. PMID:25268790

  15. How do we choose between atypical antipsychotics? The advantages of amisulpride.

    Science.gov (United States)

    Mortimer, Ann M

    2004-03-01

    Clinician choice of an atypical antipsychotic may depend on a number of factors such as perceived efficacy, tolerability and cost. It is also important that the choice of treatment takes into consideration the previous response to treatment, experience of side-effects and personal clinical characteristics. The receptor-affinity profiles of the atypical antipsychotics differ; with the exception of amisulpride, a selective D2/D3 antagonist, all the atypical antipsychotics exhibit a greater affinity for the serotonin-2A receptors than dopamine receptors. However, there is no evidence that the variation in receptor affinities is relevant to efficacy. Indeed, the crucial factor may be fast dissociation from low affinity for the D2 receptor. Tolerability also varies between the atypical antipsychotics and the side-effect profile may be related to the receptor-affinity profile of the individual drugs. Extrapyramidal side-effects are generally less of a problem with most atypical drugs than with conventional drugs, but weight gain, loss of glycaemic control, sedation and hyperprolactinaemia remain problematic in some patients. Amisulpride is effective for the treatment of both positive and negative symptoms, and is well tolerated with regard to weight gain, glucose tolerance and sedation. In two clinical trials, the AMIRIS and SOLIANOL studies, amisulpride demonstrated clear advantages over some other atypical antipsychotics with respect to negative symptoms, depressive symptoms and weight gain.

  16. Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

    Directory of Open Access Journals (Sweden)

    Fabio Panariello

    2011-01-01

    Full Text Available Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1 the role of polymorphisms in several candidate genes, (2 the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3 the state of development of animal models in this matter. We also outline major areas for future research.

  17. Rapid Growth Of Antipsychotic Prescriptions For Children Who Are Publicly Insured Has Ceased, But Concerns Remain.

    Science.gov (United States)

    Crystal, Stephen; Mackie, Thomas; Fenton, Miriam C; Amin, Shahla; Neese-Todd, Sheree; Olfson, Mark; Bilder, Scott

    2016-06-01

    The rapid growth of antipsychotic medication use among publicly insured children in the early and mid-2000s spurred new state efforts to monitor and improve prescription behavior. A starting point for many oversight initiatives was the foster care system, where most of the children are insured publicly through Medicaid. To understand the context and the effects of these initiatives, we analyzed patterns and trends in antipsychotic treatment of Medicaid-insured children in foster care and those in Medicaid but not in foster care. We found that the trend of rapidly increasing use of antipsychotics appears to have ceased since 2008. Children in foster care treated with antipsychotic medications are now more likely than other Medicaid-insured children to receive psychosocial interventions and metabolic monitoring for the side effects of the medications. However, challenges persist in increasing safety monitoring and access to psychosocial treatment. Development of specialized managed care plans for children in foster care represents a promising policy opportunity. New national quality measures for safe and judicious antipsychotic medication use are also now available to guide improvement. Oversight policies developed for foster care appear to have potential for adaptation to the broader population of Medicaid-covered children. PMID:27269012

  18. Principles of antipsychotic drugs administration and the problem of compliance of the patients

    Directory of Open Access Journals (Sweden)

    Theocharis Kyziridis

    2010-04-01

    Full Text Available The introduction of antipsychotic medications in the clinical practice of psychiatric pharmacotherapy that took place half a century ago was a real revolution. Antipsychotic medications reorientated the organic basis of mental disease and gave a clear therapeutic choice in the treatment of psychotic patients. The gradual application of their use made possible the de-institutionalization of patients as well as the 4th revolution of psychiatry, that is community and social psychiatry.Αntipsychotic medications did not prove to be the solution to every problem that patients faced. This occurred despite the fact that novel drugs were discovered being very effective and deprived of the majority of unwanted side effects of the older drugs. In any case the discovery of antipsychotic medications deserves the title that has been granted to them, and which is that of the second revolution of psychiatry. The knowledge of the basic principles of their pharmacologic actions, their unwanted side-effects and the measures of their prevention and treatment constitute a necessary tool for every nurse; especially when taking into consideration the fact that antipsychotic medications are used in a wide variety of cases even reaching up to the treatment of acute organic brain syndromes, that are highly prevalent in the medical and surgical units of general hospitals.This article deals with the basic principles of nursing process when administering antipsychotic medications. Furthermore, it also deals with the major problem of the compliance of patients to their treatment.

  19. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

    Directory of Open Access Journals (Sweden)

    Williams Sylvain

    2006-03-01

    Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

  20. Effectiveness of antipsychotics used in first-episode psychosis: a naturalistic cohort study

    Science.gov (United States)

    Whale, Richard; Harris, Michael; Kavanagh, Gail; Wickramasinghe, Vijitha; Jones, Christopher I.; Marwaha, Steven; Jethwa, Ketan; Ayadurai, Nirmalan; Thompson, Andrew

    2016-01-01

    Background One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP). Aims To investigate the effectiveness of commonly used antipsychotic medications in FEP. Method A retrospective cohort study of naturalistic treatment of patients (N=460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files. Results Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation. Conclusions Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus. Declaration of interest R.W., A.T. and S.M. have received research grant, speaker honoraria and conference attendance funding from all companies marketing antipsychotics. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27733935

  1. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

    Science.gov (United States)

    Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

    2013-03-01

    Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats.

  2. Evaluation of naltrexone augmentation to the antipsychotic drugs on positive and negative symptoms of schizophrenia

    Directory of Open Access Journals (Sweden)

    Javad Setareh

    2008-01-01

    Full Text Available Abstract Background and Purpose: In recent years, review of opioid system and its changes in the psychopathology of schizophrenia through thear probable role our on neuronal synopses and cell body of dopaminergic neurons and also decrease dopamine secretion from acumbans nuclei and effects of opium agonists in treatment of those patients has been adventajes for clinicians.Materials and methods: In a prospective double blind evaluation, 60 chronic schizophrenic inpatients on a stable regimen of neuroleptic medication with positive and negative symptom scale (PANSS score of higher than 80 and were randomly assigned to either antipsychotic plus naltrexone or antipsychotic plus placebo. Thirty patients (30 received 100 mg/day of naltrexone plus antipsychotic drug while 30 received placebo plus antipsychotic drug for 6 weeks. PANSS scores were evaluated on the base of the study, biweekly through out the study and two weeks after the trial. The treatment effect was calculated by repeated measurement ANOVA.Results: Difference between four types of symptoms (positive symptom, negative symptom, general psychopathological symptom, total score of PANSS in the case and control groups was not significant (P < 0.05. In supplement two (S2 scores, a statistically non significant difference was seen in two groups (P < 0.07. Conclusion: Additional treatment with 100 mg/day naltrexone in a 6 week trial had no significant therapeutic effect on typical or atypical antipsychotic drugs with regards to schizophrenia psychopathology. J Mazand Univ Med Sci 2008; 18(66: 10-18 (Persian

  3. Striatal Reward Activity and Antipsychotic-Associated Weight Change in Patients With Schizophrenia Undergoing Initial Treatment

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne;

    2016-01-01

    anticipation is associated with amisulpride-induced weight change in antipsychotic-naive patients with schizophrenia undergoing initial treatment and to examine the association between weight change and changes in reward anticipation activity after treatment. Design, Setting, and Participants: Sixty......-nine antipsychotic-naive inpatients and outpatients with schizophrenia were included in a multimodal longitudinal cohort study from December 16, 2008, to December 11, 2013. Fifty-eight patients underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. After 6 weeks of treatment......Importance: Weight gain is a common and serious adverse effect of antipsychotic treatment. A variable individual predisposition to development of metabolic disturbances calls for predictive biological markers. Objectives: To investigate whether attenuated striatal activity during reward...

  4. Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia

    DEFF Research Database (Denmark)

    Zakarias, Johanne Købstrup; Jensen-Dahm, Christina; Nørgaard, Ane;

    2016-01-01

    of behavioral symptoms. OBJECTIVE: To investigate potential geographical variances in use of antipsychotic drugs in dementia care. METHODS: A registry-based cross-sectional study in the entire elderly population of Denmark (≥65 years) conducted in 2012. Data included place of residence, prescriptions filled......, and hospital discharge diagnoses. Antipsychotic drug use among elderly with (n = 34,536) and without (n = 931,203) a dementia diagnosis was compared across the five regions and 98 municipalities in Denmark, adjusted for age and sex. RESULTS: In 2012, the national prevalence of antipsychotic drug use was 20.......7% for elderly patients with dementia, with a national incidence of 3.9%. The prevalence ranged from 17.0% to 23.3% in the five regions and from 7.5% to 33.1% in the 98 municipalities, demonstrating an over four-fold difference. CONCLUSION: The observed geographical variation was more pronounced at municipal...

  5. Evaluation of the antipsychotic potential of aqueous fraction of Securinega virosa root bark extract in mice.

    Science.gov (United States)

    Magaji, M G; Mohammed, M; Magaji, R A; Musa, A M; Abdu-Aguye, I; Hussaini, I M

    2014-03-01

    Securinega virosa (Roxb ex. Willd) Baill. is a plant which is commonly used in African traditional medicine in management of mental illness. Previous study showed that the crude methanolic root bark extract of the plant possesses antipsychotic activity. In this study, the antipsychotic potential of the residual aqueous fraction of the plant was evaluated using two experimental models, apomorphine induced stereotypic climbing behaviour and swim induced grooming, all in mice. The effect of the fraction on haloperidol-induced catalepsy was also evaluated. The fraction significantly reduced the mean climbing score at the highest dose tested (500 mg/kg). In the swim-induced grooming test, the fraction significantly and dose-dependently (125-500 mg/kg) decreased the mean number and mean duration of swim-induced grooming activity in mice. Similarly, the standard haloperidol (1 mg/kg) significantly (p bark extract of Securinega virosa contains biological active principle with antipsychotic potential.

  6. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Knop, Filip K; Ishøy, Pelle L;

    2012-01-01

    are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes...... between schizophrenia and overweight patients. DISCUSSION: Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogues used in the treatment of type 2 diabetes are associated with significant and sustained weight loss...... in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogues are discussed. CONCLUSIONS: We propose that adjunctive treatment with GLP-1 analogues may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies...

  7. Evaluation of Paraoxonase, Arylesterase and Malondialdehyde Levels in Schizophrenia Patients Taking Typical, Atypical and Combined Antipsychotic Treatment

    Science.gov (United States)

    Güneş, Mehmet; Camkurt, Mehmet Akif; Bulut, Mahmut; Demir, Süleyman; İbiloğlu, Aslıhan Okan; Kaya, Mehmet Cemal; Atlı, Abdullah; Kaplan, İbrahim; Sir, Aytekin

    2016-01-01

    Objective Human serum paraoxonase (PON1) prevents lipids from peroxidation and functions as an antioxidant mechanism. Malonyldialdehyde (MDA) is the final product of lipid peroxidation and can be used as an indicator of oxidative stress. The aim of this study was to investigate PON1, MDA, and arylesterase (ARY) levels in schizophrenic patients who are taking typical, atypical, or combined (typical and atypical) antipsychotic drug treatment, with respect to those of healthy controls. Methods We evaluated 41 patients (11 taking typical antipsychotics, 19 taking atypical antipsychotics, 11 taking combined anti-psychotics) and 43 healthy controls. Results MDA levels were higher in schizophrenic patients taking typical antipsychotics compared with healthy controls (p=0.001). ARY levels were higher in patients taking atypical antipsychotics compared with healthy controls (p=0.005). PON1 activity was similar in all groups. Conclusion Our results indicate that treatment with typical antipsychotic drugs could be related to increased MDA levels; and antipsychotic medication may increase PON1 levels in schizophrenic patients. PMID:27776386

  8. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study.

    NARCIS (Netherlands)

    Mulder, H.; Franke, B.; Beek, A.A. van der; Arends, J.; Wilmink, F.W.; Egberts, A.C.G.; Scheffer, H.

    2007-01-01

    The use of antipsychotics is associated with an increased risk of obesity. This consideration makes it important to search for determinants that can predict the risk for antipsychotic-induced obesity. In this cross-sectional study, we investigated whether polymorphisms in the HTR2C gene were associa

  9. Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter; Lublin, H;

    2010-01-01

    OBJECTIVE: To evaluate the effect of a multifaceted educational intervention on the frequency of antipsychotic co-prescribing in adult schizophrenia out-patients. METHOD: Controlled quasi-experimental study performed in two Danish municipalities matched for baseline prevalence of antipsychotic...

  10. Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2016-04-01

    Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapine-induced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental

  11. Antipsychotic adherence, switching, and health care service utilization among Medicaid recipients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Douglas L Noordsy

    2010-07-01

    Full Text Available Douglas L Noordsy1, Glenn A Phillips2, Daniel E Ball2, Walter T Linde-Zwirble31Department of Psychiatry, Dartmouth Medical School, Lebanon, NH, USA; 2Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 3ZD Associates, Perkasie, PA, USAObjective: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to ­different treatments.Methods: Adults with schizophrenia in the California Medicaid (MediCal database who ­initiated treatment with index medications in 1998–2001, were classified as having: 1 ­abandoned antipsychotic medications; 2 switched to another medication; or 3 continued with the index antipsychotic, for up to 6 months after the index date.Results: Of 2300 patients meeting eligibility criteria, 1382 (60.1% continued index medications, 480 (20.9% switched, and 438 (19.0% abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications. These included using psychiatric (24.2% vs 14.5%; P < 0.001 or nonpsychiatric (31.5% vs 24.3%; P < 0.05 emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05; making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05 or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05; and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001 or nonpsychiatric (82.7% vs 74.6%; P < 0.001 services.Conclusions: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment.Keywords: antipsychotics, drug therapy, resource use, treatment adherence

  12. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia

    OpenAIRE

    Honey, Garry D; Edward T Bullmore; Soni, William; Varatheesan, Malini; Williams, Steve C.R.; Sharma, Tonmoy

    1999-01-01

    Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal...

  13. Recommendations for switching antipsychotics. A position statement of the Spanish Society of Psychiatry and the Spanish Society of Biological Psychiatry.

    Science.gov (United States)

    Bernardo, Miquel; Vieta, Eduard; Saiz Ruiz, Jerónimo; Rico-Villademoros, Fernando; Alamo, Cecilio; Bobes, Julio

    2011-07-01

    Switching antipsychotics is common in the clinical practice setting and is associated with potential clinically relevant complications. An expert group selected by Spanish Society of Psychiatry and the Spanish Society of Biological Psychiatry has reviewed the evidence provided by randomized clinical trials and other relevant information to reach consensus recommendations for switching antipsychotics. In this article, we will review all the information that has led to those recommendations and which includes: indications and contraindications for switching antipsychotics, pharmacological issues, switching strategies, switching antipsychotics due to efficacy problems, switching antispychotics due to tolerability issues (including extrapyramidal symptoms and tardive dyskinesia, weight gain, metabolic disorders, hyperprolactinemia, sexual dysfunction, persistent sedation, and QT prolongation), switching antypsychotics due to lack of treatment compliance, and switching antipsychotics in patients with bipolar disorders.

  14. Post-Stroke Mortality, Stroke Severity, and Preadmission Antipsychotic Medicine Use – A Population-Based Cohort Study

    DEFF Research Database (Denmark)

    Prior, Anders; Laursen, Thomas Munk; Larsen, Karen Kjær;

    2014-01-01

    severity, length of hospital stay, and 30-day post-stroke mortality using logistic regression analysis, survival analysis, and propensity score matching. Results: Current users of antipsychotics had a higher risk of severe or very severe stroke on The Scandinavian Stroke Scale than never users...... of antipsychotics (adjusted odds ratios, 1.43; 95% CI, 1.29–1.58). Current users were less likely to be discharged from hospital within 30 days of admission than never users (probability of non-discharge, 27.0% vs. 21.9%). Antipsychotics was associated with an increased 30-day post-stroke mortality among current......Background and Purpose: It has been suggested that antipsychotic medication may be neuroprotective and may reduce post-stroke mortality, but studies are few and ambiguous. We aimed to investigate the post-stroke effects of preadmission antipsychotic use. Methods: We conducted a nationwide...

  15. A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice

    Directory of Open Access Journals (Sweden)

    Bodén R

    2013-03-01

    Full Text Available Robert Bodén,1,2 Gunnar Edman,3,4 Johan Reutfors,2 Claes-Göran Östenson,3 Urban Ösby3,4 1Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden; 2Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 4Department of Psychiatry, Tiohundra AB, Norrtälje, Sweden Abstract: It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08–3.04, reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01–2.97; and OR = 2.03, 95% CI 1.32–3.13, hypertension with perphenazine (OR = 2.00, 95% CI 1.21–3.59, and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05–0.89 and positively with haloperidol (OR = 2.02, 95% CI 1.18–3.48. There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In

  16. Metabolic syndrome in patients with severe mental illness undergoing psychiatric rehabilitation receiving high dose antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Bapu V Ravindranath

    2012-01-01

    Full Text Available Background: To review evidence of chronic antipsychotic medication and the association with metabolic syndrome in mentally ill patients. This evidence was used to analyse a cohort of patients with severe mental illness and to deduce a correlation between the prevalence of metabolic syndrome and their dose regimens. Materials and Methods: Twenty-four male patients undergoing Psychiatric rehabilitation underwent a review of current medication and assessment of risk factors for metabolic syndrome. Assessment criteria was based upon National Cholesterol Education Programme expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III (NCEP ATP III criteria, incorporating waist circumference, raised triglycerides, reduced high density lipoprotein, raised blood pressure and fasting blood glucose. PubMed, Nature and Science Direct databases have been used to compile the medical and scientific background on metabolic syndrome and antipsychotic medication and the effect on patients particularly on high dose. Results: Out of 24 patients, 10 patients (41.7% were receiving high dose antipsychotics (HDA and four were on maximum dosage limits of 100%. 8.3% (2/24 patients were receiving only one first generation antipsychotics (FGA, 37.5% (9/24 patients were receiving only one second generation antipsychotic (SGA, 45.8% patients (11/24 were receiving two or more SGA only, and only one patient was receiving two or more FGA. One patient was receiving a combination of FGA and SGA. PRN ("as needed" therapy was not included in this study as their usage was limited. Clozapine was mostly prescribed in these patients (10/24, 41.6%. Four out of the 24 patients refused blood tests therefore were excluded from the following results. In the patients evaluated, 55% (11/20 had confirmed metabolic syndrome. In these patients with metabolic syndrome, 45.4% (5/11 were on HDA and 27.3% (3/11 were on maximum British National

  17. Hunger and negative alliesthesia to aspartame and sucrose in patients treated with antipsychotic drugs and controls.

    Science.gov (United States)

    Khazaal, Y; Chatton, A; Claeys, F; Ribordy, F; Khan, R; Zullino, D

    2009-12-01

    The present study explores sweet stimuli effects on hunger and negative alliesthesia in patients treated with antipsychotic drugs and controls. Those phenomena were examined in relation to previous weight gain, eating and weight-related cognitions and type of sweet stimuli: aspartame or sucrose. Alliesthesia is delayed in participants who gained weight regardless of cross group differences. A similar reduction of hunger was observed after the intake of two kinds of sweet stimuli (aspartame or sucrose) whereas alliesthesia measures were not affected. Whereas atypical antipsychotic drug-induced weight gain is linked to delayed satiety, the phenomenon is similar in magnitude in non-psychiatric controls who gained weight.

  18. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

    Directory of Open Access Journals (Sweden)

    Ye W

    2012-01-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

  19. Exploring regional variation in antipsychotic coprescribing practice: a Danish questionnaire survey

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter N.; Nordentoft, Merete;

    2010-01-01

    The pharmacologic treatment of schizophrenia is characterized by excessive use of antipsychotic polypharmacy, which reflects a gap between evidence and practice. The aim of the present study was to investigate regional differences in treatment setting characteristics and in physician and nurse...

  20. Estimating Dopamine D-2 Receptor Occupancy for Doses of 8 Antipsychotics : A Meta-Analysis

    NARCIS (Netherlands)

    Lako, Irene M.; van den Heuvel, Edwin R.; Knegtering, Henrikus; Bruggeman, Richard; Taxis, Katja

    2013-01-01

    Rationale: Dose equivalents based on dopamine D-2 receptor occupancy can be used to compare antipsychotics on D-2 receptor-mediated (adverse) effects such as extrapyramidal symptoms and altered emotional experiences. Previous meta-analyses modeling the dose-occupancy relationship hardly addressed po

  1. Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model

    DEFF Research Database (Denmark)

    Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.

    2015-01-01

    Torsades de Pointes (TdP) is a potentially lethal cardiac arrhythmia and a known adverse effect of many drugs secondary to block of the rapidly activating delayed rectifier potassium current (IKr). In animal models antipsychotic drugs have shown reduced pro-arrhythmic potential compared to drugs...

  2. Physician and patient benefit–risk preferences from two randomized long-acting injectable antipsychotic trials

    Science.gov (United States)

    Katz, Eva G; Hauber, Brett; Gopal, Srihari; Fairchild, Angie; Pugh, Amy; Weinstein, Rachel B; Levitan, Bennett S

    2016-01-01

    Purpose To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. Methods Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. Results Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1), nonadherent: the change in efficacy studied was regarded as unimportant. Conclusion Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from an oral formulation to a LAI.

  3. Brain site- and transmitter-dependent actions of methamphetamine, morphine and antipsychotics.

    Science.gov (United States)

    Mori, Tomohisa; Iwase, Yoshiyuki; Murata, Asami; Iwata, Noriyuki; Suzuki, Tsutomu

    2016-06-01

    While several methamphetamine- and morphine-induced psychotic states are ordinarily treated by antipsychotics, the therapeutic mechanisms of antipsychotic drugs have yet been elucidated. The present study was designed to investigate the mechanisms how antipsychotic drugs suppress the behavioral changes induced by psychoactive drugs in mice. Low to medium doses of methamphetamine produced hyperlocomotion, whereas high dose of methamphetamine induced hypolocomotion. Hyperlocomotion induced by methamphetamine was potently suppressed by clozapine and 5-HT2 receptor antagonists, but not by the intra-accumbens injection of haloperidol. On the other hand, microinjection of haloperidol into the ventrolateral striatum increased locomotor activity with high dose of methamphetamine. In contrast, morphine-induced hyperlocomotion was suppressed by systemic as well as intra-accumbens injection of haloperidol, whereas relatively resistant to clozapine, compared to its effects in the case of methamphetamine. It has been widely believed that methamphetamine-induced psychosis is an animal model of schizophrenia, which is mediated by activation of accumbal dopamine receptors. Our findings suggest that methamphetamine differentially regulate monoaminergic systems (e.g., dopaminergic vs. 5-HTnergic), and accumbal dopamine receptors are not involved in methamphetamine-induced hyperlocomotion in mice. Thus, our findings may lead to a better understanding of the therapeutic mechanisms that underlie the effects of antipsychotic drugs and behavioral effects of methamphetamine and morphine. PMID:26992824

  4. Association between the ROBO1 gene and body mass index in patients using antipsychotics

    NARCIS (Netherlands)

    Vehof, Jelle; Al Hadithy, Asmar F. Y.; Burger, Huibert; Snieder, Harold; Risselada, Arne J.; Wilffert, Bob; Cohen, Dan; Arends, Johan; Wiersma, Durk; Mulder, Hans; Bruggeman, Richard

    2011-01-01

    Background Weight gain is one of the major problems in patients using antipsychotic medication, leading to relevant morbidities and reduced compliance to pharmacotherapy. Recently, an association has been reported between a single nucleotide polymorphism (rs1455832) of the roundabout axon guidance r

  5. Cognitive effects of atypical antipsychotic drugs in first-episode drug-na?ve schizophrenic patients

    Institute of Scientific and Technical Information of China (English)

    Juan Wang; Maorong Hu; Xiaofeng Guo; Renrong Wu; Lehua Li; Jingping Zhao

    2013-01-01

    Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-na?ve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.

  6. Cost prediction of antipsychotic medication of psychiatric disorder using artificial neural network model

    Directory of Open Access Journals (Sweden)

    Arash Mirabzadeh

    2013-01-01

    Full Text Available Background: Antipsychotic monotherapy or polypharmacy (concurrent use of two or more antipsychotics are used for treating patients with psychiatric disorders (PDs. Usually, antipsychotic monotherapy has a lower cost than polypharmacy. This study aimed to predict the cost of antipsychotic medications (AM of psychiatric patients in Iran. Materials and Methods: For this purpose, 790 patients with PDs who were discharged between June and September 2010 were selected from Razi Psychiatric Hospital, Tehran, Iran. For cost prediction of AM of PD, neural network (NN and multiple linear regression (MLR models were used. Analysis of data was performed with R 2.15.1 software. Results: Mean ± standard deviation (SD of the duration of hospitalization (days in patients who were on monotherapy and polypharmacy was 31.19 ± 15.55 and 36.69 ± 15.93, respectively (P < 0.001. Mean and median costs of medication for monotherapy (n = 507 were $8.25 and $6.23 and for polypharmacy (n =192 were $13.30 and $9.48, respectively (P = 0.001. The important variables for cost prediction of AM were duration of hospitalization, type of treatment, and type of psychiatric ward in the MLR model, and duration of hospitalization, type of diagnosed disorder, type of treatment, age, Chlorpromazine dosage, and duration of disorder in the NN model. Conclusion: Our findings showed that the artificial NN (ANN model can be used as a flexible model for cost prediction of AM.

  7. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ) : preliminary evidence for reliability and validity

    NARCIS (Netherlands)

    de Boer, Marrit K; Castelein, Stynke; Bous, Johan; van den Heuvel, Edwin R; Wiersma, Durk; Schoevers, Robert A; Knegtering, Henderikus

    2013-01-01

    The aim of this study is to describe the psychometric properties of the Antipsychotics and Sexual Functioning Questionnaire (ASFQ). Internal reliability, test-retest reliability, inter-rater reliability, validity and sensitivity to change were calculated in a sample of 30 patients with schizophrenia

  8. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ) : Preliminary evidence for reliability and validity

    NARCIS (Netherlands)

    de Boer, M.K.; Castelein, Stynke; Bous, Johan; van den Heuvel, Edwin R.; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus

    2013-01-01

    The aim of this study is to describe the psychometric properties of the Antipsychotics and Sexual Functioning Questionnaire (ASFQ). Internal reliability, test-retest reliability, inter-rater reliability, validity and sensitivity to change were calculated in a sample of 30 patients with schizophrenia

  9. Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?

    NARCIS (Netherlands)

    Knegtering, Henderikus; van den Bosch, Rob; Castelein, Stynke; Bruggeman, Richard; Sytema, Sjoerd; van Os, Jim

    2008-01-01

    Objective: To assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. Method: A large sample (n = 264) of patients treated for 6 weeks with protactin-raising and prolactin-sparing

  10. Postprandial prolactin suppression appears absent in antipsychotic-treated male patients

    DEFF Research Database (Denmark)

    Coello, Klara; Broberg, Brian V; Bak, Nikolaj;

    2015-01-01

    INTRODUCTION: Hyperprolactinemia is a common side-effect of antipsychotic treatment. Antipsychotics and hyperprolactinemia are both considered risk factors of metabolic disturbances and diabetes. Investigations on prolactin response to meal ingestion in antipsychotic-treated patients are missing...... circumference (96.4, SD 13.0 vs. 96.7, SD 11.9 cm). Serum-prolactin was measured in the morning and 90 min after ingestion of a standardized liquid meal (2268 kJ). RESULTS: Fasting prolactin levels varied considerably, and mean fasting prolactin levels did not significantly differ between patients and controls...... (12.33, SD 11.58 vs. 10.06, SD 8.67 ng/ml, p = 0.623). In the controls, postprandial serum prolactin was significantly reduced (Δ -2.53, SD 9.75 ng/ml, p = 0.016). In antipsychotic-treated patients postprandial serum prolactin tended to increase (Δ 2.62, SD 10.96 ng/ml, p = 0.081). Analyses...

  11. Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study.

    Science.gov (United States)

    Park, Young-Min; Lee, Seung-Hwan; Lee, Bun-Hee; Lee, Kyu Young; Lee, Kye-Seong; Kang, Seung-Gul; Lee, Hwa-Young; Kim, Won

    2016-05-30

    The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (phyperprolactinemia and macroprolactinemia in psychiatric patients. PMID:27010188

  12. Use-Dependent Inhibition of Synaptic Transmission by the Secretion of Intravesicularly Accumulated Antipsychotic Drugs

    DEFF Research Database (Denmark)

    Tischbirek, Carsten H.; Wenzel, Eva M.; Zheng, Fang;

    2012-01-01

    Tischbirek et al. find that weak-base antipsychotic drugs are accumulated in synaptic vesicles and are secreted upon exocytosis, leading to increased extracellular drug concentrations following neuronal activity. The secretion of the drugs in turn inhibits synaptic transmission in a use-dependent...

  13. Prevalence of Antipsychotic Polypharmacy and Associated Factors among Outpatients with Schizophrenia Attending Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Siranesh Tesfaye

    2016-01-01

    Full Text Available Background. Despite recommendations by guidelines to avoid combinations of antipsychotics unless after multiple trials of antipsychotic monotherapy, it is quite a common practice to use combinations. This practice leads to unnecessary expenses and exposes the patient to severe drug adverse effects. Methods. An institution based cross-sectional study was conducted from April to May 2014. Systematic random sampling technique was used to select 423 study subjects. Logistic regression analysis was conducted to identify associated factors of antipsychotic polypharmacy among schizophrenia outpatients. Result. The overall prevalence of antipsychotic polypharmacy was found to be 28.2%. Extra pyramidal side effects (AOR = 2.80; 95% CI: 1.38, 5.71, repeated psychiatric hospitalization (AOR = 2.83; 95% CI: 1.45, 5.50, history of substance use (AOR = 2.82; 95% CI: 1.36, 5.88, longer duration of treatment (AOR = 2.10; 95% CI: 1.14, 3.87, and drug nonadherence (AOR = 1.84; 95% CI: 1.14, 2.98 were found to be significantly associated with antipsychotic polypharmacy. Conclusion. Prevalence of antipsychotic polypharmacy was found to be high among the current study participants. Individuals who had extra pyramidal side effects, admission, substance use, duration of treatment, and drug nonadherence were associated with antipsychotic polypharmacy.

  14. Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation.

    Directory of Open Access Journals (Sweden)

    Feng Mei

    Full Text Available Quetiapine (Que, a commonly used atypical antipsychotic drug (APD, can prevent myelin from breakdown without immune attack. Multiple sclerosis (MS, an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells. In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE, a mouse model for MS. Que treatment was initiated on the onset of MOG(35-55 peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4(+/CD8(+ populations and the proliferation of effector T cells (CD4(+CD25(- in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4(+/CD8(+ T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4(+/CD8(+ T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG(35-55 or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4(+CD25(- isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.

  15. How pressure is applied in shared decisions about antipsychotic medication: a conversation analytic study of psychiatric outpatient consultations.

    Science.gov (United States)

    Quirk, Alan; Chaplin, Rob; Lelliott, Paul; Seale, Clive

    2012-01-01

    The professional identity of psychiatry depends on it being regarded as one amongst many medical specialties and sharing ideals of good practice with other specialties, an important marker of which is the achievement of shared decision-making and avoiding a reputation for being purely agents of social control. Yet the interactions involved in trying to achieve shared decision-making are relatively unexplored in psychiatry. This study analyses audiotapes of 92 outpatient consultations involving nine consultant psychiatrists focusing on how pressure is applied in shared decisions about antipsychotic medication. Detailed conversation analysis reveals that some shared decisions are considerably more pressured than others. At one end of a spectrum of pressure are pressured shared decisions, characterised by an escalating cycle of pressure and resistance from which it is difficult to exit without someone losing face. In the middle are directed decisions, where the patient cooperates with being diplomatically steered by the psychiatrist. At the other extreme are open decisions where the patient is allowed to decide, with the psychiatrist exerting little or no pressure. Directed and open decisions occurred most frequently; pressured decisions were rarer. Patient risk did not appear to influence the degree of pressure applied in these outpatient consultations. PMID:21812791

  16. 新型抗精神病药:阿塞那平%A new type of antipsychotic drug: asenapine

    Institute of Scientific and Technical Information of China (English)

    王娟; 李华芳

    2011-01-01

    阿塞那平(asenapine)是一种新型非典型抗精神病药物,为5-HT受体、α-肾上腺素受体、多巴胺D受体及组胺H受体的拮抗药,对M胆碱受体没有亲和力.阿塞那平主要用于治疗成人的急性精神分裂症,以及双相情感障碍Ⅰ型的急性躁狂发作或混合性发作(伴/不伴精神病性症状).现有资料提示该药具有良好的有效性和安全性,但仍需要长期使用的资料积累.%Asenapine as a new atypical antipsychotic agent is an antagonist of serotonin 5-HT, α-adrenergic, dopamine D and histamine H receptors, and displays very low affinities for muscarinic M receptor. Asenapine has been approved for the acute treatment of schizophrenia in adults and the acute treatment of manic or mixed episodes associated with bipolar I disorder, with or without psychotic features, in adults. Although the present clinical data show that it is effective and safe, further studies for long term observation are necessary.

  17. SYNTHESIS, COMPUTATIONAL STUDY AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF 2-[4-(2-CHLOROBENZYL/BENZOYL SUBSTITUTED PIPERAZIN-1-YL]-N-PHENYLACETAMIDE: POTENTIAL ANTIPSYCHOTICS

    Directory of Open Access Journals (Sweden)

    Tomar Amita

    2011-06-01

    Full Text Available Benzyl and benzoyl substituted acetamides have been synthesized and evaluated as potential antipsychotic agents. The target compounds (4a-b were prepared by reaction of substituted anilines with chloroacetylchloride which further treated with 2-chlorobenzyl or 2-chlorobenzoyl piperazine in presence of potassium carbonate and potassium iodide as catalyst in acetonitrile. The structures of the target compounds (4a-b were characterized on the basis of their M.P., TLC, IR and 1H-NMR data. Computational studies of target compounds (4a-b were carried out by using software programs. The target compounds showed good similarity with respect to standard drugs. The target compounds (4a-b showed inhibition of 5-HTP induced head twitches behavior and low induction of catalepsy in mice.

  18. Post-stroke mortality, stroke severity, and preadmission antipsychotic medicine use--a population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Anders Prior

    Full Text Available BACKGROUND AND PURPOSE: It has been suggested that antipsychotic medication may be neuroprotective and may reduce post-stroke mortality, but studies are few and ambiguous. We aimed to investigate the post-stroke effects of preadmission antipsychotic use. METHODS: We conducted a nationwide, population-based cohort study of 81,143 persons admitted with stroke in Denmark from 2003-2010. Using Danish health care databases, we extracted data on preadmission use of antipsychotics and confounding factors. We examined the association between current, former, and never use of antipsychotics and stroke severity, length of hospital stay, and 30-day post-stroke mortality using logistic regression analysis, survival analysis, and propensity score matching. RESULTS: Current users of antipsychotics had a higher risk of severe or very severe stroke on The Scandinavian Stroke Scale than never users of antipsychotics (adjusted odds ratios, 1.43; 95% CI, 1.29-1.58. Current users were less likely to be discharged from hospital within 30 days of admission than never users (probability of non-discharge, 27.0% vs. 21.9%. Antipsychotics was associated with an increased 30-day post-stroke mortality among current users (adjusted mortality rate ratios, 1.42; 95% CI, 1.29-1.55, but not among former users (adjusted mortality rate ratios, 1.05; 95% CI, 0.98-1.14. CONCLUSIONS: Preadmission use of antipsychotics was associated with a higher risk of severe stroke, a longer duration of hospital stay, and a higher post-stroke mortality, even after adjustment for known confounders. Antipsychotics play an important role in the treatment of many psychiatric conditions, but our findings do not support the hypothesis that they reduce stroke severity or post-stroke mortality.

  19. Mental health pharmacists views on shared decision-making for antipsychotics in serious mental illness.

    Science.gov (United States)

    Younas, Mediha; Bradley, Eleanor; Holmes, Nikki; Sud, Dolly; Maidment, Ian D

    2016-10-01

    Background People diagnosed with serious mental illnesses (SMIs) such as schizophrenia and bipolar affective disorder are frequently treated with antipsychotics. National guidance advises the use of shared decision-making (SDM) in antipsychotic prescribing. There is currently little data on the opinions of health professionals on the role of SDM. Objective To explore the views and experiences of UK mental health pharmacists regarding the use of SDM in antipsychotic prescribing in people diagnosed with SMI. Setting The study was conducted by interviewing secondary care mental health pharmacists in the UK to obtain qualitative data. Methods Semi-structured interviews were recorded. An inductive thematic analysis was conducted using the method of constant comparison. Main outcome measure Themes evolving from mental health pharmacists on SDM in relation to antipsychotic prescribing in people with SMI. Results Thirteen mental health pharmacists were interviewed. SDM was perceived to be linked to positive clinical outcomes including adherence, service user satisfaction and improved therapeutic relations. Despite more prescribers and service users supporting SDM, it was not seen as being practised as widely as it could be; this was attributed to a number of barriers, most predominantly issues surrounding service user's lacking capacity to engage in SDM and time pressures on clinical staff. The need for greater effort to work around the issues, engage service users and adopt a more inter-professional approach was conveyed. Conclusion The mental health pharmacists support SDM for antipsychotic prescribing, believing that it improves outcomes. However, barriers are seen to limit implementation. More research is needed into overcoming the barriers and measuring the benefits of SDM, along with exploring a more inter-professional approach to SDM. PMID:27450504

  20. Antipsychotics reverse abnormal EEG complexity in drug-naïve schizophrenia: A multiscale entropy analysis

    Science.gov (United States)

    Takahashi, Tetsuya; Cho, Raymond Y.; Mizuno, Tomoyuki; Kikuchi, Mitsuru; Murata, Tetsuhito; Takahashi, Koichi; Wada, Yuji

    2010-01-01

    Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring dynamical complexity in physiological systems over a range of temporal scales. To evaluate this analytic approach as an aid to elucidating the pathophysiologic mechanisms in schizophrenia, we examined MSE in EEG activity in drug-naïve schizophrenia subjects pre- and post-treatment with antipsychotics in comparison with traditional EEG analysis. We recorded eyes-closed resting state EEG from frontal, temporal, parietal and occipital regions in drug-naïve 22 schizophrenia and 24 age-matched healthy control subjects. Fifteen patients were re-evaluated within 2–8 weeks after the initiation of antipsychotic treatment. For each participant, MSE was calculated on one continuous 60 second epoch for each experimental session. Schizophrenia subjects showed significantly higher complexity at higher time scales (lower frequencies), than that of healthy controls in fronto-centro-temporal, but not in parieto-occipital regions. Post-treatment, this higher complexity decreased to healthy control subject levels selectively in fronto-central regions, while the increased complexity in temporal sites remained higher. Comparative power analysis identified spectral slowing in frontal regions in pre-treatment schizophrenia subjects, consistent with previous findings, whereas no antipsychotic treatment effect was observed. In summary, multiscale entropy measures identified abnormal dynamical EEG signal complexity in anterior brain areas in schizophrenia that normalized selectively in fronto-central areas with antipsychotic treatment. These findings show that entropy-based analytic methods may serve as a novel approach for characterizing and understanding abnormal cortical dynamics in schizophrenia, and elucidating the therapeutic mechanisms of antipsychotics. PMID:20149880

  1. Antipsychotics reverse abnormal EEG complexity in drug-naive schizophrenia: a multiscale entropy analysis.

    Science.gov (United States)

    Takahashi, Tetsuya; Cho, Raymond Y; Mizuno, Tomoyuki; Kikuchi, Mitsuru; Murata, Tetsuhito; Takahashi, Koichi; Wada, Yuji

    2010-05-15

    Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring dynamical complexity in physiological systems over a range of temporal scales. To evaluate this analytic approach as an aid to elucidating the pathophysiologic mechanisms in schizophrenia, we examined MSE in EEG activity in drug-naive schizophrenia subjects pre- and post-treatment with antipsychotics in comparison with traditional EEG analysis. We recorded eyes-closed resting-state EEG from frontal, temporal, parietal, and occipital regions in drug-naive 22 schizophrenia and 24 age-matched healthy control subjects. Fifteen patients were re-evaluated within 2-8 weeks after the initiation of antipsychotic treatment. For each participant, MSE was calculated on one continuous 60-s epoch for each experimental session. Schizophrenia subjects showed significantly higher complexity at higher time scales (lower frequencies) than did healthy controls in fronto-centro-temporal, but not in parieto-occipital regions. Post-treatment, this higher complexity decreased to healthy control subject levels selectively in fronto-central regions, while the increased complexity in temporal sites remained higher. Comparative power analysis identified spectral slowing in frontal regions in pre-treatment schizophrenia subjects, consistent with previous findings, whereas no antipsychotic treatment effect was observed. In summary, multiscale entropy measures identified abnormal dynamical EEG signal complexity in anterior brain areas in schizophrenia that normalized selectively in fronto-central areas with antipsychotic treatment. These findings show that entropy-based analytic methods may serve as a novel approach for characterizing and understanding abnormal cortical dynamics in schizophrenia and elucidating the therapeutic mechanisms of antipsychotics. PMID:20149880

  2. Curcumin Mitigates the Intracellular Lipid Deposit Induced by Antipsychotics In Vitro.

    Directory of Open Access Journals (Sweden)

    Alberto Canfrán-Duque

    Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, both inhibit cholesterol biosynthesis and impair the intracellular cholesterol trafficking, leading to lipid accumulation in the late endosome/lysosome compartment. In this study we examined if curcumin, a plant polyphenol that stimulates exosome release, can alleviate antipsychotic-induced intracellular lipid accumulation.HepG2 hepatocarcinoma cells were treated with antipsychotics or placebo and DiI-labelled LDL for 18 h and then exposed to curcumin for the last 2 h. Cells and media were collected separately and used for biochemical analyses, electron microscopy and immunocytochemistry. Exosomes were isolated from the incubation medium by ultracentrifugation.Curcumin treatment reduced the number of heterolysosomes and shifted their subcellular localization to the periphery, as revealed by electron microscopy, and stimulated the release of lysosomal β-hexosaminidase and exosome markers flotillin-2 and CD63 into the media. The presence of DiI in exosomes released by cells preloaded with DiI-LDL demonstrated the endolysosomal origin of the microvesicles. Furthermore, curcumin increased the secretion of cholesterol as well as LDL-derived DiI and [3H]-cholesterol, in association with a decrease of intracellular lipids. Thus, the disruption of lipid trafficking induced by FGAs or SGAs can be relieved by curcumin treatment. This polyphenol, however, did not mitigate the reduction of cholesterol esterification induced by antipsychotics.Curcumin stimulates exosome release to remove cholesterol (and presumably other lipids accumulated within the endolysosomal compartment, thereby normalizing intracellular lipid homeostasis. This action may help minimize the adverse metabolic effects of antipsychotic treatment, which should now be evaluated in clinical trials.

  3. Relationship between Dose, Drug Levels, and D2 Receptor Occupancy for the Atypical Antipsychotics Risperidone and Paliperidone

    OpenAIRE

    Muly, E.C.; Votaw, J. R.; Ritchie, J.; Howell, L.L.

    2012-01-01

    Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design. [18F]fallypride positron emission tomography scans were obtained on four different doses ...

  4. The utilization of antipsychotics in elderly inpatients of general hospital : clinical analysis%综合性医院老年住院患者抗精神病药物使用状况的临床分析

    Institute of Scientific and Technical Information of China (English)

    邢秋泓; 赵坤英; 解恒革

    2011-01-01

    Objective To study the utilization of antipsychotics and its potential effects on physiology and psychology in elderly inpatients of general hospital. Methods 280 inpatients ≥58y who were in the department of geriatrics in our hospital in November 2008 were investigated. Results Thirty-two(11. 4%) inpatients ≥80y received an antipsychotic drug,and 43. 8% of them took the drug for ≥12 months,56. 3% of them took the combination of hypnotics and sedatives. Most of the drugs were atypical antipsychotics. Dementia was the most frequently reported diagnoses a-mong the elderly inpatients using an antipsychotic agent(46. 9%). The main conditions for receiving antipsychotic treatment were the diagnosis of acute delirium or psychosis symptoms, depression and anxiety, and neuropsychiatric symptoms of dementia. Conclusions Dementia, delirium, depression and anxiety,and neuropsychiatric symptoms of dementia are the main causes of elderly inpatients in general hospital for using antipsychotics. Nearly two thirds of them use the combination of hypnotics and sedatives. The study findings suggest that there is a need to monitor antipsychotic drug use by elderly inpatients in general hospital in light of efficacy and safety of atypical agents.%目的 了解综合性医院老年住院患者抗精神病药物使用情况及其对生理心理的潜在影响.方法 选择2008年11月在我院老年病各科住院的、年龄≥58岁患者280例,随访2年,调查分析患者抗精神病药物的使用情况.结果 共32例惠者使用了抗精神病药物,年龄均≥80岁,绝大部分患者服用非经典抗精神病药物.痴呆患者占46.9%,痴呆是老年住院患者使用抗精神病药物的主要疾病.抗精神病药物的使用主要与急性谵妄或精神病性症状、焦虑抑郁、痴呆相关的精神行为症状等有关.43.8%的患者连续服用≥1年,56.3%的患者合用镇静催眠药.结论 痴呆、谵妄、焦虑抑郁症状是综合性医院老年住院

  5. Antibiotic Agents

    Science.gov (United States)

    ... either as public health or as non-public health antimicrobial agents. What is the difference between bacteriostats, sanitizers, disinfectants ... bacteria, however, there is considerable controversy surrounding their health benefits. The ... producing agents (Table of Antibacterials) have been used for many ...

  6. Paliperidone extended-release: does it have a place in antipsychotic therapy?

    Directory of Open Access Journals (Sweden)

    Carlos Schönfeldt-Lecuona

    2011-03-01

    Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

  7. Antipsychotic Medication in Children and Adolescents : A Descriptive Review of the Effects on Prolactin Level and Associated Side Effects

    NARCIS (Netherlands)

    Roke, Yvette; van Harten, Peter N.; Boot, Annemieke M.; Buitelaar, Jan K.

    2009-01-01

    Objective: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. Method: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine, clozapin

  8. Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report

    OpenAIRE

    Langan Julie; Martin Daniel; Shajahan Polash; Smith Daniel J

    2012-01-01

    Abstract Background “Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifica...

  9. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

    OpenAIRE

    Ye W; Ascher-Svanum H; Flynn JA; Tanji Y; Takahashi M

    2012-01-01

    Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study ...

  10. Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists

    OpenAIRE

    Pisano, Simone; Catone, Gennaro; Veltri, Stefania; Lanzara, Valentina; Pozzi, Marco; Clementi, Emilio; Iuliano, Raffaella; Riccio, Maria Pia; Radice, Sonia; Molteni, Massimo; Capuano, Annalisa; Gritti, Antonella; Coppola, Giangennaro; Milone, Annarita; Bravaccio, Carmela

    2016-01-01

    During the past decade, a substantial increase in the use of second generation antipsychotics (SGAs) has occurred for a number of juvenile psychiatric disorders, often as off-label prescriptions. Although they were thought to be safer than older, first generation antipsychotics, mainly due to a lower risk of neurological adverse reactions, recent studies have raised significant concerns regarding their safety regarding metabolic, endocrinological and cardiovascular side effects. Aim of this p...

  11. Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.

    Science.gov (United States)

    Kim, Il Hwan; Rossi, Mark A; Aryal, Dipendra K; Racz, Bence; Kim, Namsoo; Uezu, Akiyoshi; Wang, Fan; Wetsel, William C; Weinberg, Richard J; Yin, Henry; Soderling, Scott H

    2015-06-01

    Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, the actin-related protein 2/3 complex (Arp2/3), we report here a molecular mechanism that unexpectedly reveals the inter-relationship of progressive spine pruning, elevated frontal cortical excitation of pyramidal neurons and striatal hyperdopaminergia in a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, this antipsychotic-responsive locomotion can be mimicked in wild-type mice by optogenetic activation of this circuit. Collectively these results reveal molecular and neural-circuit mechanisms, illustrating how diverse pathologies may converge to drive behaviors relevant to psychiatric disorders.

  12. The influence of antipsychotic therapy on the cognitive functions of schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Tybura, Piotr

    2013-07-01

    Full Text Available Aim: The aim of the present study was twofold: 1. to compare the efficacy of three antipsychotics (ziprasidone, olanzapine and perazine in schizophrenia 2. to compare the improvement in cognitive functioning between groups treated with the three different neuroleptics. Method: A total of 58 Caucasian patients diagnosed with paranoid schizophrenia were recruited into the study group. We used the Polish version of the CIDI (Composite International Diagnostic Interview to obtain ICD-10 diagnoses. The intensity of psychopathological symptoms was examined using the PANSS. The patients were randomly assigned to treatment with perazine, olanzapine or ziprasidone administered as monotherapy for 3 months. The treatment efficacy was measured as a change in the PANSS (Positive and Negative Syndrome Scale total score from baseline (T0 to 3 months (T1. The WCST (The Wisconsin Card Sorting Test was used to measure working memory and executive functions in the evaluated patients.Wilcoxon’s and Kruskal-Wallis tests were applied to compare changes in the PANSS scores between the treatment groups. To analyze the cognitive functions, Kruskal-Wallis test for the WCST parameters was used. Results: The three antipsychotics similarly reduced the total PANSS score. The WCST parameters in the 3 groups of examined patients using the Kruskal-Wallis test revealed some differences between the three administered antipsychotics. Conclusions: Results suggest that the short-term efficacy of the atypical (olanzapine, ziprasidone and typical (perazine antipsychotic drugs did not differ. Based on the analysis, a conclusion can be drawn that the three neuroleptics provided similar improvements in cognitive functioning.

  13. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    OpenAIRE

    Abhilasha Shete; Vibhor Kumar Jain; Bindu nee Giri Jain

    2010-01-01

    Tinospora cordifolia is reported to have CNS active principle and is used for thetreatment of various neurological disorders. Hence, the effect of aqueous ethanolicextract of Tinospora cordifolia was investigated for its putative antipsychotic activityusing amphetamine challenged mice model. Haloperidol (1 mg/kg i.p.) was administeredacutely to mice as standard drug. Control animals received vehicle (10% DMSO). The invivo receptor binding studies were carried out to correlate the antipsychoti...

  14. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    OpenAIRE

    Bindu nee Giri Jain; Vibhor Kumar Jain; Abhilasha Shete

    2010-01-01

    Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p.) was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO). The in vivo receptor binding studies were carried out to correlate the antipsy...

  15. Comparison of patients undergoing switching versus augmentation of antipsychotic medications during treatment for schizophrenia

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2012-03-01

    Full Text Available Haya Ascher-Svanum, Alan JM Brnabic, Anthony H Lawson, Bruce J Kinon, Virginia L Stauffer, Peter D Feldman, Katarina KelinLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USAAbstract: It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients’ clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0–14 days prior and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%. Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions–Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient’s worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians’ stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research

  16. Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.

    Science.gov (United States)

    Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro

    2015-11-01

    Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. PMID:26363311

  17. Antipsychotic mediated changes in CNTNAP3 gene expression in SK-N-SH cells

    OpenAIRE

    Pazos del Olmo, Cristina

    2015-01-01

    Introduction. Schizophrenia is one of the most common and severe psychotic disorders of all. A growing number of researchers understand the need of genetic studies to unravel the pathophysiological mechanisms of mental disorders and their treatments. In this sense, a recent research reported changes in the expression of 17 genes after antipsychotic treatment. Among these genes, ADAMTS2, CD177, CNTNAP3, ENTPD2, RFX2, and UNC45B were overexpressed in patients with schizophrenia. The expression ...

  18. Behavioral and neurobiological changes in C57BL/6 mouse exposed to cuprizone: effects of antipsychotics

    Directory of Open Access Journals (Sweden)

    Haiyun Xu

    2010-03-01

    Full Text Available Recent human studies suggest a role for altered oligodendrocytes in the pathophysiology of schizophrenia. Our recent animal study has reported some schizophrenia-like behaviors in mice exposed to cuprizone (Xu et al., 2009, a copper chelator that has been shown to selectively damage the white matter. This study was to explore mechanisms underlying the behavioral changes in cuprizone-exposed mice and to examine effects of the antipsychotics haloperidol, clozapine and quetiapine on the changes in the mice. Mice given cuprizone for 14 days showed a deficit in the prepulse inhibition of acoustic startle response and higher dopamine in the prefrontal cortex (PFC, which changes were not seen in mice given cuprizone plus antipsychotics. Mice given cuprizone for 21 days showed lower spontaneous alternations in Y-maze, which was not seen in mice treated with the antipsychotics. Mice given cuprizone for 28 days displayed less social interactions, which was not seen in mice given cuprizone plus clozapine/quetiapine, but was seen in mice given cuprizone plus haloperidol. Mice given cuprizone for 42 days showed myelin sheath loss and lower myelin basic protein in PFC, caudate putamen, and hippocampus. The white matter damage in PFC was attenuated in mice given cuprizone plus clozapine/haloperidol. But the white matter damage in caudate putamen and hippocampus was only attenuated by clozapine and quetiapine, not by haloperidol. These results help us to understand the behavioral changes and provide experimental evidence for the protective effects of antipsychotics on white matter damage in cuprizone-exposed mice.

  19. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B.; Pettibone, Jeffrey R; Berke, Joshua D.

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  20. Antipsychotics reverse abnormal EEG complexity in drug-naïve schizophrenia: A multiscale entropy analysis

    OpenAIRE

    Takahashi, Tetsuya; Cho, Raymond Y; Mizuno, Tomoyuki; Kikuchi, Mitsuru; Murata, Tetsuhito; Takahashi, Koichi; Wada, Yuji

    2010-01-01

    Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring dynamical complexity in physiological systems over a range of temporal scales. To evaluate this analytic approach as an aid to elucidating the pathophysiologic mechanisms in schizophrenia, we examined MSE in EEG activity in drug-naïve schizophrenia subjects pre- and post-treatment with antipsychotics in comparison with traditional EEG analysis. We recorded eyes-closed resting state EEG from frontal, temporal, pa...

  1. Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk.

    Science.gov (United States)

    Borg, Linda; Julkunen, Anna; Rørbaek Madsen, Kristian; Strøm, Thomas; Toft, Palle

    2016-07-01

    It is often advised that patients who have ingested an overdose of antidepressants (AD) or antipsychotics (AP) are monitored with continuous ECG for minimum of 12-24 hr. These patients are often observed in an ICU. Our aim was to identify the number of patients with AD and/or AP overdose without adverse signs at hospital admission that turned out to need intensive care treatment. The effect of the antidepressants overdose risk assessment (ADORA) system was evaluated in patients with antidepressant as well as antipsychotic overdose. Our hypothesis was that patients with low ADORA do not need intensive care treatment. This retrospective study was conducted in adult patients admitted to the ICU at Odense University Hospital after an overdose with AP and/or AD between 1 January 2009 and 1 September 2014. Patients with predefined adverse signs in the emergency department were excluded due to obvious need of intensive care. Of the 157 patients included, 12 patients (8%) developed events during the ICU stay. Only 3 patients received intubation, vasoactive drugs and/or dialysis. None developed ventricular dysrhythmias. There were no fatalities. All the patients with low-risk assessment by ADORA within the first 6 hr did not develop events within the first 24 hr after hospital admission. The vast majority of patients with AD and/or AP overdose and no adverse signs at admission did not require intensive care treatment. Low-risk ADORA identified patients with antidepressant as well as antipsychotic overdose who would not require initial intensive care treatment. This is the first time the ADORA system has been evaluated in patients with antidepressant as well as antipsychotic overdose. PMID:26663682

  2. Successful Use of Add - On Topiramate for Antipsychotic - Induced Weight Gain

    OpenAIRE

    Venkataram Shivakumar; Naveen Jayaram; Rao, Naren P.; Ganesan Venkatasubramanian

    2012-01-01

    Antipsychotic induced weight gain is the most common and distressing side effect. This also affects the compliance toward the treatment and hence the prognosis. Non - pharmacological interventions such as exercise and diet modifications alone might not be sufficient most of the times; also ensuring compliance toward this is difficult in patients with psychiatric illness. So, the role of weight - reducing drugs become important. In this case report, we describe the use of low - dose topiramate...

  3. Paliperidone extended-release: does it have a place in antipsychotic therapy?

    Science.gov (United States)

    Gahr, Maximilian; Kölle, Markus A; Schönfeldt-Lecuona, Carlos; Lepping, Peter; Freudenmann, Roland W

    2011-01-01

    Paliperidone (9-hydroxy-risperidone), the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER), and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug-drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially higher costs as compared with risperidone. However, in terms of pharmacology, the available evidence cautiously suggests a place for PER in modern antipsychotic therapy. PMID:21448450

  4. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    OpenAIRE

    Montemagni C; Frieri T; Rocca P

    2016-01-01

    Cristiana Montemagni,1,2 Tiziana Frieri,1,2 Paola Rocca1,2 1Department of Neuroscience, Unit of Psychiatry, University of Turin, 2Department of Mental Health, Azienda Sanitaria Locale (ASL) Torino 1 (TO1), Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Turin, Italy Abstract: Long-acting injectable antipsychotics (LAIs) were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-gen...

  5. Animal models for predicting the efficacy and side effects of antipsychotic drugs

    OpenAIRE

    Pedro H. Gobira; Jivago Ropke; Aguiar, Daniele C; Jose A.S. Crippa; Moreira, Fabricio A.

    2013-01-01

    The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side ...

  6. Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication.

    Directory of Open Access Journals (Sweden)

    Juha Veijola

    Full Text Available Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain. The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain. In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

  7. Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity, Cognition and Antipsychotic Medication

    Science.gov (United States)

    Veijola, Juha; Guo, Joyce Y.; Moilanen, Jani S.; Jääskeläinen, Erika; Miettunen, Jouko; Kyllönen, Merja; Haapea, Marianne; Huhtaniska, Sanna; Alaräisänen, Antti; Mäki, Pirjo; Kiviniemi, Vesa; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka J.; Tanskanen, Päivikki; Tervonen, Osmo; Wink, Alle-Meije; Kehagia, Angie; Suckling, John; Kobayashi, Hiroyuki; Barnett, Jennifer H.; Barnes, Anna; Koponen, Hannu J.; Jones, Peter B.; Isohanni, Matti; Murray, Graham K.

    2014-01-01

    Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions. PMID:25036617

  8. Inhibition of mouse brown adipocyte differentiation by second-generation antipsychotics

    OpenAIRE

    Oh, Jee-Eun; Cho, Yoon Mi; Kwak, Su-Nam; Kim, Jae-Hyun; Lee, Kyung Won; Jung, Hyosan; Jeong, Seong-Whan; Kwon, Oh-Joo

    2012-01-01

    Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differe...

  9. Two Sudden and Unexpected Deaths of Patients with Schizophrenia Associated with Intramuscular Injections of Antipsychotics and Practice Guidelines to Limit the Use of High Doses of Intramuscular Antipsychotics.

    Science.gov (United States)

    Wahidi, Nasratullah; Johnson, Katie M; Brenzel, Allen; de Leon, Jose

    2016-01-01

    Intravenous haloperidol has been associated with torsades de pointes (TdP). These two sudden deaths were probable adverse drug reactions (ADRs) following intramuscular (IM) antipsychotics. The autopsies described lack of heart pathology and were highly compatible with the possibility of TdP in the absence of risk factors other than the accumulation of antipsychotics with a high serum peak after the last injection, leading to death within hours. The first case was a 27-year-old African-American male with schizophrenia but no medical issues. His death was probably caused by repeated IM haloperidol injections of 10 mg (totaling 35 mg in 2 days). The second case involves a 42-year-old African-American female with metabolic syndrome. Her probable cause of death was the last ziprasidone IM injection of 20 mg in addition to (1) three extra haloperidol doses (2 hours before the ziprasidone injection, 5 mg oral haloperidol; approximately 21 hours earlier, 5 mg oral haloperidol; and 2 days prior, one 10 mg IM haloperidol injection), (2) 10 mg/day of scheduled oral haloperidol for 6 days before death, and (3) a long-acting paliperidone injection of 156 mg 18 days before death. The study of haloperidol glucuronidation and its impairment in some African-Americans is urgently recommended. PMID:27597919

  10. Differential effect of antipsychotics on place navigation of rats in the Morris water maze. A comparative study between novel and reference antipsychotics.

    Science.gov (United States)

    Skarsfeldt, T

    1996-03-01

    A group of novel neuroleptics (e.g. olanzapine, seroquel, sertindole and ziprasidone) and already marketed compounds (e.g. clozapine, haloperidol and risperidone) were tested for acute effect on spatial learning and memory in Morris' water maze task. Young rats were trained for 4 consecutive days (three trials/day) to find a platform situated beneath the water surface. Two compounds, sertindole and seroquel, were without effect on spatial performance, whereas clozapine impaired performance on the first 2 test days but showed no effect compared to the controls on the last 2 test days. Ziprasidone and olanzapine markedly impaired spatial memory without affecting motor function (measured by the swimming speed). Risperidone and haloperidol also impaired performance but in addition both compounds significantly lowered the swimming speed. The present study indicates that several of the compounds impair spatial learning in Morris water maze. This might be of clinical importance in the treatment of schizophrenics, as many of these patients already show severe cognitive deficits. Therefore, certain antipsychotics could worsen the preexisting memory deficits in schizophrenic patients and this aspect should be considered before antipsychotic treatment.

  11. Influence of Antipsychotic and Anticholinergic Loads on Cognitive Functions in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Michael Rehse

    2016-01-01

    Full Text Available Many patients with schizophrenia show cognitive impairment. There is evidence that, beyond a certain dose of antipsychotic medication, the antipsychotic daily dose (ADD may impair cognitive performance. Parallel to their D2 receptor antagonism, many antipsychotics show a significant binding affinity to cholinergic muscarinic receptors. Pharmacological treatment with a high anticholinergic daily dose (CDD significantly impairs attention and memory performance. To examine the relationships between individual cognitive performance and ADD and/or CDD, we conducted a retrospective record-based analysis of a sample of n=104 in patients with a diagnosis of schizophrenia, all of whom had completed a comprehensive neuropsychological test battery. To calculate the individual ADD and CDD, the medication at the time of testing was converted according to equivalence models. After extracting five principal cognitive components, we examined the impact of ADD and CDD on cognitive performance in the medicated sample and subgroups using multiple regression analysis. Finally, locally weighted scatterplot smoothing (Loess was applied to further explore the course of cognitive performance under increasing dosage. Results showed significant negative effects of ADD on performance in tests of information processing speed and verbal memory. No effects were found for CDD. The potential neuropsychopharmacological and clinical implications are discussed.

  12. [Analysis of the cardiac side effects of antipsychotics: Japanese Adverse Drug Event Report Database (JADER)].

    Science.gov (United States)

    Ikeno, Takashi; Okumara, Yasuyuki; Kugiyama, Kiyotaka; Ito, Hiroto

    2013-08-01

    We analyzed the cases of side effects due to antipsychotics reported to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) from Jan. 2004 to Dec. 2012. We used the Japanese Adverse Drug Event Report Database (JADER) and analyzed 136 of 216,945 cases using the defined terms. We also checked the cardiac adverse effects listed in the package inserts of the antipsychotics involved. We found cases of Ikr blockade resulting in sudden death (49 cases), electrocardiogram QT prolonged (29 cases), torsade de pointes (TdP, 19 cases), ventricular fibrillation (VF, 10 cases). M2 receptor blockade was observed in tachycardia (8 cases) and sinus tachycardia (3 cases). Calmodulin blockade was involved in reported cardiomyopathy (3 cases) and myocarditis (1 case). Multiple adverse events were reported simultaneously in 14 cases. Our search of package inserts revealed warnings regarding electrocardiogram QT prolongation (24 drugs), tachycardia (23), sudden death (18), TdP (14), VF (3), myocarditis (1) and cardiomyopathy (1). We suggest that when an antipsychotic is prescribed, the patient should be monitored regularly with ECG, blood tests, and/or biochemical tests to avoid adverse cardiac effects. PMID:25069255

  13. Preliminary examination of microRNA expression profiling in bipolar disorder I patients during antipsychotic treatment.

    Science.gov (United States)

    Lim, Chor Hong; Zainal, Nor Zuraida; Kanagasundram, Sharmilla; Zain, Shamsul Mohd; Mohamed, Zahurin

    2016-09-01

    Although major progress has been achieved in research and development of antipsychotic medications for bipolar disorder (BPD), knowledge of the molecular mechanisms underlying this disorder and the action of atypical antipsychotics remains incomplete. The levels of microRNAs (miRNAs)-small non-coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity-are frequently altered in psychiatric disorders. This study aimed to examine changes in miRNA expression in bipolar mania patients after treatment with asenapine and risperidone. Using a miRNA microarray, we analyzed miRNA expression in the blood of 10 bipolar mania patients following 12 weeks of treatment with asenapine or risperidone. Selected miRNAs were validated by using real-time PCR. A total of 16 miRNAs were differentially expressed after treatment in the asenapine group, 14 of which were significantly upregulated and the other two significantly downregulated. However, all three differentially expressed miRNAs in the risperidone group were downregulated. MiRNA target gene prediction and gene ontology analysis revealed significant enrichment for pathways associated with immune system response and regulation of programmed cell death and transcription. Our results suggest that candidate miRNAs may be involved in the mechanism of action of both antipsychotics in bipolar mania. © 2016 Wiley Periodicals, Inc. PMID:27177356

  14. Improving physical health for people taking antipsychotic medication in the Community Learning Disabilities Service.

    Science.gov (United States)

    Hall, Ian; Shah, Amar

    2016-01-01

    Adherence with antipsychotic monitoring guidelines is notoriously low nationally. Without active monitoring and measures to improve metabolic abnormalities, more patients may develop related morbidity and mortality. An audit highlighted antipsychotic monitoring in this learning disability service in London did not match guideline recommendations. People with intellectual disability also experience health inequalities. Psychiatrists are well placed to provide advice and assistance that is suitable for those with complex communication, behaviour, and social needs. The QI team tested ideas to increase rates of antipsychotic reviews. The focus was the follow up monitoring of all universal measures recommended by NICE 2014, collected at 2-weekly intervals. We trialled interventions in four broad categories; Intervention 1: to make monitoring more structured and planned; Intervention 2: to increase staff and patient awareness of healthy eating and exercise programs; Intervention 3: to increase the collection of diet and exercise histories from patients; Intervention 4: to improve the uptake of blood tests. The interventions created an improvement in monitoring. There are lessons in the methodology for others carrying out similar projects. PMID:27335645

  15. Metacognitive Therapy (MCT+ in patients with psychosis not receiving antipsychotic medication: A case study

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    Ryan P. Balzan

    2015-07-01

    Full Text Available Background: Psychotherapies for psychosis typically aim to develop an awareness of the implausible content of a delusion or target the underlying cognitive biases (i.e., problematic thinking styles, such as hasty decisions and illusory control that foster and maintain delusional beliefs. A recently designed individual-based treatment entitled metacognitive therapy (MCT+ combines these two approaches. Emerging evidence suggests individualised MCT+, when used concurrently with antipsychotic medication, may be an effective psychological treatment for reducing delusional symptoms. However, it remains to be tested whether MCT+ can be effective in patients with active delusions who are not currently receiving psychotropic drugs. Method: We present two cases (one patient with schizophrenia and the other with delusional disorder experiencing active delusions who underwent four-weeks of intensive MCT+, without concurrent antipsychotic medication (minimum 6-months unmedicated. Baseline and 6-week follow-up data are presented on a variety of measures assessing delusion symptom severity (i.e., PANSS, PSYRATS, SAPS, clinical insight, and cognitive bias propensity. Results: After 4-weeks of MCT+, both patients showed substantial reduction in delusional symptoms, reported improved clinical insight, and were less prone to making illusory correlations. Conclusions: The presented case studies provide preliminary evidence for the feasibility of MCT+ in treating patients not taking, or resistant to, antipsychotic medication.

  16. First- and second-generation antipsychotic drug treatment and subcortical brain morphology in schizophrenia.

    Science.gov (United States)

    Jørgensen, Kjetil N; Nesvåg, Ragnar; Gunleiksrud, Sindre; Raballo, Andrea; Jönsson, Erik G; Agartz, Ingrid

    2016-08-01

    Antipsychotic medication may influence brain structure, but to what extent effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) differ is still not clear. Here we aimed to disentangle the effects of FGA and SGA on variation in volumes of subcortical structures in patients with long-term treated schizophrenia. Magnetic resonance images were obtained from 95 patients with schizophrenia and 106 healthy control subjects. Among the patients, 40 received only FGA and 42 received only SGA. FreeSurfer 5.3.0 was used to obtain volumes of 27 subcortical structures as well as total brain volume and estimated intracranial volume. Findings of reduced total brain volume, enlarged ventricular volume and reduced hippocampal volume bilaterally among patients were replicated, largely independent of medication class. In the basal ganglia, FGA users had larger putamen bilaterally and right caudate volume compared to healthy controls, and the right putamen was significantly larger than among SGA users. FGA and SGA users had similar and larger globus pallidus volumes compared to healthy controls. Post hoc analyses revealed that the difference between FGA and SGA could be attributed to smaller volumes in the clozapine users specifically. We therefore conclude that basal ganglia volume enlargements are not specific to FGA. PMID:26547434

  17. Cinnarizine has an atypical antipsychotic profile in animal models of psychosis.

    Science.gov (United States)

    Dall'Igna, Oscar P; Tort, Adriano B L; Souza, Diogo O; Lara, Diogo R

    2005-07-01

    Cinnarizine, a drug known as a calcium channel blocker, is currently used for the treatment of migraine and vertigo. Induction of extrapyramidal signs by cinnarizine has been reported in the elderly, which is related to its moderate antagonistic properties at dopamine D2 receptors, resembling the mechanism of action of most antipsychotic drugs. Despite this effect, cinnarizine has never been tested as a putative antipsychotic drug. Here we evaluate the potential effect of cinnarizine in two pharmacological models of psychosis, namely amphetamine- and MK-801-induced hyperlocomotion, as well as its ability to induce catalepsy. Cinnarizine significantly counteracted MK-801 (0.25 mg/kg) and amphetamine (5mg/kg) locomotor effects at doses as low as 20mg/kg, having no incremental effect at 60 or 180 mg/kg. Regarding side-effects, cinnarizine induced no catalepsy in mice at the effective dose of 20 mg/kg, inducing only mild catalepsy at the doses of 60 and 180 mg/kg. Based on these results and on the antagonist effect of cinnarizine on dopamine D2 receptors, we suggest that it has a potential antipsychotic effect with an atypical profile that should be evaluated clinically. PMID:15982988

  18. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    Directory of Open Access Journals (Sweden)

    Abhilasha Shete

    2010-03-01

    Full Text Available Tinospora cordifolia is reported to have CNS active principle and is used for thetreatment of various neurological disorders. Hence, the effect of aqueous ethanolicextract of Tinospora cordifolia was investigated for its putative antipsychotic activityusing amphetamine challenged mice model. Haloperidol (1 mg/kg i.p. was administeredacutely to mice as standard drug. Control animals received vehicle (10% DMSO. The invivo receptor binding studies were carried out to correlate the antipsychotic activity ofthe extract with its capacity to bind to the DAD2 receptor. The results in SLA showed thatthe hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamineinduced hyperactivity in mice when compared to standard. Extract alone treated group ata dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity whencompared to the control. The plant extract increased the DAD2 receptor binding in a dosedependent manner in treated mice compared to the control group.

  19. Antipsychotic activity of aqueous ethanolic extract of Tinospora Cordifolia in amphetamine challenged mice model

    Directory of Open Access Journals (Sweden)

    Bindu nee Giri Jain

    2010-01-01

    Full Text Available Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p. was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO. The in vivo receptor binding studies were carried out to correlate the antipsychotic activity of the extract with its capacity to bind to the DAD2 receptor. The results in SLA showed that the hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250 mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamine induced hyperactivity in mice when compared to standard. Extract alone treated group at a dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity when compared to the control. The plant extract increased the DAD2 receptor binding in a dose dependent manner in treated mice compared to the control group.

  20. Animal models for predicting the efficacy and side effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Pedro H. Gobira

    2013-01-01

    Full Text Available The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side effects of compounds for the treatment of schizophrenia. These models are based on the properties of antipsychotics to impair the conditioned avoidance response and reverse certain behavioral changes induced by psychotomimetic drugs, such as stereotypies, hyperlocomotion, and deficit in prepulse inhibition of the startle response. Other tests, which are not specific to schizophrenia, may predict drug effects on negative and cognitive symptoms, such as deficits in social interaction and memory impairment. Regarding motor side effects, the catalepsy test predicts the liability of a drug to induce Parkinson-like syndrome, whereas vacuous chewing movements predict the liability to induce dyskinesia after chronic treatment. Despite certain limitations, these models may contribute to the development of more safe and efficacious antipsychotic drugs.

  1. The METEOR study: frequency of metabolic disorders in patients with schizophrenia. Focus on first and second generation and level of risk of antipsychotic drugs.

    Science.gov (United States)

    Falissard, Bruno; Mauri, Mauro; Shaw, Ken; Wetterling, Tilman; Doble, Adam; Giudicelli, Agnès; De Hert, Marc

    2011-11-01

    The objective of this crosssectional study was to estimate the prevalence of metabolic disorders and hypertension in patients with schizophrenia and to compare prevalence between patients treated with first-generation (FGA) and second-generation (SGA) antipsychotic drugs. The study included 2270 adults with schizophrenia. Patients were assigned to an FGA or SGA stratum on the basis of current treatment. Data were collected on sociodemographic, lifestyle and clinical variables. Blood pressure, waist and hip circumference, blood glucose, triglycerides and cholesterol were measured. The primary evaluation criterion was the prevalence of a glycaemic disorder. Secondary criteria were the prevalence of dyslipidaemia, obesity, hypertension and metabolic syndrome. A propensity score was used to control imbalance between strata. The prevalence of glycaemic disorders was 31.1% (FGA) and 27.6% (SGA). No between-strata difference in prevalence was observed for glycaemic disorders, dyslipidaemia or metabolic syndrome. The prevalence of hypertension was higher (P=0.033) in the FGA group. The proportion of women (but not men) who were overweight or obese was higher in the SGA group (P=0.035), as was the proportion reporting weight gain of more than 5 kg (Pexploratory unadjusted post-hoc analysis, significantly higher frequencies of dysglycaemia (28.5 vs. 22.0%; P=0.006), low HDL cholesterol (35.3 vs. 29.7%; P=0.023) and metabolic syndrome (36.7 vs. 30.7%; P=0.021) were observed in patients taking SGAs considered to carry high metabolic risk compared with those taking low-risk agents. In conclusion, metabolic disorders are prevalent in patients with schizophrenia treated with antipsychotics and are under-diagnosed and under-treated. PMID:21876442

  2. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Science.gov (United States)

    Brzozowska, Natalia; Li, Kong M.; Wang, Xiao Suo; Booth, Jessica; Stuart, Jordyn; McGregor, Iain S.

    2016-01-01

    Cannabidiol (CBD) is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB) and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT) mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−), Bcrp knockout (Abcg2−∕−), combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕−) and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders. PMID:27257556

  3. Stimulant and atypical antipsychotic medications for children placed in foster homes.

    Directory of Open Access Journals (Sweden)

    L Oriana Linares

    Full Text Available OBJECTIVES: The purpose of this study is to examine the use of prescribed psychoactive medications in a prospective cohort of children shortly after they entered foster homes; and to identify demographics, maltreatment history, psychiatric diagnoses including ADHD comorbidity, and level of aggression that contribute to prescribed use of stimulant and atypical antipsychotic medication over time. METHODS: The sample included N = 252 children (nested in 95 sibling groups followed for three years up to 4 yearly waves. RESULTS: Nearly all (89% met criteria for at least one of eight psychiatric diagnoses and 31% (75/252 used one or more prescribed psychoactive medications. Over half (55% were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD; of these 38% used stimulants and 36% used atypical antipsychotics. Of the 75 medicated children, 19% received ≥3 different classes of drugs over the course of the study. Stimulants (69% and atypical antipsychotics (65% were the most frequently used drugs among medicated children. Adjusted odds ratios (AOR showed that male gender (AOR = 3.2; 95% CI = 1.5-9.3, African American vs Latino ethnicity (AOR = 5.4; 95% CI = 2.1-14.2, ADHD regardless of Oppositional Defiant (ODD or Conduct (CD comorbidity (AOR = 6.0, 95% CI = 1.3-27.5, ODD or CD (AOR = 11.1, 95% CI = 2.1-58.6, and Separation Anxiety (AOR = 2.0, 95% CI = 1.0-4.0 psychiatric disorders were associated with the use of prescribed stimulants; while male gender (AOR = 3.8, 95% CI = 1.5-9.3, African American vs Latino (AOR = 5.1, 95% CI = 1.2-9.2 or Mixed/Other ethnicity (AOR = 3.3, 95% CI = 1.9-13.7, ADHD regardless of ODD or CD comorbidity (AOR = 5.8, 95% CI = 1.2-28.7, ODD or CD (AOR = 13.9, 95% CI = 3.3-58.5, Major Depression/Dysthymia (AOR = 2.8, 95% CI = 1.1-6.7 psychiatric disorders, and history of sexual abuse (AOR = 4.6, 95% CI = 1.3-18.4 were

  4. Sensorimotor gating and habituation in antipsychotic-naive, first-episode schizophrenia patients before and after 6 months' treatment with quetiapine

    DEFF Research Database (Denmark)

    Aggernaes, Bodil; Glenthøj, Birte Yding; Ebdrup, Bjorn H;

    2010-01-01

    of the human startle reflex in a large group of antipsychotic-naive, first-episode schizophrenia patients, and the effect of subsequent treatment with quetiapine. Thirty-four antipsychotic-naive, first-episode schizophrenia patients (24 males, 10 females), and age- and gender-matched healthy controls were......Impaired prepulse inhibition of the startle reflex (PPI) in schizophrenia has been replicated in many studies. However, previous results may have been influenced by course of illness, and antipsychotic medication. Studies on antipsychotic-naive, first-episode schizophrenia patients are lacking...

  5. Atypical antipsychotics as augmentation therapy in anorexia nervosa.

    Directory of Open Access Journals (Sweden)

    Enrica Marzola

    Full Text Available Anorexia nervosa (AN is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings.

  6. Atypical Antipsychotics as Augmentation Therapy in Anorexia Nervosa

    Science.gov (United States)

    Marzola, Enrica; Desedime, Nadia; Giovannone, Cristina; Amianto, Federico; Fassino, Secondo; Abbate-Daga, Giovanni

    2015-01-01

    Anorexia nervosa (AN) is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs) in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings. PMID:25922939

  7. Agent, autonomous

    OpenAIRE

    Luciani, Annie

    2007-01-01

    The expression autonomous agents, widely used in virtual reality, computer graphics, artificial intelligence and artificial life, corresponds to the simulation of autonomous creatures, virtual (i.e. totally computed by a program), or embodied in a physical envelope, as done in autonomous robots.

  8. Schizophrenia spectrum participants have reduced visual contrast sensitivity to chromatic (red/green and luminance (light/dark stimuli: new insights into information processing, visual channel function and antipsychotic effects

    Directory of Open Access Journals (Sweden)

    Kristin Suzanne Cadenhead

    2013-08-01

    Full Text Available Background: Individuals with schizophrenia spectrum diagnoses have deficient visual information processing as assessed by a variety of paradigms including visual backward masking, motion perception and visual contrast sensitivity (VCS. In the present study, the VCS paradigm was used to investigate potential differences in magnocellular (M versus parvocellular (P channel function that might account for the observed information processing deficits of schizophrenia spectrum patients. Specifically, VCS for near threshold luminance (black/white stimuli is known to be governed primarily by the M channel, while VCS for near threshold chromatic (red/green stimuli is governed by the P channel. Methods: VCS for luminance and chromatic stimuli (counterphase-reversing sinusoidal gratings, 1.22 c/deg, 8.3 Hz was assessed in 53 patients with schizophrenia (including 5 off antipsychotic medication, 22 individuals diagnosed with schizotypal personality disorder and 53 healthy comparison subjects. Results: Schizophrenia spectrum groups demonstrated reduced VCS in both conditions relative to normals, and there was no significant group by condition interaction effect. Post-hoc analyses suggest that it was the patients with schizophrenia on antipsychotic medication as well as SPD participants who accounted for the deficits in the luminance condition. Conclusions: These results demonstrate visual information processing deficits in schizophrenia spectrum populations but do not support the notion of selective abnormalities in the function of subcortical channels as suggested by previous studies. Further work is needed in a longitudinal design to further assess VCS as a vulnerability marker for psychosis as well as the effect of antipsychotic agents on performance in schizophrenia spectrum populations.

  9. Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Leucht, Stefan

    2004-03-01

    The pharmacological profiles of the atypical antipsychotics, clozapine, olanzapine, quetiapine and risperidone, all show a combined serotonin (5-HT2) and dopamine type-2 (D2) receptor antagonism. Amisulpride, a highly selective dopamine D2/D3 receptor antagonist that binds preferentially to receptors in the mesolimbic system, is also an 'atypical' antipsychotic despite having a different receptor-affinity profile. A meta-analysis of 18 clinical trials was undertaken to compare the efficacy and safety of amisulpride with conventional antipsychotics. The improvement in mental state was assessed using the Brief Psychiatric Rating Scale (BPRS) or the Scale for the Assessment of Negative Symptoms (SANS). In a pooled analysis of 10 studies of acutely ill patients, amisulpride was significantly more effective than conventional neuroleptics with regard to improvement of global symptoms. Amisulpride is, to date, the only atypical antipsychotic for which several studies on patients suffering predominantly from negative symptoms have been published. In four such studies, amisulpride was significantly superior to placebo. Three small studies with conventional neuroleptics as a comparator showed only a trend in favour of amisulpride in this regard. Amisulpride was associated with fewer extrapyramidal side-effects and fewer drop-outs due to adverse events than conventional neuroleptics. These results clearly show that amisulpride is an 'atypical' antipsychotic, and they cast some doubt on the notion that combined 5-HT2-D2 antagonism is the only reason for the high efficacy against negative symptoms and fewer extrapyramidal side-effects.

  10. The effects of race and criminal justice involvement on access to atypical antipsychotic medications among persons with schizophrenia.

    Science.gov (United States)

    Van Dorn, Richard A; Swanson, Jeffrey W; Swartz, Marvin S; Elbogen, Eric B

    2005-06-01

    This study examined the impact of race and arrest history on the likelihood of being prescribed, and maintaining an atypical antipsychotic prescription for 90 or more days among patients with schizophrenia in the community. Participants were 224 adults with schizophrenia-spectrum disorders receiving services in public-sector mental health systems in North Carolina. The data used for this report were from a subsample of a larger group of participants being followed in an observational study and consisted of individuals who were prescribed either an atypical or conventional antipsychotic medication for 90 or more days. The purpose of the analyses presented here was to investigate differences in the likelihood of being prescribed an atypical antipsychotic by demographic and other characteristics. Logistic regression analysis indicated that African American patients were significantly less likely to receive atypical antipsychotics than their white counterparts, even when controlling for key clinical and demographic variables. However, white patients with a history of arrest were no more likely than black patients to receive atypical antipsychotics; that is, minority racial status and criminal involvement each functioned to limit patients' access to the novel medications. Implications for equal access to mental health services, in this case, effective psychopharmacologic treatment, are discussed.

  11. Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P; Seiner, Stephen J; Xiang, Yu-Tao

    2016-01-01

    This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (pECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4-11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2-5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. PMID:27285996

  12. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist--protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study

    DEFF Research Database (Denmark)

    Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V;

    2014-01-01

    Antipsychotic medication is widely associated with dysmetabolism including obesity and type 2 diabetes, cardiovascular-related diseases and early death. Obesity is considered the single most important risk factor for cardiovascular morbidity and mortality. Interventions against antipsychotic...

  13. Orbitofrontal lobe volume deficits in Antipsychotic-Naive schizophrenia: A 3-Tesla MRI study

    Directory of Open Access Journals (Sweden)

    Behere Rishikesh

    2009-01-01

    Full Text Available Background: Prefrontal cortex deficits have been consistently demonstrated in schizophrenia. The orbitofrontal lobe (OFL, a critical component of the prefrontal cortex, subserves social and neuro-cognitive functions. While these functional impairments are established in schizophrenia, the OFL volume deficits have not been well studied, especially in antipsychotic-naοve patients. Aim: To study OFL volume deficits in antipsychotic-naοve schizophrenia patients in comparison with matched healthy controls using high-resolution 3-tesla (3T magnetic resonance imaging (MRI. Materials and Methods: Fourteen antipsychotic-naοve schizophrenia patients (DSM-IV and 14 age-, sex-, handedness- and education-matched healthy controls were scanned using 3T MRI. Psychopathology was assessed in the patient group using the scale for assessment of negative symptoms and the scale for assessment of positive symptoms (SAPS. The OFL volume was measured using Region of Interest (ROI-based manual morphometry technique, with good inter-rater reliability (intra-class correlation coefficient = 0.98. Results: Total OFL volume was significantly smaller in schizophrenia patients (43.3 ± 9.6 mL in comparison with healthy controls (52.1 ± 12.2 mL after controlling for the potential confounding effects of age, sex and intracranial volume (F = 5.3, P = .03. Duration of untreated psychosis did not correlate significantly with OFL volumes. There was a trend towards significant negative correlation between the left and total OFL volumes and SAPS scores (r = -0.49, P = .06. Conclusion: OFL volume deficits might underlie the pathogenesis of schizophrenia symptoms with possible neuro-developmental origins.

  14. Sexual dysfunction in patients with schizophrenia treated with conventional antipsychotics or risperidone

    Directory of Open Access Journals (Sweden)

    Hong Liu-Seifert

    2009-01-01

    Full Text Available Hong Liu-Seifert1, Bruce J Kinon1, Christopher J Tennant2, Jennifer Sniadecki1, Jan Volavka31Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA; 2CJT Biomedical Consulting, South Lake Tahoe, CA, USA; 3New York University, New York, NY, USAObjective: To better understand sexual dysfunction in patients with schizophrenia and its associations with prolactin and reproductive hormones.Methods: This was a secondary analysis of an open-label, one-day study (N = 402. The primary objective of the study was to assess the prevalence of hyperprolactinemia in patients with schizophrenia who had been treated with conventional antipsychotics or risperidone. Other atypical antipsychotics available at the time of the study were not included due to a more favorable prolactin profile.Results: The majority of patients (59% of females and 60% of males reported impairment of sexual function. In postmenopausal females, risk of impaired sexual interest was increased by 31% for every 10 ng/ml increase in prolactin (p = 0.035. In males, lower testosterone was associated with higher prolactin (p < 0.001 and with orgasmic (p = 0.004 and ejaculatory dysfunction (p = 0.028.Conclusion: These findings suggest that hyperprolactinemia may be associated with sexual dysfunction. They also provide more information on the relationships between prolactin, reproductive hormones, and sexual dysfunction. Sexual dysfunction is an understudied yet important consideration in the treatment of schizophrenia. More attention is warranted in this area as it may provide opportunities for improved quality of life and adherence to treatment for patients.Keywords: sexual dysfunction, schizophrenia, hyperprolactinemia, antipsychotics, risperidone

  15. Glucoregulation in normal weight schizophrenia patients treated by first generation antipsychotics

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    Marić Nađa

    2008-01-01

    Full Text Available Introduction Schizophrenia patients are at greater risk of obesity, diabetes mellitus (DM, lipid abnormalities and cardiovascular disorders. The metabolic complications in patients are associated with several risk factors: family history of DM, lifestyle, smoking, dietary habits, physical inactivity, but also with antipsychotic medication. In literature, most publications have been focused on the effects of the second generation antipsychotics (SGA on glucose metabolism. However, less attention has been paid to abnormality in glucoregulation, patients with schizophrenia treated with the first generation antipsychotics (FGA. Objective The present study evaluated glucose metabolism in normal weight schizophrenia patients treated with FGA. METHOD The cross-sectional study included 18 patients (FGA treated and 20 healthy controls with neither group differences in sex distribution, age, nor in BMI. Inclusion criteria were normal BMI (20-25 kg/m2. The glucose levels, insulin levels and growth hormone levels during oral glucose tolerance test (OGTT were measured. Results Fasting glucose and insulin levels did not differ significantly between groups. Groups differed in OGTT glucose and insulin peak and area under curve (AUC, level of significance p<0.05 (patients vs. controls: glucose peak 8.3±0.4 vs.6.9±0.5 mmol/l, glucose AUC 758±28 vs. 640±36 mU/l/120 min; insulin peak in patients 92.7±15.6 mU/l; insulin AUC 6060±1016 mU/l/120 min, insulin peak in controls 47.9±6.5 mU/l; insulin AUC 2597±256 mU/l/120 min. Conclusion Patients with schizophrenia, although with normal body mass index, are at high risk of abnormal glucose regulation. Not only SGA increase the risk of impaired glucoregulation and metabolic syndrome, but this may also be due to FGA or schizophrenia per se. .

  16. Choice of antipsychotic treatment by European psychiatry trainees: are decisions based on evidence?

    Directory of Open Access Journals (Sweden)

    Jauhar Sameer

    2012-03-01

    Full Text Available Abstract Background Little is known about the factors influencing treatment choice in psychosis, the majority of this work being conducted with specialists (consultant in psychiatry. We sought to examine trainees' choices of treatment for psychosis if they had to prescribe it for themselves, their patients, and factors influencing decision-making. Methods Cross-sectional, semi-structured questionnaire-based study. Results Of the 726 respondents (response rate = 66%, the majority chose second-generation antipsychotics (SGAs if they had to prescribe it for themselves (n = 530, 93% or for their patients (n = 546, 94%. The main factor influencing choice was perceived efficacy, 84.8% (n = 475 of trainees stating this was the most important factor for the patient, and 77.8% (n = 404 stating this was the most important factor for their own treatment. Trainees with knowledge of trials questioning use of SGAs (CATIE, CUtLASS, TEOSS were more likely to choose second-generation antipsychotics than those without knowledge of these trials (χ2 = 3.943; p = 0.047; O.R. = 2.11; 95% C.I. = 1.0-4.48. Regarding psychotherapy, cognitive behavioural therapy (CBT was the most popular choice for self (33.1%; n = 240 and patient (30.9%; n = 224. Trainees were significantly more likely to prefer some form of psychotherapy for themselves rather than patients (χ2 = 9.98; p Conclusions Trainees are more likely to choose second-generation antipsychotic medication for patients and themselves. Despite being aware of evidence that suggests otherwise, they predominantly base these choices on perceived efficacy.

  17. Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Xianbin Li

    Full Text Available OBJECTIVE: To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. METHODS: POPULATION: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. INTERVENTIONS: adjunctive aripiprazole vs. adjunctive placebo. OUTCOME MEASURES: adverse events and efficacy of treatment. STUDIES: randomized controlled trials. RESULTS: Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158 prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed -0.05 to 0.04 (95% confidence interval -0.13 to 0.16; I(2 =0% to 68%, P=0.20 to 0.70. However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random 0.76 (95% confidence interval 0.67 to 0.85; I(2 =43%, P<0.00001. The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. CONCLUSION: Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day.

  18. Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

    Directory of Open Access Journals (Sweden)

    Bo Wang

    Full Text Available Following Food and Drug Administration (FDA approval, many drugs are prescribed for non-FDA-approved ("off-label" uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs. We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone. FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications. Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63. Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79.The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

  19. Prevalence and profile of cognitive deficits in a cohort of first-episode antipsychotic-naïve schizophrenia patients

    DEFF Research Database (Denmark)

    Jensen, Maria Høj; Glenthøj, Birte Yding; Nielsen, Mette Ødegaard;

    Background and Aims: Cognitive deficits are considered a core feature of schizophrenia with prevalence estimates ranging from ca. 75-85 %. These deficits are present in the early phase of the illness; however in most first-episode schizophrenia studies the patients are receiving antipsychotic...... medication, which can affect the results on specific domains such as processing speed. As part of the PECANS project (Pan European Collaboration on Antipsychotic Naïve Schizophrenia) the aim of the present study is to establish the prevalence and profile of cognitive deficits in a cohort of first......-episode antipsychotic-naïve schizophrenia patients, without the potential confounding effects associated with medication and chronicity. Methods: The overall design of the PECANS project is a 2-year longitudinal case-control study with assessment at baseline and follow-ups after 6 weeks, 6 months, 1 and 2 years. Sixty...

  20. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys

    DEFF Research Database (Denmark)

    Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M;

    2005-01-01

    It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were...

  1. Glutamatergic and GABAergic disturbances as markers of choice-of-treatment – part of Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANS II)

    DEFF Research Database (Denmark)

    Bojesen, Kirsten Borup; Jessen, Kasper; Rostrup, Egill;

    Background Insufficient response to antipsychotic drugs constitutes a major challenge in the treatment of patients with schizophrenia and other targets than the dopamine D2 receptors are highly warranted. Twenty to thirty % of patients do not respond sufficiently to antipsychotic medication, whic...

  2. Sensorimotor gating and habituation in antipsychotic-naive, first-episode schizophrenia patients before and after 6 months' treatment with quetiapine

    DEFF Research Database (Denmark)

    Aggernaes, Bodil; Glenthøj, Birte Yding; Ebdrup, Bjorn H;

    2010-01-01

    Impaired prepulse inhibition of the startle reflex (PPI) in schizophrenia has been replicated in many studies. However, previous results may have been influenced by course of illness, and antipsychotic medication. Studies on antipsychotic-naive, first-episode schizophrenia patients are lacking...

  3. Exposure-response relationship of typical and atypical antipsychotics assessed by the positive and negative syndrome scale (PANSS) and its subscales

    NARCIS (Netherlands)

    Pilla Reddy, Venkatesh; Suleiman, Ahmed; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2011-01-01

    Objectives: It has been suggested that atypical antipsychotics (ATAPs), are more effective towards negative symptoms than typical antipsychotics (TAPs) in schizophrenic patients.[1,2] To quantify the above statement, we aimed i) to develop a PK-PD model that characterizes the time course of PANSS sc

  4. Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

    DEFF Research Database (Denmark)

    Glenthoj, Andreas; Glenthøj, Birte Yding; Mackeprang, Torben;

    2007-01-01

    The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and...... in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin....

  5. Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

    DEFF Research Database (Denmark)

    Nielsen, R E; Lolk, A; Valentin, J B;

    2016-01-01

    mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P DDDs but less than 365: HR 1.81, 95% CI (1.74-1.89), P DDDs but less than 730: HR 1.38, 95% CI (1.428-1.49), P ... or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs...

  6. Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk

    DEFF Research Database (Denmark)

    Borg, Linda; Julkunen, Anna; Madsen, Kristian Rørbaek;

    2016-01-01

    adverse signs at hospital admission that turned out to need intensive care treatment. The effect of the antidepressants overdose risk assessment (ADORA) system was evaluated in patients with antidepressant as well as antipsychotic overdose. Our hypothesis was that patients with low ADORA do not need...... obvious need of intensive care. Of the 157 patients included, 12 patients (8%) developed events during the ICU stay. Only 3 patients received intubation, vasoactive drugs and/or dialysis. None developed ventricular dysrhythmias. There were no fatalities. All the patients with low-risk assessment by ADORA...

  7. Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents.

    Science.gov (United States)

    Correll, Christoph U; Penzner, Julie B; Parikh, Umesh H; Mughal, Tahir; Javed, Tariq; Carbon, Maren; Malhotra, Anil K

    2006-01-01

    Although second-generation antipsychotics (SGAs) are used increasingly in children and adolescents, data on the effectiveness and safety in pediatric populations are still sparse. Much of the safety information is derived from studies conducted in adults. This derivation is problematic because children and adolescents are exposed to SGAs during a phase of unparalleled physical and psychologic development that can affect pharmacokinetic and pharmacodynamic drug actions, efficacy, and side-effect patterns. This article presents an overview of SGA-related side effects in children and adolescents and strategies to monitor health outcomes effectively in youngsters receiving SGAs. PMID:16321730

  8. The influence of impaired processing speed on cognition in first-episode antipsychotic-naïve schizophrenic patients

    DEFF Research Database (Denmark)

    Andersen, Rune; Fagerlund, B; Rasmussen, Hans;

    2012-01-01

    BACKGROUND: Impaired cognition is a prominent feature of schizophrenia. To what extent the heterogeneous cognitive impairments can be accounted for by considering only a single underlying impairment or a small number of core impairments remains elusive. This study examined whether cognitive...... impairments in antipsychotic-naïve, first-episode schizophrenia patients may be determined by a relative slower speed of information processing. METHOD: Forty-eight antipsychotic-naïve patients with first-episode schizophrenia and 48 matched healthy controls were administered a comprehensive battery...

  9. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  10. Factors affecting cognitive remediation response in schizophrenia: the role of COMT gene and antipsychotic treatment.

    Science.gov (United States)

    Bosia, Marta; Zanoletti, Andrea; Spangaro, Marco; Buonocore, Mariachiara; Bechi, Margherita; Cocchi, Federica; Pirovano, Adele; Lorenzi, Cristina; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2014-06-30

    Cognitive remediation is the best available tool to treat cognitive deficits in schizophrenia and has evidence of biological validity; however results are still heterogeneous and significant predictors are lacking. Previous studies showed that cognitive remediation is able to induce changes in PFC function and dopaminergic transmission and thus the study of possible sources of variability at these levels (i.e. antipsychotic treatments and genetic variability) might help to gain a deeper understanding of neurobiological correlates and translate into optimization and personalization of interventions. In the present study, we analyzed the interaction between pharmacological treatment (clozapine vs typical/atypical D2 blockers) and COMT rs4680 polymorphism on cognitive changes after cognitive remediation therapy, in a sample of 98 clinically stabilized patients with schizophrenia. The General Linear Model showed a significant interaction of pharmacological treatment and COMT polymorphism on the improvement in "Symbol Coding" subtest, a global measure of speed of processing. Post-hoc analysis revealed a significant difference between COMT genotypes, when treated with D2 blockers, with worse results among Val/Val patients. These preliminary results suggest that genetic variability, influencing prefrontal dopamine, might affect individual capacity to improve with different patterns, depending on antipsychotic treatment.

  11. Prevalence and severity of antipsychotic related constipation in patients with schizophrenia: a retrospective descriptive study

    Directory of Open Access Journals (Sweden)

    Tack Jan

    2011-03-01

    Full Text Available Abstract Background Antipsychotic are the cornerstone in the treatment of schizophrenia. They also have a number of side-effects. Constipation is thought to be common, and a potential serious side-effect, which has received little attention in recent literature. Method We performed a retrospective study in consecutively admitted patients, between 2007 and 2009 and treated with antipsychotic medication, linking different electronic patient data to evaluate the prevalence and severity of constipation in patients with schizophrenia under routine treatment conditions. Results Over a period of 22 months 36.3% of patients (99 received at least once a pharmacological treatment for constipation. On average medication for constipation was prescribed for 273 days. Severe cases (N = 50, non-responsive to initial treatment, got a plain x-ray of the abdomen. In 68.4% fecal impaction was found. Conclusion A high prevalence of constipation, often severe and needing medical interventions, was confirmed during the study period. Early detection, monitoring over treatment and early intervention of constipation could prevent serious consequences such as ileus.

  12. Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

    Directory of Open Access Journals (Sweden)

    Kyle J. Burghardt

    2013-01-01

    Full Text Available Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1 and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226 or bipolar disorder (n=94 were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

  13. Olanzapine-high potency antipsychotic drug inducing significant weight gain: A case report

    Directory of Open Access Journals (Sweden)

    Marić Nađa P.

    2008-01-01

    Full Text Available INTRODUCTION Olanzapine is a second generation antipsychotic (SGA with a high level of therapeutic effectiveness in schizophrenia and other psychotic disorders. Along with the positive therapeutic effects, an increase of the body weight frequently occurs. According to the literature, the average weight gain is about 6-7 kg during several months of treatment. This could be valued as a moderate weight increase. CASE OUTLINE This article presents a case of a young female with schizophrenia, without clinical improvement with several antipsychotics (clozapine, risperidone, haloperidol and with the occurrence of significant neurological side effects. The treatment started with olanzapine (baseline was associated with good initial response (PANSS reduction 20% in the first two weeks and the improvement was maintained further on (PANSS reduction 50% after 16 weeks. Significant increase (20 kg, 40% in weight appeared during the following 16 weeks (BMI at baseline 17.9 kg/m2; BMI 16 weeks later 25.1 kg/m2. CONCLUSION High effectiveness of olanzapine in schizophrenia symptoms reduction was accompanied by a significant weight gain. However, this drug leads to impaired glucoregulation, dyslipidaemia etc. It also increases the risk of diabetes and cardio-vascular diseases, i.e. the main causes of mortality in schizophrenia after a suicide. Therefore, clinicians are suggested to focus on possible predictors of weight gain during olanzapine therapy, and act accordingly in order to prevent serious health consequences.

  14. Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Ana Maria Volpato

    2013-09-01

    Full Text Available Objective: Atypical antipsychotics (AAPs promote obesity and insulin resistance. In this regard, the main objective of this study was to present potential mechanisms and evidence concerning side effects of atypical antipsychotics in humans and rodents. Method: A systematic review of the literature was performed using the MEDLINE database. We checked the references of selected articles, review articles, and books on the subject. Results: This review provides consistent results concerning the side effects of olanzapine (OL and clozapine (CLZ, whereas we found conflicting results related to other AAPs. Most studies involving humans describe the effects on body weight, adiposity, lipid profile, and blood glucose levels. However, it seems difficult to identify an animal model replicating the wide range of changes observed in humans. Animal lineage, route of administration, dose, and duration of treatment should be carefully chosen for the replication of the findings in humans. Conclusions: Patients undergoing treatment with AAPs are at higher risk of developing adverse metabolic changes. This increased risk must be taken into account when making decisions about treatment. The influence of AAPs on multiple systems is certainly the cause of such effects. Specifically, muscarinic and histaminergic pathways seem to play important roles.

  15. Genome-wide association study on antipsychotic-induced weight gain in the CATIE sample.

    Science.gov (United States)

    Brandl, E J; Tiwari, A K; Zai, C C; Nurmi, E L; Chowdhury, N I; Arenovich, T; Sanches, M; Goncalves, V F; Shen, J J; Lieberman, J A; Meltzer, H Y; Kennedy, J L; Müller, D J

    2016-08-01

    Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10(-8). We observed interesting trends for rs9346455 (P=6.49x10(-6)) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10(-5)) and rs1012650 (P=1.47 × 10(-5)), and rs1059778 (P=1.49x10(-5)) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10(-7). Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59. PMID:26323598

  16. Almost all antipsychotics result in weight gain: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Maarten Bak

    Full Text Available INTRODUCTION: Antipsychotics (AP induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer. METHOD: A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss. Duration of AP-use was stratified as follows: ≤6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures. RESULTS: 307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP. CONCLUSION: Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.

  17. Behavioral and metabolic effects of the atypical antipsychotic ziprasidone on the nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Priscila Gubert

    Full Text Available Atypical antipsychotics are associated with metabolic syndrome, primarily associated with weight gain. The effects of Ziprasidone, an atypical antipsychotic, on metabolic syndrome has yet to be evaluated. Here in, we evaluated lipid accumulation and behavioral changes in a new experimental model, the nematode Caenorhabditis elegans (C. elegans. Behavioral parameters in the worms were evaluated 24 h after Ziprasidone treatment. Subsequently, lipid accumulation was examined using Nile red, LipidTox green and BODIPY labeling. Ziprasidone at 40 µM for 24 h effectively decreased the fluorescence labeling of all markers in intestinal cells of C. elegans compared to control (0.16% dimethyl sulfoxide. Ziprasidone did not alter behaviors related to energetic balance, such as pharynx pumping, defecation cycles and movement. There was, however, a reduction in egg-production, egg-laying and body-length in nematodes exposed to Ziprasidone without any changes in the progression of larval stages. The serotoninergic pathway did not appear to modulate Ziprasidone's effects on Nile red fluorescence. Additionally, Ziprasidone did not alter lipid accumulation in daf-16 or crh-1 deletion mutants (orthologous of the transcription factors DAF-16 and CREB, respectively. These results suggest that Ziprasidone alters reproductive behavior, morphology and lipid reserves in the intestinal cells of C. elegans. Our results highlight that the DAF-16 and CREB transcription factors are essential for Ziprasidone-induced fat store reduction.

  18. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  19. Bone mineral density in male adolescents with autism spectrum disorders and disruptive behavior disorder with or without antipsychotic treatment

    NARCIS (Netherlands)

    Roke, Yvette; van Harten, Peter N.; Buitelaar, Jan K.; Tenback, Diederik E.; Quekel, Lorentz G. B. A.; de Rijke, Yolanda B.; Boot, Annemieke M.

    2012-01-01

    Objective: To investigate the long-term effects of antipsychotic (AP) treatment and AP-induced hyperprolactinemia on bone mineral density (BMD) and body composition in male adolescents with autism spectrum disorders (ASDs) and/or disruptive behavior disorder (DBD). Design: Physically healthy 10- to

  20. Glycosylated hemoglobin as a screening test for hyperglycemia in antipsychotic-treated patients: A follow-up study

    NARCIS (Netherlands)

    P.M.J. Steylen (Pauline); F.M.M.A. van der Heijden (Frank); W.J.G. Hoogendijk (Witte); W.M.A. Verhoeven (Wim)

    2015-01-01

    textabstractPurpose: To assess the point prevalence of undetected prediabetes (preDM) and diabetes mellitus (DM) in patients treated with antipsychotics and to compare metabolic parameters between patients with normoglycemia (NG), preDM, and DM. Furthermore, conversion rates for preDM and DM were de

  1. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

    NARCIS (Netherlands)

    Westerink, B.H.C.; Kawahara, Y; de Boer, P; Geels, C; de Vries, J.B; Wikström, H.V; van Kalkeren, A; van Vliet, B; Kruse, C.H; Long, S.K

    2001-01-01

    Dose-effect curves were established for the effects of the antipsychotic drugs haloperidol, clozapine, olanzapine, risperidone and ziprasidone on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex, and of dopamine in the striatum. Haloperidol was more effective in sti

  2. Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter; Lublin, H;

    2010-01-01

    polypharmacy, socioeconomic status and functional level of patients. The intervention was aimed at psychiatric healthcare providers and consisted of 1 day of didactic lectures, six 3-h educational outreach visits and an electronic reminder during drug prescribing. RESULTS: Between-group use of antipsychotic...

  3. The d-amphetamine-treated Göttingen miniature pig: an animal model for assessing behavioral effects of antipsychotics

    NARCIS (Netherlands)

    Staay, van der F.J.; Pouzet, B.; Mahieu, M.; Nordquist, R.E.; Schuurman, T.

    2009-01-01

    Rationale Rodents are usually used to assess the ability of antipsychotic drugs to antagonize hyperlocomotion induced by dopamine agonists, such as the psychostimulant d-amphetamine. However, the substantial differences between rodents and humans may hinder extrapolation of experimental results to h

  4. Prediabetic increase in hemoglobin A1c compared with impaired fasting glucose in patients receiving antipsychotic drugs

    NARCIS (Netherlands)

    Manu, Peter; Correll, Christoph U.; Wampers, Martien; van Winkel, Ruud; Yu, Weiping; Mitchell, Alex J.; De Hert, Marc

    2013-01-01

    Background: In 2010, the American Diabetes Association recommended that individuals with hemoglobin A1c 5.7-6.4% be classified as prediabetic even in the absence of impaired fasting glucose (IFG). Aim of study: To compare the clinical and metabolic characteristics of patients receiving antipsychotic

  5. Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Hans; Erritzoe, David; Andersen, Rune;

    2010-01-01

    , in vivo studies of serotonin(2A) binding report conflicting results, presumably because sample sizes have been small or because schizophrenic patients who were not antipsychotic-naive were included. Furthermore, the relationships between serotonin(2A) binding, psychopathology, and central neurocognitive...

  6. Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics

    DEFF Research Database (Denmark)

    Olsen, Christina Kurre; Brennum, Lise Tøttrup; Kreilgaard, Mads

    2008-01-01

    In the rat, selective suppression of conditioned avoidance response has been widely reported as a test with high predictive validity for antipsychotic efficacy. Recent studies have shown that the relationship between dopamine D2 receptor occupancy and the suppression of conditioned avoidance resp...

  7. Atypical Antipsychotics in the Treatment of Depressive and Psychotic Symptoms in Patients with Chronic Schizophrenia: A Naturalistic Study

    Directory of Open Access Journals (Sweden)

    Marco Innamorati

    2013-01-01

    Full Text Available Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients’ awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women treated with clozapine and 23 patients (16 men and 7 women treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS, depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS, and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD. Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds.

  8. Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study

    NARCIS (Netherlands)

    De Hert, Marc; Correll, Christoph U.; Cohen, Dan

    2010-01-01

    Compared to the general Population, people with schizophrenia are at risk of dying prematurely Clue to suicide and due to different somatic illnesses. The potential role of antipsychotic treatment in affecting suicide rates and in explaining the increased mortality due to somatic disorders is highly

  9. Antipsychotic-induced extrapyramidal syndromes and cytochrome P-450 2D6 genotype : a case-control study

    NARCIS (Netherlands)

    Schillevoort, [No Value; de Boer, A; van der Weide, J; Steijns, LSW; Roos, RAC; Jansen, PAF; Leufkens, HGM

    2002-01-01

    To study the association between polymorphism of the cytochrome P-450 2D6 gene (CYP2D6) and the risk of antipsychotic-induced extrapyramidal syndromes, as measured by the use of anti parkinsonian medication. Data for this case-control study were obtained from a psychiatric hospital where newly admit

  10. The effects of typical and atypical antipsychotics on the electrical activity of the brain in a rat model

    Directory of Open Access Journals (Sweden)

    Oytun Erbaş

    2013-09-01

    Full Text Available Objective: Antipsychotic drugs are known to have strongeffect on the bioelectric activity in the brain. However,some studies addressing the changes on electroencephalography(EEG caused by typical and atypical antipsychoticdrugs are conflicting. We aimed to compare the effectsof typical and atypical antipsychotics on the electricalactivity in the brain via EEG recordings in a rat model.Methods: Thirty-two Sprague Dawley adult male ratswere used in the study. The rats were divided into fivegroups, randomly (n=7, for each group. The first groupwas used as control group and administered 1 ml/kg salineintraperitoneally (IP. Haloperidol (1 mg/kg (group 2,chlorpromazine (5 mg/kg (group 3, olanzapine (1 mg/kg(group 4, ziprasidone (1 mg/ kg (group 5 were injectedIP for five consecutive days. Then, EEG recordings ofeach group were taken for 30 minutes.Results: The percentages of delta and theta waves inhaloperidol, chlorpromazine, olanzapine and ziprasidonegroups were found to have a highly significant differencecompared with the saline administration group (p<0.001.The theta waves in the olanzapine and ziprasidonegroups were increased compared with haloperidol andchlorpromazine groups (p<0.05.Conclusion: The typical and atypical antipsychotic drugsmay be risk factor for EEG abnormalities. This studyshows that antipsychotic drugs should be used with caution.J Clin Exp Invest 2013; 4 (3: 279-284Key words: Haloperidol, chlorpromazine, olanzapine,ziprasidone, EEG, rat

  11. P-glycoprotein activity in the blood-brain barrier is affected by virus-induced neuroinflammation and antipsychotic treatment

    NARCIS (Netherlands)

    Doorduin, Janine; de Vries, Erik F. J.; Dierckx, Rudi A.; Klein, Hans C.

    2014-01-01

    A large percentage of schizophrenic patients respond poorly to antipsychotic treatment. This could be explained by inefficient drug transport across the blood-brain barrier due to P-glycoprotein mediated efflux. P-glycoprotein activity and expression in the blood-brain barrier can be affected by inf

  12. The impact of antipsychotics and neuropsychiatric symptoms on the quality of life of people with dementia living in nursing homes

    NARCIS (Netherlands)

    van de Ven-Vakhteeva, Julia; Bor, Hans; Wetzels, Roland B.; Koopmans, Raymond T. C. M.; Zuidema, Sytse U.

    2013-01-01

    Objective This study aimed to establish whether antipsychotic (AP) use in patients with dementia negatively affects quality of life (QoL) independent of neuropsychiatric symptoms (NPS). Method We tested 290 patients with dementia living in nine nursing homes throughout the Netherlands in a longitudi

  13. The Effect of Concurrent Administration of Typical or Atypical Antipsychotic Drugs and Lithium on Lithium Ratio in Acute Manic Patients

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    Seyed Sina Ahmadi abhari

    2008-12-01

    Full Text Available "nObjective: "n The lithium concentration in the plasma is assumed to give someindication as to the concentration of this ion in different organ cells especially incentral nervous system. While the practical value of intracellular lithium measurement is controversial however, erythrocytes have proved to be useful for studying lithium concentration and its transport across the membrane. There are some reports suggesting that neuroleptic drugs are able to affect the erythrocyte lithium concentration (ELCs, although these studies have yielded inconsistent results. "nMethod: In the present study the effect of risperidone and olanzapine as atypical antipsychotic and haloperidol as standard typical antipsychotic on lithium ratio in 46 acute manic patients was studied. ELCs were measured using atomic absorption spectrophotometer. Clinical response was evaluated by using Young mania rating scale (YMRS. "nResults: No significant difference was found between LRs and dose or type of antipsychotics. Also there were no significant differences between LRs and clinical response or remission. "nConclusion: The concurrent use of an atypical antipsychotics and lithium may not significantly alter the lithium transport in the erythrocyte and presumably in the nerve cells. A more comprehensive study is warranted to confirm the results of this study.

  14. Does Insight Affect the Efficacy of Antipsychotics in Acute Mania? : An Individual Patient Data Regression Meta-Analysis

    NARCIS (Netherlands)

    Welten, Carlijn C M; Koeter, Maarten W J; Wohlfarth, Tamar D; Storosum, Jitschak G; van den Brink, Wim; Gispen-de Wied, Christine C; Leufkens, Hubert G M; Denys, D.

    2016-01-01

    Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients wi

  15. Refill rate of antipsychotic drugs : an easy and inexpensive method to monitor patients' compliance by using computerised pharmacy data

    NARCIS (Netherlands)

    Rijcken, CAW; Tobi, H; Vergouwen, ACM; de Jong-van den Berg, LTW

    2004-01-01

    Purpose In the literature, noncompliance to medication in patients with schizophrenia ranges from 20 to 89%. There is an urgent need for reliable and valid techniques that measure compliance in antipsychotic drug treatment. In this study, we use pharmacy-dispensing records to assess compliance by ca

  16. The Efficacy and Safety of Antipsychotic Medications in the Treatment of Psychosis in Patients with Parkinson's Disease

    Science.gov (United States)

    Stojanović, Radan; Damjanović, Aleksandar; Prostran, Milica

    2016-01-01

    Psychotic symptoms are present in up to 50% of patients with Parkinson's disease. These symptoms have detrimental effects on patients' and caregivers' quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson's disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson's disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson's disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson's disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug's long-term safety and efficacy. PMID:27504054

  17. Sex differences in concomitant medication with benzodiazepines or antidepressants in first-break schizophrenic patients treated with antipsychotic medication

    NARCIS (Netherlands)

    Rijcken, C.A.W.; Knegtering, H; Bruggeman, R; Tobi, H; de Jong-van den Berg, Lolkje Theodora Wilhelmina

    2005-01-01

    During a first episode of psychosis, treatment with antipsychotic drugs can improve both positive and negative symptoms. If sufficient amelioration does not occur, adding psychotropic comedication may result in a favorable outcome. To establish sex differences in psychotropic comedication use, we co

  18. The Efficacy and Safety of Antipsychotic Medications in the Treatment of Psychosis in Patients with Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Nevena Divac

    2016-01-01

    Full Text Available Psychotic symptoms are present in up to 50% of patients with Parkinson’s disease. These symptoms have detrimental effects on patients’ and caregivers’ quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson’s disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson’s disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson’s disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson’s disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug’s long-term safety and efficacy.

  19. Parent Report of Antidepressant, Anxiolytic, and Antipsychotic Medication Use in Individuals with Williams Syndrome: Effectiveness and Adverse Effects

    Science.gov (United States)

    Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.

    2012-01-01

    Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…

  20. Impaired temporoparietal deactivation with working memory load in antipsychotic-naïve patients with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Nejad, Ayna B; Ebdrup, Bjørn H; Siebner, Hartwig R;

    2011-01-01

    Abstract Objectives. Neuroimaging studies have shown abnormal task-related deactivations during working memory (WM) in schizophrenia patients with recent emphasis on brain regions within the default mode network. Using fMRI, we tested whether antipsychotic-naïve schizophrenia patients were impaired...

  1. Antipsychotics for behavioural and psychological problems in elderly people with dementia: a systematic review of adverse events.

    NARCIS (Netherlands)

    Iersel, M.B. van; Zuidema, S.U.; Koopmans, R.T.C.M.; Verhey, F.R.J.; Olde Rikkert, M.G.M.

    2005-01-01

    OBJECTIVE: Although antipsychotics are important in the treatment of behavioural and psychological symptoms of dementia (BPSD), they have moderate efficacy and often cause adverse events. Recent safety warnings about increased frequency of cerebrovascular adverse events in elderly patients who use a

  2. Antipsychotics for behavioural and psychological problems in elderly people with dementia : a systematic review of adverse events

    NARCIS (Netherlands)

    van Iersel, Marianne B; Zuidema, Sytse U; Koopmans, Raymond T C M; Verhey, Frans R J; Olde Rikkert, Marcel G M

    2005-01-01

    OBJECTIVE: Although antipsychotics are important in the treatment of behavioural and psychological symptoms of dementia (BPSD), they have moderate efficacy and often cause adverse events. Recent safety warnings about increased frequency of cerebrovascular adverse events in elderly patients who use a

  3. Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model

    Directory of Open Access Journals (Sweden)

    Furiak Nicolas M

    2012-11-01

    Full Text Available Abstract The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms. A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill. Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT and once-monthly risperidone long-acting injection (RIS-LAI with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total and are estimated for LFA therapies given at three, six, and nine month intervals. The one-year results show that LFA therapy every 3 months (LFA-3 ($6,088 is less costly than either RIS-SOT ($10,721 or RIS-LAI ($9,450 with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41. Extending the interval to six (LFA-6 and nine (LFA-9 months resulted in further reductions in relapse and costs. Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health

  4. Antipsychotic-like activity of Noni (Morinda citrifolia Linn. in mice

    Directory of Open Access Journals (Sweden)

    Pandy Vijayapandi

    2012-10-01

    Full Text Available Abstract Background Noni fruit is widely consumed in tropical regions of Indonesia to the Hawaiian Islands. The noni plant has a long history of use as a medicinal plant to treat a wide variety of ailments including CNS disorders. The present investigation was designed to evaluate the antipsychotic effect of noni fruits (Morinda citrifolia Linn. using mouse models of apomorphine-induced climbing behaviour and methamphetamine-induced stereotypy (licking, biting, gnawing and sniffing. Methods In acute study, the methanolic extract of Morinda citrifolia (MMC at different doses 1, 3, 5, 10 g/kg was administered orally one hour prior to apomorphine (5 mg/kg, i.p and methamphetamine ( 5 mg/kg, i.p injection respectively in Swiss albino mice. In chronic studies, (TAHITIAN NONI® Juice, TNJ was made available freely in daily drinking water at 30, 50 and 100% v/v for 7 days; 30 and 50% v/v for 21 days respectively. On the test day, an equivalent average daily divided dose of TNJ was administered by oral gavage one hour prior to apomorphine treatment. Immediately after apomorphine/ methamphetamine administration, the animals were placed in the cylindrical metal cages and observed for climbing behaviour/ stereotypy and climbing time. Results The acute treatment of MMC (1, 3, 5, 10 g/kg, p.o significantly decreased the apomorphine-induced cage climbing behaviour and climbing time in mice in a dose dependent manner. The MMC also significantly inhibited methamphetamine-induced stereotypy behaviour and climbing time in mice dose-dependently. The 7 and 21 days treatment of TNJ in drinking water at 50 and 100%v/v significantly alleviated the apomorphine-induced climbing behaviour and climbing time in mice. Conclusions The present study results demonstrated the antidopaminergic effect of Morinda citrifolia Linn. in mice, suggesting that noni has antipsychotic-like activity which can be utilized in the treatment of psychiatric disorders. However further studies

  5. Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol.

    Science.gov (United States)

    Gomes, Felipe V; Llorente, Ricardo; Del Bel, Elaine A; Viveros, Maria-Paz; López-Gallardo, Meritxell; Guimarães, Francisco S

    2015-05-01

    NMDA receptor hypofunction could be involved, in addition to the positive, also to the negative symptoms and cognitive deficits found in schizophrenia patients. An increasing number of data has linked schizophrenia with neuroinflammatory conditions and glial cells, such as microglia and astrocytes, have been related to the pathogenesis of schizophrenia. Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects. The present study evaluated if repeated treatment with CBD (30 and 60 mg/kg) would attenuate the behavioral and glial changes observed in an animal model of schizophrenia based on the NMDA receptor hypofunction (chronic administration of MK-801, an NMDA receptor antagonist, for 28 days). The behavioral alterations were evaluated in the social interaction and novel object recognition (NOR) tests. These tests have been widely used to study changes related to negative symptoms and cognitive deficits of schizophrenia, respectively. We also evaluated changes in NeuN (a neuronal marker), Iba-1 (a microglia marker) and GFAP (an astrocyte marker) expression in the medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens core and shell, and dorsal hippocampus by immunohistochemistry. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Repeated MK-801 administration impaired performance in the social interaction and NOR tests. It also increased the number of GFAP-positive astrocytes in the mPFC and the percentage of Iba-1-positive microglia cells with a reactive phenotype in the mPFC and dorsal hippocampus without changing the number of Iba-1-positive cells. No change in the number of NeuN-positive cells was observed. Both the behavioral disruptions and the changes in expression of glial markers induced by MK-801 treatment were attenuated by repeated treatment with CBD or clozapine. These data reinforces the proposal

  6. An agent framework for dynamic agent retraining: Agent academy

    OpenAIRE

    Mitkas, P.; A. Symeonidis; Kechagias, D.; Athanasiadis, I.N.; Laleci, G.; KURT, G.; Kabak, Y.; Acar, A.; Dogac, A.

    2004-01-01

    Agent Academy (AA) aims to develop a multi-agent society that can train new agents for specific or general tasks, while constantly retraining existing agents in a recursive mode. The system is based on collecting information both from the environment and the behaviors of the acting agents and their related successes/failures to generate a body of data, stored in the Agent Use Repository, which is mined by the Data Miner module, in order to generate useful knowledge about the application domai...

  7. Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes

    Directory of Open Access Journals (Sweden)

    Lior eGreenbaum

    2015-02-01

    Full Text Available Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP and tardive dyskinesia (TD. Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of Parkinson's disease (PD. Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD sub-phenotypes, such as age at onset, disease severity or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants may also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of L-dopa induced dyskinesia (LID, is an additional relevant sub-phenotype. LID may share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.

  8. Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Wei Zheng

    Full Text Available This meta-analysis of randomized controlled trials (RCTs examined the efficacy and safety of the combination of electroconvulsive therapy (ECT and antipsychotic medication (except for clozapine versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS. Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD, risk ratio (RR ±95% confidence intervals (CIs, number needed to treat (NNT, and number needed to harm (NNH were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1 symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I(2 = 62%, separating the two groups as early as weeks 1-2 with an SMD of -0.58 (p<0.00001; I(2 = 0%; (2 study-defined response (RR = 1.48, p<0.0001 with an NNT of 6 (CI = 4-9 and remission rate (RR = 2.18, p = 0.0002 with an NNT of 8 (CI = 6-16; (3 PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009. Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3 studies. The ECT-antipsychotic combination caused more headache (p = 0.02 with an NNH of 6 (CI = 4-11 and memory impairment (p = 0.001 with an NNH of 3 (CI = 2-5. The use of ECT to augment antipsychotic treatment (clozapine excepted can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache.

  9. Effect of novel antipsychotic drugs on phencyclidine-induced stereotyped behaviour and social isolation in the rat social interaction test.

    Science.gov (United States)

    Sams-Dodd, F

    1997-06-01

    Phencyclidine (PCP) induces stereotyped behaviour and social isolation in rats; comparisons with clinical observations have suggested that these behaviours may mimic certain aspects of the positive and the negative symptoms, respectively, of an acute schizophrenic episode. Novel antipsychotics are effective in treating the positive symptoms in schizophrenic patients and have also shown some promise in treating the negative symptoms. In the present study the effects of the novel antipsychotics remoxipride (2.5-20 mg/kg), risperidone (0.02-0.63 mg/kg), sertindole (0.01-2.5 mg/kg), olanzapine (0.16-2.5 mg/kg) and quetiapine (0.16-10 mg/kg) on PCP-induced behaviours were determined. The drugs were administered daily for 3 or 21 days in combination with vehicle or 2.0 mg/kg of PCP for the last 3 days of the administration regime, and the rats were tested using the social interaction test. The antipsychotic drugs all reliably reduced the level of PCP-induced stereotyped behaviour and had distinct effects on PCP-induced social isolation. Comparison with clinical findings suggests that the PCP-induced behaviours respond to treatment with antipsychotic drugs in a manner that correlates well with clinical observations, and that this animal model of schizophrenia may be useful for evaluating novel drug candidates. However, the study also showed that additional experiments are required to determine the specificity by which antipsychotic drugs alleviate PCP-induced behaviours because most of the drugs also affected considerably the behaviour of the control animals.

  10. Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus.

    Science.gov (United States)

    Rojczyk, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard

    2015-06-01

    Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors--neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R)--both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling--a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic

  11. Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus.

    Science.gov (United States)

    Rojczyk, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard

    2015-06-01

    Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors--neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R)--both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling--a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic

  12. Do we need to consider ethno-cultural variation in the use of atypical antipsychotics for Asian patients with major depressive disorder?

    Science.gov (United States)

    Han, Changsu; Pae, Chi-Un

    2013-05-01

    Asian and western countries differ in the prevalence, symptom manifestation, diagnostic procedures, patient recognition and treatments of major depressive disorder (MDD), according to a number of studies. Ethnic differences in pharmacological profiles are also important in the prescription of certain antipsychotic medications because they may impact treatment outcomes and adverse events. Differential pharmacokinetic and pharmacodynamic properties of antipsychotics may be practically useful in the control of specific depressive symptoms. Furthermore, patient compliance with prescribed medications has been found to be different across races and ethnicities. Therefore, this article explores practical clinical issues for the use of atypical antipsychotics in patients with MDD, focusing on ethno-cultural differences.

  13. Efficacy of Adenine in the Treatment of Leukopenia and Neutropenia Associated with an Overdose of Antipsychotics or Discontinuation of Lithium Carbonate Administration: Three Case Studies

    Science.gov (United States)

    Tomita, Takashi; Goto, Hidekazu; Sumiya, Kenji; Yoshida, Tadashi; Tanaka, Katsuya; Kohda, Yukinao

    2016-01-01

    Because adenine is effective for managing cases of radiation-induced and drug-induced leukopenia, it may be effective in cases of antipsychotic-induced leukopenia and neutropenia. Here, we report our experience with patients with leukopenia and neutropenia caused by an antipsychotic overdose or discontinuation of lithium carbonate, in whom adenine administration ameliorated the white blood cell and neutrophil counts. The progress of patients suggests that adenine is effective in cases of leukopenia and neutropenia associated with lithium carbonate discontinuation and an antipsychotic overdose. PMID:27776394

  14. Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics

    DEFF Research Database (Denmark)

    Jørgensen, Anders; Knorr, Ulla Benedichte Søsted; Soendergaard, Mia Greisen;

    2015-01-01

    and the L-arginine:ADMA ratio showed no correlations with oxidative stress markers, medication load, or Positive and Negative Syndrome Scale scores. CONCLUSIONS: Schizophrenia and treatment with AAP was not associated with increased levels of plasma ADMA or the L-arginine:ADMA ratio. Furthermore, plasma......BACKGROUND: Schizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome...... in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA...

  15. Improving physical health monitoring for patients with chronic mental health problems who receive antipsychotic medications.

    Science.gov (United States)

    Abdallah, Nihad; Conn, Rory; Latif Marini, Abdel

    2016-01-01

    Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff. GP letters requesting physical health monitoring were updated; care home staff and patients were given more information about the value of regular physical health monitoring. There was an improvement in patients' engagement with the monitoring and the monitoring done by GPs was more adherent to local and national guidelines and was communicated with the mental health service.

  16. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Directory of Open Access Journals (Sweden)

    Aviva Breuer

    Full Text Available Cannabidiol (CBD is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101 (1, is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

  17. Improving physical health monitoring for patients with chronic mental health problems who receive antipsychotic medications

    Science.gov (United States)

    Abdallah, Nihad; Conn, Rory; Latif Marini, Abdel

    2016-01-01

    Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff. GP letters requesting physical health monitoring were updated; care home staff and patients were given more information about the value of regular physical health monitoring. There was an improvement in patients' engagement with the monitoring and the monitoring done by GPs was more adherent to local and national guidelines and was communicated with the mental health service. PMID:27559474

  18. Metabolic side effects and pharmacogenetics of second-generation antipsychotics in children.

    Science.gov (United States)

    Devlin, Angela M; Panagiotopoulos, Constadina

    2015-01-01

    Second-generation antipsychotics (SGAs) are increasingly being used to treat children for a range of mental health conditions, for example, anxiety disorder, attention deficit hyperactivity disorder and bipolar disorder. SGA treatment is associated with weight gain and cardiometabolic side effects such as dyslipidemia, insulin resistance and elevated blood pressure, in some, but not all children. This review provides an overview of the potential role of pharmacogenomics in predisposing a child to unhealthy weight gain and cardiometabolic side effects with SGA treatment. Specifically, the review includes a synopsis of the evidence for cardiometabolic side effects in SGA-treated children, illustrating the extent and depth of the problem; summarizes the potential long-term consequences of developing cardiometabolic risk during childhood and highlights genetic variants that may be useful in predicting cardiometabolic side effects in SGA-treated children.

  19. The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse.

    Directory of Open Access Journals (Sweden)

    Andrew P Morgan

    Full Text Available The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.

  20. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects

    Science.gov (United States)

    Fogaça, Manoela V.; Gomes, Felipe V.; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A.; Hallak, Jaime C.; Crippa, José A.; Zuardi, Antonio W.; Guimarães, Francisco S.

    2016-01-01

    Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. PMID:27416026

  1. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Science.gov (United States)

    Breuer, Aviva; Haj, Christeene G; Fogaça, Manoela V; Gomes, Felipe V; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A; Hallak, Jaime C; Crippa, José A; Zuardi, Antonio W; Mechoulam, Raphael; Guimarães, Francisco S

    2016-01-01

    Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. PMID:27416026

  2. Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.

    Science.gov (United States)

    Huang, Ling; Zhang, Wenjun; Zhang, Xiaohua; Yin, Lei; Chen, Bangyin; Song, Jinchun

    2015-11-15

    The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A receptors, but low affinities for the 5-HT2C and histamine H1 receptors and human ether-a-go-go-related gene (hERG) channels. Furthermore, compound 29 reduced apomorphine-induced climbing and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitching without observable catalepsy, even at the highest dose tested. Thus, compound 29 is a promising candidate as a multi-target antipsychotic treatment. PMID:26483200

  3. Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.

    Science.gov (United States)

    Huang, Ling; Zhang, Wenjun; Zhang, Xiaohua; Yin, Lei; Chen, Bangyin; Song, Jinchun

    2015-11-15

    The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A receptors, but low affinities for the 5-HT2C and histamine H1 receptors and human ether-a-go-go-related gene (hERG) channels. Furthermore, compound 29 reduced apomorphine-induced climbing and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitching without observable catalepsy, even at the highest dose tested. Thus, compound 29 is a promising candidate as a multi-target antipsychotic treatment.

  4. Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Hammer, Trine B; Oranje, Bob; Skimminge, Arnold;

    2013-01-01

    with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia. Methods: We performed acoustic PPI assessment...... and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes. Results: We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain...... areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed...

  5. Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia

    Directory of Open Access Journals (Sweden)

    Tomiki eSumiyoshi

    2013-10-01

    Full Text Available Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT receptors in ameliorating cognitive deficits of schizophrenia.It is noteworthy that atypical antipsychotic drugs, e.g. clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and GABA neurons. A novel strategy for cognitive enhancement in psychosis may be benefitted by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g. event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs acting directly or indirectly on 5-HT1A receptors.These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

  6. Genetic variations of PIP4K2A confer vulnerability to poor antipsychotic response in severely ill schizophrenia patients.

    Directory of Open Access Journals (Sweden)

    Harpreet Kaur

    Full Text Available Literature suggests that disease severity and neurotransmitter signaling pathway genes can accurately identify antipsychotic response in schizophrenia patients. However, putative role of signaling molecules has not been tested in schizophrenia patients based on severity of illness, despite its biological plausibility. In the present study we investigated the possible association of polymorphisms from five candidate genes RGS4, SLC6A3, PIP4K2A, BDNF, PI4KA with response to antipsychotic in variably ill schizophrenia patients. Thus in present study, a total 53 SNPs on the basis of previous reports and functional grounds were examined for their association with antipsychotic response in 423 schizophrenia patients segregated into low and high severity groups. Additionally, haplotype, diplotype, multivariate logistic regression and multifactor-dimensionality reduction (MDR analyses were performed. Furthermore, observed associations were investigated in atypical monotherapy (n = 355 and risperidone (n = 260 treated subgroups. All associations were estimated as odds ratio (OR and 95% confidence interval (CI and test for multiple corrections was applied. Single locus analysis showed significant association of nine variants from SLC6A3, PIP4K2A and BDNF genes with incomplete antipsychotic response in schizophrenia patients with high severity. We identified significant association of six marker diplotype ATTGCT/ATTGCT (rs746203-rs10828317-rs7094131-rs2296624-rs11013052-rs1409396 of PIP4K2A gene in incomplete responders (corrected p-value = 0.001; adjusted-OR = 3.19, 95%-CI = 1.46-6.98 with high severity. These associations were further observed in atypical monotherapy and risperidone sub-groups. MDR approach identified gene-gene interaction among BDNF_rs7103411-BDNF_rs1491851-SLC6A3_rs40184 in severely ill incomplete responders (OR = 7.91, 95%-CI = 4.08-15.36. While RGS4_rs2842026-SLC6A3_rs2975226 interacted synergistically in

  7. Differential effects of antipsychotic drugs on insight in first episode schizophrenia : Data from the European First-Episode Schizophrenia Trial (EUFEST)

    NARCIS (Netherlands)

    Pijnenborg, G. H. M.; Timmerman, Marieke; Derks, E.M.; Fleischhacker, W. W.; Kahn, R. S.; Aleman, A.

    2015-01-01

    Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in

  8. Post-drug consequences of chronic atypical antipsychotic drug administration on the ability to adjust behavior based on feedback in young monkeys

    NARCIS (Netherlands)

    D.J. Mandell; A. Unis; G.P. Sackett

    2011-01-01

    Rationale: Atypical antipsychotic drugs are characterized by their affinity for serotonin and dopamine receptors. The dopaminergic system undergoes developmental changes during childhood, making it vulnerable to external influences such as drug administration. Objective: The purpose of this study wa

  9. Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline

    DEFF Research Database (Denmark)

    Dencker, Ditte; Wörtwein, Gitta; Weikop, Pia;

    2011-01-01

    Disturbances in central dopaminergic neurotransmission are believed to be centrally involved in the pathogenesis of schizophrenia. Central dopaminergic and cholinergic systems interact and the cholinergic muscarinic agonist xanomeline has shown antipsychotic effects in clinical studies. Preclinical...... in mediating the antipsychotic-like effects of xanomeline. This is consistent with the hypothesis that activation of the M(4) mAChR represents a potential target for the future medical treatment of psychosis....

  10. [The comparative study on the efficacy of the combination of serotonin reuptake inhibitor antidepressants and antipsychotics in the treatment of recurrent depressive disorders].

    Science.gov (United States)

    D'iakonov, A L; Lobanova, I V

    2012-01-01

    A combination of serotonin reuptake inhibitor antidepressants (prozac and stimulaton) with atypical antipsychotics (zyprexa and solian) reduced depression in patients with recurrent depressive disorders during 10 days. The effect was evenly distributed between 10, 20 and 40 days of treatment. Other symptoms had a peculiar dynamics depending on the therapy. By the end of the study, similar effects were achieved for all groups. The addition of antipsychotics to antidepressant treatment insignificantly increased the number of adverse events.

  11. Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

    Directory of Open Access Journals (Sweden)

    Reis Helton J

    2010-06-01

    Full Text Available Abstract Background Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D2. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC: Neuronal Calcium Sensor-1 (NCS-1 and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D2 internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT and PC12 cells stably overexpressing NCS-1 (PC12 Clone with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment. Results We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol or atypical (Clozapine and Risperidone antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments. Conclusions Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.

  12. Patterns of Antipsychotic Prescription to Patients with Schizophrenia in Korea: Results from the Health Insurance Review & Assessment Service-National Patient Sample

    OpenAIRE

    Park, Seon-Cheol; Lee, Myung-Soo; Kang, Seung-Gul; Lee, Seung-Hwan

    2014-01-01

    This study aimed to analyze the patterns of antipsychotic prescription to patients with schizophrenia in Korea. Using the Health Insurance Review & Assessment Service-National Patients Sample (HIRA-NPS), which was a stratified sampling from the entire population under the Korean national health security system (2009), descriptive statistics for the patterns of the monopharmacy and polypharmacy, neuropsychiatric co-medications, and prescribed individual antipsychotic for patients with schizoph...

  13. Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology

    OpenAIRE

    Nørbak-Emig, Henrik; Ebdrup, Bjørn H; Fagerlund, Birgitte; Svarer, Claus; Rasmussen, Hans; Friberg, Lars; Allerup, Peter N.; Rostrup, Egill; Pinborg, Lars H; Glenthøj, Birte Y.

    2016-01-01

    Background: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. Methods: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Posi...

  14. Risk of Mortality (Including Sudden Cardiac Death and Major Cardiovascular Events in Atypical and Typical Antipsychotic Users: A Study with the General Practice Research Database

    Directory of Open Access Journals (Sweden)

    Tarita Murray-Thomas

    2013-01-01

    Full Text Available Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD, all-cause mortality (excluding suicide, coronary heart disease (CHD, and ventricular arrhythmias (VA. Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical, 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64–1.87; cardiac mortality 1.72 (95% CI: 1.42–2.07; SCD primary definition 5.76 (95% CI: 2.90–11.45; SCD secondary definition 2.15 (95% CI: 1.64–2.81; CHD 1.16 (95% CI: 0.94–1.44; and VA 1.16 (95% CI: 1.02–1.31. aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80–0.85; cardiac mortality 0.89 (95% CI: 0.82–0.97; and SCD secondary definition 0.76 (95% CI: 0.55–1.04. Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

  15. Agent Chameleons: Virtual Agents Real Intelligence

    OpenAIRE

    O'Hare, Gregory; Duffy, Brian; Schoen-Phelan, Bianca; Martin, Alan; Bradley, John

    2003-01-01

    Agent Chameleons provides virtual agents powered by real intelligence, delivering next generation autonomic entities that can seamlessly migrate, mutate and evolve on their journey between and within physical and digital information spaces.

  16. Assessing clinicians' perspectives about the identification and management of antipsychotic medication side-effects: Psychometric evaluation of a survey questionnaire.

    Science.gov (United States)

    Stomski, Norman J; Morrison, Paul; Meehan, Tom

    2016-04-01

    Eliciting clinicians' views about antipsychotic medication side-effects may assist in understanding strategies that could enhance the identification and management of these side-effects. The present paper details the development and psychometric evaluation of a questionnaire that captures clinicians' perceptions about these issues. An initial item set was derived from a literature review, and then refined by an expert content validity panel that assessed the relevance of the items. The online questionnaire was distributed to Australian mental health nurses and 140 fully completed questionnaires were returned. Principal components analysis yielded two robust scales that conceptually tapped "system responsibility" and "personal confidence". These scales may be used to advance knowledge about how mental health nurses' attitudes towards the assessment and management of antipsychotic medication side-effects influences their clinical behaviour.

  17. Glutamatergic Metabolites, Volume and Cortical Thickness in Antipsychotic-Naive Patients with First-Episode Psychosis: Implications for Excitotoxicity.

    Science.gov (United States)

    Plitman, Eric; Patel, Raihaan; Chung, Jun Ku; Pipitone, Jon; Chavez, Sofia; Reyes-Madrigal, Francisco; Gómez-Cruz, Gladys; León-Ortiz, Pablo; Chakravarty, M Mallar; de la Fuente-Sandoval, Camilo; Graff-Guerrero, Ariel

    2016-09-01

    Neuroimaging studies investigating patients with schizophrenia often report appreciable volumetric reductions and cortical thinning, yet the cause of these deficits is unknown. The association between subcortical and cortical structural alterations, and glutamatergic neurometabolites is of particular interest due to glutamate's capacity for neurotoxicity; elevated levels may be related to neuroanatomical compromise through an excitotoxic process. To this end, we explored the relationships between glutamatergic neurometabolites and structural measures in antipsychotic-naive patients experiencing their first non-affective episode of psychosis (FEP). Sixty antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls underwent a magnetic resonance imaging session, which included a T1-weighted volumetric image and proton magnetic resonance spectroscopy in the precommissural dorsal caudate. Group differences in precommissural caudate volume (PCV) and cortical thickness (CT), and the relationships between glutamatergic neurometabolites (ie, glutamate+glutamine (Glx) and glutamate) and these structural measures, were examined. PCV was decreased in the FEP group (pschizophrenia. PMID:27272768

  18. Atypical antipsychotics olanzapine, quetiapine, and risperidone and risk of acute major cardiovascular events in young and middle-aged adults

    DEFF Research Database (Denmark)

    Pasternak, Björn; Svanström, Henrik; Ranthe, Mattis F;

    2014-01-01

    risperidone (n = 14,134). The primary outcome was any major cardiovascular event (composite of cardiovascular mortality, acute coronary syndrome, or ischemic stroke) within 1 year following treatment initiation. Cox regression was used to estimate hazard ratios (HRs) while on current antipsychotic monotherapy......BACKGROUND: A number of serious cardiovascular safety concerns related to the use of atypical antipsychotics, compared with no use, have emerged, but nearly all reports are from studies of older patients. We aimed to compare the risk of cardiovascular events between the three most commonly used...... in the outpatient setting, adjusting for an outcome-specific disease risk score. RESULTS: The crude rate of any major cardiovascular event was 5.3 per 1,000 person-years among olanzapine users, 3.4 in quetiapine users, and 5.2 in risperidone users. Compared with risperidone, the risk of any major cardiovascular...

  19. Neural markers of negative symptom outcomes in distributed working memory brain activity of antipsychotic-naive schizophrenia patients

    DEFF Research Database (Denmark)

    Nejad, Ayna B.; Madsen, Kristoffer H.; Ebdrup, Bjørn H.;

    2013-01-01

    Since working memory deficits in schizophrenia have been linked to negative symptoms, we tested whether features of the one could predict the treatment outcome in the other. Specifically, we hypothesized that working memory-related functional connectivity at pre-treatment can predict improvement...... of negative symptoms in antipsychotic-treated patients. Fourteen antipsychotic-naive patients with first-episode schizophrenia were clinically assessed before and after 7 months of quetiapine monotherapy. At baseline, patients underwent functional magnetic resonance imaging while performing a verbal n...... but not the default mode network. These preliminary data suggest that functional patterns at baseline can predict negative symptom treatment–response in schizophrenia. This information may be used to stratify patients into subgroups thereby facilitating personalized treatment....

  20. Interacting agents in finance

    NARCIS (Netherlands)

    C. Hommes

    2008-01-01

    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response t

  1. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder

    OpenAIRE

    Correll, Christoph U.; DETRAUX, JOHAN; De Lepeleire, Jan; De Hert, Marc

    2015-01-01

    People with severe mental illness have a considerably shorter lifespan than the general population. This excess mortality is mainly due to physical illness. Next to mental illness-related factors, unhealthy lifestyle, and disparities in health care access and utilization, psychotropic medications can contribute to the risk of physical morbidity and mortality. We systematically reviewed the effects of antipsychotics, antidepressants and mood stabilizers on physical health outcomes in people wi...

  2. P-glycoprotein activity in the blood-brain barrier is affected by virus-induced neuroinflammation and antipsychotic treatment.

    Science.gov (United States)

    Doorduin, Janine; de Vries, Erik F J; Dierckx, Rudi A; Klein, Hans C

    2014-10-01

    A large percentage of schizophrenic patients respond poorly to antipsychotic treatment. This could be explained by inefficient drug transport across the blood-brain barrier due to P-glycoprotein mediated efflux. P-glycoprotein activity and expression in the blood-brain barrier can be affected by inflammation and pharmacotherapy. We therefore investigated the effect of herpes simplex virus type-1 (HSV-1) induced neuroinflammation and antipsychotic treatment on P-glycoprotein activity. Rats were inoculated with HSV-1 or PBS (control) on day 0 and treated with saline, clozapine or risperidone from day 0 up until day 4 post-inoculation. Positron emission tomography with the P-glycoprotein substrate [11C]verapamil was used to assess P-glycoprotein activity at day 6 post-inoculation. Disease symptoms in HSV-1 inoculated rats increased over time and were not significantly affected by treatment. The volume of distribution (VT) of [11C]verapamil was significantly lower (10-22%) in HSV-1 inoculated rats than in control rats. In addition, antipsychotic treatment significantly affected the VT of [11C]verapamil in all brain regions, although this effect was drug dependent. In fact, VT of [11C]verapamil was significantly increased (22-39%) in risperidone treated rats in most brain regions when compared to clozapine treated rats and in midbrain when compared to saline treated rats. No interaction between HSV-1 inoculation and antipsychotic treatment on VT of [11C]verapamil was found. In this study we demonstrated that HSV-1 induced neuroinflammation increased and risperidone treatment decreased P-glycoprotein activity. This finding is of importance for the understanding of treatment resistance in schizophrenia, and warrants further investigation of the underlying mechanism and the importance in clinical practice.

  3. An epidemiological study of concomitant use of Chinese medicine and antipsychotics in schizophrenic patients: implication for herb-drug interaction.

    Directory of Open Access Journals (Sweden)

    Zhang-Jin Zhang

    Full Text Available BACKGROUND: Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. METHODS AND FINDINGS: In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI 34.2%-38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80-4.24. However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06-4.83. Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. CONCLUSIONS: Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated.

  4. An Epidemiological Study of Concomitant Use of Chinese Medicine and Antipsychotics in Schizophrenic Patients: Implication for Herb-Drug Interaction

    Science.gov (United States)

    Zhang, Zhang-Jin; Tan, Qing-Rong; Tong, Yao; Wang, Xue-Yi; Wang, Huai-Hai; Ho, Lai-Ming; Wong, Hei Kiu; Feng, Yi-Bin; Wang, Di; Ng, Roger; McAlonan, Grainne M.; Wang, Chuan-Yue; Wong, Vivian Taam

    2011-01-01

    Background Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. Methods and Findings In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM) use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI) 34.2%–38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80–4.24). However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06–4.83). Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. Conclusions Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated. PMID:21359185

  5. A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia.

    Science.gov (United States)

    Wittkampf, Laura Christina; Arends, Johannes; Timmerman, Leo; Lancel, Marike

    2012-06-01

    Schizophrenia is characterized by reality distortion, psychomotor poverty and cognitive disturbances. These characteristics contribute to a lesser social functioning and lower quality of life in patients with schizophrenia. It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain. In this paper we review the literature relevant to the question of whether modafinil and armodafinil are beneficial as add-on therapy in antipsychotic-treated patients with schizophrenia. A total of 15 articles were included in this review; of the 15 articles, 10 were randomized controlled trials (RCTs). Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. With respect to cognitive disturbances, animal models of cognitive deficits show clear improvements with modafinil. In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to

  6. Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS: literature review and case series report

    Directory of Open Access Journals (Sweden)

    Langan Julie

    2012-11-01

    Full Text Available Abstract Background “Neuroleptic malignant syndrome” (NMS is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. Description We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1–15 to 346.9 mg/day during days 16–30 and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. Conclusions Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%, although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS.

  7. Association of different cognitive domains with lifetime history of psychosis and reported antipsychotic-treatment adverse events in bipolar disorders

    OpenAIRE

    Kałwa, Agnieszka; Piróg-Balcerzak, Agnieszka Magdalena; Święcicki, Łukasz

    2013-01-01

    Aim of the study. The present work aimed to assess the association between cognitive functions, the lifetime occurrence of psychotic symptoms, and reported adverse effects of antipsychotic treatments inpatients with bipolar disorders.Methods. In the present work, 44 bipolar disorder inpatients hospitalized in the Affective Disorders Unit of the Institute of Psychiatry and Neurology in Warsaw, were investigated. All of them met the criteria of remission and were prepared for release from the h...

  8. Association of different cognitive domains with lifetime history of psychosis and reported antipsychotic-treatment adverse events in bipolar disorders

    Directory of Open Access Journals (Sweden)

    Kałwa, Agnieszka

    2013-06-01

    Full Text Available Aim of the study. The present work aimed to assess the association between cognitive functions, the lifetime occurrence of psychotic symptoms, and reported adverse effects of antipsychotic treatments inpatients with bipolar disorders.Methods. In the present work, 44 bipolar disorder inpatients hospitalized in the Affective Disorders Unit of the Institute of Psychiatry and Neurology in Warsaw, were investigated. All of them met the criteria of remission and were prepared for release from the hospital unit. Twenty-two patients were hospitalized in the manic stage of the illness, and 22 were in the depressive stage of illness. Both groups were assessed using adequate psychiatric rating scales (HDRS or YMRS and CAMRS and neuropsychological tests (WCST, TMT, Stroop Test and Verbal Fluency Test.Results. Patients who had a prior history of psychotic symptoms had poorer verbal functioning in comparison to subjects without such a history. However, individuals hospitalized in the manic state of disease, and who reported more adverse events after antipsychotic medication during the whole course of illness, had worse results in some parameters of executive function measurements in the WCST test, namely occurring in a greater percentage of nonperseverative errors and a lower number of completed categories.Discussion. Generally the results confirm findings according to which, patients with the history of psychosis performe worse on neurocognitive tasks. However, the nature of dysfunctions found, generates questions about its relations with the experience of psychosis and antipsychotic treatment. Conclusion: Different aspects of cognitive dysfunctions may be related to the experience of psychosis and antipsychotic treatment in patients with bipolar disorders.

  9. LASSBio-579, a prototype antipsychotic drug, and clozapine are effective in novel object recognition task, a recognition memory model.

    Science.gov (United States)

    Antonio, Camila B; Betti, Andresa H; Herzfeldt, Vivian; Barreiro, Eliezer J; Fraga, Carlos A M; Rates, Stela M K

    2016-06-01

    Previous studies on the N-phenylpiperazine derivative LASSBio-579 have suggested that LASSBio-579 has an atypical antipsychotic profile. It binds to D2, D4 and 5-HT1A receptors and is effective in animal models of schizophrenia symptoms (prepulse inhibition disruption, apomorphine-induced climbing and amphetamine-induced stereotypy). In the current study, we evaluated the effect of LASSBio-579, clozapine (atypical antipsychotic) and haloperidol (typical antipsychotic) in the novel object recognition task, a recognition memory model with translational value. Haloperidol (0.01 mg/kg, orally) impaired the ability of the animals (CF1 mice) to recognize the novel object on short-term and long-term memory tasks, whereas LASSBio-579 (5 mg/kg, orally) and clozapine (1 mg/kg, orally) did not. In another set of experiments, animals previously treated with ketamine (10 mg/kg, intraperitoneally) or vehicle (saline 1 ml/100 g, intraperitoneally) received LASSBio-579, clozapine or haloperidol at different time-points: 1 h before training (encoding/consolidation); immediately after training (consolidation); or 1 h before long-term memory testing (retrieval). LASSBio-579 and clozapine protected against the long-term memory impairment induced by ketamine when administered at the stages of encoding, consolidation and retrieval of memory. These findings point to the potential of LASSBio-579 for treating cognitive symptoms of schizophrenia and other disorders. PMID:26513177

  10. LASSBio-579, a prototype antipsychotic drug, and clozapine are effective in novel object recognition task, a recognition memory model.

    Science.gov (United States)

    Antonio, Camila B; Betti, Andresa H; Herzfeldt, Vivian; Barreiro, Eliezer J; Fraga, Carlos A M; Rates, Stela M K

    2016-06-01

    Previous studies on the N-phenylpiperazine derivative LASSBio-579 have suggested that LASSBio-579 has an atypical antipsychotic profile. It binds to D2, D4 and 5-HT1A receptors and is effective in animal models of schizophrenia symptoms (prepulse inhibition disruption, apomorphine-induced climbing and amphetamine-induced stereotypy). In the current study, we evaluated the effect of LASSBio-579, clozapine (atypical antipsychotic) and haloperidol (typical antipsychotic) in the novel object recognition task, a recognition memory model with translational value. Haloperidol (0.01 mg/kg, orally) impaired the ability of the animals (CF1 mice) to recognize the novel object on short-term and long-term memory tasks, whereas LASSBio-579 (5 mg/kg, orally) and clozapine (1 mg/kg, orally) did not. In another set of experiments, animals previously treated with ketamine (10 mg/kg, intraperitoneally) or vehicle (saline 1 ml/100 g, intraperitoneally) received LASSBio-579, clozapine or haloperidol at different time-points: 1 h before training (encoding/consolidation); immediately after training (consolidation); or 1 h before long-term memory testing (retrieval). LASSBio-579 and clozapine protected against the long-term memory impairment induced by ketamine when administered at the stages of encoding, consolidation and retrieval of memory. These findings point to the potential of LASSBio-579 for treating cognitive symptoms of schizophrenia and other disorders.

  11. The predictive value of early treatment response in antipsychotic-naive patients with first-episode psychosis: Haloperidol versus olanzapine.

    Science.gov (United States)

    Rasmussen, Sean A; Rosebush, Patricia I; Anglin, Rebecca E; Mazurek, Michael F

    2016-07-30

    Early antipsychotic response predicts outcomes for psychotic patients, but recent evidence suggests that this may not be true for patients treated with olanzapine. In this study, we assessed the predictive value of early response to olanzapine or haloperidol in 75 antipsychotic-naive, first-episode psychosis inpatients. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Young Mania Rating Scale (YMRS). Regression analyses were used to determine whether improvement at week 2 or week 3 predicted improvement at hospital discharge. The majority of patients in both groups experienced a decrease in symptom severity of ≥50% at week 2. In the haloperidol group, week 2 improvement predicted improvement at discharge for all measures except the HAM-A. In the olanzapine group, week 2 improvement only predicted improvement at discharge for HAM-D scores. However, week 3 improvement in the olanzapine group predicted improvement at discharge for all measures except the HAM-A. Olanzapine non-responders at week 3 (but not week 2) benefited from having olanzapine switched to another antipsychotic. These results suggest that a 2 week trial of haloperidol is sufficient to predict treatment outcomes, while a 3 week trial is required for olanzapine. PMID:27156027

  12. Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study.

    Science.gov (United States)

    Fervaha, Gagan; Agid, Ofer; Takeuchi, Hiroyoshi; Foussias, George; Remington, Gary

    2014-07-01

    The field of schizophrenia is redefining optimal outcome, moving beyond clinical remission to a more comprehensive model including functional recovery and improved subjective well-being. Although numerous studies have evaluated subjective outcomes within the domain of subjective quality of life in patients with schizophrenia, less is known about global evaluations of subjective well-being. This study examined the effects of antipsychotic medication on overall life satisfaction in patients with chronic schizophrenia. Data were drawn from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, where participants with a DSM-IV diagnosis of schizophrenia were randomized to receive olanzapine, perphenazine, quetiapine, risperidone or ziprasidone under double-blind conditions (N=753). The primary outcome measure was prospective change in subjectively evaluated overall life satisfaction scores following 12 months of antipsychotic treatment. Psychopathology, medication side effects and functional status were also evaluated, among other variables. Patients experienced modest improvements in overall life satisfaction (d=0.22, p0.05). Change in severity of positive, negative, and depressive symptoms as well as functional status each demonstrated a small, albeit statistically significant, association with change in life satisfaction (r=0.10-0.21, p׳slife satisfaction scores (explained variance satisfaction with life. Clinicians should be aware that these two domains are not inextricably linked.

  13. Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers.

    Science.gov (United States)

    Handley, Rowena; Mondelli, Valeria; Zelaya, Fernando; Marques, Tiago; Taylor, Heather; Reinders, Antje A T S; Chaddock, Christopher; McQueen, Grant; Hubbard, Kathryn; Papadopoulos, Andrew; Williams, Steve; McGuire, Philip; Pariante, Carmine; Dazzan, Paola

    2016-07-01

    This randomized within-subject, double blind study aimed to compare the effects of a single dose of two different antipsychotics (haloperidol and aripiprazole) on cortisol, interleukin (IL)-6 and hippocampal regional Cerebral Blood Flow (rCBF) in the same 17 healthy male individuals. Subjects received a single dose of haloperidol (3mg), aripiprazole (10mg) and placebo, in a randomized order on three study appointments. We measured salivary cortisol levels at multiple time points, IL-6 levels from plasma samples, and resting cerebral blood flow (rCBF), using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T). We found significantly lower cortisol levels in the haloperidol condition (F(2,32)=5.78, p=0.007), than in either placebo (p=0.013; CI=0.45, 0.406) or aripiprazole (p=0.037; CI=-0.520, -0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22)=4.19, p=0.048) in comparison with placebo (p=0.02; CI=0.14, 1.8), but not with aripiprazole. Finally, we found a greater rCBF in the right (peak voxel: T=6.47, p<0.0001) and left (peak voxel T=5.17, p<0.01) hippocampus following haloperidol compared with placebo, and at trend level also in the left hippocampus following aripiprazole compared with placebo (T=4.07, p=0.057). These differences in hippocampal rCBF after both antipsychotics were no longer evident (haloperidol) or present at trend level (aripiprazole), after controlling for cortisol and IL-6 levels. Our findings suggest that haloperidol can directly regulate the hypothalamic-pituitary-adrenal (HPA) axis and immune system through a pharmacological action via D2 receptor antagonism. Finally, our data suggest that the increased hippocampal rCBF is a manifestation of the reduction in IL-6 and cortisol which follows the administration of haloperidol. PMID:27112637

  14. Use of second-generation antipsychotics in the acute inpatient management of schizophrenia in the Middle East

    Directory of Open Access Journals (Sweden)

    Alkhadhari S

    2015-04-01

    Full Text Available Sulaiman Alkhadhari,1 Nasser Al Zain,2 Tarek Darwish,3 Suhail Khan,4 Tarek Okasha,5 Hisham Ramy,5 Talaat Matar Tadros6 1Kuwait Center for Mental Health, Safat, Kuwait; 2Al Amal Complex for Mental Health Hospital, Dammam, Saudi Arabia; 3Behavioural Science Pavilion, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 4Jeddah Psychiatric Hospital, Jeddah, Saudi Arabia; 5Institute of Psychiatry, Ain Shams University, Cairo, Egypt; 6Ibrahim Bin Hamad Obaidallah and Seif Bin Ghubash Hospitals, Ras Alkhaimah, United Arab Emirates Background: Management of acute psychotic episodes in schizophrenic patients remains a significant challenge for clinicians. Despite treatment guidelines recommending that second-generation antipsychotics (SGAs should be used as monotherapy, first-generation antipsychotics, polypharmacy, and lower than recommended doses are frequently administered in clinical practice. Minimal data exist regarding the use of SGAs in the Middle East. The objective of this study was to examine the discrepancies between current clinical practice and guideline recommendations in the region. Methods: RECONNECT-S Beta was a multicenter, noninterventional study conducted in Egypt, Kuwait, Saudi Arabia, and the United Arab Emirates to observe the management of schizophrenic patients who were hospitalized due to an acute psychotic episode. Patients underwent one visit on the day of discharge. Demographic and medical history, together with data on antipsychotic treatment and concomitant medication during the hospitalization period and medication recommendations at discharge were recorded. Results: Of the 1,057 patients, 180 (17.0% and 692 (65.5% received SGAs as monotherapy and in combination therapy, respectively. Overall, the most frequently administered medications were given orally, and included risperidone (40.3%, olanzapine (32.5%, and quetiapine (24.6%; the doses administered varied between countries and deviated from the recommended

  15. A prospective study of monitoring practices for metabolic disease in antipsychotic-treated community psychiatric patients

    Directory of Open Access Journals (Sweden)

    Watkinson Helen MO

    2007-06-01

    Full Text Available Abstract Background Patients with severe mental illness are at increased risk for metabolic and cardiovascular disease. A number of recent guidelines and consensus statements recommend stringent monitoring of metabolic function in individuals receiving antipsychotic drugs. Methods We conducted a prospective cohort study of 106 community-treated psychiatric patients from across the diagnostic spectrum from the Northeast of England to investigate changes in metabolic status and monitoring practices for metabolic and cardiovascular disease. We undertook detailed anthropometric and metabolic assessment at baseline and follow-up, and examined clinical notes and hospital laboratory records to ascertain monitoring practices. Results A high prevalence of undiagnosed and untreated metabolic disease was present at baseline assessment. Mean follow-up time was 599.3 (SD ± 235.4 days. Body mass index (p 50% of subjects had neither blood glucose nor lipids monitored during the follow-up period. Conclusion This cohort has a high prevalence of metabolic disease and heightened cardiovascular risk. Despite the publication of a number of recommendations regarding physical health screening in this population, monitoring rates are poor, and physical health worsened during the follow-up period.

  16. A fatal intoxication related to MDPV and pentedrone combined with antipsychotic and antidepressant substances in Cyprus.

    Science.gov (United States)

    Liveri, Katerina; Constantinou, Maria A; Afxentiou, Maria; Kanari, Popi

    2016-08-01

    This is a case report of a fatal intoxication in Cyprus related to 3,4-methylenedioxypyrovalerone (MDPV) and 2-(methylamino)-1-phenylpentan-1-one (pentedrone) intake combined with antipsychotic and antidepressant substances. A 42- year old man with a history of serious psychiatric illness was found unresponsive in his bed. Seized materials were also found close to his body. The forensic autopsy reported myocardial infarction due to multidrug intoxication. Toxicology screening in blood and urine was applied. Biological specimens were analysed by enzyme immunoassay procedure and GC/MS. MDPV, pentedrone and etizolam detected and quantitated in blood and urine. Other drugs quantitated in blood were also olanzapine, mirtazapine, and ephedrine. This was the first fatal case reported in Cyprus associated with new psychoactive substances. Additionally, this was the first case reported to Early Warning System of the European Monitoring Center of Drugs and Drug Abuse (EMCDDA), related to multidrug intoxication, attributed to the consumption of cathinones, designer benzodiazepines, and other drugs. PMID:26930452

  17. Neural changes induced by antipsychotic administration in adolescence: A review of studies in laboratory rodents.

    Science.gov (United States)

    Moe, Aung Aung Kywe; Scott, James G; Burne, Thomas Hj; Eyles, Darryl W

    2016-08-01

    Adolescence is characterized by major remodelling processes in the brain. Use of antipsychotic drugs (APDs) in adolescents has increased dramatically in the last 20 years; however, our understanding of the neurobiological consequences of APD treatment on the adolescent brain has not kept the same pace and significant concerns have been raised. In this review, we examined currently available preclinical studies of the effects of APDs on the adolescent brain. In animal models of neuropsychiatric disorders, adolescent APD treatment appears to be protective against selected structural, behavioural and neurochemical phenotypes. In "neurodevelopmentally normal" adolescent animals, a range of short- and long-term alterations in behaviour and neurochemistry have been reported. In particular, the adolescent brain appears to be sensitive to long-term locomotor/reward effects of chronic atypical APDs in contrast with the outcomes in adults. Long-lasting changes in dopaminergic, glutamatergic and gamma-amino butyric acid-ergic systems induced by adolescent APD administration have been observed in the nucleus accumbens. A detailed examination of other potential target regions such as striatum, prefrontal cortex and ventral tegmental area is still required. Through identification of specific neural pathways targeted by adolescent APD treatment, future studies will expand the current knowledge on long-term neural outcomes which are of translational value. PMID:27413140

  18. Subtyping Schizophrenia by Treatment Response: Antipsychotic Development and the Central Role of Positive Symptoms.

    Science.gov (United States)

    Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Sin, Gwen Li; Foussias, George; Agid, Ofer; Farooq, Saeed; Remington, Gary

    2015-11-01

    We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.

  19. Explaining Attitudes and Adherence to Antipsychotic Medication: The Development of a Process Model

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    Martin Wiesjahn

    2014-01-01

    Full Text Available Although nonadherence to antipsychotic medication poses a threat to outcome of medical treatment, the processes preceding the intake behavior have not been investigated sufficiently. This study tests a process model of medication adherence derived from the Health Belief Model which is based on cost-benefit considerations. The model includes an extensive set of potential predictors for medication attitudes and uses these attitudes as a predictor for medication adherence. We conducted an online study of 84 participants with a self-reported psychotic disorder and performed a path analysis. More insight into the need for treatment, a higher attribution of the symptoms to a mental disorder, experience of less negative side effects, presence of biological causal beliefs, and less endorsement of psychological causal beliefs were significant predictors of more positive attitudes towards medication. The results largely supported the postulated process model. Mental health professionals should consider attitudes towards medication and the identified predictors when they address adherence problems with the patient in a shared and informed decision process.

  20. Adherence to Antipsychotic Medication in Bipolar Disorder and Schizophrenic Patients: A Systematic Review.

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    García, Saínza; Martínez-Cengotitabengoa, Mónica; López-Zurbano, Saioa; Zorrilla, Iñaki; López, Purificación; Vieta, Eduard; González-Pinto, Ana

    2016-08-01

    Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients. PMID:27307187

  1. Working alliance and its relationship to outcomes in a randomized controlled trial (RCT of antipsychotic medication

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    Wykes Til

    2013-01-01

    Full Text Available Abstract Background Long acting injections (LAI have been associated with perceptions of coercion in cross sectional studies but there have been no longitudinal studies of the effects on clinical relationships with newer depot medications. Method Randomized controlled trial with (50 participants with a diagnosis of schizophrenia randomized to risperidone LAI or oral atypical antipsychotic medication. The main outcome was the Working Alliance Inventory (WAI with background variables (symptoms, side effect, social functioning, quality of life measured before randomization and at two years. Results At follow-up (14 risperidone LAI and 16 oral medication analyses including predictors of missing data and baseline score showed a trend for those on risperidone LAI to reduce WAI score and those on oral medication showing no change. Sensitivity analyses showed (i a significant detrimental effect of LAI on WAI and (ii the pattern of results was not affected by change in symptoms over the study. Conclusion This is the first study to show that the prescription of depot atypical depot medication is associated with detrimental effects on clinical relationships after 2 years of continual treatment.

  2. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia

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    Honey, Garry D.; Bullmore, Edward T.; Soni, William; Varatheesan, Malini; Williams, Steve C. R.; Sharma, Tonmoy

    1999-01-01

    Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology. PMID:10557338

  3. The second cross-sectional study on antipsychotic drug patterns of schizophrenia in China%2006年我国十省市抗精神病药处方方式的现况调查

    Institute of Scientific and Technical Information of China (English)

    司天梅; 陈宪生; 梅其一; 栗克清; 舒良; 于欣; 马崔; 王高华; 白培深; 刘协和; 孙立忠; 师建国

    2010-01-01

    Objective To uncover the antipsychotic drug use patterns for treating schizophrenia in China in 2006, and the developing tendency from 2002 to 2006.Methods Based on the investigation in 2002, the same methods and same hospitals were selected, totally 41 hospitals from 10 provinces and cities.The investigation was conducted during 22th to 28th, May, 2006, using the revised self-made modified questionnaire.Results The total number of sample was 5898, including outpatients (46.0%) and inpatients (54.0% ) ( male: female = 51.6%: 47.4% ).The most common clinical characteristics were the personal and social dysfunction.Antipsychotic medication most frequently prescribed was clozapine (31.7%), subsequently were risperidone (30.5%), sulpiride (14.5%), chlorpromazine (10.8%),perphenazine (9.2%), quetiapine (7.2%) and haloperidol (5.8%) .The mean chlorpromazine equivalent dosage was higher in inpatients than outpatients.In all the patients, 75.6% were treated with mono-pharmacy, in which 72.7% with atypical antipsychotics (while 38.3% with typical drugs), and the percentage of patients with depot antipsychotics was 6.2%.24.4% of the patients were treated with 2 or more than 2 types of antipsychotics.The common concomitant medications were anticholinergic agents,benzodiazepine, β-receptor blockade, antidepressants and mood stabilizers, in order to control the adverse effects or augment the efficacy of antipsychotics.Conclusions Atypical drugs are the mainstream to treat schizophrenia in China, the tendency of antipsychotics prescription pattern matches the development of treatment outcome and treatment techniques for schizophrenia.%目的 调查2006年我国10省市抗精神病药处方方式;分析4年间我国抗精神病药处方方式的变化趋势.方法 按照作者2002年的调查方法,选择10省市41所精神疾病专科医院或综合医院精神科的5898例精神分裂症门诊和住院患者,于2006年5月22-28日使用自制修订的调查问卷进行精神

  4. Erythropoietin as a possible neuroprotective agent in patients with schizophrenia

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    George E. Barreto

    2015-02-01

    Full Text Available It is estimated that about 1% of the world population has Schizophrenia. Recently, even without consensus among researchers, Schizophrenia has been defined as a progressive neurodevelopmental disorder, a disease with variable progression and altered brain development. Similarly to other neurodegenerative disorders, Schizophrenia is characterized by increased cell apoptosis, glutamate excitotoxicity and oxidative stress processes. Potential protective molecules shall include neurosteroids, and antipsychotic agents that have been successfully used in diseases with similar characteristics such as Alzheimer´s Disease or Parkinson´s Syndrome. For example, erythropoietin (EPO, a hematopoietic growth factor synthesized in the liver and in the brain by astrocytes and neurons has been extensively studied as a promising neuroprotective agent. At the cellular level, it is known that EPO binds to its specific receptor, EPOR, activating a signaling cascade associated with anti-apoptotic factors such as bcl-2 and augmented expression of superoxide dismutase, in which these molecules might be trigger protective responses in the brain. In this context, understanding the mechanisms of action at the cellular and molecular level and the effects of this molecule in patients with neurodegenerative diseases will allow to establish future perspectives on the use of this cytokinin as a neuroprotective agent in patients with Schizophrenia.

  5. A Non-Interventional Naturalistic Study of the Prescription Patterns of Antipsychotics in Patients with Schizophrenia from the Spanish Province of Tarragona.

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    Ana M Gaviria

    Full Text Available The analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes.To determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain.A naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013.The most used antipsychotic was risperidone, identified in 463 (26.3% patients, followed by olanzapine in 249 (14.1%, paliperidone in 225 (12.7%, zuclopenthixol in 201 (11.4%, quetiapine in 141 (8%, aripiprazole in 100 (5.7%, and clozapine in 100 (5.7%. Almost 8 out of 10 patients (79.3% were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6% were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94-40.97, LAI (OR 9.99, 95% CI 6.45-15.45, psychiatric co-medications (OR 4.25, 95% CI 2.72-6.64, and paliperidone (OR 3.13, 95% CI 1.23-7.92 were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35-0.83 and older age (OR 0.98, 95% CI 0.97-0.99 were related to a low polypharmacy probability.Polypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or antidepressants. Polypharmacy is associated with the use of quetiapine or

  6. A longitudinal study of alterations of hippocampal volumes and serum BDNF levels in association to atypical antipsychotics in a sample of first-episode patients with schizophrenia.

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    Emmanouil Rizos

    Full Text Available BACKGROUND: Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels. METHODS: In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP. MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs. RESULTS: We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024. CONCLUSIONS: The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.

  7. QSAR–CoMSIA applied to antipsychotic drugs with their dopamine D2 and serotonine 5HT2A membrane receptors

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    SPERANTA AVRAM

    2011-02-01

    Full Text Available Antipsychotic drugs are psychiatric medication primarily used to manage psychosis (e.g., delusions or hallucinations, particularly in schizophrenia and bipolar disorder. First and second generations of antipshychotics tend to block receptors in the brain's dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets. The inhibition constant, Ki, at the level of membrane receptors is a major determinant of their pharmacokinetic behavior and, consequently, it can affect their antipsychotic activity. Here, predicted inhibition constants, Ki for 71 antipsychotics, already approved for clinical treatment, as well as representative new chemical structures which exhibit antipsychotic activity, were evaluated using 3D-QSAR–CoMSIA models. Significant values of the cross-validated correlation q2 (higher than 0.70 and the fitted correlation r2 (higher than 0.80 revealed that these models have reasonable power to predict the biological affinity of the 15 new risperidone and 12 new olanzapine derivatives in interactions with dopamine D2 and serotonin 5HT2A receptors; these compounds are suggested for further studies.

  8. MEIS1, a Promising Candidate Gene, Is Not Associated with the Core Symptoms of Antipsychotic-Induced Restless Legs Syndrome in Korean Schizophrenia Patients

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    Kang, Seung-Gul; Lee, Seung-Hwan; Kim, Leen

    2015-01-01

    Objective Restless legs syndrome (RLS) is a distressing sleep disorder to which individuals appear to be genetically predisposed. In the present study, we assumed that antipsychotic-induced RLS symptoms were attributable to differences in individual genetic susceptibility, and investigated whether MEIS1, a promising candidate gene, was associated with antipsychotic-induced RLS symptoms in schizophrenia patients. Methods All subjects were diagnosed with schizophrenia by board-certified psychiatrists using the Korean version of the Structured Clinical Interview for DSM-IV. We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. Genotyping was performed for the rs2300478 and rs6710341 polymorphisms of the MEIS1 gene. Results We divided subjects into RLS symptom (n=96) and non-symptom (n=94) groups. There was no significant between-group difference in the genotype or allele frequencies of the two polymorphisms investigated, nor in the frequency of the rs2300478-rs6710341 haplotype. Conclusion Our data do not suggest that the rs2300478 and rs6710341 polymorphisms of the MEIS1 gene are associated with the core symptoms of antipsychotic-induced RLS in schizophrenia; different genetic mechanisms may underlie antipsychotic-induced vs. primary RLS. PMID:25866529

  9. Inhibition of mouse brown adipocyte differentiation by second-generation antipsychotics.

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    Oh, Jee-Eun; Cho, Yoon Mi; Kwak, Su-Nam; Kim, Jae-Hyun; Lee, Kyung Won; Jung, Hyosan; Jeong, Seong-Whan; Kwon, Oh-Joo

    2012-09-30

    Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 μM) and partially by quetiapine (30 μM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPβ, PPARγ2, UCP-1, PGC-1α, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARγ 2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 μM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.

  10. Antipsychotic Dose Mediates the Association between Polypharmacy and Corrected QT Interval.

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    Barbui, Corrado; Bighelli, Irene; Carrà, Giuseppe; Castellazzi, Mariasole; Lucii, Claudio; Martinotti, Giovanni; Nosè, Michela; Ostuzzi, Giovanni

    2016-01-01

    Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy. PMID:26840602

  11. Metabolic syndrome and obesity among users of second generation antipsychotics: A global challenge for modern psychopharmacology.

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    Rojo, Leonel E; Gaspar, Pablo A; Silva, H; Risco, L; Arena, Pamela; Cubillos-Robles, Karen; Jara, Belen

    2015-11-01

    Second generation antipsychotics (SGAs), such as clozapine, olanzapine, risperidone and quetiapine, are among the most effective therapies to stabilize symptoms schizophrenia (SZ) spectrum disorders. In fact, clozapine, olanzapine and risperidone have improved the quality of life of billions SZ patients worldwide. Based on the broad spectrum of efficacy and low risk of extrapyramidal symptoms displayed by SGAs, some regulatory agencies approved the use of SGAs in non-schizophrenic adults, children and adolescents suffering from a range of neuropsychiatric disorders. However, increasing number of reports have shown that SGAs are strongly associated with accelerated weight gain, insulin resistance, diabetes, dyslipidemia, and increased cardiovascular risk. These metabolic alterations can develop in as short as six months after the initiation of pharmacotherapy, which is now a controversial fact in public disclosure. Although the percentage of schizophrenic patients, the main target group of SGAs, is estimated in only 1% of the population, during the past ten years there was an exponential increase in the number of SGAs users, including millions of non-SZ patients. The scientific bases of SGAs metabolic side effects are not yet elucidated, but the evidence shows that the activation of transcriptional factor SRBP1c, the D1/D2 dopamine, GABA2 and 5HT neurotransmitions are implicated in the SGAs cardiovascular toxicity. Polypharmacological interventions are either non- or modestly effective in maintaining low cardiovascular risk in SGAs users. In this review we critically discuss the clinical and molecular evidence on metabolic alterations induced by SGAs, the evidence on the efficacy of classical antidiabetic drugs and the emerging concept of antidiabetic polyphenols as potential coadjutants in SGA-induced metabolic disorders. PMID:26218604

  12. Peripherally administered oxytocin modulates latent inhibition in a manner consistent with antipsychotic drugs

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    Feifel, D.; Shilling, P. D.; Hillman, J.; Maisel, M.; Winfield, J.; Melendez, G.

    2014-01-01

    Background Peripherally administered oxytocin (OT) has produced antipsychotic drug (APD)-like effects in animal tests that are predictive of APD efficacy. However, these effects have mainly been demonstrated using animal models of schizophrenia-like deficits in prepulse inhibition (PPI) of the startle reflex. Another schizophrenia-relevant abnormality that is the basis of a predictive animal test for APD efficacy is deficient latent inhibition (LI). LI is the normal suppression of a classically conditioned response when the subject is pre-exposed to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (UCS). Conditioned taste aversion (CTA), the normal avoidance of ingesting a food or liquid by animals when its taste is associated with an aversive experience, was used to test whether OT facilitates LI consistent with APDs. Methods Brown Norway rats, known to naturally display attenuated LI, were aversively conditioned on two consecutive exposures to flavored drinking water (0.1% saccharin) by pairing it with malaise-inducing lithium chloride injections. Concurrent with conditioning, rats received subcutaneous OT (0.02, 0.1, 0.5 mg/kg) or saline. Some rats were pre-exposed to the flavored water prior to its aversive conditioning (pre-exposed) while others were not (non pre-exposed). Two days after aversive conditioning the amount of flavored water consumed during a 20-minute session was recorded. Results As expected, LI, defined as greater consumption by pre-exposed vs. non pre-exposed rats was only weakly exhibited in Brown Norway rats and OT enhanced LI by reducing CTA in pre-exposed rats in a dose-dependent manner, with the 0.02 mg/kg dose producing the strongest effect. Conclusions The facilitation of LI by OT is consistent with the effects produced by APDs and provides further support for the notion that OT has therapeutic potential for schizophrenia. PMID:25447298

  13. Metabolic Disturbances Independent of Body Mass in Patients with Schizophrenia Taking Atypical Antipsychotics

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    Lee, Jong Il

    2015-01-01

    Objective Atypical antipsychotic (AAP) treatment is associated with weight gain and metabolic disturbances such as dyslipidemia and dysglycemia. The metabolic disturbances are usually considered to develop secondary to weight gain. We performed the comparison of metabolic disturbances of three AAP group with different risk of metabolic side effect after adjusting for body mass to investigate whether any metabolic disturbances develop independently from body mass index (BMI). Methods This cross-sectional study included 174 subjects with schizophrenia who were on 1) monotherapy with clozapine (CL), olanzapine (OL), or quetiapine (QT) (n=61), 2) monotherapy with risperidone (RSP) (n=89), or 3) monotherapy with aripiprizole (ARP), or ziprasidone (ZPS) (n=24) more than 1 year. Association between the prevalence of metabolic disturbances and groups were analysed using logistic regression after adjusting confounding variables including BMI. Analysese of covariance were used to compare the AAP groups in terms of the levels of metabolic parameters. Results There were significant differences among groups in terms of the prevalence of hypertriglyceridemia (p=0.015), low HDL-cholesterol (p=0.017), and hyperglycemia (p=0.022) after adjusting for BMI. Triglyceride level (p=0.014) and the ratio of triglyceride to HDL-cholesterol (p=0.004) were significantly different among groups after adjusting for BMI. Conclusion In conclusion, metabolic disturbances are significantly different in AAP groups even after adjusting BMI. AAPs may have direct effect on metabolic parameters. Blood lipid and glucose levels should be monitored regularly regardless of whether patients tend to gain weight. PMID:25866526

  14. Involvement of Basal Ganglia network in motor disabilities induced by typical antipsychotics.

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    Jonathan Chetrit

    Full Text Available BACKGROUND: Clinical treatments with typical antipsychotic drugs (APDs are accompanied by extrapyramidal motor side-effects (EPS such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, alpha-flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat. METHODS AND FINDINGS: The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that alpha-flupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr and subthalamic nucleus (STN. Furthermore, alpha-flupentixol induced an increase in the firing rate of globus pallidus (GP neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by alpha-flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by alpha-flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP. Indeed, after selective GP lesion, alpha-flupentixol failed to induce EPS and to alter STN neuronal activity. CONCLUSION: Our study reports strong evidence to show that hypokinesia and catalepsy induced by alpha-flupentixol are triggered by dramatic changes occurring in basal ganglia network. We provide new insight into the key role of GP in the pathophysiology of APD-induced EPS suggesting that the GP can be considered as a potential target for the treatment of EPS.

  15. Novos antipsicóticos para o tratamento da esquizofrenia New antipsychotics for the treatment of schizophrenia

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    Hélio Elkis

    2007-01-01

    Full Text Available CONTEXTO: Os antipsicóticos de segunda geração representam o grande avanço na terapêutica da esquizofrenia das últimas décadas, porém nos últimos anos foram sintetizados novos antipsicóticos que estão abrindo maiores perspectivas no campo do tratamento da esquizofrenia. Alguns desses medicamentos já foram lançados, enquanto outros estão em fase de testes. OBJETIVO: Apresentar uma síntese do conhecimento dos novos antipsicóticos de segunda geração. MÉTODOS: Busca por meio do PubMed e literatura específica fornecida pelos fabricantes dos medicamentos. RESULTADOS E CONCLUSÕES: São apresentadas as principais características farmacológicas, de eficácia, segurança e tolerabilidade dos seguintes antipsicóticos: Asenapina, ACP-103, Bifeprunox, Paliperidona, Risperidona de Ação Prolongada e Sertindol.BACKGROUND: The second generation antipsychotics represent the great achievement in the treatment of schizophrenia of the last decades. However in the last years some new antipsychotics were synthesized and such new compounds may represent great perspectives for the field of the treatment of schizophrenia. Some of these compounds are in use while others are still on evaluation through clinical trials. OBJECTIVE: Summarize the current knowledge of new antipsychotics. METHODS: PubMed search as well literature provided by the manufactures. RESULTS AND CONCLUSIONS: We present the main pharmacological characteristics as well as profiles of efficacy, security and tolerability of the following compounds: Asenapine, ACP-103, Bifeprunox, Paliperidone, Long Acting Injectable Risperidone and Sertindole.

  16. Volume and asymmetry abnormalities of insula in antipsychotic-naive schizophrenia: A 3-Tesla magnetic resonance imaging study

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    Harve Shanmugam Virupaksha

    2012-01-01

    Full Text Available Context: Insula, which is a vital brain region for self-awareness, empathy, and sensory stimuli processing, is critically implicated in schizophrenia pathogenesis. Existing studies on insula volume abnormalities report inconsistent findings potentially due to the evaluation of ′antipsychotic-treated′ schizophrenia patients as well as suboptimal methodology. Aim: To understand the role of insula in schizophrenia. Materials and Methods: In this first-time 3-T magnetic resonance imaging study, we examined antipsychotic-naive schizophrenic patients (N=30 and age-, sex-, handedness- and education-matched healthy controls (N=28. Positive and negative symptoms were scored with good interrater reliability (intraclass correlation coefficient (ICC>0.9 by using the scales for negative and positive symptoms. Gray matter volume of insula and its anterior/posterior subregions were measured by using a three-dimensional, interactive, semiautomated software based on the valid method with good interrater reliability (ICC>0.85. Intracranial volume was automatically measured by using the FreeSurfer software. Results: Patients had significantly deficient gray matter volumes of left (F=33.4; Pleft in male patients in comparison with male controls (left>right (t=2.7; P=0.01. Conclusions: Robust insular volume deficits in antipsychotic-naive schizophrenia support intrinsic role for insula in pathogenesis of this disorder. The first-time demonstration of a relationship between right posterior insular deficit and negative symptoms is in tune with the background neurobiological literature. Another novel observation of sex-specific anterior insular asymmetry reversal in patients supports evolutionary postulates of schizophrenia pathogenesis.

  17. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder.

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    Correll, Christoph U; Detraux, Johan; De Lepeleire, Jan; De Hert, Marc

    2015-06-01

    People with severe mental illness have a considerably shorter lifespan than the general population. This excess mortality is mainly due to physical illness. Next to mental illness-related factors, unhealthy lifestyle, and disparities in health care access and utilization, psychotropic medications can contribute to the risk of physical morbidity and mortality. We systematically reviewed the effects of antipsychotics, antidepressants and mood stabilizers on physical health outcomes in people with schizophrenia, depression and bipolar disorder. Updating and expanding our prior systematic review published in this journal, we searched MEDLINE (November 2009 - November 2014), combining the MeSH terms of major physical disease categories (and/or relevant diseases within these categories) with schizophrenia, major depressive disorder and bipolar disorder, and the three major psychotropic classes which received regulatory approval for these disorders, i.e., antipsychotics, antidepressants and mood stabilizers. We gave precedence to results from (systematic) reviews and meta-analyses wherever possible. Antipsychotics, and to a more restricted degree antidepressants and mood stabilizers, are associated with an increased risk for several physical diseases, including obesity, dyslipidemia, diabetes mellitus, thyroid disorders, hyponatremia; cardiovascular, respiratory tract, gastrointestinal, haematological, musculoskeletal and renal diseases, as well as movement and seizure disorders. Higher dosages, polypharmacy, and treatment of vulnerable (e.g., old or young) individuals are associated with greater absolute (elderly) and relative (youth) risk for most of these physical diseases. To what degree medication-specific and patient-specific risk factors interact, and how adverse outcomes can be minimized, allowing patients to derive maximum benefits from these medications, requires adequate clinical attention and further research. PMID:26043321

  18. AgentChess : An Agent Chess Approach

    OpenAIRE

    Fransson, Henric

    2003-01-01

    The game of chess has many times been discussed and used for test purpose by science departments of Artificial Intelligence (AI). Although the technique of agent and as well multi-agent systems is quite old, the use of these offspring of AI within chess is limited. This report describes the project performed applying the use of agents to a chess program. To measure the performance of the logic has tests between the developed program main parts been performed. Further tests against a tradition...

  19. Quetiapine versus aripiprazole in children and adolescents with psychosis - protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers;

    2014-01-01

    weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. DISCUSSION: Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information......BACKGROUND: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus...... aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. METHODS/DESIGN: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients...

  20. Antipsychotic-like Effects of M4 Positive Allosteric Modulators Are Mediated by CB2 Receptor-Dependent Inhibition of Dopamine Release.

    Science.gov (United States)

    Foster, Daniel J; Wilson, Jermaine M; Remke, Daniel H; Mahmood, M Suhaib; Uddin, M Jashim; Wess, Jürgen; Patel, Sachin; Marnett, Lawrence J; Niswender, Colleen M; Jones, Carrie K; Xiang, Zixiu; Lindsley, Craig W; Rook, Jerri M; Conn, P Jeffrey

    2016-09-21

    Muscarinic receptors represent a promising therapeutic target for schizophrenia, but the mechanisms underlying the antipsychotic efficacy of muscarinic modulators are not well understood. Here, we report that activation of M4 receptors on striatal spiny projection neurons results in a novel form of dopaminergic regulation resulting in a sustained depression of striatal dopamine release that is observed more than 30 min after removal of the muscarinic receptor agonist. Furthermore, both the M4-mediated sustained inhibition of dopamine release and the antipsychotic-like efficacy of M4 activators were found to require intact signaling through CB2 cannabinoid receptors. These findings highlight a novel mechanism by which striatal cholinergic and cannabinoid signaling leads to sustained reductions in dopaminergic transmission and concurrent behavioral effects predictive of antipsychotic efficacy. PMID:27618677

  1. A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes

    DEFF Research Database (Denmark)

    de Jong, Simone; Boks, Marco P M; Fuller, Tova F;

    2012-01-01

    of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co......-expression modules associated with schizophrenia. Several of these disease related modules are likely to reflect expression changes due to antipsychotic medication. However, two of the disease modules could be replicated in an independent second data set involving antipsychotic-free patients and controls. One...... of these robustly defined disease modules is significantly enriched with brain-expressed genes and with genetic variants that were implicated in a GWAS study, which could imply a causal role in schizophrenia etiology. The most highly connected intramodular hub gene in this module (ABCF1), is located in...

  2. Differential Effects of Antipsychotic Medications on Polyunsaturated Fatty Acid Biosynthesis in Rats: Relationship with Liver Delta6-Desaturase Expression

    OpenAIRE

    McNamara, Robert K.; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W

    2011-01-01

    Polyunsaturated fatty acids (PUFA), a lipid family comprised of omega-3 (n-3) and n-6 fatty acids, are a critical component of cellular membranes, and recent in vitro studies have found that antipsychotic medications up-regulate genes responsible for PUFA biosynthesis. To evaluate this effect in vivo, rats were treated with risperidone (1.5, 3, 6 mg/kg/d), paliperidone (1.5, 3, 6 mg/kg/d), olanzapine (2.5, 5, 10 mg/kg/d), quetiapine (5, 10, 20 mg/kg/d), haloperidol (1, 3 mg/kg/d) or vehicle t...

  3. Adverse Effects of Second-Generation Antipsychotics as Adjuncts to Antidepressants: Are the Risks Worth the Benefits?

    Science.gov (United States)

    Thase, Michael E

    2016-09-01

    Over the past decades, several adjunctive therapies have been introduced for treatment-resistant depression (TRD), and these strategies have ebbed and flowed in popularity. Currently, adjunctive therapy with the second-generation antipsychotics (SGAs) is most commonly used by psychiatrists. Four SGAs are FDA approved for indications related to TRD (aripiprazole, brexpiprazole, olanzapine, and quetiapine extended release); some evidence also supports use of risperidone and ziprasidone as adjunctive therapies. This article briefly reviews the role of adjunctive therapy with SGAs in contemporary algorithms for TRD, considering both the evidence of benefit and the adverse effects. PMID:27514300

  4. Metabolic syndrome and psychiatrists' choice of follow-up interventions in patients treated with atypical antipsychotics in Denmark and Sweden

    DEFF Research Database (Denmark)

    Larsen, J. T.; Fagerquist, M.; Holdrup, M.;

    2011-01-01

    Introduction: The aim of the present study was to obtain point prevalence estimates of the metabolic syndrome according to the NCEP III criteria in a sample of patients with schizophrenia spectrum disorders treated with atypical antipsychotic drugs in Denmark and Sweden, and to assess...... population of patients with schizophrenia spectrum disorders, metabolic syndrome remains underdiagnosed and undertreated....... the psychiatrists' choice of recommendations for follow-up interventions based on the patients' laboratory results. Method: This was a cross-sectional, observational multi-center study in Denmark and Sweden, in consecutively screened in- and outpatients with schizophrenia spectrum disorders and continuously treated...

  5. Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment

    DEFF Research Database (Denmark)

    Nørbak-Emig, Henrik; Ebdrup, Bjørn H; Fagerlund, Birgitte;

    2016-01-01

    the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. METHODS: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test.......56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016). CONCLUSIONS: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association...

  6. Cognitive effects of six months of treatment with quetiapine in antipsychotic-naïve first-episode schizophrenia

    DEFF Research Database (Denmark)

    Andersen, Rune; Fagerlund, Birgitte; Rasmussen, Hans;

    2011-01-01

    Effects of quetiapine on cognition were assessed in a group of first-episode antipsychotic-naïve patients with schizophrenia (N=24). A comprehensive battery of neuropsychological tests was administered at baseline and after 6months of treatment with quetiapine. In order to examine retest effects...... on sustained attention and working memory that were found in healthy controls. The main result of the study is that there was very little evidence of efficacy of quetiapine on cognition. The study also indicated a lack of normal retest effects in patients compared to controls....

  7. Riot Control Agents

    Science.gov (United States)

    ... a person has been exposed to riot control agents. Long-term health effects of exposure to riot control agents Prolonged ... person is removed from exposure to riot control agents, long-term health effects are unlikely to occur. How you can ...

  8. Reasoning about emotional agents

    NARCIS (Netherlands)

    Meyer, J.-J.

    2008-01-01

    In this paper we discuss the role of emotions in artificial agent design, and the use of logic in reasoning about the emotional or affective states an agent can reside in. We do so by extending the KARO framework for reasoning about rational agents appropriately. In particular we formalize in this f

  9. Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: Effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Haiyun eXu

    2011-07-01

    Full Text Available Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator-feeding C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for five weeks then returned to normal food for three weeks, during which period mice were treated with different antipsychotic drugs. Various behaviors were measured at the end of CPZ-feeding phase as well as on the 14th and 21st days after CPZ-withdrawal. The damage to and recovery status of white matter in the brains of mice were examined. Dietary CPZ resulted in white matter damage and behavioral abnormalities in the elevated plus-maze, social interaction and Y-maze test. Elevated plus-maze performance recovered to normal range within two weeks after CPZ withdrawal. But, alterations in social interaction showed no recovery. Antipsychotics did not alter animals’ behavior in either of these tests during the recovery period. Altered performance in the Y-maze showed some recovery in the vehicle group; atypical antipsychotics, but not haloperidol, significantly promoted this recovery process. The recovery of damaged white matter was incomplete during the recovery period. None of the drugs significantly promoted the recovery of damaged white matter. These results suggest that CPZ-induced white matter damage and social interaction deficit may be resistant to the antipsychotic treatment employed in this study. They are in good accordance with the clinical observations that positive symptoms in schizophrenic patients respond well to antipsychotic drugs while social dysfunction is usually intractable.

  10. Agents modeling agents in information economies

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, J.M.; Durfee, E.H. [Univ. of Michigan, Ann Arbor, MI (United States)

    1996-12-31

    Our goal is to design and build agents that act intelligently when placed in an agent-based information economy, where agents buy and sell services (e.g. thesaurus, search, task planning services, etc.). The economy we are working in is the University of Michigan Digital Library (UMDL), a large scale multidisciplinary effort to build an infrastructure for the delivery of library services. In contrast with a typical economy, an information economy deals in goods and services that are often derived from unique sources (authors, analysts, etc.), so that many goods and services are not interchangeable. Also, the cost of replicating and transporting goods is usually negligible, and the quality of goods and services is difficult to measure objectively: even two sources with essentially the same information might appeal to different audiences. Thus, each agent has its own assessment of the quality of goods and services delivered.

  11. Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

    DEFF Research Database (Denmark)

    Glenthoj, Andreas; Glenthoj, Birte Y; Mackeprang, Torben;

    2007-01-01

    The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients...... or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two...

  12. Discontinuing financial incentives for adherence to antipsychotic depot medication: long-term outcomes of a cluster randomised controlled trial

    Science.gov (United States)

    Priebe, Stefan; Bremner, Stephen A; Pavlickova, Hana

    2016-01-01

    Objectives In a cluster randomised controlled trial, offering financial incentives improved adherence to antipsychotic depot medication over a 1-year period. Yet, it is unknown whether this positive effect is sustained once the incentives stop. Methods and analyses Patients in the intervention and control group were followed up for 2 years after the intervention. Primary and secondary outcomes were assessed at 6 months and 24 months post intervention. Assessments were conducted between September 2011 and November 2014. Results After the intervention period, intervention and control groups did not show any statistically significant differences in adherence, neither in the first 6 months (71% and 77%, respectively) nor in the following 18 months (68%, 74%). There were no statistically significant differences in secondary outcomes, that is, adherence ≥95% and untoward incidents either. Conclusions It may be concluded that incentives to improve adherence to antipsychotic maintenance medication are effective only for as long as they are provided. Once they are stopped, adherence returns to approximately baseline level with no sustained benefit. Trial registration number ISRCTN77769281; Results. PMID:27655261

  13. Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study

    Directory of Open Access Journals (Sweden)

    Sacristán Jose A

    2001-12-01

    Full Text Available Abstract Background In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. Method Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10, and treatment compliance was measured using a physician-rated 4 point categorical scale. Results A total of 2128 patients initiated treatment (as monotherapy with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. Conclusion Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS.

  14. Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients.

    Science.gov (United States)

    Misiak, Błażej; Frydecka, Dorota; Beszłej, Jan A; Moustafa, Ahmed A; Tybura, Piotr; Kucharska-Mazur, Jolanta; Samochowiec, Agnieszka; Bieńkowski, Przemysław; Samochowiec, Jerzy

    2016-07-01

    We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms. PMID:26836264

  15. Dermatoglyphic correlates of hippocampus volume: Evaluation of aberrant neurodevelopmental markers in antipsychotic-naïve schizophrenia.

    Science.gov (United States)

    Kalmady, Sunil V; Shivakumar, Venkataram; Gautham, S; Arasappa, Rashmi; Jose, Dania A; Venkatasubramanian, Ganesan; Gangadhar, B N

    2015-10-30

    Schizophrenia is a disorder of aberrant neurodevelopment is marked by abnormalities in brain structure and dermatoglyphic traits. However, the link between these two (i.e. dermatoglyphic parameters and brain structure) which share ectodermal origin and common developmental window has not been explored extensively. The current study examined dermatoglyphic correlates of hippocampal volume in antipsychotic-naïve schizophrenia patients in comparison with matched healthy controls. Ridge counts and asymmetry measures for palmar inter-digital areas (a-b, b-c, c-d) were obtained using high resolution digital scans of palms from 89 schizophrenia patients [M:F=48:41] and 48 healthy controls [M:F=30:18]. Brain scans were obtained for subset of subjects including 26 antipsychotic-naïve patients [M:F=13:13] and 29 healthy controls [M:F=19:10] using 3 T-MRI. Hippocampal volume and palmar ridge counts were measured by blinded raters with good inter-rater reliability using valid methods. Directional asymmetry (DA) of b-c and bilateral hippocampal volume were significantly lower in patients than controls. Significant positive correlation was found between DA and ridge count of b-c with bilateral anterior hippocampal volume. Study demonstrates the utility of dermatoglyphic markers in identifying structural changes in the brain which may form the basis for neurodevelopmental pathogenesis in schizophrenia.

  16. Does Insight Affect the Efficacy of Antipsychotics in Acute Mania?: An Individual Patient Data Regression Meta-Analysis.

    Science.gov (United States)

    Welten, Carlijn C M; Koeter, Maarten W J; Wohlfarth, Tamar D; Storosum, Jitschak G; van den Brink, Wim; Gispen-de Wied, Christine C; Leufkens, Hubert G M; Denys, Damiaan A J P

    2016-02-01

    Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients with acute mania. We used individual patient data from 7 randomized, double-blind, placebo-controlled registration studies of 4 antipsychotics in patients with acute mania (N = 1904). Insight was measured with item 11 of the Young Mania Rating Scale (YMRS) at baseline and study endpoint 3 weeks later. Treatment outcome was defined by (a) mean change score, (b) response defined as 50% or more improvement on YMRS, and (c) remission defined as YMRS score less than 8 at study endpoint. We used multilevel mixed effect linear (or logistic) regression analyses of individual patient data to assess the interaction between baseline insight and treatment outcomes. At treatment initiation, 1207 (63.5%) patients had impaired or no insight into their condition. Level of insight significantly modified the efficacy of treatment by mean change score (P = 0.039), response rate (P = 0.033), and remission rate (P = 0.043), with greater improvement in patients with more impaired insight. We therefore recommend that patients experiencing acute mania should be treated immediately and not be delayed until patients regain insight.

  17. Does Insight Affect the Efficacy of Antipsychotics in Acute Mania?: An Individual Patient Data Regression Meta-Analysis.

    Science.gov (United States)

    Welten, Carlijn C M; Koeter, Maarten W J; Wohlfarth, Tamar D; Storosum, Jitschak G; van den Brink, Wim; Gispen-de Wied, Christine C; Leufkens, Hubert G M; Denys, Damiaan A J P

    2016-02-01

    Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients with acute mania. We used individual patient data from 7 randomized, double-blind, placebo-controlled registration studies of 4 antipsychotics in patients with acute mania (N = 1904). Insight was measured with item 11 of the Young Mania Rating Scale (YMRS) at baseline and study endpoint 3 weeks later. Treatment outcome was defined by (a) mean change score, (b) response defined as 50% or more improvement on YMRS, and (c) remission defined as YMRS score less than 8 at study endpoint. We used multilevel mixed effect linear (or logistic) regression analyses of individual patient data to assess the interaction between baseline insight and treatment outcomes. At treatment initiation, 1207 (63.5%) patients had impaired or no insight into their condition. Level of insight significantly modified the efficacy of treatment by mean change score (P = 0.039), response rate (P = 0.033), and remission rate (P = 0.043), with greater improvement in patients with more impaired insight. We therefore recommend that patients experiencing acute mania should be treated immediately and not be delayed until patients regain insight. PMID:26647231

  18. The effect of verbalization strategy on wisconsin card sorting test performance in schizophrenic patients receiving classical or atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Cavallaro Roberto

    2006-01-01

    Full Text Available Abstract Background A number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed. The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST remediation, in subjects on classical vs atypical antipsychotic (AP treatment. Methods Sixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable and AP treatment (i.e. atypical vs. classical. Results Subjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs. Conclusion Subjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs.

  19. First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

    Directory of Open Access Journals (Sweden)

    Alberto Canfrán-Duque

    2016-03-01

    Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2 and LBPA (lysobisphosphatidic acid, which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1 and coatomer subunit β (β-COP were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality.

  20. First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

    Science.gov (United States)

    Canfrán-Duque, Alberto; Barrio, Luis C.; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A.; Busto, Rebeca

    2016-01-01

    First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality. PMID:26999125

  1. The ticking of the epigenetic clock: antipsychotic drugs in old age

    Directory of Open Access Journals (Sweden)

    Adonis Sfera

    2016-08-01

    Full Text Available AbstractBackground: Exposed to antipsychotic drugs (APDs, older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE, including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs, however they seldom progresses to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear.CNS small vessel disease (SVD is a well-known age-related risk factor for strokes, dementia and sudden death, which may constitute the initial CVAE-predisposing pathology. We therefore propose a two strike CVAE paradigm in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities (WMH may be directly proportional with the CVAE risk.To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1-4. Since microRNA-29 has shown efficacy against the same malignancies, and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 up-regulation, which in turn facilitates the development of SVD. Aim: to assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk.Method: we conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity, and may be relevant for CVAE

  2. THE INTEGRATED AGENT IN MULTI-AGENT SYSTEMS

    OpenAIRE

    Maleković, Mirko; Čubrilo, Mirko

    2000-01-01

    [n this paper, we characterize the integrated agent in multi-agent systems. The following result is proved: if a multi-agent system is reflexive (symmetric, transitive, Euclidean) then the integrated agent of the multi-agent system is reflexive (symmetric, transitive, Euclidean), respectively. We also prove that the analogous result does not hold for multi-agent system's serial ness. A knowledge relationship between the integrated agent and agents in a multiagent system is presented.

  3. A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment.

    Science.gov (United States)

    Song, Hong-tao; Sun, Xin-yang; Zhang, Liang; Zhao, Lin; Guo, Zhong-min; Fan, Hui-min; Zhong, Ai-fang; Niu, Wei; Dai, Yun-hua; Zhang, Li-yi; Shi, Zheng; Liu, Xiao-ping; Lu, Jim

    2014-07-01

    Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p treatment in the patient group, the symptomatology scores were significantly lower (p treatment (p treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses.

  4. Haloperidol dose when used as active comparator in randomized controlled trials with atypical antipsychotics in schizophrenia : Comparison with officially recommended doses

    NARCIS (Netherlands)

    Hugenholtz, Gerard W. K.; Heerdink, Eibert R.; Stolker, Joost J.; Meijer, Welmoed E. E.; Egberts, Antoine C. G.; Nolen, Willem A.

    2006-01-01

    Objective: To determine the doses of haloperidol as a comparator drug in randomized controlled trials (RCTs) with atypical antipsychotics in patients with schizophrenia and to compare these doses with the officially recommended doses for haloperidol in the United States and the United Kingdom. Data

  5. Costs, Control or Just Good Clinical Practice? The Use of Antipsychotic Medications and Formulary Decision-Making in Large U.S. Prisons and Jails

    Science.gov (United States)

    Veysey, Bonita M.; Stenius, Vanja; Mazade, Noel; Schacht, Lucille

    2007-01-01

    Medications are central to the psychiatric armamentorium in U.S. jails and prisons. Psychiatric medications are used both to stabilize acute symptoms as well as maintain mental health once symptoms are reduced. Both jails and prisons rely heavily on traditional antipsychotics, but both have a full array of atypical medications in their…

  6. Cognitive Effects of Antipsychotic Drugs in First-Episode Schizophrenia and Schizophreniform Disorder: A Randomized, Open-Label Clinical Trial (EUFEST)

    NARCIS (Netherlands)

    M. Davidson; S. Galderisi; M. Weiser; N. Werbeloff; W.W. Fleischhacker; R.S. Keefe; H. Boter; I.P.M. Keet; D. Prelipceanu; J.K. Rybakowski; J. Libiger; M. Hummer; S. Dollfus; J.J. López-Ibor; L.G. Hranov; W. Gaebel; J. Peuskens; N. Lindefors; A. Riecher-Roessler; R.S. Kahn

    2009-01-01

    Objective: Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive per

  7. The effects of atypical and conventional antipsychotics on reduced processing speed and psychomotor slowing in schizophrenia: A cross-sectional exploratory study

    NARCIS (Netherlands)

    Morrens, M.; Hulstijn, W.; Sabbe, B.G.C.C.

    2008-01-01

    Background: Psychomotor slowing is an intrinsic feature of schizophrenia, but little is known about its nature or to what extent it is influenced by antipsychotics. The Symbol-Digit Substitution Test (SDST) is an appropriate tool for assessing reduced processing speed, whereas performance on copying

  8. Effectiveness of antipsychotics in first-episode schizophrenia and schizophreniform disorder on response and remission : An open randomized clinical trial (EUFEST)

    NARCIS (Netherlands)

    Boter, Han; Peuskens, Joseph; Libiger, Jan; Fleischhacker, W. Wolfgang; Davidson, Michael; Galderisi, Silvana; Kahn, Rene S.

    2009-01-01

    Background: Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales. We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics (SGAs) on >= 50% response and remission. Methods: In an open rand

  9. Haloperidol dose when used as active comparator in randomized controlled trials with atypical antipsychotics in schizophrenia: Comparison with officially recommended doses

    NARCIS (Netherlands)

    Hugenholtz, Greg; Heerdink, E.R.; Stolker, J.J.; Meijer, W.E.E.; Egberts, A.C.G.; Nolen, W.A.

    2006-01-01

    Objective: To determine the doses of haloperidol as a comparator drug in randomized controlled trials (RCTs) with atypical antipsychotics in patients with schizophrenia and to compare these doses with the officially recommended doses for haloperidol in the United States and the United Kingdom. Data

  10. Augmentation of antipsychotics with glycine may ameliorate depressive and extrapyramidal symptoms in schizophrenic patients – a preliminary 10-week open-label study

    Directory of Open Access Journals (Sweden)

    Strzelecki, Dominik

    2013-07-01

    Full Text Available Aim. The objective of this study was to analyze the changes in depressive and extrapyramidal symptomatology during glycine augmentation of antipsychotic treatment in patients with schizophrenia.Materials and methods. Twenty-nine schizophrenic patients (ICD-10 with predominant negative symptoms in stable mental state participated in a 10-week open-label prospective study. Patients received stable doses of antipsychotic drugs for at least 3 months before glycine application. During the next 6 weeks patients received augmentation of antipsychotic treatment with glycine (up to 60 g per day. The first and last two weeks of observation were used to assess stability of mental state. Symptom severity was assessed using the Hamilton Depression Rating Scale (HDRS, the Positive and Negative Syndrome Scale (PANSS, and the Simpson-Angus Extrapyramidal Symptom Rating Scale (SASResults. In the studied group after 6 weeks of administration of glycine a significant improvement in depressive symptoms (reduced scores by 25.8% in HDRS, p <0.001 and reduced scoring in mood symptoms of PANSS were observed. In SAS a reduction of extrapyramidal symptoms’ severity (p <0.05 was also noted. Two weeks after the glycine augmentation the symptom severity in the HDRS, PANSS, and SAS remained at similar levels.Conclusions. Glycine augmentation of antipsychotic treatment may reduce the severity of depressive and extrapyramidal symptoms. Glycine use was safe and well tolerated.

  11. Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism.

    Science.gov (United States)

    Nagashima, Takuya; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

    2016-01-01

    Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function. PMID:27199286

  12. Differences in body mass index z-scores and weight status in a Dutch pediatric psychiatric population with and without use of second-generation antipsychotics

    NARCIS (Netherlands)

    Hoogd, S. de; Overbeek, W.A.; Heerdink, E.R.; Correll, C.U.; Graeff, E.R. de; Staal, W.G.

    2012-01-01

    OBJECTIVE: Weight gain and metabolic adverse effects of second-generation antipsychotics (SGAs) have become a major concern, particularly in youth. However, the specific contribution of SGAs versus other medications or the underlying illness is unclear. METHODS: In a chart review study of psychiatri

  13. Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication

    NARCIS (Netherlands)

    Vehof, Jelle; Risselada, Arne J.; Al Hadithy, Asmar F. Y.; Burger, Huibert; Snieder, Harold; Wilffert, Bob; Arends, Johan; Wunderink, Lex; Knegtering, Henrikus; Wiersma, Durk; Cohen, Dan; Mulder, Hans; Bruggeman, Richard

    2011-01-01

    Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor ge

  14. Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication

    NARCIS (Netherlands)

    J. Vehof (Jelle); A.J. Risselada (Arne); A.F.Y. Al Hadithy (Asmar); H. Burger (Herman); H. Snieder (Harold); B. Wilffert (Bob); J. Arends (Johan); L. Wunderink (Lex); H. Knegtering (Henrikus); D. Wiersma (Durk); D. Cohen (Daniel); H. Mulder (Hans Sipko); R. Bruggeman (Richard)

    2011-01-01

    textabstractRationale: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. Objectives: We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylchol

  15. Efficacy of Atypical Antipsychotic Medication in the Management of Behaviour Problems in Children with Intellectual Disabilities and Borderline Intelligence: A Systematic Review

    Science.gov (United States)

    Unwin, Gemma L.; Deb, Shoumitro

    2011-01-01

    The use of medications to manage problem behaviours is widespread. However, robust evidence to support their use seems to be lacking. The aim was to review research evidence into the efficacy of atypical antipsychotic medication in managing problem behaviour in children with intellectual disabilities and borderline intelligence. A systematic…

  16. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents : A systematic review of randomized, placebo controlled trials and guidelines for clinical practice

    NARCIS (Netherlands)

    De Hert, M.; Dobbelaere, M.; Sheridan, E. M.; Cohen, D.; Correll, C. U.

    2011-01-01

    Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still fre

  17. Chemical crowd control agents.

    Science.gov (United States)

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian

    2016-03-01

    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  18. Decontamination Data - Blister Agents

    Data.gov (United States)

    U.S. Environmental Protection Agency — Decontamination efficacy data for blister agents on various building materials using various decontamination solutions This dataset is associated with the following...

  19. Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications

    Science.gov (United States)

    Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A.; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique

    2016-01-01

    Purpose The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. Method A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. Results The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. Conclusions In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system. PMID:27764107

  20. Relationship between Interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naive schizophrenia: evidence for differential susceptibility?

    Directory of Open Access Journals (Sweden)

    Sunil Vasu Kalmady

    Full Text Available BACKGROUND: Various lines of evidence including epidemiological, genetic and foetal pathogenetic models suggest a compelling role for Interleukin-6 (IL-6 in the pathogenesis of schizophrenia. IL-6 mediated inflammatory response triggered by maternal infection or stress induces disruption of prenatal hippocampal development which might contribute towards psychopathology during adulthood. There is a substantial lack of knowledge on how genetic predisposition to elevated IL-6 expression effects hippocampal structure in schizophrenia patients. In this first-time study, we evaluated the relationship between functional polymorphism rs1800795 of IL-6 and hippocampal gray matter volume in antipsychotic-naïve schizophrenia patients in comparison with healthy controls. METHODOLOGY: We examined antipsychotic-naïve schizophrenia patients [N = 28] in comparison with healthy controls [N = 37] group matched on age, sex and handedness. Using 3 Tesla - MRI, bilateral hippocampi were manually segmented by blinded raters with good inter-rater reliability using a valid method. Additionally, Voxel-based Morphometry (VBM analysis was performed using hippocampal mask. The IL-6 level was measured in blood plasma using ELISA technique. SNP rs1800795 was genotyped using PCR and DNA sequencing. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms. RESULTS: Schizophrenia patients had significantly deficient left and right hippocampal volumes after controlling for the potential confounding effects of age, sex and total brain volume. Plasma IL-6 levels were significantly higher in patients than controls. There was a significant diagnosis by rs1800795 genotype interaction involving both right and left hippocampal volumes. Interestingly, this effect was significant only in men but not in women. CONCLUSION: Our first time observations suggest a significant relationship between IL-6 rs1800795 and reduced

  1. Psychiatrists' awareness of partial and nonadherence to antipsychotic medication in schizophrenia: results from an Asia–Pacific survey

    Directory of Open Access Journals (Sweden)

    Olivares JM

    2013-08-01

    Full Text Available Jose Manuel Olivares,1 Manickam Thirunavukarasu,2 Jayashri Kulkarni,3 Hong Yan Zhang,4 Mingyuan Zhang,5 Fan Zhang61Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario de Vigo, Vigo, Spain; 2Department of Psychiatry, SRM Medical College Hospital and Research Center, Tamil Nadu, India; 3Department of Psychiatry, Monash University and the Alfred Hospital, Prahran, Vic, Australia; 4Department of Psychiatry, Peking University Institute of Mental Health, Beijing, People's Republic of China; 5Department of Psychiatry, Shanghai Mental Health Center, Shanghai, People's Republic of China; 6Medical Affairs, Xian Janssen Pharmaceutical, Beijing, People's Republic of ChinaBackground: Nonadherence is a well-known problem among schizophrenia patients, among whom relapse is fivefold more likely, adversely affecting health, employment, and social functioning. The Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES survey was developed to determine the scope and causes of medication nonadherence in schizophrenia.Methods: The 20-question ADHES survey was distributed to 19,370 psychiatrists in 13 Asia–Pacific countries in January–April 2012, to ascertain psychiatrists' perceptions of antipsychotic medication adherence levels among their schizophrenia patients, reasons for partial/nonadherence, their preferred methods of assessing adherence, and strategies to improve adherence. Responses are reported as mean and range across countries.Results: Four thousand, six hundred sixty one psychiatrists (24% of recipients completed the survey (highest contributors: People's Republic of China, 1854; India, 1616. Psychiatrists perceived that 56% (range, 30%-71% of schizophrenia patients were non- or partially adherent to medication. Patients discontinue medication primarily due to lack of insight into their condition (mean, 37%; 1%–65% and because patients consider medication unnecessary when feeling better (mean, 27%; 15%–68%. Over

  2. Prevalence and trends in the use of antipsychotic medications during pregnancy in the U.S., 2001–2007: A population-based study of 585,615 deliveries

    Science.gov (United States)

    Toh, Sengwee; Li, Qian; Cheetham, T. Craig; Cooper, William O.; Davis, Robert L.; Dublin, Sascha; Hammad, Tarek A.; Li, De-Kun; Pawloski, Pamala A.; Pinheiro, Simone P.; Raebel, Marsha A.; Scott, Pamela E.; Smith, David H.; Bobo, William V.; Lawrence, Jean M.; Dashevsky, Inna; Haffenreffer, Katherine; Avalos, Lyndsay A.; Andrade, Susan E.

    2013-01-01

    Purpose To estimate the prevalence of and temporal trends in prenatal antipsychotic medication use within a cohort of pregnant women in the U.S. Methods We identified live born deliveries to women aged 15–45 years in 2001–2007 from 11 U.S. health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). We ascertained prenatal exposure to antipsychotics from health plan pharmacy dispensing files, gestational age from linked infant birth certificate files, and ICD-9-CM diagnosis codes from health plan claims files. We calculated the prevalence of prenatal use of atypical and typical antipsychotics according to year of delivery, trimester of pregnancy, and mental health diagnosis. Results Among 585,615 qualifying deliveries, 4,223 (0.72%) were to women who received an atypical antipsychotic and 548 (0.09%) were to women receiving a typical antipsychotic any time from 60 days before pregnancy through delivery. There was a 2.5-fold increase in atypical antipsychotic use during the study period, from 0.33% (95% confidence interval: 0.29%, 0.37%) in 2001 to 0.82% (0.76%, 0.88%) in 2007, while the use of typical antipsychotics remained stable. Depression was the most common mental health diagnosis among deliveries to women with atypical antipsychotic use (63%), followed by bipolar disorder (43%) and schizophrenia (13%). Conclusions The number and proportion of pregnancies exposed to atypical antipsychotics has increased dramatically in recent years. Studies are needed to examine the comparative safety and effectiveness of these medications relative to other therapeutic options in pregnancy. PMID:23389622

  3. (S)-amisulpride as a discriminative stimulus in C57BL/6 mice and its comparison to the stimulus effects of typical and atypical antipsychotics.

    Science.gov (United States)

    Donahue, Timothy J; Hillhouse, Todd M; Webster, Kevin A; Young, Richard; De Oliveira, Eliseu O; Porter, Joseph H

    2014-07-01

    Amisulpride, a substituted benzamide derivative, exerts atypical antipsychotic and antidepressant clinical effects and its (S)-stereoisomer is thought to underlie these actions. In the present study, male C57BL/6 mice were trained to discriminate (S)-amisulpride (10mg/kg, s.c.) from vehicle in a two-lever drug discrimination task for food reward. The (S)-amisulpride stimulus was rapidly acquired and was shown to be dose-related, time dependent (effective between 30 and 120min) and stereoselective: (S)-amisulpride (ED50=1.77mg/kg; 4.2µmol/kg) was about three times more potent than rac-amisulpride (ED50=4.94mg/kg; 13.4µmol/kg) and ten times more potent than (R)-amisulpride (ED50=15.84mg/kg; 42.9µmol/kg). In tests of stimulus generalization, the (S)-amisulpride stimulus generalized completely to sulpiride (ED50=12.67mg/kg; 37.1µmol/kg), a benzamide analog that also is purported to be an atypical antipsychotic, but did not fully generalize to the typical antipsychotic drug haloperidol (maximum of 45% drug-lever responding) nor to the atypical antipsychotic drugs clozapine (partial substitution of 65% drug-lever responding) or aripiprazole (~30% drug-lever responding). These results demonstrated that (S)-amisulpride appears to exert a unique discriminative stimulus effect that is similar to other benzamides, but which differs from other structural classes of antipsychotic drugs.

  4. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Vik-Mo Audun O

    2006-10-01

    Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

  5. Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic treatment

    Institute of Scientific and Technical Information of China (English)

    XU Leping; JI Juying; DUAN Yiyang; SHI Hui; ZHANG Bin; SHAO Yaqin; SUN Jian

    2007-01-01

    The aim of this study was to observe the changes in glucose metabolism after antipsychotic(APS)therapy,to note the influencing factors,as well as to dicuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin(HbA1c)levels.One hundred and fifty-two patients with schizophrenia,whose fasting plasma glucose(FPG)and 2-h plasma glucose (2hPG)in the oral glucose tolerance test(2HPG)were normal,were grouped according to the HbA1c levels,one normal and the other abnormal,and were randomly enrolled into risperidone,clozapine and chlorpromazine treatment for six weeks.The FPG and 2hPG were measured at the baseline and at the end of the study.In the group with abnormal HbA1c and clozapine therapy,2HPG was higher after the study[(9.5±1.8)mmol/L]than that before the study[(7.2±1.4)mmol/L]and the difierence was statistically significant(P<0.01).FPG had no statistically significant difference before and after the study in any group(P>0.05).HbA1c levels and drugs contributing to 2HPG at the end of study had statistical cross-action(P<0.01).In the abnormal HbA1c group,2HPG after the study was higher in the clozapine treatment group [(9.5±1.8)mmol/L]than in the risperidone treatment group [(7.4±1.7)mmol/L]and the chlorpromazine treatment group[(7.3±1.6)mmol/L].The differences were statistically significant(P<0.01).In the normal HbA1c group there was no statistically significant difierence before and after the study in any group(P>0.05).2HPG before[(7.1±1.6)mmol/L]and after the study[(8.1±1.9)mmol/L]was higher in the abnormal HbA1c group than in the normal HbA1c group[(6.2±1.4)mmol/L vs(6.5±1.4)mmol/L]with the difierence being statistically significant(P<0.01 vs P<0.001).As compared with normal HbA1c group,the relative risk (RR)of glucose metabolism disease occurrence was 4.7 in the abnormal HDA1C group wlth the difierence being statistically significant(P<0.001).Patients with abnormal HbA1c

  6. Radiographic scintiscanning agent

    International Nuclear Information System (INIS)

    A new technetium-based scintiscanning agent has been prepared comprising a water soluble sup(99m)Tc-methanehydroxydiphosphonate in combination with a reducing agent selected from stannous, ferrous, chromous and titanous salts. As an additional stabilizer salts and esters of gentisic or ascorbic acids have been used. (E.G.)

  7. Agent Development Toolkits

    CERN Document Server

    Singh, Aarti; Sharma, A K

    2011-01-01

    Development of agents as well as their wide usage requires good underlying infrastructure. Literature indicates scarcity of agent development tools in initial years of research which limited the exploitation of this beneficial technology. However, today a wide variety of tools are available, for developing robust infrastructure. This technical note provides a deep overview of such tools and contrasts features provided by them.

  8. Asimovian Adaptive Agents

    CERN Document Server

    Gordon, D F

    2011-01-01

    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  9. How do agents represent?

    Science.gov (United States)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

  10. Effects of Antipsychotics on Dentate Gyrus Stem Cell Proliferation and Survival in Animal Models: A Critical Update

    Directory of Open Access Journals (Sweden)

    Gerburg Keilhoff

    2012-01-01

    Full Text Available Schizophrenia is a complex psychiatric disorder. Although a number of different hypotheses have been developed to explain its aetiopathogenesis, we are far from understanding it. There is clinical and experimental evidence indicating that neurodevelopmental factors play a major role. Disturbances in neurodevelopment might result in alterations of neuroanatomy and neurochemistry, leading to the typical symptoms observed in schizophrenia. The present paper will critically address the neurodevelopmental models underlying schizophrenia by discussing the effects of typical and atypical antipsychotics in animal models. We will specifically discuss the vitamin D deficiency model, the poly I:C model, the ketamine model, and the postnatal ventral hippocampal lesion model, all of which reflect core neurodevelopmental issues underlying schizophrenia onset.

  11. Tobacco smoking is causally associated with antipsychotic medication use and schizophrenia, but not with antidepressant medication use or depression

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne

    2015-01-01

    BACKGROUND: Tobacco smoking is more common among patients with schizophrenia and depression than among healthy individuals. We tested the hypothesis that high tobacco smoking intensity is causally associated with antipsychotic medication use, schizophrenia, antidepressant medication use and....../or depression in the general population, and compared results with those for chronic obstructive pulmonary disease. METHODS: We used self-reported smoking intensity in cigarettes/day and a polymorphism in the CHRNA3 gene cluster (rs1051730) associated with smoking intensity, on 63,296 20-100-year......-old individuals from the Danish general population; 23,282 were never-smokers and 40,014 ever-smokers. For schizophrenia, we compared our results with those in the Psychiatric Genomics Consortium. RESULTS: In smokers, heterozygotes (CT) and homozygotes (TT) for rs1051730 genotype had higher smoking intensity...

  12. The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, M B; Fuxe, K; Werge, T;

    2002-01-01

    The adenosine A2A receptor agonist CGS 21680 has shown effects similar to dopamine antagonists in behavioural assays in rats predictive for antipsychotic activity, without induction of extrapyramidal side-effects (EPS). In the present study, we examined whether this functional dopamine antagonism...... and lack of EPS in rodents could also be observed in non-human primates. We investigated the effects of CGS 21680 on behaviours induced by D-amphetamine and (-)-apomorphine in EPS-sensitized Cebus apella monkeys. CGS 21680 was administered s.c. in doses of 0.01, 0.025 and 0.05 mg/kg, alone......-induced behaviours (unrest, stereotypies, arousal) were unaffected. EPS were not observed at any dose. At 0.05 mg/kg CGS 21680 produced vomiting. The two lower doses did not produce observable side-effects. Though the differential effect on amphetamine- and apomorphine-induced behaviours is intriguing, CGS 21680...

  13. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda;

    2003-01-01

    . To this end, we investigated the effects of xanomeline on the behavior induced by D-amphetamine and (-)-apomorphine in drug-naive Cebus apella monkeys. Antipsychotic compounds antagonize amphetamine-induced motor unrest and stereotypies in this species. Xanomeline inhibited D-amphetamine-induced motor unrest...... xanomeline was tested in EPS-sensitized Cebus apella monkeys, EPS were not observed at the dose range of xanomeline used in the D-amphetamine-apomorphine combination study (0.5-3 mg/kg). However, when xanomeline was tested at 4 mg/kg, moderate dystonia was seen in two out of three monkeys. It is concluded...... that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis....

  14. The prescribing pattern of a new antipsychotic: A descriptive study of aripiprazole for psychiatric in-patients

    DEFF Research Database (Denmark)

    Johansson, M.; Manniche, C.; Andersen, Stig Ejdrup

    2008-01-01

    (range 0-8) psychoactive drugs parallel with aripiprazole. This study demonstrates reality in psychopharmacology and quote aripiprazole as example. In day-to-day practice, aripiprazole is used as part of highly individualized regimens comprising polypharmacy and excessive dosing. Although theoretically......In June 2004, aripiprazole was marketed as a second-generation antipsychotic with an entire new mechanism of action. The objective of this descriptive study is to examine the day-to-day prescriptions of aripiprazole to an unselected population of psychiatric in-patients. From 1 February to 1 May...... 2006, present and former in-patients treated with aripiprazole were identified. Prescriptions of aripiprazole and psychoactive comedication were collected retrospectively from the patient records. Seventy-one patients, mainly schizophrenic, received aripiprazole 2.5 to 55 mg/day for median 350 days...

  15. Altered Patterns of Reward Activation in a Large Cohort of Antipsychotic Naïve First Episode Schizophrenia Patients

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne;

    2014-01-01

    not have been caught by the focused analyses. By using a multivariate approach we want to confirm previous findings in a smaller group of patients, and further we expect this method to reveal other important alterations in reward processing. METHODS 53 antipsychotic-naïve first-episode patients...... with schizophrenia and 48 age and gender matched healthy controls were included in a large first episode study. Among several other examinations, the participants went through a functional Magnetic Resonance Imaging (fMRI) while playing a monetary reward task. The functional images were analyzed using...... parts of striatum and medial and dorso-lateral prefrontal cortex LV 4 described a widespread network with group difference related the period right after the action applied to target when the outcome was uncertain. LV 5 defined among others small areas in medial prefrontal and anterior cingulated cortex...

  16. Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN).

    Science.gov (United States)

    Mattson, Margaret E; Albright, Victoria A; Yoon, Joanna; Council, Carol L

    2015-01-01

    Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional). Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN) for prevalence of emergency department (ED) visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA. PMID:26056465

  17. Risk of hospitalization for acute pancreatitis associated with conventional and atypical antipsychotics: a population-based case-control study

    DEFF Research Database (Denmark)

    Gasse, Christiane; Jacobsen, Jacob; Pedersen, Lars;

    2008-01-01

    STUDY OBJECTIVE: To examine the association of atypical and conventional antipsychotics with the risk of hospitalization for acute pancreatitis. DESIGN: Population-based, case-control study. DATA SOURCE: Health care databases of Northern Denmark. PATIENTS: A total of 3083 adults hospitalized...... as the index date for the matched control subjects. Conditional logistic regression analysis was used to estimate rate ratios (RRs) for hospitalization due to acute pancreatitis in current users (0-90 days before admission or index date) and former users (> 90 days before admission or index date) of atypical...... with acute pancreatitis (case patients) and 30,830 control subjects. MEASUREMENTS AND MAIN RESULTS: Controls were selected from the general population by using risk-set sampling and were matched to case patients by age and sex. The date of the case patients' admission for acute pancreatitis was used...

  18. Prevalence and Profile of Cognitive Deficits in a Cohort of First-Episode Antipsychotic-Naïve Schizophrenia Patients

    DEFF Research Database (Denmark)

    Jensen, Maria Høj; Glenthøj, Birte Yding; Nielsen, Mette Ødegaard;

    2014-01-01

    in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery). Premorbid intelligence is estimated using DART (Danish Adult Reading Test) and current intelligence is estimated from 4 subtests from WAIS-III (Wechsler´s Adult Intelligence Scale, 3rd ed.). Psychopathology ratings are obtained......Prevalence and profile of cognitive deficits in a cohort of first-episode antipsychotic-naïve schizophrenia patients M Høj Jensen, B Y Glenthøj, M Ødegaard Nielsen, S Wulff, B Fagerlund. Lundbeck Foundation Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Psychiatric...... Centre Glostrup, Copenhagen University Hospital Glostrup, Nordre Ringvej 29-67, 2600 Glostrup, Denmark Background and aims: Cognitive deficits are considered a core feature of schizophrenia with prevalence estimates ranging from ca. 75-85 %. These deficits are present in the early phase of the illness...

  19. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment.

    Science.gov (United States)

    Cooper, Stephen J; Reynolds, Gavin P; Barnes, Tre; England, E; Haddad, P M; Heald, A; Holt, Rig; Lingford-Hughes, A; Osborn, D; McGowan, O; Patel, M X; Paton, C; Reid, P; Shiers, D; Smith, J

    2016-08-01

    Excess deaths from cardiovascular disease are a major contributor to the significant reduction in life expectancy experienced by people with schizophrenia. Important risk factors in this are smoking, alcohol misuse, excessive weight gain and diabetes. Weight gain also reinforces service users' negative views of themselves and is a factor in poor adherence with treatment. Monitoring of relevant physical health risk factors is frequently inadequate, as is provision of interventions to modify these. These guidelines review issues surrounding monitoring of physical health risk factors and make recommendations about an appropriate approach. Overweight and obesity, partly driven by antipsychotic drug treatment, are important factors contributing to the development of diabetes and cardiovascular disease in people with schizophrenia. There have been clinical trials of many interventions for people experiencing weight gain when taking antipsychotic medications but there is a lack of clear consensus regarding which may be appropriate in usual clinical practice. These guidelines review these trials and make recommendations regarding appropriate interventions. Interventions for smoking and alcohol misuse are reviewed, but more briefly as these are similar to those recommended for the general population. The management of impaired fasting glycaemia and impaired glucose tolerance ('pre-diabetes'), diabetes and other cardiovascular risks, such as dyslipidaemia, are also reviewed with respect to other currently available guidelines.These guidelines were compiled following a consensus meeting of experts involved in various aspects of these problems. They reviewed key areas of evidence and their clinical implications. Wider issues relating to primary care/secondary care interfaces are discussed but cannot be resolved within guidelines such as these.

  20. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment.

    Science.gov (United States)

    Cooper, Stephen J; Reynolds, Gavin P; Barnes, Tre; England, E; Haddad, P M; Heald, A; Holt, Rig; Lingford-Hughes, A; Osborn, D; McGowan, O; Patel, M X; Paton, C; Reid, P; Shiers, D; Smith, J

    2016-08-01

    Excess deaths from cardiovascular disease are a major contributor to the significant reduction in life expectancy experienced by people with schizophrenia. Important risk factors in this are smoking, alcohol misuse, excessive weight gain and diabetes. Weight gain also reinforces service users' negative views of themselves and is a factor in poor adherence with treatment. Monitoring of relevant physical health risk factors is frequently inadequate, as is provision of interventions to modify these. These guidelines review issues surrounding monitoring of physical health risk factors and make recommendations about an appropriate approach. Overweight and obesity, partly driven by antipsychotic drug treatment, are important factors contributing to the development of diabetes and cardiovascular disease in people with schizophrenia. There have been clinical trials of many interventions for people experiencing weight gain when taking antipsychotic medications but there is a lack of clear consensus regarding which may be appropriate in usual clinical practice. These guidelines review these trials and make recommendations regarding appropriate interventions. Interventions for smoking and alcohol misuse are reviewed, but more briefly as these are similar to those recommended for the general population. The management of impaired fasting glycaemia and impaired glucose tolerance ('pre-diabetes'), diabetes and other cardiovascular risks, such as dyslipidaemia, are also reviewed with respect to other currently available guidelines.These guidelines were compiled following a consensus meeting of experts involved in various aspects of these problems. They reviewed key areas of evidence and their clinical implications. Wider issues relating to primary care/secondary care interfaces are discussed but cannot be resolved within guidelines such as these. PMID:27147592

  1. Psychiatrists’ awareness of partial and nonadherence to antipsychotic medication in schizophrenia: results from an Asia–Pacific survey

    Science.gov (United States)

    Olivares, Jose Manuel; Thirunavukarasu, Manickam; Kulkarni, Jayashri; Zhang, Hong Yan; Zhang, Mingyuan; Zhang, Fan

    2013-01-01

    Background Nonadherence is a well-known problem among schizophrenia patients, among whom relapse is fivefold more likely, adversely affecting health, employment, and social functioning. The Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES) survey was developed to determine the scope and causes of medication nonadherence in schizophrenia. Methods The 20-question ADHES survey was distributed to 19,370 psychiatrists in 13 Asia–Pacific countries in January–April 2012, to ascertain psychiatrists’ perceptions of antipsychotic medication adherence levels among their schizophrenia patients, reasons for partial/nonadherence, their preferred methods of assessing adherence, and strategies to improve adherence. Responses are reported as mean and range across countries. Results Four thousand, six hundred sixty one psychiatrists (24% of recipients) completed the survey (highest contributors: People’s Republic of China, 1854; India, 1616). Psychiatrists perceived that 56% (range, 30%–71%) of schizophrenia patients were non- or partially adherent to medication. Patients discontinue medication primarily due to lack of insight into their condition (mean, 37%; 1%–65%) and because patients consider medication unnecessary when feeling better (mean, 27%; 15%–68%). Over half of psychiatrists (mean, 55%; 42%–99%) assess medication adherence at every visit, almost exclusively (81%) by asking their patients, versus quantitative measures. One in three psychiatrists expressed their preference to switch to or add a long-acting antipsychotic to improve adherence (15%–82%). Conclusions The substantial prevalence of partial/nonadherence to medication demonstrates that more proactive management of patients with schizophrenia is needed to improve adherence and thereby treatment outcomes. Registration Registration of this study was not required. PMID:23976858

  2. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents.

    Science.gov (United States)

    Miyamoto, S; Miyake, N; Jarskog, L F; Fleischhacker, W W; Lieberman, J A

    2012-12-01

    Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of action of APDs have been explored over the past 40 years but none has definitively been proven effective. At the same time, the effectiveness of treatments and range of outcomes for patients are far from satisfactory. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged. Consequently, there is an urgent need for more effective and better-tolerated antipsychotic agents, and to identify new molecular targets and develop mechanistically novel compounds that can address the various symptom dimensions of schizophrenia. In recent years, a variety of new experimental pharmacological approaches have emerged, including compounds acting on targets other than the dopamine D(2) receptor. However, there is still an ongoing debate as to whether drugs selective for singe molecular targets (that is, 'magic bullets') or drugs selectively non-selective for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs' or 'intramolecular polypharmacy') will lead to more effective new medications for schizophrenia. In this context, current and future drug development strategies can be seen to fall into three categories: (1) refinement of precedented mechanisms of action to provide drugs

  3. Biological warfare agents

    Directory of Open Access Journals (Sweden)

    Duraipandian Thavaselvam

    2010-01-01

    Full Text Available The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  4. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  5. Users, Bystanders and Agents

    DEFF Research Database (Denmark)

    Krummheuer, Antonia Lina

    2015-01-01

    Human-agent interaction (HAI), especially in the field of embodied conversational agents (ECA), is mainly construed as dyadic communication between a human user and a virtual agent. This is despite the fact that many application scenarios for future ECAs involve the presence of others. This paper...... the construction of the agent’s identity, and (3) how HAI, as a mediated interaction, is framed by an asymmetric participation framework. The paper concludes by suggesting various participation roles, which may inform development of ECAs....

  6. Neurochemical and structural markers in the brain predicting best choice-of-treatment in patients with schizophrenia - The Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANS II) study

    DEFF Research Database (Denmark)

    Jessen, Kasper; Bojesen, Kirsten Borup; Sigvard, Anne Mette;

    Background: Insufficient treatment response to dopaminergic antipsychotics constitutes a major challenge in the treatment of patients with schizophrenia and seems to be related to persistently high levels of the neurotransmitter glutamate. Excess glutamate is neurotoxic and may cause the progress...

  7. Agent Standards Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The innovation of the work herein proposed is the development of standards for software autonomous agents. These standards are essential to achieve software...

  8. Programming Service Oriented Agents

    OpenAIRE

    Hirsch, Benjamin; Konnerth, Thomas; Burkhardt, Michael; Albayrak, Sahin

    2010-01-01

    This paper introduces a programming language for service-oriented agents. JADL++ combines the ease of use of scripting-languages with a state-of-the-art service oriented approach which allows the seamless integration of web-services. Furthermore, the language includes OWL-based ontologies for semantic descriptions of data and services, thus allowing agents to make intelligent decisions about service calls.

  9. Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial

    OpenAIRE

    Tek, Cenk; Guloksuz, Sinan; Srihari, Vinod H.; Reutenauer, Erin L.

    2013-01-01

    Background Obesity is a growing health problem leading to high rates of mortality and morbidity in patients with severe mental illness (SMI). The increased rate of obesity is largely attributed to antipsychotic use. The effect of antipsychotic medications on H1 and 5HT2 receptors has been associated with weight gain, but there is also a substantial amount of evidence showing that D2 receptor blockade may be responsible for weight gain by interacting with the dopamine-opioid system. Unfortunat...

  10. Antipsychotic Medications in Major Depression and the Association with Treatment Satisfaction and Quality of Life:Findings of Three National Surveys on Use of Psychotropics in China Between 2002 and 2012

    Institute of Scientific and Technical Information of China (English)

    Yu-Xi Wang; Yu-Tao Xian; Yun-Ai Su; Qian Li; Liang Shu; Chee H Ng; Gabor S Ungvari

    2015-01-01

    Background:Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice.Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression,but few studies have investigated trends and patterns of their use over time.This study aimed to examine the prescription patterns of antipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life (QOL).Methods:A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012.Patients' socio-demographic and clinical characteristics including psychopathology,medication side effects,satisfaction with treatment and QOL were recorded using a standardized protocol and data collection.Results:The frequency ofantipsychotic use was 24.9% in the whole sample;the corresponding figures were 17.1%,20.3%,and 32.8% in 2002,2006,and 2012,respectively (x2 =90.3,df=2,P < 0.001).Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations,longer illness duration,greater side effects,and more likely to be treated as inpatients and in major hospitals (i.e.,Levcl-Ⅲ hospital).Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups.Conclusions:Concurrent antipsychotic use was found in about one in four treated depressed patients in China,which has increased over a 10-year period.Considering the association of drug-induced side effects and the lack of patients' and relatives' satisfaction with antipsychotic treatment,further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.

  11. Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder

    Science.gov (United States)

    Umehara, Hidehiro; Numata, Shusuke; Tajima, Atsushi; Nishi, Akira; Nakataki, Masahito; Imoto, Issei; Sumitani, Satsuki; Ohmori, Tetsuro

    2016-01-01

    Background Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. Methods We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. Results While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. Conclusions Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients. PMID:27281126

  12. Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2)-deficient mice: do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?

    Science.gov (United States)

    O'Callaghan, Matthew J; Bay-Richter, Cecilie; O'Tuathaigh, Colm Mp; Heery, David M; Waddington, John L; Moran, Paula M

    2014-10-01

    Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner's 'two-headed' model indicates that antipsychotics not only reverse LI disruption, 'disrupted LI', but also potentiate LI when low/absent in controls, 'persistent' LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2 -/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1 -/- and wild-type mice, indicating no such moderation in Drd1 -/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis. PMID:25122042

  13. Atypical antipsychotics in the treatment of bipolar depression%非典型抗精神病药物治疗双相抑郁

    Institute of Scientific and Technical Information of China (English)

    吴彦; 杨杰; 施慎逊

    2012-01-01

      Bipolar depression is a type of bipolar disorder which is hard to treat. Atypical antipsychotics, which have mood-stabilizing effect, are mainly used to treat bipolar mania, but their influence on bipolar depression remains controversial. Some atypical antipsychotics are effective in the treatment of bipolar depression.%  双相抑郁是双相障碍的一种发作形式,临床治疗困难。非典型抗精神病药物具有心境稳定作用,目前主要用于治疗双相躁狂,但对双相抑郁的治疗尚有争议。部分非典型抗精神病药物治疗双相抑郁有效。

  14. Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Raghava, Jayachandra M; Nielsen, Mette Ødegaard;

    2016-01-01

    of fractional anisotropy (FA) using voxelwise tract-based spatial statistics (TBSS) and anatomic region of interest (ROI)-based analyses. Subsequently, patients underwent 6 weeks of antipsychotic monotherapy with amisulpride. We repeated the examinations after 6 weeks. RESULTS: We included 38 patients...... longitudinal fasciculus (z = -3.31, p= 0.001). At re-examination, all correlations between positive symptoms and frontal fasciculi had resolved. Fractional anisotropy in the ATR increased more in patients than in controls (z = -4.92, pamisulpride dose correlated positively with FA changes...... in the right CT (t= 2.52, p= 0.019). LIMITATIONS: Smoking and a previous diagnosis of substance abuse were potential confounders. Long-term effects of amisulpride on white matter were not evaluated. CONCLUSION: Antipsychotic-naive patients with schizophrenia displayed subtle deficits in white matter...

  15. Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients

    DEFF Research Database (Denmark)

    Düring, Signe; Glenthøj, Birte Y; Andersen, Gitte Saltoft;

    2014-01-01

    , the effects of a potent D2/D3 receptor antagonist, amisulpride, were investigated on PPI and P50 gating in a large sample of antipsychotic-naive, first-episode patients with schizophrenia. A total of 52 initially antipsychotic-naive, first-episode schizophrenia patients were assessed for their P50 gating, PPI......, and habituation/sensitization abilities at baseline and after 2 and 6 weeks of treatment with flexible doses of amisulpride. In addition, 47 matched healthy controls were assessed at baseline and after 6 weeks. At baseline, the patients showed significantly reduced PPI, yet normal levels of P50 gating......, habituation, and sensitization. Treatment with amisulpride showed no effects on these measures, either at 2 or 6 weeks of follow-up. This is the first study investigating the effects of monotherapy with a relatively selective dopamine D2/D3 receptor antagonist (amisulpride) on sensory and sensorimotor gating...

  16. Effects of Blocking D2/D3 Receptors on Mismatch Negativity and P3a Amplitude of Initially Antipsychotic Naïve, First Episode Schizophrenia Patients

    DEFF Research Database (Denmark)

    Düring, Signe; Glenthøj, Birte Yding; Oranje, Bob

    2016-01-01

    in mismatch negativity and P3a amplitude are related to increased dopaminergic activity. This is the first study investigating the effect of amisulpride, a potent D2-antagonist, on mismatch negativity and P3a amplitude in a large group of antipsychotic-naïve, first-episode schizophrenia patients. METHODS......: Fifty-one antipsychotic-naïve, first-episode schizophrenia patients were tested in a mismatch negativity paradigm at baseline and after 6 weeks of treatment with amisulpride. We further examined 48 age- and gender-matched controls in this paradigm. RESULTS: At baseline, the patients showed significantly...... reduced P3a amplitude compared with healthy controls, but no differences in mismatch negativity. Although the treatment with amisulpride significantly improved the patients' psychopathological (PANSS) and functional (GAF) scores, it did not influence their mismatch negativity amplitude, while also...

  17. Biological Warfare Agents

    Directory of Open Access Journals (Sweden)

    Dev Vrat Kamboj

    2006-10-01

    Full Text Available There is a long historic record of use of biological warfare (BW agents by warring countriesagainst their enemies. However, the frequency of their use has increased since the beginningof the twentieth century. World war I witnessed the use of anthrax agent against human beingsand animals by Germans, followed by large-scale field trials by Japanese against war prisonersand Chinese population during world war II. Ironically, research and development in biologicalwarfare agents increased tremendously after the Geneva Protocol, signed in 1925, because ofits drawbacks which were overcome by Biological and Toxin Weapons Convention (BTWC in1972. Biological warfare programme took back seat after the 1972 convention but biologicalagents regained their importance after the bioterrorist attacks of anthrax powder in 2001. In thelight of these attacks, many of which turned out to be hoax, general awareness is required aboutbiological warfare agents that can be used against them. This review has been written highlightingimportant biological warfare agents, diseases caused by them, possible therapies and otherprotection measures.

  18. Unremitting Impulsive Aggression in a Child with Childhood Onset Schizophrenia and Pervasive Development Disorder-Not Otherwise Specified: The Role of Stimulants, Atypical Antipsychotics and Mood Stabilizers

    OpenAIRE

    Taşkıran, Sarper; Coffey, Barbara J.

    2013-01-01

    Advanced Pediatric Psychopharmacology Unremitting Impulsive Aggression in a Child with Childhood Onset Schizophrenia and Pervasive Development Disorder-Not Otherwise Specified: The Role of Stimulants, Atypical Antipsychotics and Mood Stabilizers Presenter: Sarper Taskiran, MD1 Discussant: Barbara J. Coffey, MD, MS2 Chief Complaint and Presenting Problem C. is a 7 ½-year-old, right-handed, elementary school student in a special education class, who carries a...

  19. New Insights in the Management of Antipsychotics in the Treatment of Schizophrenia in a Patient with Prolactinoma: A Case Report and Review of the Literature

    OpenAIRE

    Elvis Henrique Santos Andrade; Pedro Mario Pan; Paula F. Ramalho da Silva; Ary Gadelha

    2010-01-01

    Prolactinomas are the commonest pituitary adenomas and the major pathological cause of hyperprolactinaemia. Symptomatic prolactinomas are treated mainly by dopamine agonists; surgery and radiotherapy are options for nonresponders. Schizophrenia treatment is based on antipsychotics, which acts mainly at serotonergic and dopaminergic systems. We report a case of a 39-year-old schizophrenic male patient that was diagnosed with a macroprolactinoma 8 years after his first psychotic episode. The a...

  20. Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials

    OpenAIRE

    Michele Fornaro; Brendon Stubbs; Domenico De Berardis; Giampaolo Perna; Alessandro Valchera; Nicola Veronese; Marco Solmi; Licínia Ganança

    2016-01-01

    Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label...