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Sample records for antipsychotic drug chlorpromazine

  1. 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

  2. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin

    2009-01-01

    -glycoprotein in cancer cells. In this study, we have investigated the effect of chlorpromazine on tamoxifen response of human breast cancer cells. We found that chlorpromazine worked synergistically together with tamoxifen with respect to reduction of cell growth and metabolic activity, both in the antiestrogen......-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen...

  3. Comparative Cytochrome P450 In Vitro Inhibition by Atypical Antipsychotic Drugs

    OpenAIRE

    Guillermo Gervasini; Caballero, Maria J.; Carrillo, Juan A.; Julio Benitez

    2013-01-01

    The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5  μ M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1′-hydroxybufuralol (IC50 range, 3.5–25.5  μ M). Olanzapine inhibited CYP3A-catalyze...

  4. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    van Marum, Rob J.; Wegewijs, Michelle A.; Loonen, Anton J. M.; Beers, Erna

    2007-01-01

    Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Methods Case reports of hypothermia in APD-users found in PUBMED or E

  5. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    Marum, R.J. van; Wegewijs, M.A.; Loonen, A.J.M.; Beers, E.

    2007-01-01

    Objective: Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method: Case reports of hypothermia in APD-users found in PUBMED or

  6. [Photodegradation of chlorpromazine, a drug-related adverse event].

    Science.gov (United States)

    Chabi, Yossounon; Brahim, Kheira; Da Costa, Maryline; Caffin, Anne-Gaëlle; Camus, Gisèle; Paillet, Michel; Bohand, Xavier

    2016-04-01

    The photodegradation of an active substance during treatment is a rare drug-related adverse event which can sometimes have serious consequences. Health professionals must be aware of the specific storage and administration instructions with regard to chlorpromazine and ensure that they are respected.

  7. 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

  8. A case of tinnitus induced by chlorpromazine in a pediatric patient

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    Carla Carnovale

    2014-01-01

    Full Text Available Chlorpromazine is a well-known antipsychotic agent that binds with a variety of receptors in the central nervous system. To date, chlorpromazine has never been associated with onset of hearing disorders and tinnitus. We report on an unexpected suspect adverse reaction to chlorpromazine that occurred in a 12-year-old boy, affected by severe generalized anxiety disorder. After treatment with chlorpromazine, the patient experienced an enhanced sensitivity to sounds accompanied by perception of noises of the buzzing or ringing type. This clinical case is of great clinical interest as chlorpromazine is not currently included among potentially ototoxic drugs.

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

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    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.

  10. Temporal and spatial transcriptional fingerprints by antipsychotic or propsychotic drugs in mouse brain.

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    Kensuke Sakuma

    Full Text Available Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs, raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR. Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist, olanzapine (antagonist, and aripiprazole (partial agonist all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development.

  11. The effect of anti-parkinsonian drugs on chlorpromazine-induced depression of operant behaviour.

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    Székely, J I; Dunai-Kovács, Z; Borsy, J

    1976-01-01

    Rats were conditioned in automatic Skinner boxes on a discrete trial avoidance-escape schedule. The chlorpromazine-induced conditioned reflex inhibition could be reversed by apomorphine and amantadine, but not by atropine, trihexyphenidyl and diethazine. These findings seem to provide an additional tool for differentiating the atropine-like and dopaminergic anti-parkinsonian drugs.

  12. [A difficult stabilisation. Chlorpromazine in the fifties in Belgium].

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    Majerus, Benoît

    2010-01-01

    Through a Belgian case study the article tries to trace the gradual stabilisation of chlorpromazine as an antipsychotic in the 1950s. By varying ranges and angles of approach it shows the heterogeneity of actors involved and the semantic bricolage that accompany the marketing of the first antipsychotic. Far from being a revolution, the presence of Largactil in psychiatric practice is rather characterised by integration into a wider range of medicines and sinuous searching to give sense to this new drug.

  13. NOVEL ATYPICAL ANTIPSYCHOTIC AGENTS

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    Vijay Vinay

    2011-05-01

    Full Text Available Antipsychotics are a group of drugs commonly but not exclusively used to treat psychosis. Antipsychotic agents are grouped in two categories: Typical and Atypical antipsychotics. The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. The first atypical anti-psychotic medication, clozapine, was discovered in the 1950s, and introduced in clinical practice in the 1970s. Both typical and atypical antipsychotics are effective in reducing positive and negative symptoms of schizophrenia. Blockade of D2 receptor in mesolimbic pathway is responsible for antipsychotic action. Typical antipsychotics are not particularly selective and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects. Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2-receptor binding and high ratio of serotonin type 2 (5-HT2-receptor binding to D2. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, narcoleptic malignant syndrome, and hyperprolactinemia. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs and tardive dyskinesia (TD.

  14. [Treatment of tics in Tourette syndrome with atypical antipsychotic drugs].

    Science.gov (United States)

    Sindø, Ingrid; Jørgensen, Jan Ib

    2002-08-05

    We reviewed articles in English dealing with research into the effect of atypical antipsychotic drugs on tic reduction in Tourette's syndrome. In Denmark, there are four registered atypical antipsychotic drugs; clozapine, sulpiride, olanzapine, and risperidone. The topic of interest is the effectiveness and side effects of these drugs as compared to the conventional antipsychotic, pimozide, which is today the preferred pharmacological treatment of Tourette's syndrome among the antipsychotics. The conclusion is that risperidone would be a good first-line antipsychotic drug for the treatment of Tourette's syndrome. It is as effective as pimozide, its side effect profile is overall much more favourable, and unlike pimozide it does not contain the risk of causing heart arrhythmia.

  15. A comparative study of the plasma membrane permeabilization and fluidization induced by antipsychotic drugs in the rat brain

    OpenAIRE

    Murata, Tetsuhito; Maruoka, Nobuyuki; Omata, Naoto; Takashima, Yasuhiro; Fujibayashi, Yasuhisa; Yonekura, Yoshiharu; Wada, Yuji

    2007-01-01

    We compared the potency of the interaction of three antipsychotic drugs, i.e., chlorpromazine (CPZ), haloperidol (HAL) and sulpiride (SUL), with the plasma membrane in the rat brain. CPZ loading ( 100 M) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concent...

  16. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs.

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    Trollor, Julian N; Chen, Xiaohua; Sachdev, Perminder S

    2009-01-01

    Neuroleptic malignant syndrome (NMS) is a rare but potentially severe idiosyncratic adverse reaction usually seen in the context of treatment with antipsychotic drugs. Although NMS is historically associated with the classic or 'typical' antipsychotic drugs, it is also a potential adverse effect of atypical antipsychotic drugs. The widespread use of atypical antipsychotic drugs highlights the need to examine the data relating to the symptomatology, diagnosis, classification and management of NMS with these newer agents. We used MEDLINE and EMBASE to identify NMS case reports and systematic reviews published to June 2008 related to the atypical antipsychotic drugs clozapine, olanzapine, risperidone, paliperidone, aripiprazole, ziprasidone, amisulpride and quetiapine. Case reports and reviews were systematically examined. Our review suggests that, in general, NMS associated with atypical antipsychotic drugs manifests in a typical manner. One notable exception is clozapine-induced NMS, which appears less likely to manifest with extrapyramidal features, including rigidity and tremor. The available literature highlights the divergence of opinion relating to the core diagnostic features of NMS and its conceptualization as a categorical versus dimensional disorder. Both these issues have relevance for the identification of atypical or milder forms of NMS, which are sometimes seen with atypical antipsychotic drugs.

  17. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

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    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.

  18. 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...

  19. 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...

  20. Hyperprolactinemia with antipsychotic drugs in children and adolescents.

    Science.gov (United States)

    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-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  1. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

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    Arlan L. Rosenbloom

    2010-01-01

    Full Text Available 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-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  2. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Rosenbloom ArlanL

    2010-08-01

    Full Text Available 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-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide. OBJECTIVE......: To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses......, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012...

  4. Sudden cardiac death secondary to antidepressant and antipsychotic drugs.

    Science.gov (United States)

    Sicouri, Serge; Antzelevitch, Charles

    2008-03-01

    A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use.

  5. Prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital, Assam

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    Pinaki Chakravarty

    2016-01-01

    Full Text Available Objective: To study the prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital (SMCH of Assam. Methods: It is a prospective cross-sectional study which was carried out for three months from August to November 2015 in the outpatient department of psychiatry. All patients irrespective of their ages and sexes were included in this study. Inpatients, referred patients, patients not willing to give consent, patients of epilepsy as well as those cases where diagnoses were not certain were excluded from the study. The prescription patterns of antipsychotic drugs and the occurrences of various psychiatric diseases on both the sexes were studied after taking permission from the Institutional Ethical Committee (SMCH. Results: A total of 112 prescriptions were analysed. The most common disease was found to be schizophrenia. Total drugs prescribed were 265 and average number of drugs per prescription was 2.36. It was seen that out of the 112 prescriptions, monotherapy was practiced in 19.64% (22 compared to polytherapy in 80.35% (90. Out of 265 prescribed drugs atypical antipsychotics were 112 (42.26%, typical antipsychotics 12 (4.52%, antiepileptics 57 (21.50%, antidepressants 29 (10.94%, antiparkinsonian 29 (10.94%, and others 26 (9.81%. Antipsychotics given orally were 122 of which olanzapine was 54 (44.26%, risperidone 40 (32.78%, chlorpromazine ten (8.19%, quetiapine eight (6.55%, aripiprazole five (4.09%, amisulpiride five (4.09% were seen. Injectable antipsychotics were two, of which only haloperidol two (100%. Antipsychotics in combination prescription with same groups were 14 (12.5%, with antidepressants, antipileptics, antiparkinsonian were 88 (78.57% and other agents were ten (8.92%, which included pantoprazole, multivitamins, and benfotiamine. Conclusion: This study shows that atypical antipsychotics are the most common drugs prescribed in patients with psychotic illness and

  6. Antipsychotic-induced extrapyramidal syndromes - Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, [No Value; de Boer, A; Herings, RMC; Roos, RAC; Jansen, PAF; Leufkens, HGM

    2001-01-01

    Aim: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous clinica

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

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    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.

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

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    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.

  9. Behavioral indices in antipsychotic drug discovery.

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    Porsolt, Roger D; Moser, Paul C; Castagné, Vincent

    2010-06-01

    Schizophrenia is characterized by three major symptom classes: positive symptoms, negative symptoms, and cognitive deficits. Classical antipsychotics (phenothiazines, thioxanthenes, and butyrophenones) are effective against positive symptoms but induce major side effects, in particular, extrapyramidal symptoms (EPS). The discovery of clozapine, which does not induce EPS and is thought effective against all three classes of symptom, has driven research for novel antipsychotics with a wider activity spectrum and lower EPS liability. To increase predictiveness, current efforts aim to develop translational models where direct parallels can be drawn between the processes studied in animals and in humans. The present article reviews existing procedures in animals for their ability to predict compound efficacy and EPS liability in relation to their translational validity. Rodent models of positive symptoms include procedures related to dysfunction in central dopamine and glutamatergic (N-methyl-D-aspartate) and serotonin (5-hydroxytryptamine) neurotransmission. Procedures for evaluating negative symptoms include rodent models of anhedonia, affective flattening, and diminished social interaction. Cognitive deficits can be assessed in rodent models of attention (prepulse inhibition) and of learning/memory (object and social recognition, Morris water maze and operant-delayed alternation). The relevance of the conditioned avoidance response is also discussed. A final section reviews procedures for assessing EPS liability, in particular, parkinsonism (catalepsy in rodents), acute dystonia (purposeless chewing in rodents, dystonia in monkeys), akathisia (defecation in rodents), and tardive dyskinesia (long-term antipsychotic treatment in rodents and monkeys). It is concluded that, with notable exceptions (attention, learning/memory, EPS liability), current predictive models for antipsychotics fall short of clear translational validity.

  10. Chlorpromazine-induced status epilepticus: A case report

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    Momčilović-Kostadinović Dragana

    2013-01-01

    Full Text Available Introduction. It is largely known that some antipsychotic agents could have proconvulsive and proepileptogenic effects in some patients and could induce EEG abnormalities as well. However, the association of status epilepticus with certain antipsychotic drugs has been very rarely reported. Case Report. A case of an 18-year-old adolescent girl, with chlorpromazine therapy started for anxiety-phobic disorder was reported. Her personal history disclosed delayed psychomotor development. Shortly after the introduction of the neuroleptic chlorpromazine therapy in minimal daily dose (37.5 mg, she developed myoclonic status epilepticus, confirmed by the EEG records. Frequent, symmetrical bilateral myoclonic jerks and altered behavior were associated with bilateral epileptiform discharges of polyspikes and spike-wave complexes. This epileptic event lasted 3.5 hours and it was stopped by the parenteral administration of valproate and lorazepam; she was EEG monitored until stable remission. Status epilepticus as initial epileptic event induced by neuroleptic agent was not previously reported in our national literature. Conclusion. Introduction of chlorpromazine to a patient without history of seizures is associated with the evolution of an epileptic activity, including the occurrence of status epilepticus. Clinical evaluation of the risk factors possibly related to chlorpromazine-induced seizure is recommended in individual patients before administering this drug.

  11. Antipsychotic drug use and risk of pneumonia in elderly people

    NARCIS (Netherlands)

    Knol, Wilma; Van Marum, Rob J.; Jansen, Paul A. F.; Souverein, Patrick C.; Schobben, Alfred F. A. M.; Egberts, Antoine C. G.

    2008-01-01

    OBJECTIVES: To investigate the association between antipsychotic drug use and risk of pneumonia in elderly people. DESIGN: A nested case-control analysis. SETTING: Data were used from the PHARMO database, which collates information from community pharmacies and hospital discharge records. PARTICIPAN

  12. 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

  13. Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.

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    Oka, Takuro; Hamamura, Takashi; Lee, Youmei; Miyata, Shinji; Habara, Toshiaki; Endo, Shiro; Taoka, Hideki; Kuroda, Shigetoshi

    2004-11-26

    Acute administration of typical and atypical antipsychotics has been reported to induce regionally distinct patterns of c-Fos expression in the rat forebrain. Furthermore, atypical index, the difference in the extent of increased Fos-like immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into typical or atypical antipsychotics. The present study was conducted to investigate the atypical properties of 24 antipsychotics that are used in Japan and blonanserin, a novel 5-HT2A and D2 receptor antagonist. We systematically examined the effects of the drugs on Fos-LI in the NAc and DLSt in the rat brain using immunohistochemistry and calculated the atypical index, comparing with those of haloperidol and clozapine. Floropipamide, oxypertine, nemonapride, pimozide and mosapramine, as well as clozapine, olanzapine, quetiapine and risperidone, showed high positive atypical index. Zotepine, perospirone, sulpiride, moperone, sultopride, thioridazine, carpipramine, clocapramine and blonanserin showed moderate ones. In contrast, fluphenazine, bromperidol, timiperone, spiperone, propericiazine, perphenazine, chlorpromazine and levomepromazine had negative atypical index like haloperidol. These results suggest that not only so-called atypical antipsychotics, but also several conventional drugs, possess atypical properties.

  14. 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

  15. Potential adverse effects of discontinuing psychotropic drugs. Part 3: Antipsychotic, dopaminergic, and mood-stabilizing drugs.

    Science.gov (United States)

    Howland, Robert H

    2010-08-01

    Abrupt discontinuation of antipsychotic drugs in patients with schizophrenia is associated with earlier, and often more severe, illness episodes than are seen with gradual discontinuation. Antipsychotic drugs can cause various abnormal motor syndromes, but abruptly stopping them has been associated with the seemingly paradoxical development of similar motor syndromes, such as withdrawal dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant syndrome. Dopamine-releasing and dopamine-agonist drugs are used to treat some of the motor syndromes caused by antipsychotic drugs, but their abrupt discontinuation can also be associated with abnormal syndromes. When antipsychotic drugs, lithium, or certain anticonvulsant drugs are used for treatment of bipolar disorder, rapid versus gradual discontinuation is more likely to lead to greater mood instability and manic relapse. If necessary, these medications should be gradually tapered to minimize all types of adverse discontinuation effects. Patients should be educated about the possible adverse effects of abrupt medication discontinuation.

  16. The influence of atypical antipsychotic drugs on sexual function

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    Just MJ

    2015-07-01

    Full Text Available Marek J Just Department of General and Endocrine Surgery, Piekary Medical Centre, Piekary Slaskie, Poland Abstract: Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido, physiological arousal (lubrication/erection, orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (α-adrenergic, dopaminergic, histaminic, and muscarinic. Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. Keywords: schizophrenia, galactorrhea, hyperprolactinemia, mood disorders, anorgasmia

  17. A comparative study of the plasma membrane permeabilization and fluidization induced by antipsychotic drugs in the rat brain.

    Science.gov (United States)

    Murata, Tetsuhito; Maruoka, Nobuyuki; Omata, Naoto; Takashima, Yasuhiro; Fujibayashi, Yasuhisa; Yonekura, Yoshiharu; Wada, Yuji

    2007-10-01

    We compared the potency of the interaction of three antipsychotic drugs, i.e. chlorpromazine (CPZ), haloperidol (Hal) and sulpiride (Sul), with the plasma membrane in the rat brain. CPZ loading (> or = 100 microM) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concentration of Hal (1 mM) was required to observe these effects. However, Sul failed to change membrane permeability and fluidity even at a high concentration (1 mM). These results indicated the following ranking of the potency to interact with the membrane: CPZ>Hal>Sul. The difference among antipsychotic drugs in the potency to interact with the plasma membrane as revealed in the present study may be partly responsible for the difference among the drugs in the probability of inducing extrapyramidal side-effects such as parkinsonism and tardive dyskinesia.

  18. Atypical antipsychotic drugs and tardive dyskinesia: relevance of D2 receptor affinity.

    Science.gov (United States)

    Bressan, Rodrigo A; Jones, Hugh M; Pilowsky, Lyn S

    2004-03-01

    Evidence suggests atypical antipsychotic treatment is associated with a lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for olanzapine alleviated her TD symptoms. The case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D2 receptor occupancy by atypical antipsychotic drugs for TD.

  19. Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

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    Kjell A Svensson

    2012-05-01

    Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

  20. Sex-dependent antipsychotic capacity of 17β-estradiol in the latent inhibition model: a typical antipsychotic drug in both sexes, atypical antipsychotic drug in males.

    Science.gov (United States)

    Arad, Michal; Weiner, Ina

    2010-10-01

    The estrogen hypothesis of schizophrenia suggests that estrogen is a natural neuroprotector in women and that exogenous estrogen may have antipsychotic potential, but results of clinical studies have been inconsistent. We have recently shown using the latent inhibition (LI) model of schizophrenia that 17β-estradiol exerts antipsychotic activity in ovariectomized (OVX) rats. The present study sought to extend the characterization of the antipsychotic action of 17β-estradiol (10, 50 and 150 μg/kg) by testing its capacity to reverse amphetamine- and MK-801-induced LI aberrations in gonadally intact female and male rats. No-drug controls of both sexes showed LI, ie, reduced efficacy of a previously non-reinforced stimulus to gain behavioral control when paired with reinforcement, if conditioned with two but not five tone-shock pairings. In both sexes, amphetamine (1 mg/kg) and MK-801 (50 μg/kg) produced disruption (under weak conditioning) and persistence (under strong conditioning) of LI, modeling positive and negative/cognitive symptoms, respectively. 17β-estradiol at 50 and 150 μg/kg potentiated LI under strong conditioning and reversed amphetamine-induced LI disruption in both males and females, mimicking the action of typical and atypical antipsychotic drugs (APDs) in the LI model. 17β-estradiol also reversed MK-induced persistent LI, an effect mimicking atypical APDs and NMDA receptor enhancers, but this effect was observed in males and OVX females but not in intact females. These findings indicate that in the LI model, 17β-estradiol exerts a clear-cut antipsychotic activity in both sexes and, remarkably, is more efficacious in males and OVX females where it also exerts activity considered predictive of anti-negative/cognitive symptoms.

  1. A perspective on molecular genetic studies of tardive dyskinesia: one clue for individualized antipsychotic drug therapy.

    Science.gov (United States)

    Ohmori, Osamu; Shinkai, Takahiro; Hori, Hiroko; Matsumoto, Chima; Nakamura, Jun

    2003-06-01

    Interindividual genetic profile differences related to antipsychotic drug therapy may be determined based on molecular genetic studies of the pathogenesis of schizophrenia and studies of antipsychotic drug responses (therapeutic as well as adverse responses). In the present article, we review molecular genetic studies of tardive dyskinesia (TD), which is a representative adverse response to antipsychotic drugs. Such studies have been performed to explore the gene-associated pharmacokinetic and pharmacodynamic processes of antipsychotic drugs. Positive associations between several genes and TD have been reported. The accumulation of results from such studies will hopefully lead to individualized antipsychotic drug therapies that involve the application of new genomic techniques, including DNA microarrays. Subsequently, antipsychotic drugs may in the future be prescribed for smaller subgroups of patients who have been classified as having a particular genetic profile.

  2. 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

      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-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...... 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.  ...

  3. Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study.

    Science.gov (United States)

    Habermann, Frank; Fritzsche, Juliane; Fuhlbrück, Frederike; Wacker, Evelin; Allignol, Arthur; Weber-Schoendorfer, Corinna; Meister, Reinhard; Schaefer, Christof

    2013-08-01

    Women of childbearing age are often affected with psychotic disorders, requiring the use of antipsychotic medication during pregnancy. In the present study, we prospectively followed the pregnancies of 561 women exposed to second-generation antipsychotic agents (SGAs; study cohort) and compared these to 284 pregnant women exposed to first-generation antipsychotic agents (FGAs; comparison cohort I) and to 1122 pregnant women using drugs known as not harmful to the unborn (comparison cohort II). Subjects were enrolled through the Institute's consultation service. Major malformation rates of SGA exposed were higher compared to comparison cohort II (adjusted odds ratio, 2.17; 95% confidence interval, 1.20-3.91), possibly reflecting a detection bias concerning atrial and ventricular septal defects. Postnatal disorders occurred significantly more often in infants prenatally exposed to SGAs (15.6%) and FGAs (21.6%) compared to 4.2% of comparison cohort II. Cumulative incidences of elective terminations of pregnancy were significantly higher in both the study cohort (17%) and comparison cohort I (21%) compared to comparison cohort II (3%), whereas the rates of spontaneous abortions did not differ. The numbers of stillbirths and neonatal deaths were within the reference range. Preterm birth and low birth weight were more common in infants exposed to FGAs. To conclude, our findings did not reveal a major teratogenic risk for SGAs, making the better studied drugs of this group a treatment option during pregnancy. Because neonates exposed to SGAs or FGAs in the last gestational week are at higher risk of postnatal disorders, delivery should be planned in clinics with neonatal intensive care units.

  4. 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.

  5. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

    Science.gov (United States)

    Bakker, Ilse C A; Schubart, Chris D

    2016-01-01

    Summary In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. Learning points Prolactinoma coinciding with psychosis can represent a therapeutic challenge. In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels. Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis. PMID:27284453

  6. Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.

    Science.gov (United States)

    Yang, S-Y; Kao Yang, Y-H; Chong, M-Y; Yang, Y-H; Chang, W-H; Lai, C-S

    2007-04-01

    To compare the prevalence of extrapyramidal syndrome (EPS) between the first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), the co-prescribing rate of anti-Parkinson drugs (APDs) of each antipsychotic drug was analyzed using population database. Fourteen antipsychotics had been prescribed during the 5-year study period. Among the SGAs, quetiapine had the lowest crude co-prescribing rate of APDs (27.09%), whereas risperidone had the highest rate (66.50%). Among the FGAs, thioridazine and loxapine had the lowest (60.99%) and highest rates (96.35%), respectively. The rankings of the co-prescribing rate of APDs among antipsychotics, in increasing order, were quetiapine, clozapine, olanzapine, thioridazine, zotepine, chlorpromazine, risperidone, sulpiride, clotiapine, flupentixol, haloperidol, zuclopentixol, trifluoperazine, and loxapine. The results indicate that the risk of EPS appears to be lower in SGAs than in FGAs; however, the considerably high rate of EPS in some of the newer generation of antipsychotics warrants clinical attention.

  7. 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

  8. 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.

  9. [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.

  10. Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects.

    Science.gov (United States)

    Jafari, Somayeh; Fernandez-Enright, Francesca; Huang, Xu-Feng

    2012-02-01

    Antipsychotic drugs have various neuropharmacological properties as a result of their structural diversity. Despite their therapeutic benefits, most of the prescribed atypical antipsychotics can induce severe side effects, including weight gain, type II diabetes mellitus, and cardiovascular diseases. Among the developed atypical antipsychotic agents, tetracyclic dibenzodiazepine and thienobenzodiazepine compounds, particularly clozapine and olanzapine, are associated with the greatest weight gain and metabolic disturbances. However, the unique chemical structure of these compounds causes the low risk of side effects reported for typical antipsychotics (e.g. extrapyramidal symptoms and tardive dyskinesia). This report reviews the recent discovery of the potential role of the chemical structure of antipsychotics in their therapeutic properties and metabolic disturbances. By developing structure-activity relationship studies for atypical antipsychotics, we will improve our understanding of the structural modifications of these chemical classes that lead to reduced weight gain, which will be an invaluable step toward the discovery of the next generation of atypical antipsychotics. In this review, we suggest that a novel dibenzodiazepine or thienobenzodiazepine antipsychotic drug with lower affinity for H(1) receptors may significantly advance schizophrenia therapy.

  11. Use and misuse of antipsychotic drugs in patients with dementia in Alzheimer special care units.

    Science.gov (United States)

    Nobili, Alessandro; Pasina, Luca; Trevisan, Silvia; Riva, Emma; Lucca, Ugo; Tettamanti, Mauro; Matucci, Marina; Tarantola, Massimo

    2009-03-01

    The objective of this study was to estimate the prevalence of antipsychotic use and investigate their association with behavioural and psychological symptoms of dementia (BPSD) and other clinical predictors. Patients with dementia, aged 65 and above and resident in 35 Alzheimer special care units were sequentially enrolled into a 18-month prospective observational study. Data on sociodemographic, cognitive, functional, behavioural and clinical characteristics and drug exposure were collected at baseline and at 6-month intervals up to 18 months. The prevalence of antipsychotic use and the association with BPSD and clinical predictors were analysed. Of the 349 patients with dementia enrolled in the study, 209 (60%) were taking at least one antipsychotic. Risperidone and promazine were the most frequently prescribed antipsychotic; 40.7% simultaneously received a benzodiazepine, 20% an antidepressant. More than 50% were still taking antipsychotics at 18 months of follow-up. No associations were found between antipsychotic use and level of cognitive impairment, basal activity of daily living disability and comorbidity. Multivariate analysis showed that the use of antipsychotics was highest in patients in the highest quartiles of Neuropsychiatric Inventory Scale score (III quartile, odds ratio: 1.63; 95% confidence interval: 1.19-2.23; IV quartile, odds ratio: 2.27; 95% confidence interval: 1.61-3.26). This study found high rate of use of antipsychotics in patients with dementia resident in Alzheimer special care units, frequent associations with other psychotropic medications and a strong correlation with BPSD.

  12. Efficacy and safety of atypical antipsychotic drugs (quetiapine, risperidone, aripiprazole and paliperidone compared with placebo or typical antipsychotic drugs for treating refractory schizophrenia: overview of systematic reviews

    Directory of Open Access Journals (Sweden)

    Tamara Melnik

    Full Text Available CONTEXT AND OBJECTIVE: According to some cohort studies, the prevalence of refractory schizophrenia (RS is 20-40%. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS. METHODS: This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline (1966-2009, Controlled Trials of the Cochrane Collaboration (2009, Issue 2, Embase (Excerpta Medica (1980-2009, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs (1982-2009. There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included. RESULTS: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine. CONCLUSIONS: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.

  13. Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans.

    Science.gov (United States)

    Donohoe, Dallas R; Weeks, Kathrine; Aamodt, Eric J; Dwyer, Donard S

    2008-01-01

    Antipsychotic drugs are increasingly being prescribed for children and adolescents, and are used in pregnant women without a clear demonstration of safety in these populations. Global effects of these drugs on neurodevelopment (e.g., decreased brain size) have been reported in rats, but detailed knowledge about neuronal effects and mechanisms of action are lacking. Here we report on the evaluation of a comprehensive panel of antipsychotic drugs in a model organism (Caenorhabditis elegans) that is widely used to study neuronal development. Specifically, we examined the effects of the drugs on neuronal migration and axonal outgrowth in mechanosensory neurons visualized with green fluorescent protein expressed from the mec-3 promoter. Clozapine, fluphenazine, and haloperidol produced deficits in the development and migration of ALM neurons and axonal outgrowth in PLM neurons. The defects included failure of neuroblasts to migrate to the proper location, and excessive growth of axons past their normal termination point, together with abnormal morphological features of the processes. Although the antipsychotic drugs are potent antagonists of dopamine and serotonin receptors, the neurodevelopmental deficits were not rescued by co-incubation with serotonin or the dopaminergic agonist, quinpirole. Other antipsychotic drugs, risperidone, aripiprazole, quetiapine, trifluoperazine and olanzapine, also produced modest, but detectable, effects on neuronal development. This is the first report that antipsychotic drugs interfere with neuronal migration and axonal outgrowth in a developing nervous system.

  14. 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...

  15. Chlorpromazine induced ocular myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Nitya S

    2013-10-01

    Full Text Available Drug induced bilateral ptosis is a very rare adverse drug reaction. Here we report a case of ten year old male child with chlorpromazine induced bilateral ptosis due to ocular myasthenia. [Int J Basic Clin Pharmacol 2013; 2(5.000: 653-654

  16. -Amphetamine and Antipsychotic Drug Effects on Latent Inhibition in Mice Lacking Dopamine D2 Receptors

    OpenAIRE

    Bay-Richter, C.; O'Callaghan, M J; N Mathur; O'Tuathaigh, C.M.P.; Heery, D M; Fone, K C F; Waddington, J. L.; Moran, P.M.

    2013-01-01

    Drugs that induce psychosis, such as -amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd 2 −/−), we first investigated whether D2 is required for AMP disruption ...

  17. 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...

  18. 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

    limited experimental information exists about the effects of α1-adrenergic receptor activity of antipsychotic drugs in pro-arrhythmic models, we have decided to investigate this. In this study we show that four antipsychotic drugs all have high affinity for α1-adrenergic receptor (sertindole>risperidone......>haloperidol>olanzapine) and all block IKr (sertindole>haloperidol>risperidone>olanzapine). In canine Purkinje fibres, α1-adrenergic stimulation prolonged action potential duration; however, the stimulation does not cause afterdepolarizations, even in the presence of dofetilide-induced delayed repolarization. We showed...

  19. 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.

  20. Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs.

    Science.gov (United States)

    Bai, Ou; Chlan-Fourney, Jennifer; Bowen, Rudy; Keegan, David; Li, Xin-Min

    2003-01-01

    Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P BDNF mRNA expression in rat hippocampus.

  1. 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

  2. Antipsychotic treatment and the Rorschach Perceptual Thinking Index (PTI) in psychotic disorder patients: Effects of treatment.

    Science.gov (United States)

    Biagiarelli, Mario; Curto, Martina; Di Pomponio, Ileana; Comparelli, Anna; Baldessarini, Ross J; Ferracuti, Stefano

    2017-02-16

    The Rorschach-based Perceptual Thinking Index (PTI) is used to identify and rate features of psychotic disorders, but effects of antipsychotic treatment on such ratings is not clear. Accordingly, we examined potential effects of antipsychotic drugs on PTI measures in 114 patients with a psychotic or bipolar-I disorder. Use and doses of antipsychotic drugs (as chlorpromazine-equivalent [CPZ-eq] mg/day) were unrelated to PTI total or subscale scores in any diagnostic group. PTI scores were independently and significantly associated with psychotic symptomatic severity (PANSS score) and less with female sex. These findings support the validity and value of the PTI in identifying features of psychosis even in the presence of antipsychotic treatment.

  3. Benzodiazepines, benzodiazepine-like drugs, and typical antipsychotics impair manual dexterity in patients with schizophrenia.

    Science.gov (United States)

    Sasayama, Daimei; Hori, Hiroaki; Teraishi, Toshiya; Hattori, Kotaro; Ota, Miho; Matsuo, Junko; Kinoshita, Yukiko; Okazaki, Mitsutoshi; Arima, Kunimasa; Amano, Naoji; Higuchi, Teruhiko; Kunugi, Hiroshi

    2014-02-01

    Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia.

  4. Molecular analysis of the interaction of the four histamine receptor subtypes with antidepressant and antipsychotic drugs

    OpenAIRE

    Appl, Heidrun

    2010-01-01

    Antidepressant and antipsychotic drugs are known to affect multiple molecular targets. Beside their determinant effects on the neurotransmission of serotonin, norepinephrine and dopamine via several transporters and receptors, they may also modulate muscarinic acetylcholine receptors and the histamine H1 receptor (H1R). Consequently, these drugs do not only yield unique profiles of desired effects but also several unwanted side effects that may impact therapy. In addition to the H1R, the hist...

  5. 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...

  6. 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.

  7. 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.

  8. The Impact of Cannabis Use on the Dosage of Antipsychotic Drugs in Patients Admitted on the Psychiatric Ward at the University Hospital of the West Indies

    Directory of Open Access Journals (Sweden)

    P Thomas

    2015-03-01

    Full Text Available Objective: To assess the impact of cannabis use on the efficacy of antipsychotic drugs in male subjects presenting to the University Hospital of the West Indies (UHWI with psychotic episodes. Methods: Male subjects, 18–40 years old, admitted to the psychiatric ward of the UHWI between February 2013 and May 2013, diagnosed with schizophrenia, schizophreniform disorder and who tested positive for ∆9-tetrahydrocannabinol were recruited for the study. On day one, consenting subjects were assessed using the Brief Psychiatric Rating Scale (BPRS. Patients were prescribed seven days of an oral antipsychotic medication (haloperidol, chlorpromazine, risperidone, quetiapine, olanzapine. Medicated subjects were then reassessed using the BPRS on days three and seven. Statistical analysis involved the use of Student’s t-test and repeated measure analysis of variance. Results: In total, 20 subjects were recruited (mean age = 26.00 ± 5.96 years. Subjects were grouped based on the daily chlorpromazine equivalent (CPZE dose given on day one into CPZE1 (CPZE dose of 100–300mg; n = 8 and CPZE2 (CPZE dose of 400–1250 mg; n = 12. There was no significant difference in the total BPRS score between the groups on day one (CPZE1 = 41.38 ± 16.47 versus CPZE2 = 49.42 ± 25.58; p = 0.44; similar findings were obtained for the positive (26.75 ± 9.27 versus 31.83 ± 17.30; p = 0.46 and negative (14.63 ± 7.73 versus 17.58 ± 9.74; p = 0.48 symptom component on the BPRS. For subjects in CPZE1, there was no significant decrease in total BPRS score [F(2,21 = 0.07, p = 0.93] over the study period. For CPZE2, significant reduction in total BPRS scores was achieved [F(2,33 =7.12, p = 0.01], contributed by significant decrease in the positive [F(2,33 = 5.64, p = 0.02 and negative [F(2,33 = 7.53, p = 0.01 symptom components of the BPRS. Conclusion: The findings of this study purport that male cannabis users presenting with psychotic disorders may not achieve optimal

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

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    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

  10. Post-drug consequences of chronic atypical antipsychotic drug administration on the ability to adjust behavior based on feedback in young monkeys

    NARCIS (Netherlands)

    Mandell, D.J.; Unis, A.; Sackett, G.P.

    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

  11. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

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    Ilse C A Bakker

    2016-06-01

    Full Text Available In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs.

  12. Association of typical versus atypical antipsychotics with symptoms and quality of life in schizophrenia.

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    Koichiro Fujimaki

    Full Text Available BACKGROUND: Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. METHODOLOGY AND PRINCIPAL FINDINGS: The Hasegawa Dementia Scale-Revised (HDS-R, Brief Psychiatric Rating Scale (BPRS, the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS, and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ-equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. CONCLUSION AND SIGNIFICANCE: These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia.

  13. Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder.

    Science.gov (United States)

    Elie, D; Poirier, M; Chianetta, Jm; Durand, M; Grégoire, Ca; Grignon, S

    2010-07-01

    Antipsychotic polypharmacy and high doses have been associated with poorer outcome, longer hospital stays, and increased side effects. The present naturalistic study assessed the cognitive effects of antipsychotics in 56 patients with a diagnosis of schizophrenia or schizoaffective disorder, using the Brief Assessment of Cognition in Schizophrenia (BACS). Antipsychotic daily dose (ADD) was expressed as mg risperidone equivalents/day (RIS eq), using a model based on drug doses from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study for second generation antipsychotics (SGA) and chlorpromazine equivalents for first generation antipsychotics (FGA), with a 1/1 equivalence between haloperidol and risperidone. Increasing age was associated with polypharmacy, FGA prescription and decreasing BACS score. FGA prescription, in turn, predicted a poorer cognitive functioning, independently of age, PANSS subscores and ADD. ADD was associated with decreasing cognitive scores, an effect that remained significant after controlling for age, PANSS or polypharmacy. The detrimental cognitive effects of polypharmacy, in turn, appeared to be mediated by ADD. Different methods of data fitting suggested that ADD above 5-6 mg RIS eq/day were associated with lower BACS scores. Overall, these results show that increasing antipsychotic daily dose is associated with poorer cognitive functioning at doses lower than previously thought, independently of the number of antipsychotic drugs.

  14. 抗精神疾病药物对首发分裂症患者泌乳素及性功能影响的对照研究%Prolactin-control study on prolactin and sexual function change with antipsychotic drugs in ifrst-episode schizophrenics

    Institute of Scientific and Technical Information of China (English)

    孙霞

    2014-01-01

    目的:探讨抗精神疾病药物对首发分裂症患者泌乳素及性功能影响的对照研究。方法:对72例患者随机分为三组,使用不同药物首发精神疾病患者的泌乳素以及性功能影响进行分析。结果:①氯丙嗪以及利培酮这两组药物对于精神分裂患者泌乳素的波动有显著影响,治疗前后,相关系数有显著差异。②氯丙嗪组以及利培酮组性功能明显下降,达到60%~70%。结论:氯丙嗪及利培酮泌乳素升高明显,性功能下降明显,奎硫平表现良好。%Objective Prolactin and sexual function change with antipsychotic drugs in first-episode schizophrenics were investigated in this study.Methods 72 patients were randomly divided into three groups,and Prolactin and sexual function change with antipsychotic drugs in first episode schizophrenia were analyzed.Results①Chlorpromazine and risperidone have a significant impact in prolactin change,and the correlation coefficient was significantly different before and after treatment.②Sexual function in chlorpromazine and risperidone group was decreased to 60%~70%.Conclusion Prolactin change in chlorpromazine and risperidone increased significantly,and sexual function was significantly decreased as well.Quetiapine have good performance.

  15. 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.

  16. Antipsychotic Medicines for Schizophrenia and Bipolar Disorder: What You Should Know

    Science.gov (United States)

    Antipsychotic Drugs for Schizophrenia and Bipolar Disorder: What You Should Know What are antipsychotic drugs? Antipsychotics are prescription drugs used to treat schizophrenia. They can also be used— ...

  17. 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...

  18. Antipsychotic Drugs and the Risk of Ventricular Arrhythmia and/or Sudden Cardiac Death: A Nation‐wide Case‐Crossover Study

    OpenAIRE

    2015-01-01

    Background Antipsychotics have been linked to prolongation of the QT interval. However, little is known about the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with individual antipsychotic drug use. This study was designed to investigate the association between specific antipsychotic drugs and the risk of VA and/or SCD. Methods and Results We conducted a case‐crossover study using a nation‐wide population‐based sample obtained from Taiwan's National Health ...

  19. Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Mizushima Jin

    2012-07-01

    Full Text Available Abstract Dopamine dysregulation syndrome (DDS consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD. Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

  20. A Survey of the Tardive Dyskinesia Induced by Antipsychotic Drugs in Patients with Schizophrenia

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    Naser tabibi

    2010-11-01

    Full Text Available "nObjective: Tardive Dyskinesia (TD, is one of the important problems of the patients with schizophrenia. The emergence of these side effects depends on so many factors such as the patients' age and the duration of antipsychotic treatment. By discovering new drugs (Atypical, there has been an outstanding decrease in the emergence of these side effects. The present study investigates the symptoms of TD in the Patients with schizophrenia who were under  treatments for more than 6 months. "nMethod: The sample of this study was 200 Patients with schizophrenia of four wards in Razi hospital (two acute and two chronic wards who were hospitalized in the winter of 2006 and were qualified for this study. The subjects were 101 males and 99 females who were younger than 60 and had received antipsychotic drugs for at least 6 months. After psychiatric interview and filling the demographic questionnaire by the patients, the required information about the drugs and the intensity of the symptoms was acquired. Then clinical and physical examinations of tardive dyskinesia were done. Next, the tardive dyskinesia disorders' check list (AIMS was used. Findings of this cross-sectional, descriptive study were analyzed by SPSS. "nResults: There was a high ratio of 95% between TD and the age factor (P=0.05. There was no relationship between symptoms frequency and duration of treatment (P=0.68. Facial muscles and oral zones were mostly involved in T.D disorder (72%. "nConclusion: No significant difference was observed between nine fold symptoms of T.D in patients who were using traditional drugs and those who were using the new ones (typical and atypical. Findings showed that in the intensity of the symptoms, gender does not play a major role.

  1. Scopolamine induces disruption of latent inhibition which is prevented by antipsychotic drugs and an acetylcholinesterase inhibitor.

    Science.gov (United States)

    Barak, Segev; Weiner, Ina

    2007-05-01

    The fact that muscarinic antagonists may evoke a psychotic state ('antimuscarinic psychosis'), along with findings of cholinergic alterations in schizophrenia, have kindled an interest in the involvement of the cholinergic system in this disorder. Latent inhibition (LI) is a cross-species phenomenon manifested as a poorer conditioning of a stimulus seen when the stage of conditioning is preceded by a stage of repeated nonreinforced pre-exposure to that stimulus, and is considered to index the capacity to ignore irrelevant stimuli. Amphetamine-induced LI disruption and its reversal by antipsychotic drugs (APDs) is a well-established model of positive symptoms of schizophrenia. Here, we tested whether the muscarinic antagonist scopolamine would disrupt LI and whether such disruption would be reversed by APDs and by the acetylcholinesterase inhibitor physostigmine. The results showed that scopolamine at doses of 0.15 and 0.5 mg/kg disrupted LI, and that this effect was due to the action of the drug in the pre-exposure stage, suggesting a role of muscarinic transmission in attentional processes underlying LI. Both the typical and the atypical APDs, haloperidol and clozapine, reversed scopolamine-induced LI disruption when given in conditioning or in both stages, but not in pre-exposure, indicating that the mechanism of antipsychotic action in this model is independent of the mechanism of action of the propsychotic drug. Scopolamine-induced LI disruption was reversed by physostigmine (0.05 and 0.15 mg/kg), which was ineffective in reversing amphetamine-induced LI disruption, pointing to distinct mechanisms underlying LI disruption by these two propsychotic drugs. The latter was further supported by the finding that unlike amphetamine, the LI-disrupting doses of scopolamine did not affect activity levels. We propose scopolamine-induced LI disruption as a model of cholinergic-related positive symptoms in schizophrenia.

  2. 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.

  3. Clinical evaluation of sulpiride in schizophrenic patients--a double-blind comparison with chlorpromazine.

    Science.gov (United States)

    Härnryd, C; Bjerkenstedt, L; Björk, K; Gullberg, B; Oxenstierna, G; Sedvall, G; Wiesel, F A; Wik, G; Aberg-Wistedt, A

    1984-01-01

    To evaluate the clinical potential of sulpiride for the treatment of schizophrenic patients, a double-blind study was performed comparing fixed doses of sulpiride (800 mg daily) and chlorpromazine (400 mg daily). Twenty-five schizophrenic (RDC) patients participated in each treatment group. Antipsychotic effects were evaluated by CPRS and NOSIE ratings before and after 1, 2, 4 and 8 weeks of treatment. Interrater reliabilities for CPRS items and subscales were satisfactory. Treatment with sulpiride or chlorpromazine resulted in a significant reduction of psychotic morbidity as estimated by CPRS and global ratings. CPRS scores reflecting autism were significantly reduced in all ratings of sulpiride-treated patients, but only after four weeks in the chlorpromazine group. Total NOSIE scores indicated improvement in both treatment groups. A significant difference in favour of sulpiride was obtained for the NOSIE subscale "retardation". Extrapyramidal side effects occurred at a similar frequency in both treatment groups. Autonomic side effects occurred to a greater extent in chlorpromazine-treated patients. Lactation was reported only in four sulpiride-treated patients. Liver transaminase enzymes in serum were markedly elevated only in chlorpromazine-treated patients. The results indicate that sulpiride has a marked antipsychotic effect which is at least not inferior to that of chlorpromazine. A better effect on autistic components of behaviour was demonstrated for sulpiride. The results indicate a higher risk of lactation but a lower risk of anticholinergic side effects and liver toxicity for treatment with sulpiride than with chlorpromazine.

  4. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

    Directory of Open Access Journals (Sweden)

    Wentzel-Larsen Tore

    2009-05-01

    Full Text Available Abstract Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA. The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800. In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in

  5. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

    Science.gov (United States)

    Kroken, Rune A; Johnsen, Erik; Ruud, Torleif; Wentzel-Larsen, Tore; Jørgensen, Hugo A

    2009-01-01

    Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also

  6. Hyperglycemia and antipsychotic medications.

    Science.gov (United States)

    Haupt, D W; Newcomer, J W

    2001-01-01

    Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and

  7. 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

  8. 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

  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. The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

    Science.gov (United States)

    McCartan, D; Bell, R; Green, J F; Campbell, C; Trimble, K; Pickering, A; King, D J

    2001-06-01

    Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye

  11. Detection of the antipsychotic drug quetiapine in the blood, urine and hair samples of the victim of a drug-facilitated sexual assault

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe

    2017-01-01

    A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she was a...

  12. 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.

  13. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in elderly patients with dementia

    OpenAIRE

    Declercq, Tom; Petrovic, Mirko; Azermai, Majda; Vander Stichele, Robert; De Sutter, An; van Driel, Marie; Christiaens, Thierry

    2013-01-01

    Background Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in dementia, although the literature is sceptical about their long-termuse for this indication. Their effectiveness is limited and there is concern about adverse effects, including higher mortality with long-term use. When behavioural strategies have failed and drug therapy is instituted, regular attempts to withdraw these drugs are recommended. Physicians, nurses and families of older people with dementia...

  14. Antipsychotic-induced hyperprolactinemia.

    Science.gov (United States)

    Bostwick, Jolene R; Guthrie, Sally K; Ellingrod, Vicki L

    2009-01-01

    Use of antipsychotic agents has been associated with hyperprolactinemia, or elevated prolactin levels; this hormonal abnormality can interfere with the functioning of reproductive, endocrine, and metabolic systems. As antipsychotic agents are increasingly used for both United States Food and Drug Administration-approved and nonapproved indications, many individuals are at risk for developing antipsychotic-induced hyperprolactinemia. First-generation antipsychotics pose the greatest risk of causing this adverse effect; however, second-generation antipsychotics, particularly risperidone and paliperidone, also often increase prolactin secretion. Hyperprolactinemia has short- and long-term consequences that can seriously affect quality of life: menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, infertility, decreased bone mineral density, and breast cancer. Although many of these are definitively connected to elevated prolactin levels, some, such as breast cancer, require further study. Both clinicians and patients should be aware of hyperprolactinemia-associated effects. To prevent or alleviate the condition, tailoring an antipsychotic drug regimen to each individual patient is essential. In addition, the risk of hyperprolactinemia can be minimized by using the lowest effective dose of the antipsychotic agent. If the effects of prolactin are evident, the drug can be changed to another agent that is less likely to affect prolactin levels; alternatively, a dopamine agonist may be added, although this may compromise antipsychotic efficacy. Additional research is needed to clarify the appropriate level of monitoring, the long-term effects, and the optimal treatment of antipsychotic-induced hyperprolactinemia.

  15. D-amphetamine and antipsychotic drug effects on latent inhibition in mice lacking dopamine D2 receptors.

    Science.gov (United States)

    Bay-Richter, C; O'Callaghan, M J; Mathur, N; O'Tuathaigh, C M P; Heery, D M; Fone, K C F; Waddington, J L; Moran, P M

    2013-07-01

    Drugs that induce psychosis, such as D-amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd2-/-), we first investigated whether D2 is required for AMP disruption of latent inhibition (LI). LI is a process of learning to ignore irrelevant stimuli. Disruption of LI by AMP models impaired attention and abnormal salience allocation consequent to dysregulated dopamine relevant to schizophrenia. AMP disruption of LI was seen in both wild-type (WT) and Drd2-/-. This was in contrast to AMP-induced locomotor hyperactivity, which was reduced in Drd2-/-. AMP disruption of LI was attenuated in mice lacking dopamine receptor D1 (Drd1-/-), suggesting that D1 may play a role in AMP disruption of LI. Further supporting this possibility, we found that D1 antagonist SKF83566 attenuated AMP disruption of LI in WT. Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd2-/-. This demonstrates that antipsychotic drugs can attenuate AMP disruption of learning to ignore irrelevant stimuli in the absence of D2 receptors. Data suggest that D2 is not essential either for AMP to disrupt or for antipsychotic drugs to reverse AMP disruption of learning to ignore irrelevant stimuli and further that D1 merits investigation in the mediation of AMP disruption of these processes.

  16. Association between antipsychotic/antidepressant drug treatments and hospital admissions in schizophrenia assessed using a mental health case register

    OpenAIRE

    2015-01-01

    This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npjschz.2015.35 Background: The impact of psychotropic drug choice upon admissions for schizophrenia is not well understood. Aims: To examine the association between antipsychotic/antidepressant use and time in hospital for patients with schizophrenia. Methods: We conducted an observational study, using 8 years? admission records and electronically gene...

  17. Evaluating early preventive antipsychotic and antidepressant drug treatment in an infection-based neurodevelopmental mouse model of schizophrenia.

    Science.gov (United States)

    Meyer, Urs; Spoerri, Erica; Yee, Benjamin K; Schwarz, Markus J; Feldon, Joram

    2010-05-01

    Current pharmacotherapy of schizophrenia remains unsatisfactory with little hope for complete functional restoration in patients once the disease has developed. A preventive approach based on intervention in the prodromal stage of the disease aiming to preserve functional integrity by halting the progress of the disease is therefore extremely attractive. Here, we investigated the effects of preventive antipsychotic or antidepressant drug treatment in a well-established neurodevelopmental mouse model of multiple schizophrenia-related abnormalities. Pregnant mice on gestation day 9 were exposed to the viral mimic polyriboinosinic-polyribocytidylic acid (2 mg/kg, intravenously) or corresponding vehicle treatment, and the resulting offspring from both prenatal treatment conditions were subjected to chronic antipsychotic (haloperidol or clozapine), antidepressant (fluoxetine), or placebo treatment during the periadolescent stage of development. The effects of the preventive pharmacotherapy on behavioral and pharmacological functions were then investigated in adulthood using paradigms relevant to schizophrenia, namely prepulse inhibition, latent inhibition, and sensitivity to psychostimulant drugs. We show that periadolescent treatment with the reference antipsychotic and antidepressant drugs can successfully block the emergence of multiple psychosis-related behavioral and pharmacological abnormalities in subjects predisposed to adult brain pathology by exposure to prenatal immune challenge. At the same time, however, our study reveals numerous negative influences of the early pharmacological intervention on normal behavioral development in control subjects. Hence, even though preventive pharmacotherapy may be beneficial in individuals with predisposition to psychosis-related brain dysfunctions, chronic antipsychotic or antidepressant drug treatment in false-positive subjects is associated with substantial risk for long-term behavioral disturbances in adulthood.

  18. Evaluating Early Preventive Antipsychotic and Antidepressant Drug Treatment in an Infection-Based Neurodevelopmental Mouse Model of Schizophrenia

    OpenAIRE

    Meyer, Urs; Spoerri, Erica; Yee, Benjamin K.; Schwarz, Markus J; Feldon, Joram

    2008-01-01

    Current pharmacotherapy of schizophrenia remains unsatisfactory with little hope for complete functional restoration in patients once the disease has developed. A preventive approach based on intervention in the prodromal stage of the disease aiming to preserve functional integrity by halting the progress of the disease is therefore extremely attractive. Here, we investigated the effects of preventive antipsychotic or antidepressant drug treatment in a well-established neurodevelopmental mous...

  19. Survey of antipsychotic druGs usinG status in patients with schizophrenia in Suzhou%苏州市精神分裂症患者抗精神病药物使用现况调查

    Institute of Scientific and Technical Information of China (English)

    杨勇; 盖海军; 王秀艳; 丁若水; 杨忠; 王新达; 杜向东; 梅其一; 吴爱勤

    2015-01-01

    Objective:To infestigate the status quo of antipsychotic drugs using in patients with schizo-phrenia in Suzhou. Method:The drugs using questionnaire was used to infestigate the drug using situation in 544 schizophrenic patients( including inpatients and outpatients)from 3 mental disease hospitals in Suzhou. Results:The first 6 drugs used frequently were clozapine( 25. 6%),risperidone( 16. 5%),olanzapine (13. 9%),quetiapine(11. 4%),aripiprazole(9. 1%)and chlorpromazine(6. 8%). The usage frequency of an-tipsychotic was significantly different between inpatients and outpatients(χ2 =37. 361,P=0. 003). Compared with inpatients,the dose of clozapine,risperidone,olanzapine,quetiapine,aripiprazole and chlorpromazine in outpatients were significantly lower,sulpiride,ziprasidone and haloperidol were significantly higher( all P ﹤0. 01). The rate of using single antipsychotic drug(54. 4%,293 cases)was higher than combination(45. 6%, 246 cases). Among the patients treated with single antipsychotic drug,84. 2%(247 cases)used the second gen-eration antipsychotics(SGAs);and among the patients treated with combination therapy,97. 8%(241 cases) main drug and 65. 0%(160 cases)secondary drugs were SGAs. The most common combinatife drugs were sed-atife hypnotics( 20. 2%),then mood stabilizers( 12. 2%),anticholinergics( 12. 1%),antidepressants (7. 8%)andβ-blockers(4. 3%). Conclusion:The major treatment model of schizophrenia in Suzhou is u-sing single antipsychotic drug and choosing SGAs.%目的:调查苏州市精神分裂症患者抗精神病药物使用现况。方法:采用患者药物使用调查表,对苏州市3家精神疾病专科医院的544例住院和门诊精神分裂症患者进行抗精神病药物使用情况调查。结果:使用居前6位的抗精神病药物分别是氯氮平(25.6%)、利培酮(16.5%)、奥氮平(13.9%)、奎硫平(11.4%)、阿立哌唑(9.1%)、氯丙嗪(6.8%)。门诊和住院

  20. Association between antipsychotic/antidepressant drug treatments and hospital admissions in schizophrenia assessed using a mental health case register

    Science.gov (United States)

    Cardinal, Rudolf N; Savulich, George; Mann, Louisa M; Fernández-Egea, Emilio

    2015-01-01

    Background: The impact of psychotropic drug choice upon admissions for schizophrenia is not well understood. Aims: To examine the association between antipsychotic/antidepressant use and time in hospital for patients with schizophrenia. Methods: We conducted an observational study, using 8 years’ admission records and electronically generated drug histories from an institution providing secondary mental health care in Cambridgeshire, UK, covering the period 2005–2012 inclusive. Patients with a coded ICD-10 diagnosis of schizophrenia were selected. The primary outcome measure was the time spent as an inpatient in a psychiatric unit. Antipsychotic and antidepressant drugs used by at least 5% of patients overall were examined for associations with admissions. Periods before and after drug commencement were compared for patients having pre-drug admissions, in mirror-image analyses correcting for overall admission rates. Drug use in one 6-month calendar period was used to predict admissions in the next period, across all patients, in a regression analysis accounting for the effects of all other drugs studied and for time. Results: In mirror-image analyses, sulpiride, aripiprazole, clozapine, and olanzapine were associated with fewer subsequent admission days. In regression analyses, sulpiride, mirtazapine, venlafaxine, and clozapine–aripiprazole and clozapine–amisulpride combinations were associated with fewer subsequent admission days. Conclusions: Use of these drugs was associated with fewer days in hospital. Causation is not implied and these findings require confirmation by randomized controlled trials. PMID:27336041

  1. Recent advances in understanding and mitigating adipogenic and metabolic effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Julia M Gohlke

    2012-06-01

    Full Text Available Although offering many benefits for several psychiatric disorders, antipsychotic drugs (APDs as a class have a major liability in their tendency to promote adiposity, obesity, and metabolic dysregulation in an already metabolically vulnerable population. The past decade has witnessed substantial research aimed at investigating the mechanisms of these adverse effects and mitigating them. On July 11 and 12, 2011, with support from 2 NIH institutes, leading experts convened to discuss current research findings and to consider future research strategies. Five areas where significant advances are being made emerged from the conference: (1 methodological issues in the study of APD effects; (2 unique characteristics and needs of pediatric patients; (3 genetic components underlying susceptibility to APD-induced metabolic effects; (4 APD effects on weight gain and adiposity in relation to their acute effects on glucose regulation and diabetes risk; and (5 the utility of behavioral, dietary, and pharmacological interventions in mitigating APD-induced metabolic side effects. This paper summarizes the major conclusions and important supporting data from the meeting.

  2. 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

  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. 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".

  5. 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

  6. Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study

    OpenAIRE

    Hughes, S; Cohen, D.; Jaggi, R

    2014-01-01

    Objective: To examine the degree of concordance in reporting serious adverse events (SAEs) from antidepressant and antipsychotic drug trials among journal articles and clinical trial summaries, and to categorise types of discrepancies. Design: Cross-sectional study of summaries of all antidepressant and antipsychotic trials included in an online trial registry and their first associated stand-alone journal articles. Setting: Clinicalstudyresults.org, sponsored by Pharmaceutical Research and M...

  7. Epidemiology of tardive dyskinesia before and during the era of modern antipsychotic drugs.

    Science.gov (United States)

    Tarsy, Daniel; Lungu, Codrin; Baldessarini, Ross J

    2011-01-01

    Late or tardive dyskinesias/dystonias (TD), contrary to expectation, have not disappeared with the use of expensive, modern antipsychotic drugs (APDs). Risk appears to be substantially lower than with older neuroleptics, and there is sparing of most acute movement disorders traditionally associated with APD treatment. However, risks of TD with modern APDs have been reduced much less than expected, by perhaps two- to threefold or even less, with substantial risks in the elderly. Major challenges in assessing prevalence or, preferably, incidence of TD arise from prolonged and erratic past exposure to various APDs, relatively recent use of modern APDs, and the occurrence of spontaneous movement disorders (about 5% and more in the elderly). TD risks associated with modern APDs may be similar to some older neuroleptics, especially those of low-moderate potency. Risperidone (and its active metabolite paliperidone), at high doses, may carry unusually high TD risk, whereas TD risk is low with clozapine, and perhaps quetiapine and aripiprazole. Optimistic expectations for the efficacy and neurological safety of modern APDs have encouraged their wide use in many conditions, sometimes off-label or in combinations, with little research support, increasing the chance of a higher prevalence of TD, especially at older ages. Measures to limit TD risk include: (1) critical, objective indications for APD use; (2) long-term use only for compelling or research-supported indications, primarily chronic psychotic illness that worsens when APD is slowly discontinued; (3) avoiding off-label indications; (4) using alternative treatments when APD treatment is elective, or early dyskinesia is identified; (5) using low but effective doses of single APDs, especially in the elderly; and (6) regular and specific examination for early TD.

  8. Acute antipsychotic treatments induce distinct c-Fos expression patterns in appetite-related neuronal structures of the rat brain.

    Science.gov (United States)

    Rajkumar, Ramamoorthy; See, Lionel Kee Yon; Dawe, Gavin Stewart

    2013-05-01

    A number of atypical antipsychotic drugs are known to perturb appetite regulation causing greater hyperphagia in humans and rodents than earlier generation typical agents. However, the neuronal structures that underlie hyperphagic effects are poorly understood. Arcuate nucleus (ArcN), paraventricular hypothalamic nucleus (PVN), paraventricular thalamic nucleus (PVA) and nucleus incertus (NI) have been implicated in appetite regulation. The NI is the principal source of the relaxin-3 (RLN3) peptide, which is reported to have orexigenic effects. Moreover, ArcN, PVN, and PVA receive RLN3 immunoreactive fibers from the NI and express relaxin family peptide type 3 (RXFP3) receptor. The present study was designed to evaluate the acute effects of clozapine (atypical), chlorpromazine (typical) and fluphenazine (typical) on c-Fos expression (a marker of neuronal response) in these appetite-related centers of the rat brain. The numbers of c-Fos expressing neurons in these structures were counted in immunofluorescence stained brain sections. Acute treatment with clozapine, chlorpromazine and fluphenazine differentially influenced c-Fos expression in these brain structures. This study is also the first demonstration that antipsychotics influence the NI. The patterns of the effects of these antipsychotics are related to their reported hyperphagic properties.

  9. Antipsychotic poisoning in young children: a systematic review.

    Science.gov (United States)

    Isbister, Geoffrey K; Balit, Corrine R; Kilham, Henry A

    2005-01-01

    The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment. In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children

  10. 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 (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-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.

  11. Observation of Clinical Effects of Buspirone Combined with Antipsychotic Drugs in the Treatment of Schizophrenia with Psychopathology and Drug-induced Anxiety%丁螺环酮与抗精神病药物联用治疗精神分裂症患者病理性或药源性焦虑的疗效观察

    Institute of Scientific and Technical Information of China (English)

    周慧民; 韦德会

    2013-01-01

    目的:观察丁螺环酮与抗精神病药物联用治疗精神分裂症患者病理性或药源性焦虑的疗效.方法:将2008年2月-2012年2月在我院就诊的精神分裂症患者240例,按疾病类型的不同随机分为单用抗精神病药物组(A组)和抗精神病药物联用丁螺环酮组(B组).A组患者用药包括氯丙嗪、氯氮平、阿立哌唑、利培酮,B组患者为氯丙嗪、氯氮平、阿立哌唑、利培酮分别与丁螺环酮联用.然后进行各药物的单用和联用两两配对观察,共计4对、8小组,每小组纳入病例30例.采用汉密尔顿焦虑量表(HAMA)和阳性与阴性症状量表(PANSS)于入组前和入组后1、2、4、8、12周末各评定1次,对焦虑症状缓解程度及治疗效果进行比较.结果:各个时间点的HAMA和PANSS减分B组均快于A组(P<0.05或P<0.01),B组的抗精神病药物用量也少于A组(P<0.01),但总有效率两组比较差异无统计学意义(P>0.05).所有患者用药过程中均未见不良反应发生.结论:抗精神病药物与丁螺环酮联合使用可快速缓解精神病患者的精神症状,且可减少抗精神病药物的用量,安全性较好.%OBJECTIVE: To investigate therapeutic efficacies of buspirone combined with antipsychotic drugs in the treatment of schizophrenia with psychopathology and drug-induced anxiety. METHODS: 240 patients with schizophrenia were randomly divided into antipsychotic drugs alone group (group A) and antipsychotic drugs combined with buspirone (group B) in our hospital during Feb. 2008 -Feb. 2012. Group A received chlorpromazine, clozapine, aripiprazole and risperidone, and group B was given buspirone combined with clozapine, aripiprazole or risperidone. Therapy of single drug and two-drug were observed. A total of 4 pairs and 8 groups were formulated with 30 cases in each group. Therapeutic efficacy was evaluated with HAMA and PANSS before and 1, 2, 4, 8, 12 weeks of therapy. RESULTS: The reduction rates of HAMA and

  12. The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia

    Directory of Open Access Journals (Sweden)

    Stefanović Vesna

    2015-01-01

    Full Text Available Background/Aim. Immune system disorder, including inflammation, takes a significant place when considering still unclear etiology of schizophrenia. The aim of this study was to determine the blood levels of nonspecific inflammation markers in the first episode of schizophrenia and their relation to the therapy response. Methods. In this study we determined the blood levels of nonspecific inflammation markers: white blood cells count (WBC, C-reactive protein (CRP, erythrocytes sedimentation rate (ESR and the elements of differential white blood cell counts (or the leukocyte formula: granulocytes (Gra, lymphocytes (Lym and monocytes (Mon, in the first episode of schizofrenia, in 78 patients hospitalized at the Clinic for Psychiatric Disorders “Dr Laza Lazarević” in Belgrade. The levels were measured at admission to the clinic, as well as after 4 weeks of antipsychotic treatment. The Positive and negative syndrome scale for schizophrenia (PANSS was applied to measure the severity of psychopathology and response to the treatment. Results. During the first episode of schizophrenia, before initiation of antipsychotic treatment, the frequency of abnormal values was high (≥ 25% of the patients for the following non-specific inflammation markers: WBC, CRP, ESR and Gra, in the leukocyte formula, but dropped after 4 weeks of antipsychotic treatment at the level of high statistical significance for WBC and Gra (p < 0.001. The ESR remained unchanged in as many as 50% of the patients even after 4-week antipsychotic treatment, at the level of statistical significance in the non-responders compared to the responders (p = 0.045. Conclusion. The obtained results indicate that in the first episode of schizophrenia the blood levels of non-specific inflammation markers (WBS, CRP, ESR and Gra from the leukocyte formula were high in the subpopulation of patients with the tendency towards normalization of inflammation parameters after a 4-week antipsychotic

  13. Effects of vitamin E supplementation on plasma membrane permeabilization and fluidization induced by chlorpromazine in the rat brain.

    Science.gov (United States)

    Maruoka, Nobuyuki; Murata, Tetsuhito; Omata, Naoto; Takashima, Yasuhiro; Fujibayashi, Yasuhisa; Wada, Yuji

    2008-03-01

    Neurotransmitter receptors play a key role in most research on antipsychotic drugs, but little is known about the effects of these drugs on the plasma membrane in the central nervous system. Therefore, we investigated whether chlorpromazine (CPZ), a typical phenothiazine antipsychotic drug, affects the plasma membrane integrity in the rat brain, and if so, whether these membrane alterations can be prevented by dietary supplementation with vitamin E, which has been shown to be an antioxidant and also a membrane-stabilizer. Leakage of [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG)-6-phosphate from rat striatal slices and decrease in 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy were used as indexes for plasma membrane permeabilization and fluidization, respectively. CPZ induced leakage of [(18)F]FDG-6-phosphate from striatal slices, and the leakage was delayed in the vitamin E-supplemented group compared to that in the normal diet group. The decrease in plasma membrane anisotropy induced by CPZ was significantly attenuated by vitamin E supplementation. Chronic treatment with alpha-phenyl-N-tert-butyl nitrone, a free radical scavenger, had no effect on CPZ-induced plasma membrane permeabilization, and the treatment with CPZ did not induce lipid peroxidation. CPZ can reduce plasma membrane integrity in the brain, and this reduction can be prevented by vitamin E via its membrane-stabilizing properties, not via its antioxidant activity.

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

    Science.gov (United States)

    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

  15. 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

  16. Incident users of antipsychotics

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kruse, Marie

    2016-01-01

    initial antipsychotic prescribing patterns and associated use of mental health care services. METHOD: Population-based cohort study linking the following Danish national registers: the Central Psychiatric Research Register, the Register of Medicinal Product Statistics, and Statistics Denmark. RESULTS....... 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....

  17. Schizophrenia risk gene CAV1 is both pro-psychotic and required for atypical antipsychotic drug actions in vivo.

    Science.gov (United States)

    Allen, J A; Yadav, P N; Setola, V; Farrell, M; Roth, B L

    2011-08-16

    Caveolin-1 (Cav-1) is a scaffolding protein important for regulating receptor signaling cascades by partitioning signaling molecules into membrane microdomains. Disruption of the CAV1 gene has recently been identified as a rare structural variant associated with schizophrenia. Although Cav-1 knockout (KO) mice displayed no baseline behavioral disruptions, Cav-1 KO mice, similar to schizophrenic individuals, exhibited increased sensitivity to the psychotomimetic N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). Thus, PCP disruption of prepulse inhibition (PPI) and PCP-induced mouse locomotor activity were both enhanced by genetic deletion of Cav-1. Interestingly, genetic deletion of Cav-1 rendered the atypical antipsychotics clozapine and olanzapine and the 5-HT(2A)-selective antagonist M100907 ineffective at normalizing PCP-induced disruption of PPI. We also discovered that genetic deletion of Cav-1 attenuated 5-HT(2A)-induced c-Fos and egr-1 expression in mouse frontal cortex and also reduced 5-HT(2A)-mediated Ca(2+) mobilization in primary cortical neuronal cultures. The behavioral effects of the 5-HT(2A) agonist (2,5-dimethoxy-4-iodoamphetamine) including head twitch responses and disruption of PPI were also attenuated by genetic deletion of Cav-1, indicating that Cav-1 is required for both inverse agonist (that is, atypical antipsychotic drug) and agonist actions at 5-HT(2A) receptors. This study demonstrates that disruption of the CAV1 gene--a rare structural variant associated with schizophrenia--is not only pro-psychotic but also attenuates atypical antipsychotic drug actions.

  18. The 2-year follow-up of schizophrenic patients treated with different antipsychotic drugs maintenance therapy%不同抗精神病药维持治疗的精神分裂症患者2年复发的随访

    Institute of Scientific and Technical Information of China (English)

    兰胜作; 陈明; 江昆伙; 黄声江; 王文华; 黄腊根; 武剑锋

    2013-01-01

    目的:探讨不同抗精神病药维持治疗的精神分裂症患者的复发率是否存在差异. 方法:对首次发病住院的425例精神分裂症患者出院时分别采用氯丙嗪(n=38),奋乃静(n=41),舒必利(n=52),氯氮平(n=81),利培酮(n=63),奥氮平(n=58),奎硫平(n=44),阿立哌唑(n=48)等8种抗精神病药维持治疗,以自制调查表及阳性和阴性症状量表(PANSS)观察其2年内复发率及服药依从性.结果:425例患者2年内总复发率为64.06%.复发率从高到低依次为氯丙嗪、奋乃静、舒必利、阿立哌唑、奎硫平、利培酮、氯氮平、奥氮平.奥氮平组的复发率显著低于氯丙嗪、奋乃静及舒必利组(x2=5.01,4.63,4.35;P均<0.05);氯氮平组的复发率显著低于氯丙嗪组、奋乃静组(x2=4.06,4.05,P均<0.05),其余各组间复发率比较均无统计学意义(P>0.05).8种药物的服药依从性差异无统计学意义(P>0.05).结论:精神分裂症首次发病患者出院后不同种类抗精神病药维持治疗2年的复发率存在差异.%Objective:Explore the relapse rate of schizophrenia with the use of different antipsychotic drugs maintenance and whether there are significant differences.Method:The first onset of schizophrenia hospitalized patients discharged chlorprumazine(n =38),perphenazine (n =41),sulpiride (n =52),clozapine (n =81),risperidone (n =63),olanzapine (n =58),quetiapine (n =44),aripiprazole (n =48) and eight antipsychotics drugs maintenance treatment,the self-made questionnaire and the positive and negative symptoms scale (PANSS) were used to observe their relapse rate and drug compliance within 2 years.Results:The total relapse rate of 425 patients was 64.06% within 2 years; the relapse rate from high to low in turn is chlorpromazine,perphenazine,sulpiride,aripiprazole,quetiapine,risperidone,clozapine,olanzapine.Olanzapine group relapse rate significantly lower than chlorpromazine,perphenazine and sulpiride group (x2 =5

  19. Association of allelic variation in genes mediating aspects of energy homeostasis with weight gain during administration of antipsychotic drugs (CATIE Study

    Directory of Open Access Journals (Sweden)

    Hemant K Tiwari

    2011-09-01

    Full Text Available Antipsychotic drugs are widely used in treating schizophrenia, bipolar disorder, and other psychiatric disorders. Many of these drugs, despite their therapeutic advantages, substantially increase body weight. We assessed the association of alleles of 31 genes implicated in body weight regulation with weight gain among patients being treated with specific antipsychotic medications in the CATIE trial, we found that rs2237988 in ATP-binding cassette subfamily C member 8 (ABCC8 , and rs11643744 and rs9922047 in Fat Mass and Obesity Associated (FTO were associated with such weight gain.

  20. Tardive dyskinesia occurring in a young woman after withdrawal of an atypical antipsychotic drug.

    Science.gov (United States)

    Alblowi, Mohammed A; Alosaimi, Fahad D

    2015-10-01

    Tardive dyskinesia (TD) is one of the most serious and disturbing side-effects of dopamine receptor antagonists. It affects 20-50% of patients on long-term antipsychotic therapy. The pathophysiology of TD remains poorly understood, and treatment is often challenging. Here, we present a 32-year-old woman presenting with a 9-month history of TD occurring after risperidone withdrawal, and characterized almost exclusively by tongue protrusion. After being seen by different specialties and undergoing multiple investigations, she was eventually correctly diagnosed with TD by a specialist team and successfully treated with amantadine. Vigilance and awareness of this condition and its risk factors are required to make the correct diagnosis, especially in cases with unusual presentations caused by atypical antipsychotics, and treatment can be challenging.

  1. 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

  2. Antipsychotic-induced Hyperprolactinemia

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    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

  3. 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.

  4. Pharm GKB: chlorpromazine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available tine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ne citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...ipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxami...tine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan...lorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan

  5. Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients

    Institute of Scientific and Technical Information of China (English)

    Sheng-nan WU; Rui GAO; Qing-he XING; Hua-fang LI; Yi-feng SHEN; Niu-fan GU; Guo-yin FENG; Lin HE

    2006-01-01

    Aim: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazineinduced EPS in schizophrenic patients. Methods: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). Results: Polymorphisms TaqID, Ser311 Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA. or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. Conclusion: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.

  6. Inactivation of the Scrapie agent by ultraviolet irradiation in the presence of chlorpromazine

    Energy Technology Data Exchange (ETDEWEB)

    Dees, C.; Wade, W.F.; German, T.L.; Marsh, R.F. (Wisconsin Univ., Madison (USA). Dept. of Veterinary Science)

    1985-04-01

    The sensitivity of the scrapie agent to u.v. inactivation was found to be related to the purity of the tissue preparation. Scrapie infectivity associated with membrane vesicles was unaffected when irradiated with 10/sup 4/ J/m/sup 2/. Irradiation of more highly purified preparations from detergent-extracted CsCl gradient fractions reduced scrapie infectivity from 10sup(7.8) log/sub 10/ LD/sub 50/ per ml to as low as 10sup(4.5). Sensitivity of membrane-associated scrapie infectivity to inactivation by u.v. irradiation could be increased by addition of chlorpromazine, a phenthiazine antipsychotic which penetrates lipid bilayers and induces single-strand breaks in nucleic acids under irradiation. Chlorpromazine without irradiation, and a semiquinone protein-binding radical of chlorpromazine, failed to decrease scrapie infectivity by themselves. A closely related phenthiazine antipsychotic, trifluoperazine, which does not bind to nucleic acids, did not reduce scapie infectivity. These findings suggest that the target of u.v. radiation for inactivation of scrapie infectivity in the presence of chlorpromazine is an essential nucleic acid.

  7. 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

  8. 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

    and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks...... medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry...

  9. Minimizing Cardiovascular Adverse Effects of Atypical Antipsychotic Drugs in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Fadi T. Khasawneh

    2014-01-01

    Full Text Available The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients.

  10. Conventional and atypical antipsychotics in the elderly : a review.

    Science.gov (United States)

    Gareri, Pietro; De Fazio, Pasquale; Stilo, Mariagrazia; Ferreri, Guido; De Sarro, Giovambattista

    2003-01-01

    Psychoses are major mental disorders marked by derangement of personality and loss of contact with reality, and are common in the elderly. Various hypotheses suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in psychotic patients, the most studied of which are the dopaminergic, serotonergic and glutamatergic systems. In particular, long-term treatment with antagonists at dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at glutamate receptors may improve symptoms. Treatment with antipsychotics is very common in the elderly and often indispensable. However, for successful treatment it is essential to have an adequate multidimensional assessment of the geriatric patient and of his or her polypathology and polypharmacy, together with knowledge of age-dependent pharmacokinetics and pharmacodynamic changes and drug-drug interactions.Conventional antipsychotics such as haloperidol, chlorpromazine, promazine, tiapride and zuclopenthixol are D(2)-receptor antagonists and inhibit dopaminergic neurotransmission in a dose-related manner. They decrease the intensity of all psychotic symptoms, although not necessarily to the same extent and with the same time course. Negative symptoms may persist to a much more striking extent than delusions, hallucinations and thought disorders, and there is a dose-related incidence of extrapyramidal side effects (EPS). Newer antipsychotics, such as clozapine, olanzapine, risperidone, quetiapine and ziprasidone, have a different receptor-binding profile, interacting with both D and 5-HT receptors; they less frequently cause EPS and are better tolerated in the elderly. Their use is advantageous because they are effective both on positive and negative symptoms of schizophrenia and may also be used in the treatment of behavioural disturbances in elderly and/or demented individuals. The use of clozapine is limited by the onset of agranulocytosis, whereas olanzapine, risperidone, quetiapine

  11. Effects of antipsychotics on bone mineral density and prolactin levels \\ud in patients with schizophrenia: a 12-month prospective study

    OpenAIRE

    2014-01-01

    Objective: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia.\\ud \\ud Methods: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole)\\ud was prescribed for 12 months as appropria...

  12. 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.

  13. Kv3.1-containing K(+) channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs.

    Science.gov (United States)

    Yanagi, M; Joho, R H; Southcott, S A; Shukla, A A; Ghose, S; Tamminga, C A

    2014-05-01

    Neuronal firing is a fundamental element of cerebral function; and, voltage-gated potassium (K(+)) channels regulate that firing through the repolarization of action potentials. Kv3-type channels (Kv3.1-Kv3.4) represent a family of voltage-gated K(+) channels that have fast-spiking properties. Kv3.1 channel subunits are predominantly localized to cortical parvalbumin (PV)-positive, inhibitory interneurons. The firing properties of these interneurons participate in establishing the normal gamma oscillations and synchrony of cortical neuronal populations, thought to be the signature of higher information processing in human brain. Schizophrenia (SZ) is associated with abnormalities in cortical gamma synchrony and in information processing, particularly with dysfunction in working memory and executive function. Here, we report the distribution of Kv3.1b and Kv3.2 protein in normal human brain, showing that Kv3.1b is limited to neocortical areas, whereas Kv3.2 is abundantly represented in neo- and subcortical regions. In SZ cases, levels of Kv3.1b protein are decreased in the neocortex, but only in cases without antipsychotic drug (APD) treatment; Kv3.1 levels are normal in antipsychotic-treated cases. Kv3.2 is not different in distribution or in level between normal and SZ cases, nor influenced by APD, in any region tested. The apparent increase in Kv3.1b protein levels by APDs in SZ neocortex was confirmed in laboratory rodents treated with chronic APDs. These findings show a decrease in Kv3.1b channel protein in SZ neocortex, a deficit that is restored by APDs. This alteration could be fundamentally involved in the cortical manifestations of SZ and in the therapeutic response to APDs.

  14. Region-specific induction of deltaFosB by repeated administration of typical versus atypical antipsychotic drugs.

    Science.gov (United States)

    Atkins, J B; Chlan-Fourney, J; Nye, H E; Hiroi, N; Carlezon, W A; Nestler, E J

    1999-08-01

    Whereas acute administration of many types of stimuli induces c-Fos and related proteins in brain, recent work has shown that chronic perturbations cause the region-specific accumulation of novel Fos-like proteins of 35-37 kD. These proteins, termed chronic FRAs (Fos-related antigens), have recently been shown to be isoforms of DeltaFosB, which accumulate in brain due to their enhanced stability. In the present study, we sought to extend earlier findings that documented the effects of acute administration of antipsychotic drugs (APDs) on induction of Fos-like proteins by investigating the ability of typical and aytpical APDs, after chronic administration, to induce these DeltaFosB isoforms in several brain regions implicated in the clinical actions of these agents. By Western blotting we found that chronic administration of the typical APD, haloperidol, dramatically induces DeltaFosB in caudate-putamen (CP), a brain region associated with the extrapyramidal side effects of this drug. A smaller induction was seen in the nucleus accumbens (NAc) and prefrontal cortex (PFC), brain regions associated with the antipsychotic effects of the drug. In contrast, chronic administration of the prototype atypical APD clozapine failed to significantly increase levels of DeltaFosB in any of the three brain regions, and even tended to reduce DeltaFosB levels in the NAc. Two putative atypical APDs, risperidone and olanzapine, produced small but still significant increases in the levels of DeltaFosB in CP, but not NAc or PFC. Studies with selective receptor antagonists suggested that induction of DeltaFosB in CP and NAc is most dependent on antagonism of D2-D3 dopamine receptors, with antagonism of D1-like receptors most involved in the PFC. Immunohistochemical analysis confirmed the greater induction of DeltaFosB in CP by typical versus atypical APDs, with no significant induction seen in PFC with either class of APD. Together, these findings demonstrate that repeated administration

  15. Compound list: chlorpromazine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available chlorpromazine CPZ 00016 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/chlorproma...zine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/chlorproma.../in_vivo/Liver/Single/chlorpromazine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc...iencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/chlorpromazine.Rat.in_vivo.Liver.Repeat.zip ...

  16. Melanogenesis and antioxidant defense system in normal human melanocytes cultured in the presence of chlorpromazine.

    Science.gov (United States)

    Otreba, Michał; Wrześniok, Dorota; Beberok, Artur; Rok, Jakub; Buszman, Ewa

    2015-02-01

    Chlorpromazine is used in the treatment of schizophrenia and psychotic disorders and belongs to phenothiazine class of neuroleptic drugs. It shows severe side effects such as extrapyramidal symptoms as well as ocular and skin disorders, but the mechanism is still not fully established. The aim of this study was to examine the effect of chlorpromazine on cell viability, melanogenesis and antioxidant defense system in normal human melanocytes. It has been demonstrated that chlorpromazine induces concentration dependent loss in cell viability. The value of EC(50) was calculated to be 2.53 μM. Chlorpromazine in lower concentrations (0.0001, 0.001 and 0.01 μM) increased the melanin and microphthalmia-associated transcription factor (MITF) content and tyrosinase activity, while changes of antioxidant enzymes activity were not observed. It suggests that long-term chlorpromazine therapy, even with low drug doses, may lead to hyperpigmentation disorders in skin and/or eye. The use of the analyzed drug in higher concentrations (0.1 and 1.0 μM) caused significant alterations of antioxidant enzymes activity in normal melanocytes, what may explain a potential role of chlorpromazine in the depletion of cellular antioxidant status leading to other adverse effects associated with the high-dose and/or long-term therapy.

  17. Acute variations of cytokine levels after antipsychotic treatment in drug-naïve subjects with a first-episode psychosis: A meta-analysis.

    Science.gov (United States)

    Capuzzi, Enrico; Bartoli, Francesco; Crocamo, Cristina; Clerici, Massimo; Carrà, Giuseppe

    2017-03-08

    Schizophrenia is likely to be associated with immunological abnormalities. However, antipsychotics may induce immunomodulatory effects, by influencing plasma cytokines. In order to distinguish these influences, we carried out a systematic review and meta-analysis exploring the acute effect of antipsychotics on candidate cytokines plasma levels (IL-1β, IL-2, IL-6, IL-17, IFN-γ, TNF-α) among drug-naïve subjects with first episode psychosis. We searched main Electronic Databases, identifying eight studies meeting our inclusion criteria. Pre and post-treatment plasma cytokines values were used to estimate standardized mean differences. Heterogeneity was estimated using the I(2) index. Heterogeneity-based sensitivity analyses were performed. IL-2 (p=0.023) and IL-6 (p=0.012) levels showed a significant decrease after four weeks of antipsychotic treatment. Relevant sensitivity analysis confirmed these findings. IL-1β had high between-study heterogeneity. However, leaving out one study, significant after treatment decrease was found. IL-6 and IL-2, and possibly IL-1β, could be considered state markers, decreasing after antipsychotic treatment, whilst TNF-α, IL-17, and IFN-γ might be considered trait markers. Options for novel treatments in FEP, involving cytokine-modulating agents, should be further studied.

  18. Weight change in Parkinson and Alzheimer patients taking atypical antipsychotic drugs.

    Science.gov (United States)

    Sitburana, Oraporn; Rountree, Susan; Ondo, William G

    2008-09-15

    Atypical antipsychotics (AA) are generally associated with weight gain. We determined body mass index (BMI) change in Parkinson's disease (PD) before and after taking AA and compared against PD controls and Alzheimer's disease (AD) patients on AA. In 66 consecutive PD subjects started on AA who had accurate weights for more than 6 months before and after initiation of AA, we compared weight change before and after AA use, against a control group of sixty-one sex-matched PD subjects, and against twenty-eight AD subjects taking AA. A linear regression model was created to compare weight changes. Fifty-nine PD subjects had complete data, quetiapine (n=53) and clozapine (n=6). The mean BMI change in the period before starting AA was 0.00 kg/m(2)/month over 1.95+/-1.41 years. After starting AA, subjects lost 0.03 kg/m(2)/month (95% CI 0.62-1.21, P<0.0001), comparing PD before AA to the same PD patients after AA. In 61 PD controls, the mean BMI loss was 0.01 kg/m(2)/month (95% CI 0.15-0.94, P=0.007) comparing PD on AA vs. PD controls. The BMI for 28 AD subjects on AA increased 0.01 kg/m(2)/month (95% CI 0.26-0.83, P<0.0001), comparing PD on AA vs. AD on AA. The weight loss seen in the PD/AA group, compared to AD, suggest uniquely altered weight homeostasis in PD.

  19. Enhanced latent inhibition in dopamine receptor-deficient mice is sex-specific for the D1 but not D2 receptor subtype: implications for antipsychotic drug action.

    Science.gov (United States)

    Bay-Richter, Cecilie; O'Tuathaigh, Colm M P; O'Sullivan, Gerard; Heery, David M; Waddington, John L; Moran, Paula M

    2009-04-01

    Latent inhibition (LI) is reduced learning to a stimulus that has previously been experienced without consequence. It is an important model of abnormal allocation of salience to irrelevant information in patients with schizophrenia. In rodents LI is abolished by psychotomimetic drugs and in experimental conditions where LI is low in controls, its expression is enhanced by antipsychotic drugs with activity at dopamine (DA) receptors. It is however unclear what the independent contributions of DA receptor subtypes are to these effects. This study therefore examined LI in congenic DA D1 and D2 receptor knockout (D1 KO and D2 KO) mice. Conditioned suppression of drinking was used as the measure of learning in the LI procedure. Both male and female DA D2 KO mice showed clear enhancement of LI reproducing antipsychotic drug effects in the model. Unexpectedly, enhancement was also seen in D1 KO female mice but not in D1 KO male mice. This sex-specific pattern was not replicated in locomotor or motor coordination tasks nor in the effect of DA KOs on baseline learning in control groups indicating some specificity of the effect to LI. These data suggest that the dopaminergic mechanism underlying LI potentiation and possibly antipsychotic action may differ between the sexes, being mediated by D2 receptors in males but by both D1 and D2 receptors in females. These data suggest that the DA D1 receptor may prove an important target for understanding sex differences in the mechanisms of action of antipsychotic drugs and in the aetiology of aberrant salience allocation in schizophrenia.

  20. The role of antipsychotics in the management of fibromyalgia.

    Science.gov (United States)

    Calandre, Elena P; Rico-Villademoros, Fernando

    2012-02-01

    Fibromyalgia is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety. It has been estimated to affect roughly the 2-4% of the general population in most countries studied, and it has been shown to be much more prevalent in women than in men. Although its pathophysiology is not yet fully understood, it is known that both genetic and environmental factors are involved in its development. Fibromyalgia shares a high degree of co-morbidity with other conditions, including chronic headache, temporomandibular disorder, irritable bowel syndrome, major depression, anxiety disorders and chronic fatigue syndrome. Therefore, this is a syndrome difficult to treat for which multimodal treatments including physical exercise, psychological therapies and pharmacological treatment are recommended. Although different kinds of drugs have been studied for the treatment of fibromyalgia, the most widely used drugs that have the higher degree of evidence for efficacy include the α(2)δ ligands pregabalin and gabapentin, and the tricyclic antidepressants (TCAs) and serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). However, there is a need to look for newer additional therapeutic pharmacological options for the treatment of this complex and disabling disease. First- and second-generation antipsychotics have shown analgesic properties both in an experimental setting and in humans, although most of the available evidence for the treatment of human pain concerns older antipsychotics and involves clinical trials performed several decades ago. In addition, several second-generation antipsychotics, risperidone, olanzapine and quetiapine, have shown efficacy in the treatment of some anxiety disorders. Some second-generation antipsychotics, mainly quetiapine, aripiprazole and

  1. 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

  2. Towards an animal model of an antipsychotic drug-resistant cognitive impairment in schizophrenia: scopolamine induces abnormally persistent latent inhibition, which can be reversed by cognitive enhancers but not by antipsychotic drugs.

    Science.gov (United States)

    Barak, Segev; Weiner, Ina

    2009-03-01

    Schizophrenia symptoms segregate into positive, negative and cognitive, which exhibit differential sensitivity to drugs. Recent efforts to identify treatments targeting cognitive impairments in schizophrenia have directed attention to the cholinergic system for its well documented role in cognition. Relatedly, muscarinic antagonists (e.g. scopolamine) produce an 'antimuscarinic syndrome', characterized by psychosis and cognitive impairments. Latent inhibition (LI) is the poorer conditioning to a stimulus resulting from its non-reinforced pre-exposure. LI indexes the ability to ignore irrelevant stimuli and aberrations of this capacity produced by pro-psychotic agents (e.g. amphetamine, MK-801) are used extensively to model attentional impairments in schizophrenia. We recently showed that LI was disrupted by scopolamine at low doses, and this was reversed by typical and atypical antipsychotic drugs (APDs) and the acetylcholinesterase inhibitor physostigmine. Here, at a higher dose (1.5 mg/kg), scopolamine produced an opposite pole of attentional impairment, namely, attentional perseveration, whereby scopolamine-treated rats persisted in expressing LI under strong conditioning that prevented LI expression in controls. Scopolamine-induced persistent LI was reversed by cholinergic and glycinergic cognitive enhancers (physostigmine and glycine) but was resistant to both typical and atypical APDs (haloperidol and clozapine). The latter sets scopolamine-induced persistent LI apart from scopolamine- and amphetamine-induced disrupted LI, which are reversed by both typical and atypical APDs, as well as from other cases of abnormally persistent LI including MK-801-induced persistent LI, which is reversed by atypical APDs. Thus, scopolamine-induced persistent LI may provide a pharmacological LI model for screening cognitive enhancers that are efficient for the treatment of APD-resistant cognitive impairments in schizophrenia.

  3. 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

  4. Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and schizophrenia: effects of antidepressants and antipsychotic drugs.

    Science.gov (United States)

    Maes, M; De Meester, I; Scharpe, S; Desnyder, R; Ranjan, R; Meltzer, H Y

    1996-01-01

    Recently, our laboratory reported that the activity of dipeptidyl-peptidase IV (DPP IV) was significantly lower in the peripheral blood of major depressed patients than in normal controls. The present study examines plasma DPP IV activity in 43 major depressed and 13 schizophrenic subjects versus 21 normal controls and the effects of antidepressants and antipsychotic drugs on plasma DPP IV activity. DPP IV activity was significantly lower in major depressed subjects than in normal controls and schizophrenic subjects. There was a trend towards higher DPP IV activity in schizophrenic patients than in normal controls. There were no significant effects of antidepressants or neuroleptics on plasma DPP IV activity in depressed and schizophrenic patients, respectively. There were no significant relationships between plasma DPP IV activity and plasma cortisol or immune-inflammatory markers, such as serum interleukin-6 (IL-6) or soluble IL-2 receptor. A significant and positive correlation was found between plasma DPP IV and prolyl endopeptidase (PEP) enzyme activity in the study group as a whole and in schizophrenic subjects. The results support the hypothesis that lower and higher plasma DPP IV activities are trait markers of major depression and schizophrenia, respectively. It is concluded that alterations in the enzyme activity of peptidases, such as DPP IV and PEP, play a role in the pathophysiology of major depression and schizophrenia.

  5. Antipsychotic Drugs May Up Risk of Early Death in Alzheimer's Patients

    Science.gov (United States)

    ... Drugs May Up Risk of Early Death in Alzheimer's Patients Increased odds were nearly doubled if two ... significantly increases the risk of premature death among Alzheimer's patients, a new study indicates. Researchers analyzed data ...

  6. The novel combination of chlorpromazine and pentamidine exerts synergistic antiproliferative effects through dual mitotic action.

    Science.gov (United States)

    Lee, Margaret S; Johansen, Lisa; Zhang, Yanzhen; Wilson, Amy; Keegan, Mitchell; Avery, William; Elliott, Peter; Borisy, Alexis A; Keith, Curtis T

    2007-12-01

    Combination therapy has proven successful in treating a wide variety of aggressive human cancers. Historically, combination treatments have been discovered through serendipity or lengthy trials using known anticancer agents with similar indications. We have used combination high-throughput screening to discover the unexpected synergistic combination of an antiparasitic agent, pentamidine, and a phenothiazine antipsychotic, chlorpromazine. This combination, CRx-026, inhibits the growth of tumor cell lines in vivo more effectively than either pentamidine or chlorpromazine alone. Here, we report that CRx-026 exerts its antiproliferative effect through synergistic dual mitotic action. Chlorpromazine is a potent and specific inhibitor of the mitotic kinesin KSP/Eg5 and inhibits tumor cell proliferation through mitotic arrest and accumulation of monopolar spindles. Pentamidine treatment results in chromosomal segregation defects and delayed progression through mitosis, consistent with inhibition of the phosphatase of regenerating liver family of phosphatases. We also show that CRx-026 synergizes in vitro and in vivo with the microtubule-binding agents paclitaxel and vinorelbine. These data support a model where dual action of pentamidine and chlorpromazine in mitosis results in synergistic antitumor effects and show the importance of systematic screening for combinations of targeted agents.

  7. The antipsychotic sultopride is overdosed--a PET study of drug-induced receptor occupancy in comparison with sulpiride.

    Science.gov (United States)

    Takano, Akihiro; Suhara, Tetsuya; Yasuno, Fumihiko; Suzuki, Kazutoshi; Takahashi, Hidehiko; Morimoto, Takuya; Lee, Young-Joo; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Okubo, Yoshiro

    2006-10-01

    Conventional antipsychotics tend to elicit extrapyramidal symptoms at clinical doses, but dose optimization could reduce the risk of such side-effects. In-vivo receptor-binding studies have suggested that 70-80% of dopamine D2 receptor occupancy provides the desired antipsychotic effects without extrapyramidal symptoms. In terms of dose optimization based on the occupancy, there has not been enough supporting data regarding the clinical doses of the respective antipsychotics. In this study, we measured dopamine D2 receptor occupancy of two conventional benzamide antipsychotics, sulpiride and sultopride, using positron emission tomography, to investigate the rationale of their clinical dose. Although they are prescribed at similar doses (300-1200 mg), the doses required to obtain similar receptor occupancy (70-80%) were quite different: 1010-1730 mg for sulpiride but 20-35 mg for sultopride. In terms of dose, sultopride has about 50 times greater potency than sulpiride based on dopamine D2 receptor occupancy. Evidence for the optimal doses of conventional antipsychotics based on dopamine D2 receptor occupancy would be helpful for rational antipsychotic therapy.

  8. 非典型抗精神病药物用于治疗双相情感障碍%Atypical antipsychotic drugs used to treat bipolar disorder

    Institute of Scientific and Technical Information of China (English)

    殷好贵

    2015-01-01

    As the clinical application of universal, atypical antipsychotics have not just as the treatment of schizophrenia, in bipolar disorder treatment, its application is becoming more and more attention by clinical workers. Atypical antipsychotics for bipolar mania and depression phase in the acute phase of treatment, curative effect and adverse reaction of rare, safety tolerance. This paper mainly introduces the atypical antipsychotic drugs in the treatment of bipolar disorder, provide reference for clinical rational drug use.%随着临床应用的普遍,非典型抗精神病药物已不单纯作为精神分裂症的治疗,在双相障碍治疗中,其应用也越来越受到临床工作者的关注。非典型抗精神病药物对于双相障碍躁狂相和抑郁相的急性发作期的治疗,疗效肯定,不良反应少见,安全耐受。本文主要介绍非典型抗精神病药物在双相障碍治疗中的应用,为临床合理用药提供参考。

  9. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    Science.gov (United States)

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-01

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  10. Medication and participation: A qualitative study of patient experiences with antipsychotic drugs.

    Science.gov (United States)

    Lorem, Geir F; Frafjord, Jartrud S; Steffensen, Marie; Wang, Catharina E A

    2014-05-01

    Patient autonomy is recognised within mental healthcare, although the capacity to participate in one's own treatment planning is often reduced during a psychotic crisis. The patient may not be sufficiently competent to give consent or express preferences at the time treatment decisions are made. Nine participants were interviewed shortly after a crisis. We discussed participation in the treatment planning and recovery process with particular emphasis on interactions with professionals and understanding treatment. The participants recognised the need for drugs and mental healthcare but emphasised the need for better cooperation and communication. To facilitate the development of patient autonomy, we recommend an increased emphasis on providing information and participating in a dialogue about drug treatment options. This could counteract many of the negative experiences reported. The use of debriefing during hospitalisation and following coercion can be a practical tool for clarifying patient preferences and mutual understanding.

  11. Behavioral and molecular neuroepigenetic alterations in prenatally stressed mice: relevance for the study of chromatin remodeling properties of antipsychotic drugs

    Science.gov (United States)

    Dong, E; Tueting, P; Matrisciano, F; Grayson, D R; Guidotti, A

    2016-01-01

    We have recently reported that mice born from dams stressed during pregnancy (PRS mice), in adulthood, have behavioral deficits reminiscent of behaviors observed in schizophrenia (SZ) and bipolar (BP) disorder patients. Furthermore, we have shown that the frontal cortex (FC) and hippocampus of adult PRS mice, like that of postmortem chronic SZ patients, are characterized by increases in DNA-methyltransferase 1 (DNMT1), ten-eleven methylcytosine dioxygenase 1 (TET1) and exhibit an enrichment of 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) at neocortical GABAergic and glutamatergic gene promoters. Here, we show that the behavioral deficits and the increased 5MC and 5HMC at glutamic acid decarboxylase 67 (Gad1), reelin (Reln) and brain-derived neurotrophic factor (Bdnf) promoters and the reduced expression of the messenger RNAs (mRNAs) and proteins corresponding to these genes in FC of adult PRS mice is reversed by treatment with clozapine (5 mg kg−1 twice a day for 5 days) but not by haloperidol (1 mg kg−1 twice a day for 5 days). Interestingly, clozapine had no effect on either the behavior, promoter methylation or the expression of these mRNAs and proteins when administered to offspring of nonstressed pregnant mice. Clozapine, but not haloperidol, reduced the elevated levels of DNMT1 and TET1, as well as the elevated levels of DNMT1 binding to Gad1, Reln and Bdnf promoters in PRS mice suggesting that clozapine, unlike haloperidol, may limit DNA methylation by interfering with DNA methylation dynamics. We conclude that the PRS mouse model may be useful preclinically in screening for the potential efficacy of antipsychotic drugs acting on altered epigenetic mechanisms. Furthermore, PRS mice may be invaluable for understanding the etiopathogenesis of SZ and BP disorder and for predicting treatment responses at early stages of the illness allowing for early detection and remedial intervention. PMID:26756904

  12. 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

  13. ATYPICAL ANTIPSYCHOTICS FROM SCRATCH TO THE PRESENT

    Directory of Open Access Journals (Sweden)

    Ashish Chauhan*, Amit Mittal, Pradeep Kumar Arora

    2013-01-01

    Full Text Available Mental illness constitutes the second-largest disease burden in the United States. Psychosis is one of the most common and severe mental illnesses. It is an extremely devastating condition characterised by delusions, hallucinations, distortion of thoughts and deteriorating social functioning experiences. Psychosis in all human societies has approximately same incidence of occurrence as in accordance to “anthropo-parity principle.” It has large economic impact on various aspects of cognition, health, and quality of life which has devastated effects on its sufferers and facing them large economic burden. Psychosis (Schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyper-stimulation of dopamine function in the brain, particularly in the mesolimbic pathway. Consequences of antipsychotic treatment are far reaching and expensive. Detrimental extrapyramidal side effects associated with conventional antipsychotics and non-compliance among patients limits long term treatment with conventional antipsychotics. It gives rise to a new class, atypical antipsychotics owning low propensity to cause EPS, efficacy against refractory cases and better control over negative symptoms, better tolerance and compliance along with lower relapse rate and safer adverse effect profile. Atypical antipsychotics have revolutionized the treatment of psychosis, now being the treatment of choice for patients with psychosis. The positive therapeutic experience with the atypical antipsychotics in the treatment of psychosis and their favourable effects outweighs their unfavourable adverse effects. Though atypical antipsychotics are widely prescribed in the treatment of schizophrenia, however not a single atypical antipsychotic drug having any exceptional efficacy and safety profile. Thus, there is still a lot of research needed to be carried out in the development of novel atypical antipsychotics. This review is comprehensive appraisal about

  14. Chlorpromazine

    Science.gov (United States)

    ... of interest in life, and strong or inappropriate emotions) and other psychotic disorders (conditions that cause difficulty ... menstrual periods decreased sexual ability changes in skin color dry mouth stuffed nose difficulty urinating widening or ...

  15. Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects?

    Science.gov (United States)

    Le Hellard, S; Theisen, F M; Haberhausen, M; Raeder, M B; Fernø, J; Gebhardt, S; Hinney, A; Remschmidt, H; Krieg, J C; Mehler-Wex, C; Nöthen, M M; Hebebrand, J; Steen, V M

    2009-03-01

    Atypical antipsychotics are nowadays the most widely used drugs to treat schizophrenia and other psychosis. Unfortunately, some of them can cause major metabolic adverse effects, such as weight gain, dyslipidemia and type 2 diabetes. The underlying lipogenic mechanisms of the antipsychotic drugs are not known, but several studies have focused on a central effect in the hypothalamic control of appetite regulation and energy expenditure. In a functional convergent genomic approach we recently used a cellular model and demonstrated that orexigenic antipsychotics that induce weight gain activate the expression of lipid biosynthesis genes controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We therefore hypothesized that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight gain. We genotyped a total of 44 HapMap-selected tagging single nucleotide polymorphisms in a sample of 160 German patients with schizophrenia that had been monitored with respect to changes in body mass index during antipsychotic drug treatment. We found a strong association (P=0.0003-0.00007) between three markers localized within or near the INSIG2 gene (rs17587100, rs10490624 and rs17047764) and antipsychotic-related weight gain. Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects.

  16. 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

  17. Benzodiazepine augmentation of antipsychotic drugs in schizophrenia: a meta-analysis and Cochrane review of randomized controlled trials.

    Science.gov (United States)

    Dold, Markus; Li, Chunbo; Gillies, Donna; Leucht, Stefan

    2013-09-01

    Applying various psychopharmacological combination and augmentation strategies in schizophrenia is common clinical practice. This meta-analysis evaluated the efficacy of benzodiazepines added to antipsychotics. The Cochrane Schizophrenia Group trial register (until February 2011) and PubMed/Medline (until July 2012) were searched for randomized controlled trials (RCTs) with a minimum duration of one week that compared benzodiazepine augmentation of antipsychotics with a control group receiving antipsychotic monotherapy in schizophrenia and schizophrenia-like psychoses. Study selection and data extraction were conducted independently by at least two authors. The primary outcome was response to treatment. Secondary outcomes were positive and negative schizophrenic symptoms, anxiety symptoms, and dropouts due to any reason, inefficacy of treatment, and adverse events. Pooled risk ratios (RRs) with the 95% confidence intervals (CIs) were calculated using a random-effects model, with number-needed-to-treat/harm (NNT/H) calculations where appropriate. Overall, 16 relevant RCTs with 1045 participants were identified. Benzodiazepine augmentation was not associated with statistically significantly more responders (N=6; n=511; RR 0.97, 95% CI 0.77-1.22). Adjunctive benzodiazepines were well accepted and tolerated according to dropout-rates and adverse effects apart from dizziness (N=3; n=190; RR 2.58, 95% CI 1.08-6.15) and somnolence (N=2; n=118; RR 3.30, 95% CI 1.04-10.40). There is no evidence for antipsychotic efficacy of additional benzodiazepine medication in schizophrenia. Therefore, benzodiazepines should be considered primarily for desired ultra short-term sedation of acutely agitated patients but not for augmentation of antipsychotics in the medium- and long-term pharmacotherapy of schizophrenia and related disorders.

  18. A TYPICAL ANTIPSYCHOTIC: A REVIEW

    Directory of Open Access Journals (Sweden)

    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.

  19. Lurasidone:新型非典型抗精神分裂症药物%Lurasidone:a new atypical antipsychotic drug

    Institute of Scientific and Technical Information of China (English)

    王婷婷; 张四喜; 张文锐; 徐宏

    2015-01-01

    Lurasidone is a new atypical antipsychotic drug, it was approved by the Food and Drug Administration ( FDA ) for treatment of schizophrenia on october 28,2010.The article is to provide an review about pharmacological effects, clinical applications, pharmacokinetics, dosage, drug interactions, adverse reactions of Lurasidone.%Lurasidone是一种新型非典型抗精神病药,已于2010年10月28日经美国FDA批准用于治疗成人精神分裂症,本文对该药的药理作用、临床应用、药代动力学、用法用量、药物相互作用、不良反应进行综述。

  20. The Effects of Chlorpromazine on Reproductive System and Function in Female Rats

    Directory of Open Access Journals (Sweden)

    Zahra Zamani

    2015-07-01

    Full Text Available Background: Chlorpromazine (CPZ, an antipsychotic drug, is associated with increased risk of sexual dysfunction through increasing prolactin levels. The current study evaluates the effect of CPZ-induced hyperprolactinemia on ovarian follicular growth, gonadotropins, and alteration of ovarian source hormones. Materials and Methods: In this experimental study, animals were divided into four groups, control and CPZ (n=8 per group. In the treated groups, CPZ was administered by gavage at doses of 3, 10 and 30 mg/kg per day for 28 days. On day 29 the animals were killed after which histopathological and histomorphometric analyses of the ovaries were performed. We evaluated the levels of prolactin serum, luteinizing hormone (LH, follicle-stimulating hormone (FSH, estradiol (E2 and progesterone. Results: The ovaries of the test groups showed numerous atretic follicles of various sizes. CPZ caused a significant difference between the test groups and the control group (P<0.05 on the amount of atresia and the size of the normal corpora lutea (CL. The increased dysfunction of the ovaries from the different groups depended on the amount of CPZ administered. The serum concentrations of prolactin and progesterone significantly increased (P<0.05, while the serum concentrations of estradiol, LH and FSH notably decreased (P<0.05, depending on the CPZ dose. CPZ-induced animals had unsuccessful mating and decreased pregnancy rate. Conclusion: The present findings suggest that CPZ-induced disturbances not only depend on prolactin level but the increased prolactin level is largely dose-dependent.

  1. Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin

    Directory of Open Access Journals (Sweden)

    Silva D.

    2004-01-01

    Full Text Available The binding of chlorpromazine (CPZ and hemin to bovine serum albumin was studied by the fluorescence quenching technique. CPZ is a widely used anti-psychotic drug that interacts with blood components, influences bioavailability, and affects function of several biomolecules. Hemin is an important ferric residue of hemoglobin that binds within the hydrophobic region of albumin with high specificity. Quenching of the intrinsic fluorescence of bovine serum albumin (BSA was observed by selectively exciting tryptophan residues at 290 nm. Emission spectra were recorded in the range from 300 to 450 nm for each quencher addition. Stern-Volmer graphs were plotted, and the quenching constant estimated for BSA solution titrated with hemin at 25ºC was 1.44 (± 0.05 x 10(5 M-1. Results showed that bovine albumin tryptophans are not equally accessible to CPZ, in agreement with the idea that polar or charged quenchers have more affinity for amino acid residues on the outer wall of the protein. Hemin added to albumin solution at a molar ratio of 1:1 quenched about 25% of their fluorescence. The quenching effect of CPZ on albumin-hemin solution was stronger than on pure BSA. This increase can be the result of combined conformational changes in the structure of albumin caused firstly by hemin and then by CPZ. Our results suggest that the primary binding site for hemin on bovine albumin may be located asymmetrically between the two tryptophans along the sequence formed by subdomains IB and IIA, closer to tryptophan residue 212.

  2. 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

  3. 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.

  4. Psychotropic drug effects on gene transcriptomics relevant to Alzheimer disease.

    Science.gov (United States)

    Lauterbach, Edward C

    2012-01-01

    Psychotropics are widely prescribed in Alzheimer disease (AD) without regard to their pathobiological effects. Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression for 52 genes linked to AD. Pending future investigations, current data indicate that atypical antipsychotics, lithium, and fluoxetine reduce AD risk, whereas other drug classes promote risk. Risk may be attenuated by antipsychotics and lithium (down-regulate TNF), atypical antipsychotics (down-regulate TF), risperidone (down-regulates IL1B), olanzapine (up-regulates TFAM, down-regulates PRNP), fluoxetine (up-regulates CLU, SORCS1, NEDD9, GRN, and ECE1), and lithium coadministered with antipsychotics (down-regulates IL1B). Risk may be enhanced by neuroleptics (up-regulate TF), haloperidol (up-regulates IL1B and PION), olanzapine (down-regulates THRA and PRNP, up-regulates IL1A), and chlorpromazine, imipramine, maprotiline, fluvoxamine, and diazepam (up-regulate IL1B). There were no results for dextromethorphan-plus-quinidine. Fluoxetine effects on CLU, NEDD9, and GRN were statistically robust. Drug effects on specific variants, polymorphisms, genotypes, and other genes (CCR2, TF, and PRNP) are detailed. Translational AD risk applications and their limitations related to specific genes, mutations, variants, polymorphisms, genotypes, brain site, sex, clinical population, AD stage, and other factors are discussed. This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on AD-relevant genes.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Natalia Brzozowska

    2016-05-01

    Full Text Available 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.

  7. Antipsychotic treatments; Focus on lurasidone

    Directory of Open Access Journals (Sweden)

    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.

  8. Pharmacogenetics and antipsychotic treatment response.

    Science.gov (United States)

    Naumovska, Z; Nestorovska, A K; Filipce, A; Sterjev, Z; Brezovska, K; Dimovski, A; Suturkova, L J

    2015-01-01

    Antipsychotic drugs are widely used in the treatment of schizophrenia and psychotic disorder. The lack of antipsychotic response and treatment-induced side-effects, such as neuroleptic syndrome, polydipsia, metabolic syndrome, weight gain, extrapyramidal symptoms, tardive dyskinesia or prolactin increase, are the two main reasons for non-compliance and increased morbidity in schizophrenic patients. During the past decades intensive research has been done in order to determine the influence of genetic variations on antipsychotics dosage, treatment efficacy and safety. The present work reviews the molecular basis of treatment response of schizophrenia. It highlights the most important findings about the impact of functional polymorphisms in genes coding the CYP450 metabolizing enzymes, ABCB1 transporter gene, dopaminergic and serotonergic drug targets (DRD2, DRD3, DRD4, 5-HT1, 5HT-2A, 5HT-2C, 5HT6) as well as genes responsible for metabolism of neurotransmitters and G signalling pathways (5-HTTLPR, BDNF, COMT, RGS4) and points their role as potential biomarkers in everyday clinical practice. Pharmacogenetic testing has predictive power in the selection of antipsychotic drugs and doses tailored according to the patient's genetic profile. In this perception pharmacogenetics could help in the improvement of treatment response by using different medicinal approaches that would avoid potential adverse effects, reduce stabilization time and will advance the prognosis of schizophrenic patients.

  9. Molecular cytotoxic mechanisms of chlorpromazine in isolated rat hepatocytes.

    Science.gov (United States)

    MacAllister, Stephanie L; Young, Cheryl; Guzdek, Anna; Zhidkov, Nickholas; O'Brien, Peter J

    2013-01-01

    Chlorpromazine (CPZ), a member of the largest class of first-generation antipsychotic agents, is known to cause hepatotoxicity in the form of cholestasis and hepatocellular necrosis in some patients. The mechanism of CPZ hepatotoxicity is unclear, but is thought to result from reactive metabolite formation. The goal of this research was to assess potential cytotoxic mechanisms of CPZ using the accelerated cytotoxicity mechanism screening (ACMS) technique with freshly isolated rat hepatocytes. This study identified CPZ cytotoxicity and inhibition of mitochondrial membrane potential (MMP) to be concentration-dependent. Furthermore, inhibition of cytochrome P450s (CYPs), including CYP2D1 and 1A2, delayed CPZ cytotoxicity, suggesting a role for CYP activation of CPZ to a toxic metabolite(s) in this model. Metabolism studies also demonstrated glucuronide and glutathione (GSH) requirement for CPZ detoxification in hepatocytes. Inactivating the 2-electron reduction pathway, NAD(P)H quinone oxidoreductase (NQO1), caused a significant increase in hepatocyte susceptibility to CPZ, indicating quinoneimine contribution to CPZ cytotoxicity. Nontoxic concentrations of peroxidase/H(2)O(2) (inflammatory model) increased cytotoxicity in CPZ-treated hepatocytes and caused additional mitochondrial toxicity. Inflammation further depleted GSH and increased oxidized glutathione (GSSG) levels. Results suggest activation of CPZ to reactive metabolites by 2 pathways in hepatocytes: (i) a CYP-catalyzed quinoneimine pathway, and (ii) a peroxidase-catalyzed oxidation of CPZ to CPZ radicals.

  10. Analysis of the Application of Antipsychotic Drugs in the Inpatients in Our Hospital from 2005 to 2010%我院2005-2010年住院患者抗精神病药应用分析

    Institute of Scientific and Technical Information of China (English)

    刘秀平

    2012-01-01

    目的:分析我院抗精神病药的应用情况.方法:采用回顾性方法,对我院2005-2010年住院患者抗精神病药的应用情况进行统计、分析.结果:我院抗精神病药销售金额和用药频度(DDDs)逐年增加,销售金额从588 329元逐年上升至5312869元、DDDs从237176日逐年上升至528822日.其中,经典抗精神病药的销售金额呈下降趋势,非经典抗精神病药的销售金额呈上升趋势.结论:疗效好、副作用小的非经典抗精神病药有逐渐取代经典抗精神病药的趋势.%OBJECTIVE: To evaluate the utilization of the antipsychotic drugs in our hospital. METHODS: By using retrospective method, the utilization of antipsychotic drugs in our hospital during 2005 - 2010 was analyzed statistically. RESULTS: The DDDs and consumption sum were increasing year by year in our hospital, and the consumption sum was increased from 588 329 yuan to 5 312 869 yuan, the DDDs increased from 237 176 days to 528 822 days. The consumption sum of typical antipsychotics showed a tendency of decreasing. Otherwise, the consumption sum of atypical antipsychotics showed a tendency of increasing. CONCLUSION: The typical antipsychotics show a tendency of being substituted by atypical antipsychotics which are more effective and have less side effect.

  11. Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells.

    Science.gov (United States)

    Tan, Qing-Rong; Wang, Xin-Zhao; Wang, Chuan-Yue; Liu, Xiao-Jun; Chen, Yun-Chun; Wang, Huai-Hai; Zhang, Rui-Guo; Zhen, Xue-Chu; Tong, Yao; Zhang, Zhang-Jin

    2007-12-01

    Although classical and atypical antipsychotics may have different effects against neurotoxicity, the underlying mechanisms remain to be elucidated. In the present study, we compared the atypical agents, risperidone (RIP), olanzapine (OLZ), and quetiapine (QTP), with the classical agent haloperidol (HAL) in reducing cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor, in PC12 cells. We also determined whether there were differential effects of RIP and HAL on the expression of brain-derived neurotrophic factor (BDNF), signal transducers and activators of transcription-3 (STAT-3), and the immediate early gene c-fos, as well as intracellular levels of calcium. Exposure to 6 muM rotenone for 24 h resulted in a significant decrease in cell viability and apoptotic alteration. The rotenone-induced cytotoxicity was dose-dependently worsened by pretreatment with HAL, but significantly improved by the aforementioned atypical agents at low doses. Real-time PCR analysis revealed that HAL pretreatment significantly increased BDNF mRNA expression but did not alter c-fos and STAT-3 expression compared to rotenone-exposed cells. Unlike HAL, RIP pretreatment produced a significant elevation of all the three substance mRNA expression and the expression intensity was 2.6- to 4.6-fold greater than HAL. Pretreatment with RIP, but not HAL, also effectively prevented an elevation of intracellular levels of calcium provoked by rotenone. These results suggest that the protective effects of atypical antipsychotics are associated with a greater capacity to enhance pro-cell survival factors, therapeutic biomarker expression, and blockade of calcium influx. This may provide an alternative for explaining therapeutic advantages of atypical agents observed in clinical use.

  12. Chlorpromazine, haloperidol, metoclopramide and domperidone release prolactin through dopamine antagonism at low concentrations but paradoxically inhibit prolactin release at high concentrations.

    Science.gov (United States)

    Besser, G. M.; Delitala, G.; Grossman, A.; Stubbs, W. A.; Yeo, T.

    1980-01-01

    1. The effects of chlorpromazine, haloperidol, metoclopramide and domperidone on the release of prolactin from perfused columns of dispersed rat anterior pituitary cells were studied. 2. Chlorpromazine, haloperidol, metoclopramide and domperidone antagonized the dopamine-mediated inhibition of prolactin release at low concentrations. 3. Each dopamine antagonist displaced the dose-response curve for dopamine-induced suppression of prolactin release to the right in a parallel manner. 4. At higher concentrations, the four drugs became less effective as dopamine antagonists. 5. At high concentrations in the absence of dopamine, chlorpromazine, haloperidol, metoclopramide and domperidone paradoxically suppressed prolactin secretion by an unknown mechanism. PMID:6110459

  13. Tardive dyskinesia in children treated with atypical antipsychotic medications.

    Science.gov (United States)

    Wonodi, Ikwunga; Reeves, Gloria; Carmichael, Dana; Verovsky, Ilene; Avila, Matthew T; Elliott, Amie; Hong, L Elliot; Adami, Helene M; Thaker, Gunvant K

    2007-09-15

    Recent years have witnessed increased antipsychotic treatment of children despite limited long-term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic-naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fisher's exact test). Nine of 62 African-American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European-American children (P = 0.003, Fisher's exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side-effect profile of the atypical antipsychotic drugs in children may be much different than that in adults.

  14. Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

    Science.gov (United States)

    Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

    2013-01-01

    Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

  15. Purchase data analysis of antipsychotics medication in 2011 in 686 Program demonstration cities%“686项目”示范市(州)2011年抗精神病药物采购情况

    Institute of Scientific and Technical Information of China (English)

    张五芳; 马弘; 马宁; 管丽丽; 吴霞民; 王勋; 阎丹峰; 于欣

    2012-01-01

    Objective: Since 2004, the central government started a program to provide free medication for impoverished patients who were rated high on a risk assessment in China. This program is known as the " 686 Program". This paper was aimed to investigate the antipsychotic drug use patterns for treating mental illness in cities in 686 Program. Methods: The procurement of antipsychotic varieties and purchase cost data of 160 cities in 686 Program in 2011 year was surveyed and analyzed. Results: The total purchase amount of antipsychotics was 16. 5996 million Yuan. Second-generation antipsychotics accounted for 74. 46% of the total purchase amount, in which ris-peridone accounted for 46. 74%. The top six defined daily doses of antipsychotics were clozapine, sulpiride, chlor-promazine, risperidone, haloperidol decanoate and perphenazine. First-generation antipsychotics accounted for 62. 45% of total drug usage. Conclusion: It suggests that first-generation antipsychotics have higher proportion utilization than second-generation antipsychotics in the communities which are supported by the 686 Program.%目的:了解中央补助地方重性精神疾病管理治疗项目(686项目)示范市(州)2011年抗精神病药物采购种类和费用的特征.方法:对2011年“686项目”160个示范市(州)采购的抗精神病药品种、购药金额、用药频度进行统计分析.结果:2011年“686项目”160个示范市(州)采购的抗精神病药品总金额为1659.96万元.第二代抗精神病药采购金额占总金额的74.46%,其中利培酮占采购总金额的46.74%.用药频度排在前6位的为氯氮平、舒必利、氯丙嗪、利培酮、癸酸氟哌啶醇注射液和奋乃静.第一代抗精神病药物总用药频度占62.45%.结论:本项目主要支持的社区精神疾病患者中,第一代抗精神病药使用比例较高.

  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. Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia.

    Science.gov (United States)

    Pardo, Bernardo M; Garolera, Maite; Ariza, Mar; Pareto, Deborah; Salamero, Manel; Valles, Vicenç; Delgado, Luis; Alberni, Joan

    2011-12-30

    The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas.

  18. The novel antipsychotic drug brexpiprazole, alone and in combination with escitalopram, facilitates prefrontal glutamatergic transmission via a dopamine D1 receptor-dependent mechanism.

    Science.gov (United States)

    Björkholm, Carl; Marcus, Monica M; Konradsson-Geuken, Åsa; Jardemark, Kent; Svensson, Torgny H

    2017-02-09

    Brexpiprazole (Rexulti(®)), a novel D2/3 receptor (R) partial agonist, was recently approved as monotherapy for schizophrenia, demonstrating effectiveness against both positive and negative symptoms, and also approved as add-on treatment to antidepressant drugs, inducing a potent antidepressant effect with a faster onset compared to an antidepressant given alone. Moreover, brexpiprazole has demonstrated pro-cognitive effects in preclinical studies. To explore whether the observed effects may be mediated via modulation of prefrontal glutamatergic transmission, we investigated the effect of brexpiprazole, alone and in combination with the SSRI escitalopram, on prefrontal glutamatergic transmission using in vitro electrophysiological intracellular recordings of deep layer pyramidal cells of the rat medial prefrontal cortex (mPFC). Nanomolar concentrations of brexpiprazole potentiated NMDAR-induced currents and electrically evoked EPSPs via activation of dopamine D1Rs, in similarity with the effect of the atypical antipsychotic drug clozapine. The effect of an ineffective concentration of brexpiprazole was significantly potentiated by the addition of escitalopram. When combined with escitalopram, brexpiprazole also potentiated AMPAR-mediated transmission, in similarity with the clinically rapid acting antidepressant drug ketamine. The effect on the AMPAR-mediated currents was also D1R dependent. In conclusion, our data propose that brexpiprazole exerts a clozapine-like potentiation of NMDAR-mediated currents in the mPFC, which can explain its efficacy on negative symptoms of schizophrenia and the pro-cognitive effects observed preclinically. Moreover, add-on brexpiprazole to escitalopram also potentiated AMPAR-mediated transmission, which may provide a neurobiological explanation to the faster antidepressant effect of add-on brexpiprazole in major depression.

  19. Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis--Preliminary fMRI findings.

    Science.gov (United States)

    Raij, Tuukka T; Mäntylä, Teemu; Kieseppä, Tuula; Suvisaari, Jaana

    2015-08-30

    The dopamine theory proposes the relationship of delusions to aberrant signaling in striatal circuitries that can be normalized with dopamine D2 receptor-blocking drugs. Localization of such circuitries, as well as their upstream and downstream signaling, remains poorly known. We collected functional magnetic resonance images from first-episode psychosis patients and controls during an audiovisual movie. Final analyses included 20 patients and 20 controls; another sample of 10 patients and 10 controls was used to calculate a comparison signal-time course. We identified putamen circuitry in which the signal aberrance (poor correlation with the comparison signal time course) was predicted by the dopamine theory, being greater in patients than controls; correlating positively with delusion scores; and correlating negatively with antipsychotic-equivalent dosage. In Granger causality analysis, patients showed a compromised contribution of the cortical salience network to the putamen and compromised contribution of the putamen to the default mode network. Results were corrected for multiple comparisons at the cluster level with primary voxel-wise threshold p < 0.005 for the salience network contribution, but liberal primary threshold p < 0.05 was used in other group comparisons. If replicated in larger studies, these findings may help unify and extend current hypotheses on dopaminergic dysfunction, salience processing and pathogenesis of delusions.

  20. 不同药物致神经阻滞剂恶性综合征的护理%Nursing of malignant syndrome neuroleptic induced by antipsychotic drugs

    Institute of Scientific and Technical Information of China (English)

    李素琴; 邵志梅; 孙长艳

    2015-01-01

    Objective:To explore the nursing of malignant syndrome neuroleptic induced by antipsychotic drugs. Methods:Clinical features of 44 cases with mental disease were analyzed retrospectively with the Levenson malignant syndrome diagnostic criteria and received supportive nursing. Results:44 cases of patients in the use of high potency antipsychotics appeared with the manifestations of fever,muscle tension,disturbance of consciousness,elevated serum cre-atine kinase and the plant nerve function disorder,obviously,with supportive care in early recognition and stop the medicine promptly and effectively,the dis-ease has been effictively controlled and mitigation. Conclusion:Require medication in patients with nursing staff to understand,especially in the process of the doctor treatment, medicine should focus on monitoring,strengthen the observation after medication. The early detection of abnormal situation timely with-drawal and supportive care,avoid to cause serious adverse reaction.%目的::探讨不同抗精神病药物致神经阻滞剂恶性综合征的护理方法。方法:采用Levenson的恶性综合征诊断标准,对44例精神病患者的临床特征进行回顾性分析,在早期识别和及时停药后进行支持性护理。结果:44例患者在使用高效价抗精神病药物时出现以发热、肌张力增高、意识障碍、血清肌酸磷酸激酶升高以及植物神经功能紊乱等明显的临床表现,在治疗1~4周内,临床症状逐渐消失,病情得到有效控制和缓解。结论:要求护理人员了解患者用药情况,尤其在医师换药、调药的过程中应重点监护,加强患者服药后的观察。早期发现异常情况及时停药并给予支持性护理,避免造成严重不良反应的发生。

  1. Severe Agranulocytosis following Simultaneous Administration of Chlorpromazine and Trimethoprim-Sulfamethoxazole in a Patient with Sepsis: A Possible Toxic Combination

    Directory of Open Access Journals (Sweden)

    Anil Jha

    2016-01-01

    Full Text Available Background. Chlorpromazine and trimethoprim-sulfamethoxazole (TMP/SMX are two commonly prescribed medications by physicians. Either of those medications could cause fatal drug-induced agranulocytosis, with an unclear underlying mechanism. The likelihood of simultaneous prescription of both medications is high and could hypothetically result in severe agranulocytosis that is resistant to treatment. Case Presentation. We are presenting a case of a patient with psychosis on chlorpromazine who was prescribed TMP/SMX for a urinary tract infection. Consequently, the patient developed severe agranulocytosis and septicemia. Patient was managed by granulocyte colony-stimulating factor; however, the time to neutrophil recovery was delayed when compared to the average reported time published by previous studies. Conclusions. Simultaneous use of chlorpromazine and TMP/SMX is a possible toxic combination that could induce severe agranulocytosis. Further reports are needed to confirm this observation.

  2. 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

  3. Side effects of antipsychotic agents--neuroleptic malignant syndrome.

    Science.gov (United States)

    Cvjetković-Bosnjak, Mina; Soldatović-Stajić, Branislava

    2010-01-01

    Summary - Neuroleptic malignant syndrome is a rare, potentially life-threatening complication which is an unpredictable, idiosyncratic reaction to antipsychotics. In patients receiving traditional antipsychotics, neuroleptic malignant syndrome occurs with an incidence of 0.2-3.3%. However, neuroleptic malignant syndrome also appears in patients treated with atypical antipsychotics, especially Clozapine. A possible cause of neuroleptic malignant syndrome is blockade of dopamine receptors in the nigrostriatal tracts or hypothalamic nuclei. If signs and symptoms of the Neuroleptic malignant syndrome are identified in time, full recovery is possible. This is a report of a female patient with neuroleptic malignant syndrome treated by traditional antipsychotics. As soon as neuroleptic malignant syndrome symptoms were recognized, the antipsychotic drugs were discontinued, symptomatic therapy was initiated and symptoms of neuroleptic malignant syndrome disappeared. However, the patient's psychotic symptoms persisted and an atypical antipsychotic was administered. During the next few days the psychotic symptoms gradually disappeared and the patient accomplished good recovery.

  4. Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder.

    Science.gov (United States)

    Abdolmaleky, Hamid M; Pajouhanfar, Sara; Faghankhani, Masoomeh; Joghataei, Mohammad Taghi; Mostafavi, Ashraf; Thiagalingam, Sam

    2015-12-01

    Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance.

  5. Chlorpromazine inhibits mitosis of mammalian cells.

    Science.gov (United States)

    Boder, G B; Paul, D C; Williams, D C

    1983-09-01

    Chlorpromazine (CPZ) at minimally effective concentrations accumulates mammalian cells in mitosis without lethal effects on the cells. Star-metaphase morphology similar to effects seen with classical antimitotic compounds probably results from the preferential action of CPZ on a specific class of microtubules--the pole-to-pole microtubules of the mitotic spindle. At CPZ concentrations of 8 X 10(-6) M, flow cytometry indicates no effect of CPZ on the progress of cells through phases of the cell cycle other than mitosis (M). These results suggest a possible mechanism for toxic side effects of CPZ in man such as granulocytopenia and light sensitization.

  6. Short-Term Effects of Chlorpromazine on Oxidative Stress in Erythrocyte Functionality: Activation of Metabolism and Membrane Perturbation

    Directory of Open Access Journals (Sweden)

    Silvana Ficarra

    2016-01-01

    Full Text Available The purpose of this paper is to focus on the short-term effects of chlorpromazine on erythrocytes because it is reported that the drug, unstable in plasma but more stable in erythrocytes, interacts with erythrocyte membranes, membrane lipids, and hemoglobin. There is a rich literature about the side and therapeutic effects or complications due to chlorpromazine, but most of these studies explore the influence of long-term treatment. We think that evaluating the short-term effects of the drug may help to clarify the sequence of chlorpromazine molecular targets from which some long-term effects derive. Our results indicate that although the drug is primarily intercalated in the innermost side of the membrane, it does not influence band 3 anionic flux, lipid peroxidation, and protein carbonylation processes. On the other hand, it destabilizes and increases the autooxidation of haemoglobin, induces activation of caspase 3, and, markedly, influences the ATP and reduced glutathione levels, with subsequent exposure of phosphatidylserine at the erythrocyte surface. Overall our observations on the early stage of chlorpromazine influence on erythrocytes may contribute to better understanding of new and interesting characteristics of this compound improving knowledge of erythrocyte metabolism.

  7. 临床药师与药物中毒:镇静催眠和抗精神病药物%Clinical Pharmacists in the Management of Drug Overdose:Sedative-Hypnotic and Antipsychotic Drugs

    Institute of Scientific and Technical Information of China (English)

    孙树森; 赵志刚

    2016-01-01

    The trend of drug overdose and poisoning has been rising steadily over the past several decades, and the related rate of mortality has also increased. Pharmacists are an integral part of the healthcare team, playing a vital role in the management of overdose patients. The objectives of this series of articles are to update pharmacists with the latest trends on drug overdose and drug overdose management, including the appropriate use of antidotes. This third paper discusses patient management with sedative-hypnotic and antipsychotic drug overdose.%世界范围包括药物在内的有毒物质中毒情形近几十年来每年呈上升趋势,死亡人数不断增加。药师作为医疗团队成员应当积极参与对药物中毒患者的救治。药师应当熟悉和掌握药物中毒和患者管理相关知识,本系列文章为临床药师提供这方面必备的资讯。本文阐述镇静催眠和抗精神病药物中毒患者管理。

  8. Lactational exposure to atypical antipsychotic drugs disrupts the pituitary-testicular axis in mice neonates during post-natal development.

    Science.gov (United States)

    Mishra, Akash C; Mohanty, Banalata

    2010-07-01

    Olanzapine (OLNZ) and risperidone (RISP), two widely prescribed drugs for post-partum psychosis, transfer through milk to the neonates. Hence, neonates are susceptible to their adverse side effects. In the present study, the pituitary-testicular axis of lactationally exposed mice neonates (PND 28) was examined to evaluate the reproductive adverse effects. Testicular histopathology, immunocytochemistry and morphometric analysis of pituitary PRL (prolactin) and LH (luteinizing hormone) cells and plasma hormonal (PRL, LH and testosterone) levels were the various end points studied. Significantly regressed testes, reduced seminiferous tubules with disrupted germ-cell alignment, spermatogonial exfoliation into the tubule lumens and sparse sperms in the lumens were observed. PRL-immunointensity and plasma levels were elevated, whereas immunoreactivity and plasma levels of LH were decreased. Plasma testosterone levels were also decreased. The hypogonadism thus observed might be mediated by drug-induced hyperprolactinemia, which further inhibited secretions of LH and testosterone. Age may be the factor which made the neonates vulnerable to the PRL elevation by OLNZ which otherwise causes transient elevation in adults and is considered safe. The adverse impact was persistent until adulthood with higher doses of both of the drugs as evident by the analysis of testicular weight, histology and hormonal profiles of post-pubertal mice (PND 63) lactationally exposed as neonates.

  9. Pharmaco-epidemiological description of the population of the Marche Region (central Italy treated with the antipsychotic drug olanzapine

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    Fiorenzo Mignini

    2013-03-01

    Full Text Available BACKGROUND. In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA promulgated a cautionary note. MATERIALS AND METHODS. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. RESULTS. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. CONCLUSIONS. Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions.

  10. Experimental and in silico assessment of fate and effects of the antipsychotic drug quetiapine and its bio- and phototransformation products in aquatic environments.

    Science.gov (United States)

    Herrmann, Manuel; Menz, Jakob; Gassmann, Matthias; Olsson, Oliver; Kümmerer, Klaus

    2016-11-01

    The antipsychotic drug quetiapine (QUT) has been frequently detected in sewage treatment plants. However, information on the fate of QUT in aquatic environments and its behavior during UV treatment is limited. In this study, QUT is shown not to be readily biodegradable in the Closed Bottle Test and the Manometric Respirometry Test according to OECD guidelines. The main biotransformation product (BTP) formed in the tests, a carboxylic acid derivative, was identified by means of high-resolution mass spectrometry. This BTP is presumably a human metabolite and showed higher detection rates than QUT in a river sampling campaign conducted in northern Germany. UV elimination kinetics of QUT at different initial concentrations (226.5, 45.3, 11.3, and 2.3 μmol L(-1)) were faster at lower initial concentrations. All seven phototransformation products (PTPs) could be still identified at initial concentration of 11.3 μmol L(-1). The photolytic mixture generated after 128 min of photolysis of QUT was not better biodegradable than QUT. Initial UV treatment of QUT led to the formation of several additional BTPs. Four of them were identified. The bacterial cytotoxicity and genotoxicity before and after phototransformation of QUT in a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829) showed cytotoxic effects in the LBT for QUT. Furthermore, PTPs had similar cytotoxic effects on luminescent bacteria. The umu-test did not reveal any genotoxic activity for QUT or PTPs. In conclusion, the release of QUT into sewage treatment plants and aquatic environments could result in the formation of a main BTP. Additional UV treatment of QUT would lead to the formation of additional BTPs. Moreover, treatment did not result in lower toxicity to tested organisms. In conclusion, UV treatment of QUT should be considered critically as a potential treatment for QUT in aquatic systems.

  11. Effects of antipsychotic drugs on neurotoxicity, expression of fos-like protein and c-fos mRNA in the retrosplenial cortex after administration of dizocilpine.

    Science.gov (United States)

    Fujimura, M; Hashimoto, K; Yamagami, K

    2000-06-09

    In this study, we examined the effect of clozapine, olanzapine, risperidone and haloperidol on the neuropathology (i.e. neuronal vacuolization) and the expression of Fos-like protein and c-fos mRNA in the retrosplenial cortex of female Sprague-Dawley rats induced by the NMDA receptor antagonist dizocilpine. Pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, blocked the neuronal vacuolization produced by dizocilpine (0.5 mg/kg, s.c.) in the rat retrosplenial cortex in a dose-dependent manner. Furthermore, pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, significantly attenuated the expression of Fos-like protein in the retrosplenial cortex induced by dizocilpine (0.5 mg/kg, s.c.) in a dose-dependent manner. The marked expression of c-fos mRNA in the rat retrosplenial cortex induced by the administration of dizocilpine (0.5 mg/kg, s.c.) was significantly attenuated by pretreatment (15 min) with clozapine (10 mg/kg) or olanzapine (10 mg/kg), but not risperidone (10 mg/kg) or haloperidol (10 mg/kg). The present results suggest that pharmacologically relevant doses of clozapine or olanzapine, but not risperidone or haloperidol, block the neuropathological changes and the expression of Fos-like protein and c-fos mRNA in the rat retrosplenial cortex elicited by the administration of dizocilpine. It is possible that the blockade of dizocilpine-induced neuropathological changes by clozapine and olanzapine may be related to the unique antipsychotic actions of these drugs in schizophrenic patients, although this remains to be verified.

  12. 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.

  13. Alterations in plasma prolyl endopeptidase activity in depression, mania, and schizophrenia: effects of antidepressants, mood stabilizers, and antipsychotic drugs.

    Science.gov (United States)

    Maes, M; Goossens, F; Scharpé, S; Calabrese, J; Desnyder, R; Meltzer, H Y

    1995-10-16

    The activity of prolyl endopeptidase (PEP), a serine proteinase, has been found to be significantly lower in the blood of patients with major depression than in normal volunteers. The present study investigates plasma PEP activity in 25 major depressed, 10 manic, and 14 schizophrenic subjects versus 30 normal volunteers. It also examines the effects of antidepressants, valproate, and neuroleptic drugs on plasma PEP activity. PEP activity was significantly lower in major depressed subjects than in normal volunteers and in patients with mania and schizophrenia. In depressed subjects, plasma PEP activity was significantly increased during treatment with antidepressant drugs, such as fluoxetine. Plasma PEP activity was significantly increased in manic and schizophrenic subjects compared with normal volunteers. In manic subjects, short-term treatment with valproate had a significant suppressive effect on PEP activity. No significant effects of neuroleptics on PEP activity could be found in the schizophrenic patients. The results support the hypothesis that lower PEP activity could play a role in the pathophysiology of major depression, while increased PEP activity may be related to psychotic conditions, such as mania and schizophrenia.

  14. Analysis of the Utilization of Antipsychotic Drugs in 26 Hospitals from Hangzhou Area during 2009-2011%杭州市26家医院2009-2011年抗精神病药利用分析

    Institute of Scientific and Technical Information of China (English)

    张霞; 徐领城; 黄堃

    2013-01-01

    OBJECTIVE:To evaluate the clinical application of antipsychotic drugs in Hangzhou area.METHODS:Using DDD and consumption sum sorting method recommended by WHO,the utilization of antipsychotic drugs in 26 hospitals from Hangzhou area during 2009-2011 were evaluated and analyzed in terms of consumption sum and its rank(B),DDDs and its rank (A),DDC and the ratio of B/A.RESULTS:The consumption sum and DDDs of antipsychotic drugs increased year by year,and consumption sum and DDDs of antipsychotic drugs in 2011 were 1.8 times of 2009.Atypical antipsychotic drugs were effective with low side effects; the consumption sum of them was 98.92% in total,and their DDDs was 70.26% of total.Risperidone,olanzapine and aripiprazole were used more frequently in Hangzhou area,and their B/A value was 1 or close to 1.These drugs had a good performance-to-price ratio.CONCLUSIONS:The atypical antipsychotics drugs occupy a leading place in consumption sum and clinical use in Hangzhou area.%目的:评价杭州市医院抗精神病药的利用情况.方法:采用世界卫生组织(WHO)推荐的限定日剂量和销售金额排序法,通过统计销售金额及排序(B)、用药频度(DDDs)及排序(A)、日均费用(DDC)和排序比(B/A),对杭州市26家医院2009-2011年抗精神病药的利用数据进行评价与分析.结果:该市医院抗精神病药的销售金额、DDDs呈逐年增长趋势,2011年的销售金额是2009年的1.8倍;非经典类抗精神病药由于不良反应少、疗效好,其年均销售金额占精神病药总销售金额的98.92%,年均DDDs占总DDDs的70.26%.利培酮、奥氮平和阿立哌唑是目前杭州地区医院应用较多的药物,其B/A值为1或逐年接近1,显示了良好的性价比.结论:该市医院非经典抗精神病药占据销售金额与临床应用的主导地位.

  15. The quality of lactation studies including antipsychotics

    NARCIS (Netherlands)

    Hummels, Hazel; Bertholee, Daphne; van der Meer, Douwe; Smit, Jan Pieter; Wilffert, Bob; ter Horst, Peter

    2016-01-01

    The aim of this study is to determine the quality of lactation studies that investigated antipsychotics in breast milk according to the Food and Drug Administration (FDA) and International Lactation Consultant Association (ILCA) draft guidelines. We used the draft FDA and ILCA guidelines to review t

  16. Electroanalytical characteristics of antipsychotic drug ziprasidone and its determination in pharmaceuticals and serum samples on solid electrodes.

    Science.gov (United States)

    Kul, Dilek; Gumustas, Mehmet; Uslu, Bengi; Ozkan, Sibel A

    2010-06-30

    Ziprasidone is a psychotropic agent used for the treatment of schizophrenia. Its oxidation was investigated electrochemically at boron-doped diamond and glassy carbon electrodes using cyclic, differential pulse, and square wave voltammetry. The dependence of the peak current and peak potentials on pH, concentration, nature of the buffer, and scan rate were examined. The process was diffusion and adsorption controlled for boron-doped diamond and glassy carbon electrodes, respectively. The possible mechanism of oxidation was discussed with some model compounds that have indole and piperazine oxidations. A linear response was obtained between 8 x 10(-7) and 8 x 10(-5) M for the first peak in acetate buffer (pH 5.5) and between 2 x 10(-6) and 2 x 10(-4) M for the second peak in 0.1 M H(2)SO(4) with boron-doped diamond electrode for differential pulse and square wave voltammetric techniques. The reproducibility and accuracy of the proposed methods were found between 0.31 and 1.20, 99.27 and 100.22, respectively. The recovery studies were also achieved to check selectivity and accuracy of the methods. The proposed methods were applied for the determination of ziprasidone from pharmaceutical dosage forms and human serum samples without any time-consuming extraction, separation, evaporation or adsorption steps prior to drug assay except precipitation of the proteins using acetonitrile. The results were statistically compared with those obtained through an established LC-UV technique, no significant differences were been found between the voltammetric and LC methods.

  17. Randomised clinical trial of Levonantradol and Chlorpromazine in the prevention of radiotherapy-induced vomiting

    Energy Technology Data Exchange (ETDEWEB)

    Lucraft, H.H.; Palmer, M.K. (Christie Hospital and Holt Radium Inst., Manchester (UK))

    1982-11-01

    Levonantradol is a cannabis derivative. Cannabinoid anti-emetics are being assessed in cancer chemotherapy but have been little used in radiotherapy to date. A pilot study and randomised trial compared the anti-emetic effect of a standard drug (Chlorpromazine 25 mg) with Levonantradol at two doses (0.5 and 0.75 mg) in patients receiving palliative single fraction radiotherapy to sites likely to cause nausea and vomiting. Most patients were out-patients. Both drugs were well tolerated. The frequency of vomiting was similar in all three groups in both the pilot study and randomised trial.

  18. 2009年乌鲁木齐市第四人民医院住院患者抗精神病类药物使用分析%Analysis of using antipsychotic drugs in the Fourth People's Hospital of Urumqi

    Institute of Scientific and Technical Information of China (English)

    张冰; 杨晓君

    2010-01-01

    目的 了解乌鲁木齐市第四人民医院2009年抗精神病类药物的用药现状. 方法 以乌鲁木齐市第四人民医院2009年1~12月住院精神病患者处方为依据,从抗精神病药物的分类,精神病患者的年龄、性别、职业,单一用药、联合用药、药物的用法用量等方面,用药物利用指数(DUI)来分析抗精神病药物的应用情况. 结果 除了利培酮、碳酸锂、阿普唑仑的DUI>1.0(分别为1.089、1.574、1.011),其他均≤1.0. 结论 精神类药物在乌鲁木齐市第四人民医院临床使用基本合理,无滥用倾向.在用药选择上,患者的经济状况影响药物的选用,给患者用药时以单一用药为主,必要时辅以联合用药.%Objective To understand the medication situation of curing psychosis by analyzing the using of antipsychotic in the Fourth People Hospital in 2008. Methods According to the drug utilization index(DUI),analysis of the application of antipsychotic based on the medical order and prescription from classification of antipsychotic,age,sex,occupation of mental patients,single medication,drug combinationin the Fourth People's Hospital in 2008,was done. Results DUIs of risperidone,lithium carbonateand alprazolam were greater than 1.0,while other drugs' DUIs were less than 1.0.The cost influenced on the choice of drugs.The single medication was mainly used. Conclusion The use of antipsychotic is rational in the fourth people's hospital.

  19. Analysis of the Utilization of Antipsychotic Drugs in 45 Hospitals of Shanghai Area during the Period of 2006-2010%上海地区45家医院2006-2010年抗精神病药利用分析

    Institute of Scientific and Technical Information of China (English)

    毛叶萌; 黄堃; 张明岛

    2011-01-01

    目的:了解上海地区45家医院2006-2010年抗精神病药的使用情况,为该类药的研究、生产、临床应用等提供参考.方法:采用回顾性方法,对上海地区45家医院2006-2010年抗精神病药的销售金额、用药频度(DDDs)及日均费用(DDC)等进行统计、分析,比较一、二、三级医院之间的用药差异.结果:该地区医院抗精神病药的DDDs和销售金额均呈逐年增长趋势,2010年药品的总DDDs和总销售金额分别是2006年的2.2倍和3.4倍;第2代抗精神病药的DDDs及销售金额均增长较快,销售金额增幅最大的是阿立哌唑,DDDs增幅最大的是奥氮平.抗精神病药的使用以口服药为主.结论:该地区医院抗精神病药销售金额的增长大于数量的增长,涨幅主要来自第2代抗精神病药.控制第2代抗精神病药的研发和生产成本,对第1、2代抗精神病药作进一步临床应用研究与评价,对具有确切疗效的第1代抗精神病药重新核价、确保生产供应,是促进抗精神病药有效、方便、经济和合理应用的有效手段.%OBJECTIVE: To probe into the utilization of antipsychotic drugs in 45 hospitals of Shanghai area during the period of 2006-2010, and to provide reference for the research, production and clinical application of these drugs.METHODS: By retrospective study, the utilization of antipsychotic drugs in 45 hospitals of Shanghai area during the period of 2006-2010 was analyzed statistically in respect of consumption sum, DDDs, DDC, etc.The difference of drug use among first, second and third level hospitals was compared.RESULTS: DDDs and consumption sum of antipsychotic drugs in Shanghai area increased year by year.Total DDDs and consumption sum of antipsychotic drugs in 2010 was 2.2 and 3.4 times as much as in 2006 respectively.The DDDs and consumption sum of second generation antipsychotic drugs increased rapidly.The increase of consumption sum of olanzapine was the biggest and aripiprazole

  20. Antipsychotic agents: efficacy and safety in schizophrenia

    Directory of Open Access Journals (Sweden)

    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

  1. 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.

  2. Neurotrophic corneal ulcer after retrobulbar injection of chlorpromazine.

    Science.gov (United States)

    Hauck, Matthew J; Lee, Hb Harold; Timoney, Peter J; Shoshani, Yochai; Nunery, William R

    2012-01-01

    An 80-year-old woman with a painful, poorly seeing right eye underwent retrobulbar chlorpromazine injection for pain control. After the injection, the patient's symptoms improved; however, a neurotrophic ulcer developed within 2 weeks after the procedure. It is postulated that chlorpromazine may lead to sensory denervation to the cornea with the subsequent development of neurotrophic keratopathy, as observed in this case. Awareness of this potential adverse effect is important for proper patient safety, education, and postinjection management.

  3. Drugs affecting the eye.

    Science.gov (United States)

    Taylor, F

    1985-08-01

    cataract suspected to be induced by allopurinol; numerous additional cases have been reported to the registry since. Phenothiazine, with an estimated 3% incidence of side effects, appears to be safer than other antipsychotic drugs, but the rate of ocular effects increases with the duration of therapy. Thioridazine and chlorpromazine are known to cause lens deposits and pigmentary retinopathy. There is a significantly high prevalence of thrombophlebitis and pseudotumor cerebri among women who use OCs and thrombotic retinal vascular disease, such as retinal vein occulsion, might be linked with them. It also is probable that, because of altered hydration of the cornea, there is a decreased tolerance to contact lenses.

  4. EPS profiles: the atypical antipsychotics are not all the same.

    Science.gov (United States)

    Weiden, Peter J

    2007-01-01

    Within the first few years after chlorpromazine began to be used to treat psychosis, it was observed that it could cause many kinds of neurologic reactions that resembled those seen in idiopathic Parkinson's disease. These reactions were termed "extrapyramidal side effects" (EPS) because of their resemblance to the signs of Parkinson's disease, which were associated with degeneration of the dopamine nerve tracks located in the extrapyramidal region of the central nervous system. Eventually this association of dopamine loss, antipsychotics, and parkinsonism became a central part of the dopamine hypothesis of schizophrenia. Unfortunately, this association was also used to support the hypothesis that EPS were absolutely necessary for antipsychotic efficacy--hence the term "neuroleptic" rather than "antipsychotic." This theory, now discredited, was used to justify the practice of inducing EPS as a means to gauge whether an antipsychotic would be effective. The demonstration that clozapine, an antipsychotic virtually devoid of EPS, has better efficacy for psychosis than any other "neuroleptic" disproved the theory that EPS were fundamentally linked to efficacy. Because the idea of a relationship between EPS and efficacy was so ingrained in clinical practice, clozapine was called "atypical." Our understanding of the relationship between EPS and antipsychotic response has come full circle. With the introduction of clozapine and other newer antipsychotics, it has become clear that EPS are harmful and serve no beneficial purpose. The availability of newer antipsychotics with a lower EPS burden means that, at least in theory, it is now possible to treat psychosis without EPS in the vast majority of patients. In practice, however, EPS remain a significant problem even in the era of atypical or second generation antipsychotics (SGAs). One limitation is that the concept of "atypicality," when used to denote antipsychotic efficacy without EPS, is a relative not an absolute

  5. Antipsychotic drug binding in the substantia nigra: an examination of high metoclopramide binding in the brains of normal, Alzheimer's disease, Huntington's disease, and Multiple Sclerosis patients, and its relation to tardive dyskinesia.

    Science.gov (United States)

    Chen, Sheng; Seeman, Philip; Liu, Fang

    2011-02-01

    This project was done in order to determine why the annual incidence of metoclopramide-associated tardive dyskinesia is much higher than that for the commonly used antipsychotics. To test the hypothesis that metoclopramide tardive dyskinesia may be associated with high concentrations of metoclopramide in the substantia nigra under clinical conditions, the nonspecific binding of tritiated antipsychotics to the dissected melaninized regions of postmortem human substantia nigra was measured. The nonspecific binding at 1 nM [³H]ligand was 7.3, 4.2, 2.6, 0.91 and 0.66 fmoles/mg for [³H]haloperidol, [³H]clozapine, [³H]raclopride, [³H]metoclopramide, and [³H]olanzapine, respectively. After adjusting these values for the known free concentrations of these drugs in plasma or spinal fluid, the amounts that would be bound under clinical conditions would be 231, 113, 15, 11, and 3.4 fmoles/mg for metoclopramide, clozapine, raclopride, haloperidol, and olanzapine, respectively. Using rat striatum as baseline to define antipsychotic binding to nonnigral tissue, the excess amount of binding to the Alzheimer nigral tissue under clinical conditions would be 209, 19, 0, 3.4 and 0.8 fmole/mg for metoclopramide, clozapine, raclopride, haloperidol, and olanzapine, respectively, with a similar pattern for nigral tissues from Huntington and Multiple Sclerosis patients. The high accumulation of metoclopramide is sufficiently high to cause nigral nerve cell membrane damage by metoclopramide's detergent-like action, possibly explaining metoclopramide's toxic ability to elicit early tardive dyskinesia. In addition, the nonspecific binding of metoclopramide was much higher in Alzheimer-diseased substantia nigra, consistent with the fact that older individuals are relatively more vulnerable to metoclopramide tardive dyskinesia.

  6. In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug.

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    Xi-Nan Shi

    Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg. Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history

  7. 流浪精神分裂症患者抗精神病药物使用的性别差异%Gender difference on antipsychotic drug use patterns for vagrant mental patients with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    刘芙蓉; 李桂云; 朱永梅

    2013-01-01

    Objective To explore the gender difference on antipsychotic drug use patterns for vagrant mental patients with schizophrenia. Methods Based on the investigation from February 18th in 2012, the treatment for 159 male and 111 female vagrant mental patients with schizophrenia was studied. Results ①The majority medication method was signle drug use( male:57. 2% ,female:79. 3% );the rest of patients were treated with 2 or more than 2 types of antipsychotics( male:42. 8% ,female:20. 7% ),there was significant differences between male and female( P 0. 05 ). Conclusion It is relatively canonical and reasonable for the usage condition of antipsychotic drug in vagrant mental patients with schizophrenia in our hospital, the usage frequency of single]/combination drug use is different between male and female,and it's not obvious for the average of daily dose in sexuality.%目的 调查我院流浪精神分裂症患者抗精神病药物使用的性别差异.方法 采用一日法,以2012年2月18日为时间节点,对我院流浪精神分裂症住院患者(男159例,女111例)的治疗情况进行对比研究.结果 ①单一使用抗精神病药物:占首位(男性为57.2%,女性为79.3%);联用两种以上抗精神病药物者男性为42.8%,女性为20.7%,男性明显多于女性,差异有统计学意义(P0.05).结论 本调查提示,目前,我院流浪精神分裂症患者抗精神病药物的使用情况比较规范合理,在联合用药方面及部分药物使用频度方面存在性别差异,日均剂量方面性别差异无统计学意义.

  8. Effect of chlorpromazine on rat arterial lipid synthesis, in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bell, F.P.; Hubert, E.V.

    1982-10-01

    The effect of chlorpromazine, a major tranquilizer, on arterial lipid metabolism was studied in vitro in rat aortas incubated with (/sup 14/C)acetate and (/sup 14/C)mevalonate as lipid precursors. Chlorpromazine at a level of 0.25 mM in the incubation medium significantly reduced the incorporation of (/sup 14/C)acetate into free fatty acids (p less than 0.01) and total phospholipids (p less than 0.001) but not triglycerides. Chlorpromazine also altered the pattern of arterial phospholipids synthesized from (/sup 14/C)acetate by significantly increasing the relative proportion of phosphatidylinositol plus phosphatidylserine (p less than 0.02) and reducing the relative proportion of sphingomyelin (p less than 0.001). (/sup 14/C) Acetate incorporation into the combined fractions of steryl esters plus hydrocarbons and sterols plus diglycerides was also significantly reduced (p less than 0.001) by 0.25 mM chlorpromazine. Studies with (/sup 14/C)mevalonate showed that chlorpromazine is also an inhibitor of sterol biosynthesis in arterial tissues as evidenced by 35-40% reductions (p less than 0.05) in the formation of /sup 14/C-labeled squalene and C27 sterols.

  9. 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

  10. Progress in studies on tardive dystonia induced by antipsychotic drugs%抗精神病药物引起的迟发性肌张力障碍研究进展

    Institute of Scientific and Technical Information of China (English)

    孙振晓; 于相芬

    2012-01-01

    迟发性肌张力障碍(TDt)是长期应用抗精神病药物引起的锥体外系症状之一.据报道,发生率为2.7%~5.3%.临床主要表现为单个或多个随意肌自主运动困难,或因自主运动困难所致姿势异常.发病机制一般认为是多巴胺神经递质的持久抑制引起突触后多巴胺受体敏感性过度增高所致或与抗精神病药的抗去甲肾上腺素能效应有关.TDt须与急性肌张力障碍、迟发性运动障碍、特发性肌张力障碍、继发性肌张力障碍,家族性肌张力障碍、转换症状等进行鉴别诊断.一旦发生TDt应停药,换用非典型抗精神病药或其他药物治疗,或进行脑深部电刺激治疗.经治疗后症状可能有所改善.%Objective; Tardive dystonia (TDt) is one of extrapyramidal symptoms that starts after long-term use of antipsychotic drugs. It has been reported that the incidence of TDt ranged from 2.7% to 5. 3%. Its main clinical feature is that voluntary movements of one or more voluntary muscles are difficult , or abnormal postures because of difficult voluntary movements . The mechanism of TDt is generally considered to be associated with postsynaptic dopamine receptor supersensitivity caused by sustained inhibition of the dopaminergic neurotransmission or anti-noradrenergic effect of antipsychotics . TDt should be distinguished from acute dystonia , tardive dyskinesia, idiopathic dystonia, secondary dystonia, familial dystonia and conversion symptoms. Once TDt developed, dopamine receptor antagonists should be stopped , atypical antipsychotic drugs or other drugs or deep brain stimulation could be used . Symptoms might improve after such treatment.

  11. Abnormal dissolutions of chlorpromazine hydrochloride tablets in water by paddle method under a high agitation condition.

    Science.gov (United States)

    Aoyagi, Nobuo; Rimando, Annie Policarpio; Izutsu, Kenichi; Katori, Noriko; Kojima, Shigeo

    2003-09-01

    All sugar-coated tablets of chlorpromazine hydrochloride except for those produced by one manufacture showed concave dissolution profiles in water by paddle method at 100 rpm but not at 50 rpm. The study was undertaken to clarify the agitation-dependent abnormal dissolutions. The strange dissolutions were also observed in water at different ionic strengths but not in buffer solutions of pH 1.2, 4.0 and 6.8. When monitored, the pH's of water in dissolution vessels for the abnormal tablets increased with time at 100 rpm and some of them exceeded pH 8 but did not at 50 rpm. The solubility of chlorpromazine hydrochloride decreased with the increase of pH which was too low to dissolve the whole amount of drug contained in a tablet at pH 8. The elevation of pH seemed to be mainly brought about by dissolution of calcium carbonate popularly used for sugar-coated tablets, because larger amount of calcium ion was dissolved out from the abnormal tablets at 100 rpm than from a normal tablet and from them at 50 rpm. These findings indicate that the concave dissolution profiles should be caused by the decrease of drug solubility with increase in pH of water, probably because of dissolution of calcium carbonate. We should pay attention to the change in pH of water which may differ depending on the agitation speed of dissolution tests.

  12. EFFECT OF ANTIPSYCHOTIC DRUG COMBINING WITH BENZHEXOL ON PSYCHOPATHS%抗精神病药物联合苯海索对精神病患者的疗效分析

    Institute of Scientific and Technical Information of China (English)

    刘明秋

    2015-01-01

    目的:对精神病患者使用抗精神病药物联合苯海索的用药情况以及治疗效果进行评价。方法对入住该院进行治疗的精神病患者的临床资料进行回顾性分析,按照是否将抗精神病药物与苯海索联用将全部269例患者分为联用组(156例)以及未联用组(113例),并对二组患者的治疗效果以及不良反应进行分析。结果二组患者在治疗后2,4,6周PANSS评分均较治疗前有明显下降,差异有统计学意义(P<0.05),联合组的PANSS评分较未联合组略高,但组间比较差异无统计学意义(P>0.05),联合组的总不良反应发生率(66.03%)明显高于未联合组(38.05%),且差异有统计学意义( P<0.05),但短期内联合组的椎体外系反应的发生率(9.62%)低于未联合组(31.86%),差异有统计学意义( P<0.05)。结论抗精神病药物联合苯海索对精神病患者进行治疗可以明显减轻患者因服用抗精神病药物而引起的锥体外系反应,但需要合理控制其剂量及使用的时间。%Objective To access the drug use situation and treatment effect of antipsychotic drug combining with benzhexol on psychopath .Methods Totally 269 psychopaths who were accepted by author's hospital during July 2007 and March 2012 as research subjects ,whose clinical data were analyzed respectively .All cases were divided into combination group with 156 cases and non - combination group with 113 cases ac‐cording to whether antipsychotic drug combining with benzhexol or not .The treatment effect and adverse reaction in two groups of patients were analyzed .Results Compared with pre -treatment ,after two -weeks ,four-weeks and six -weeks treatment ,PANSS score in two groups was decrease obviously ,The difference had a statistical significance(P0 .05) .The incidence rate of total adverse reaction with 66 .03% in combination group was obviously higher than

  13. 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.

  14. Intervention of Psychology and Behavior on Obesity Induced by Antipsychotic Drugs in Schizophrenia%心理行为干预在降低抗精神病药源性肥胖中的作用

    Institute of Scientific and Technical Information of China (English)

    张华; 庞礼娟; 宋学勤

    2012-01-01

    现今世界,肥胖已是一个世界性的问题,抗精神病药所致药源性肥胖也已成为困扰精神病患者的一大难题,它不仅容易引起糖尿病、心血管疾病等躯体疾病,同时也给患者造成了严重的心理负担.目前,对于肥胖的治疗主要集中在膳食结构调整以及运动方面,而心理干预作为一种新的肥胖干预治疗方法逐渐被人们所接受,越来越多的实践表明,心理行为干预是一种有效、可行的防治抗精神病药源性肥胖的方法,值得推广.%Obesity is a worldwide problem in the modern world,as a member of obesity,weight gain by antipsychotic drugs has becoming a big problem to mental disorder patients. It is not only lead to diabetes and cardiovascular disease easily,but also is a heavy burden in psychological to patients. Currently, the treatment to obesity focus in diet and exercise, more and more people accept intervention of psychology and behavior as a new treatment to obesity. There is growing data suggesting that the dietary adjustment-based intervention of psychology and behavior is an effective and practical way to prevent obesity induced by antipsychotic drugs and be worth spreading.

  15. Priapisme induit par la chlorpromazine: A propos de deux cas

    Directory of Open Access Journals (Sweden)

    I. Marrag

    2016-06-01

    Le priapisme veineux est une urgence urologique. Il constitue un des effets secondaires des neuroleptiques parmi les quels la chlorpromazine. Cet effet iatrogène, qui est rare mais grave, doit être connu par les cliniciens afin d’être mieux prévenu pour éviter les séquelles érectiles.

  16. Sexual dysfunction with antihypertensive and antipsychotic agents.

    Science.gov (United States)

    Smith, P J; Talbert, R L

    1986-05-01

    The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

  17. Some adverse effects of antipsychotics: prevention and treatment.

    Science.gov (United States)

    Lader, M

    1999-01-01

    Antipsychotic medication causes a wide range of adverse effects, which can be serious and may further imperil both the physical and psychological health of schizophrenic patients. The range of side effects patients commonly encounter includes weight gain, endocrine disturbances, sedation, anticholinergic effects, hypotension, seizures, and extrapyramidal symptoms. Less common and unpredictable reactions are blood dyscrasias, cardiotoxicity, sudden death, and the neuroleptic malignant syndrome. Antipsychotic drugs differ significantly regarding their propensity to cause these reactions. Patients should undergo comprehensive health checks before an antipsychotic is prescribed, and drug therapy should be individualized to take account of any preexisting symptoms. Side effects and the wider implications of drug treatment, such as effects on occupational and social functioning, should be discussed with the patient before initiating therapy. Patients should be regularly monitored for side effects during treatment and switched to alternative therapy if side effects are serious and/or persistent.

  18. Drug: D02615 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available PTICS N05C HYPNOTICS AND SEDATIVES N05CB Barbiturates, combinations N05CB02 Barbiturates in combination with other drugs D02615 Chlorpromazine - promethazine mixt PubChem: 17396785 ...

  19. New users of antipsychotic medication

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    BACKGROUND: Treatment with antipsychotic medication is thoroughly investigated in schizophrenia and bipolar disorder but is also widely applied for a diversity of off-label conditions, despite an uncertain risk-benefit ratio. This study examined the relationship between antipsychotic prescribing...

  20. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2007-08-01

    were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence. Conclusion Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine. There is insufficient data confidently to distinguish between different atypical antipsychotics.

  1. The effect of antipsychotics on sexual function in male patients with schizophrenia, a correlation analysis%抗精神病药对男性精神分裂症患者性功能影响的相关性分析

    Institute of Scientific and Technical Information of China (English)

    占归来; 沈文龙; 饶顺曾; 李晨虎; 张红

    2011-01-01

    -munosorbent assay was used for the detection of serum prolacti and radioimmunoassay for testosterone levels before and 12 wks after the treatments.Brief male sexual function scale,including the positive and negative symptom scale ( PANSS ),and side reaction scale ( TESS ) were used to assess patient sexualfunction,psychiatric symptoms,nd treatment -induced adverse reactions at the 12th wk of treatment.Results After twelve weeks treatment,the sexual function scores of chlorpromazine group ,clozapine group,risperidone group were decreased from those before treatment (P < 0.05).The serum prolactin level of Risperidone and chlorpromazine group increased at the 12 th week from baseline level O risperidone group: (12±5)ng/ml,(22±6)ng/ml,t= 13.92,P < 0.01; chlorpromazine group: (13±6)ng/ml,(19± 5) ng/ml,t = 8.27,P < 0.01],quetiapine group and clozapine group showed no significant change.The 12 week blood testosterone levels of Risperidone group and chlorpromazine group decreasedfrom baseline level [risperidone group: (0.77 ± 0.21)ng/ml,(0.27 ± 0.Ll)ng/ml,t = 13.22,P < 0.01); chlorpromazine group: ( 0.90 ±0.11) ng/ml,( 0.32 ±0.14)ng/ml,t = 11.27,P < 0.01],while quetiapine group and clozapine group showed no significant change.Conclusions antipsychotic drug risperidone and chlorpromazine can cause serum prolactin elevation and serum testosterone reduction while Clozapine showed more adverse drug reactions.The results suggest that these antipsychotics may result in impaired sexual function in male schizophrenia patients.

  2. Membrane specific drugs as radiosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    George, K.C.; Mishra, K.P.; Shenoy, M.A.; Singh, B.B.; Srinivasan, V.T.; Verma, N.C.

    1981-01-01

    Procaine, paracetamol, and chlorpromazine showed inhibition of post irradiation repair. The chlorpromazie effect could be further augmented by treatment of cells with procaine. Chlorpromazine was also found to be preferentially toxic to hypoxid bacterial cells, and the survivors showed extreme radiosensitivity to gamma rays. Chlorpromazine was found to inhibit tumour growth in swiss mice when given intraperitoneally as well as when injected directly into the tumour. When combined with single x-ray doses, significant radiosensitization was observed in two in vivo tumours sarcoma 180A and fibrosarcoma. These results indicated that chlorpromazine may prove a good drug for combined chemo-radiotherapy of solid tumours. Investigations continued studying various aspects such as effectiveness in other tumour lines, distribution in healthy and tumour bearing animals, hyperthermia and drug combination effects, and encapsulation of the drug in artificial liposomes and blood cells. (ERB)

  3. 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.

  4. 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.

  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. Voltammetric Determination of Captopril Using Chlorpromazine as a Homogeneous Mediator

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    Hossein Bahramipur

    2011-01-01

    Full Text Available Chlorpromazine was used as a homogeneous electrocatalyst in the oxidation of captopril. The anodic peak current of chlorpromazine was increased substantially in the presence of low concentrations of captopril (pH 4. Cyclic voltammetry and chronoamperometry were used to study the kinetics of the catalytic electron transfer reaction. The values of electron transfer coefficient ( and catalytic rate constant (cat were estimated to be 0.34 and 8.48×102M−1sec−1, respectively. Linear sweep voltammetry was used for the determination of captopril in the presence of chlorpromazine. A linear calibration curve was obtained in the concentration range of captopril of 10.0–300.0 μM, with a limit of detection of 3.65 μM. The relative standard deviation (RSD% for 5 replicate measurements of captopril (100 μM was 1.96%. The method was applied to the determination of captopril in pharmaceutical formulations and blood serum samples with satisfactory results.

  7. The role of 5-HT7 receptor antagonism in the amelioration of MK-801-induced learning and memory deficits by the novel atypical antipsychotic drug lurasidone.

    Science.gov (United States)

    Horisawa, Tomoko; Nishikawa, Hiroyuki; Toma, Satoko; Ikeda, Atsushi; Horiguchi, Masakuni; Ono, Michiko; Ishiyama, Takeo; Taiji, Mutsuo

    2013-05-01

    Lurasidone is a novel atypical antipsychotic with high affinity for dopamine D2, serotonin 5-HT7 and 5-HT2A receptors. We previously reported that lurasidone and the selective 5-HT7 receptor antagonist, SB-656104-A improved learning and memory deficits induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, in the rat passive avoidance test. In this study, we first examined the role of the 5-HT7 receptor antagonistic activity of lurasidone in its pro-cognitive effect to ameliorate MK-801-induced deficits in the rat passive avoidance test. The 5-HT7 receptor agonist, AS19, (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino) tetralin, (3 mg/kg, s.c.) completely blocked the attenuating effects of lurasidone (3 mg/kg, p.o.), highlighting the importance of 5-HT7 receptor antagonism in the pro-cognitive effect of lurasidone. AS19 (3 mg/kg, s.c.) also blocked the ameliorating effect of SB-656104-A (10 mg/kg, i.p.) in the same experimental paradigm. To further extend our observation, we next tested whether 5-HT7 receptor antagonism still led to the amelioration of MK-801-induced deficits when combined with D2 and 5-HT2A receptor antagonists, and found that SB-656104-A (10 mg/kg, i.p.) significantly ameliorated MK-801-induced deficits even in the presence of the D2 receptor antagonist raclopride (0.1 mg/kg, s.c.) and 5-HT2A receptor antagonist ketanserin (1 mg/kg, s.c.). Taken together, these results suggest that the 5-HT7 receptor antagonistic activity of lurasidone plays an important role in its effectiveness against MK-801-induced deficits, and may contribute to its pharmacological actions in patients with schizophrenia.

  8. Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to the Channel of Botulinum Neurotoxin

    Science.gov (United States)

    2006-09-01

    M2 protein2 and its derivative, memantine, which blocks the NMDA receptor channel3, and is approved by the FDA for the treatment of dementia ...The antipsychotic chlorpromazine4, an open channel blocker of the nicotinic acetylcholine receptor (nAChR) channel5, and numerous local

  9. Examining dopamine D3 receptor occupancy by antipsychotic drugs via [3H]7-OH-DPAT ex vivo autoradiography and its cross-validation via c-fos immunohistochemistry in the rat brain.

    Science.gov (United States)

    Davoodi, Nima; te Riele, Paula; Langlois, Xavier

    2014-10-05

    Dopamine D3 receptors are a major target for drug discovery programs related to psychiatric disorders such as schizophrenia. The ability of a compound to occupy significant levels of D3 receptors is important for achieving therapeutic efficacy in both pre-clinical and clinical settings. Here we attempt to characterise antipsychotic drug-effects at D3 receptors by measuring receptor occupancy via ex-vivo [3H]7-OH-DPAT autoradiography, and further validating this outcome via analysis of Fos-like immunoreactivity (Fos-LI) in the rat major islands of Calleja (ICjM), a brain structure with high D3 expression. Rats were treated subcutaneously with haloperidol (0.04 mg/kg), clozapine (20 mg/kg) and olanzapine (0.63 mg/kg), the selective D2 antagonist L-741626 (2.5 mg/kg) and the selective D3 antagonist SB-277011-A (10 mg/kg). Doses were based on levels of D2 occupancy considered clinically relevant (60-80%). When measuring D3 occupancy, clozapine and SB-277011-A displayed meaningful levels of occupancy (60% and 77%, respectively), haloperidol and olanzapine showed limited occupancy (16% and 27%, respectively), whereas L-741626 showed no occupancy. There were no significant changes in ICjM Fos-LI after L-741626 and haloperidol treatment, minor but significant increases after olanzapine treatment, whereas highly significant increases were seen with SB-277011-A and clozapine. Additionally, pre-treating clozapine with the D1 antagonist SCH23390 caused a significant, albeit non-complete, reduction in Fos-LI, highlighting the D1 agonist property of clozapine. In conclusion, it appears that drugs occupying >50% D3 receptors produce robust increases in ICjM Fos-LI. This study may help to identify the appropriate D3 receptor antagonists that have the potential to be tested in the clinic.

  10. Antipsychotics dosage and antiparkinsonian prescriptions

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    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.

  11. Bilateral skin conductance and the pupillary light-dark reflex: manipulation by chlorpromazine, haloperidol, scopolamine, and placebo.

    Science.gov (United States)

    Patterson, T; Venables, P H

    1981-01-01

    Cholinergic blocking with scopolamine produces skin conductance orientating response (SCOR) nonresponding in normal subjects. This may be one of a number of causes for nonresponding in schizophrenic subjects. Blockade of dopamine with haloperidol produces an increase in amplitude and shortening of recovery time in the SCOR of normal subjects. This result closely resembles that of Nielsen and Petersen (1976) who found a similar pattern of responding in normal subjects who scored high on a scale of schizophrenism. These results, along with those for chlorpromazine and the pupillographic effects of the three drugs are discussed in terms of biochemical working hypotheses of schizophrenic subclassification.

  12. Utilización de Neurolépticos atípicos en el Centro Penitenciario de Málaga Study of the use of atypical antipsychotic drugs in Málaga Prison

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    C. Salinas Rosillo

    2007-06-01

    . Materials and Methods: A retrospective study was carried out on the use of antipsychotic drugs from 2003 to 2004 in Malaga State Prison. A comparison was then made with the use of this type of medication in the Primary Health Care District of Guadalhorce. Data on medication consumption was taken from medical orders received at the prison during this study. The ATC (Anatomical Therapeutic and Chemical Classifying System was used for classifying the active principles. The prison"s own data base (SANIT was used for calculating the number of containers. For calculating the DDD, the ratio DDD/1000 inmates/day was utilised. Results: The use of atypical antipsychotic medication in the prison increased. There is an increasing trend towards the use of quetiapine in small doses. The use of risperidone went down during the period of this study, although it is still the most commonly used drug in DDD and in consumed containers. The Primary Health care results indicate a trend in the opposite direction. Conclusion: The use of the group of drugs in this study has decreased in the Primary Health Care area, possibly because of special medical control measures such as the control stamp. In Malaga Prison use of these drugs has increased. The reasons for this difference are as yet unknown.

  13. [Antipsychotic medication change and reduction of rehospitalization in clients of ACT-J].

    Science.gov (United States)

    Satake, Naoko

    2011-01-01

    Polypharmacy and high-dose treatment of antipsychotics have been major problems in Japanese mental health. Although importance of simplifying prescription has been recognized, polypharmacy and high-dose medication especially for Schizophrenia remains prevalent. It's considered that psycho-social approach; for example, improvement of coping skills and social support such as care management can make reform of treatment efficiently and also improve patient's QOL. In ACT service, Medication, rehabilitation and social support work closely together and it could make prescription change even for SMI patients. Low-dose medication leads improvement of cognitive function and furthermore social activity. Considering the higher dose of antipsychotics prescribed concurrency in Japan, it's important to evaluate the change in medication for patients of ACT in Japan. We did one year follow up study about prescription change for 52 patients who have used ACT program at ACT-J team for more than one year at the end of December 2009. It was found that the dosage antipsychotics significantly decreased from 1131.3 mg converted to the relative potency equivalent of 100 mg of Chlorpromazine (CPZ eq), to 731.3 mg (CPZ eq) over the course of the 12 months. But there was no significant change about polyphamacy. Also it could be possible to reduce rehospitalization under the ACT program. Because recovery model could make improve not only drop out from psychiatric service, but user's dependency for hospitalization.

  14. Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review.

    Science.gov (United States)

    Yin, John; Barr, Alasdair M; Ramos-Miguel, Alfredo; Procyshyn, Ric M

    2017-01-01

    Chronic prescription of antipsychotics seems to lose its therapeutic benefits in the prevention of recurring psychotic symptoms. In many instances, the occurrence of relapse from initial remission is followed by an increase in dose of the prescribed antipsychotic. The current understanding of why this occurs is still in its infancy, but a controversial idea that has regained attention recently is the notion of iatrogenic dopamine supersensitivity. Studies on cell cultures and animal models have shown that long-term antipsychotic use is linked to both an upregulation of dopamine D2-receptors in the striatum and the emergence of enhanced receptor affinity to endogenous dopamine. These findings have been hypothesized to contribute to the phenomenon known as dopamine supersensitivity psychosis (DSP), which has been clinically typified as the foundation of rebound psychosis, drug tolerance, and tardive dyskinesia. The focus of this review is the update of evidence behind the classification of antipsychotic induced DSP and an investigation of its relationship to treatment resistance. Since antipsychotics are the foundation of illness management, a greater understanding of DSP and its prevention may greatly affect patient outcomes.

  15. Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients.

    Science.gov (United States)

    Cutler, N R

    2001-01-01

    In clinical trials of dopamine-blocking antipsychotics, significant adverse events may occur in healthy volunteers at dose levels that are well tolerated by schizophrenic patients. Because of these differences in tolerability, bioequivalence and pharmacokinetic studies of antipsychotics should be performed in schizophrenic patients rather than in healthy volunteers. When clozapine is the drug being investigated, pharmacokinetic and bioequivalence studies should be carried out in real-life dosage conditions because the half-life of clozapine increases with multiple doses. Under real-life conditions, the evaluation of multiple doses of clozapine in a population of schizophrenic patients can provide direct therapeutic relevance to bioavailability findings. This article discusses patient recruitment and informed consent in pharmacokinetic trials of schizophrenia, issues in studying antipsychotic agents in healthy volunteers versus schizophrenic patients, and a bioequivalency study of Clozaril (Novartis Pharmaceuticals) and generic clozapine (Creighton [Sandoz]) in schizophrenic patients.

  16. 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.

  17. 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

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

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    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.

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

    Science.gov (United States)

    Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

    2016-01-01

    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. PMID:27727180

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

    Science.gov (United States)

    Pompili, Maurizio; Baldessarini, Ross J; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

    2016-10-11

    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.

  1. PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

    Science.gov (United States)

    Halayqa, Mohammed; Domańska, Urszula

    2014-12-22

    In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  2. PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

    Directory of Open Access Journals (Sweden)

    Mohammed Halayqa

    2014-12-01

    Full Text Available In our study, poly(dl-lactide-co-glycolide (PLGA nanoparticles loaded with perphenazine (PPH and chlorpromazine hydrochloride (CPZ-HCl were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol (PVA concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4 by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  3. 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

  4. The poorly membrane permeable antipsychotic drugs amisulpride and sulpiride are substrates of the organic cation transporters from the SLC22 family.

    Science.gov (United States)

    Dos Santos Pereira, Joao N; Tadjerpisheh, Sina; Abu Abed, Manar; Saadatmand, Ali R; Weksler, Babette; Romero, Ignacio A; Couraud, Pierre-Olivier; Brockmöller, Jürgen; Tzvetkov, Mladen V

    2014-11-01

    Variations in influx transport at the blood-brain barrier might affect the concentration of psychotropic drugs at their site of action and as a consequence might alter therapy response. Furthermore, influx transporters in organs such as the gut, liver and kidney may influence absorption, distribution, and elimination. Here, we analyzed 30 commonly used psychotropic drugs using a parallel artificial membrane permeability assay. Amisulpride and sulpiride showed the lowest membrane permeability (P e sulpiride by the organic cation transporters of the SLC22 family OCT1, OCT2, OCT3, OCTN1, and OCTN2 Amisulpride was found to be transported by all five transporters studied. In contrast, sulpiride was only transported by OCT1 and OCT2. OCT1 showed the highest transport ability both for amisulpride (CLint = 1.9 ml/min/mg protein) and sulpiride (CLint = 4.2 ml/min/mg protein) and polymorphisms in OCT1 significantly reduced the uptake of both drugs. Furthermore, we observed carrier-mediated uptake that was inhibitable by known OCT inhibitors in the immortalized human brain microvascular endothelial cell line hCMEC/D3. In conclusion, this study demonstrates that amisulpride and sulpiride are substrates of organic cation transporters of the SLC22 family. SLC22 transporters may play an important role in the distribution of amisulpride and sulpiride, including their ability to penetrate the blood-brain barrier.

  5. [Atypical antipsychotic-induced weight gain].

    Science.gov (United States)

    Godlewska, Beata R; Olajossy-Hilkesberger, Luiza; Marmurowska-Michałowska, Halina; Olajossy, Marcin; Landowski, Jerzy

    2006-01-01

    Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.

  6. Towards better non-selectivity: the role of 5-HT7 receptors in therapeutic efficacy of a second-generation antipsychotic, lurasidone

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    Przemysław Bieńkowski

    2015-04-01

    Full Text Available Effectiveness of currently available antipsychotic medications is far from satisfactory with many patients showing incomplete therapeutic response even after many trials with different antipsychotic drugs. Hence, there is an ongoing interest in searching for pharmacological mechanisms, which could potentiate therapeutic response to antipsychotic drugs and/or reduce its typical side effects. The primary aim of this mini-review is to summarize available evidence supporting the role of serotonin receptors, especially 5-HT7 receptors, in therapeutic effects of a second-generation antipsychotic drug, lurasidone.

  7. 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

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    Yu-Xi Wang

    2015-01-01

    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.

  8. Application of on-line electrochemistry/electrospray/tandem mass spectrometry to a quantification method for the antipsychotic drug zotepine in human serum.

    Science.gov (United States)

    Nozaki, Kazuyoshi; Osaka, Issey; Kawasaki, Hideya; Arakawa, Ryuichi

    2009-10-01

    A simple, rapid, and sensitive on-line liquid chromatographic electrochemistry/electrospray/tandem mass spectrometry (LC-EC/ESI-MS/MS) method for the determination of zotepine in human serum was developed using a new generated-electrochemically fragment ion, and was validated. A recent novel technique of LC-EC/ESI-MS/MS that combines LC-MS/MS and the on-line EC reaction is potentially applicable to developing a quantification method for drugs in biological samples. Newly formed products generated by the on-line EC cell are expected to provide appropriate precursor and product ions for the MS/MS determination method. This technique was successfully applied to a drug assay in a biological matrix. After adding imipramine (IS) to a 30-microL aliquot of human serum, the resulting sample was simply deproteinated with acetonitrile for a measurement. The analytical run time was 5 min. The calibration curve was linear in the concentration range of 10-2000 ng/mL. The intra-assay precision and accuracy were in the range of 1.8-8.9 and 98.4-113%, respectively.

  9. Experimental treatment of antipsychotic-induced movement disorders

    Science.gov (United States)

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  10. Diabetic control and atypical antipsychotics: a case report

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    Gaston Romina

    2008-05-01

    Full Text Available Abstract Introduction People with schizophrenia are at increased risk of developing metabolic disturbances. This risk may be further exacerbated by the use of antipsychotic agents. Research is still ongoing to determine the metabolic impact of antipsychotics on glucose regulation. In this case report we review some of the possible mechanisms of action of antipsychotic medication on glucose regulation. Case presentation We present the case of a 50-year-old man diagnosed with paranoid schizophrenia who developed type 2 diabetes mellitus whilst on treatment with second generation antipsychotics (SGA. His diabetes was controlled by a combination of antidiabetic drugs that were associated with his psychotropic treatment. Due to deterioration in his mental state, the patient was admitted on two occasions to a psychiatric unit during which his prescribed medication (olanzapine and risperidone was discontinued and changed to aripiprazole. On both occasions, the patient suffered hypoglycaemic episodes and his antidiabetic treatment had to be adjusted accordingly. The patient did not require any antidiabetic treatment whilst on aripiprazole during the follow up period. Conclusion Clinicians face regular dilemmas in trying to find the right balance between achieving control over a patient's mental illness and reducing any adverse effects associated with the prescribed medication. In patients receiving concomitant antidiabetic therapy, caution should be exercised when changing from one SGA to another. Whilst more longitudinal data are required, a trial of alternative SGAs, including aripiprazole in those developing type 2 diabetes and impaired glucose tolerance may be a worthwhile therapeutic option.

  11. Dopamine D{sub 2} receptor occupancy in normal humans treated with a novel antipsychotic drug YKP1358 measured by PET and [11c]raclopride

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. S.; Kim, S. J.; Lee, K. J.; Kim, E.; Yu, K. S.; Jang, I. J.; Kwon, J. S.; Kang, W. J.; Jeong, J. M.; Lee, D. S.; Chung, J. K.; Lee, M. C. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    YKP1358 is a novel serotonin (5-HT{sub 2A}) and dopamine (D{sub 2}) antagonist, and fitted the general profile of an atypical neuroleptic agent in preclinical studies. The time course of D{sub 2} receptor occupancy in the brain of living human after a single oral dose of YKP1358 was measured using PET and related to the plasma drug levels. A single oral dose, dose escalation (100 mg, 200 mg, and 250 mg), open-label study was performed in 9 healthy male volunteers (3 per each dose) using the [{sup 11}C]raclopried PET. After the baseline scan, each subject was studied at 2, 5, and 10 hours after the single administration of YKP1358. Blood samples for evaluation of plasma concentration of YKP1358 were also taken at various time points (0-32 hours post-dose). Binding potential (BP) of [{sup 11}C]raclopride in the putamen was estimated with simplified reference tissue model and percent reduction of the BP was calculated to obtain the D{sub 2} receptor occupancy. BP parametric image was generated using a pixel-wise Logan noninvasive plot. T{sub max} of plasma concentration-time profiles was 0.67 hours, and elimination half-life was 5.71, 7.46, and 8.58 hours in 100 mg, 200 mg, and 250 mg dosing groups, respectively. D{sub 2} receptor occupancy of YKP1358 was 60 to 80% at 2 hours, 40 to 60% at 5 hours, and 20 to 50% at 10 hours. The relationship of plasma concentration and D{sub 2} receptor occupancy of YKP1358 was well predicted by Emax model, and Emax was 100 %, EC50 was 8.9 (=1.1) ng/mI, and Hills coefficient was 0.525. PK profile of YKP1358 showed individual variation, but the D{sub 2} receptor occupancy was less variable and well predicted by an Emax model. Since D{sub 2} antagonists show therapeutic effects at 50 to 80% D{sub 2} occupancy and the EC50 of YKP1358 is less than 10 ng/ml, doses of YKP1358 which maintain plasma concentrations above 10 ng/ml are expected to show therapeutic effects.

  12. 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......% confidence interval [CI]:1.23-1.89) as was use with typical antipsychotics (OR= 1.66, CI: 1.27-2.17). By contrast, overall atypical antipsychotics drug use was not (OR= 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs were associated with OHCA, haloperidol (OR= 2.43, CI: 1.......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....

  13. Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence

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    Cathrin Rohleder

    2016-11-01

    Full Text Available There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9 THC, cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial had been conducted and demonstrated that cannabidiol exerts antipsychotic properties in acute schizophrenia comparable to the antipsychotic drug amisulpride accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. However, a plethora of mechanisms of action has been suggested, but their potential relevance for the antipsychotic effects of cannabidiol needs still to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

  14. Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

    Science.gov (United States)

    Rohleder, Cathrin; Müller, Juliane K.; Lange, Bettina; Leweke, F. M.

    2016-01-01

    There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials. PMID:27877130

  15. Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia, before and after antipsychotic treatment

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    Rayees Ahmad Wani

    2015-01-01

    Full Text Available Background: Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different. Moreover, there may be an independent link between schizophrenia and diabetes. So we plan to study the prevalence of glucose dysregulation in patients of schizophrenia before and after treatment with various antipsychotics. Materials and Methods: Fifty patients (32 males and 18 females diagnosed with schizophrenia were evaluated for glucose dysregulation using oral glucose tolerance test, initially (drug naive and after antipsychotic treatment. Age- and sex-matched healthy volunteer group of 50 subjects (35 males and 15 females was taken for comparison. Results were interpreted using American Diabetic Association criteria. Results: Though the glycemic status of the patient group was comparable with healthy controls initially but antipsychotic treatment was associated with glucose dysregulation. For first 6 weeks the antipsychotic (olanzapine, risperidone, haloperidol and aripiprazole-induced glucose dysregulation was comparable, which was seen to be maximum with the olanzapine-treated group at the end of this study, 14 weeks. Conclusion: We conclude that antipsychotic treatment of nondiabetic drug naive schizophrenia patients was associated with adverse effects on glucose regulation. For initial 6 weeks the antipsychotic-induced glucose dysregulation was comparable, which was seen to be maximum with olanzapine at the end of study, i.e. 14 weeks. Keeping this at the back of mind we can stabilize a patient initially with a more effective drug, olanzapine, and later on shift to one with less metabolic side effects.

  16. 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

  17. 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

  18. Prolactin gene polymorphism (-1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics

    NARCIS (Netherlands)

    Ivanova, Svetlana A; Osmanova, Diana Z; Boiko, Anastasia S; Pozhidaev, Ivan V; Freidin, Maxim B; Fedorenko, Olga Yu; Semke, Arkadiy V; Bokhan, Nikolay A; Kornetova, Elena G; Rakhmazova, Lubov D; Wilffert, Bob; Loonen, Antonius

    2016-01-01

    BACKGROUND: Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin product

  19. 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.

  20. Neuroleptic malignant syndrome induced by atypical antipsychotics.

    Science.gov (United States)

    Farver, Debra K

    2003-01-01

    A review of the English literature confirms that neuroleptic malignant syndrome (NMS) occurs with both traditional and atypical antipsychotic medications. Published reports of NMS induced by the traditional antipsychotics have given the practitioner valuable information on the prevention and treatment of this adverse effect. Case reports have also been published concerning NMS and clozapine, risperidone, olanzapine and quetiapine. By evaluating the case reports of atypical antipsychotic-induced NMS, valuable information may be obtained concerning similarities or differences from that induced by the traditional antipsychotics. The case reports of NMS with atypical antipsychotics were evaluated for diagnosis, age/sex of patient, risk factors, antipsychotic doses and duration of use, symptoms of NMS, and clinical course.

  1. Dopamine and incentive learning: a framework for considering antipsychotic medication effects.

    Science.gov (United States)

    Beninger, Richard J

    2006-12-01

    Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

  2. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats.

    Science.gov (United States)

    Bordia, Tanuja; McIntosh, J Michael; Quik, Maryka

    2012-03-01

    Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.

  3. Effect of tricyclic drugs on mitochondrial membrane.

    Directory of Open Access Journals (Sweden)

    Eto,Kohei

    1985-08-01

    Full Text Available The effects of tricyclic drugs (clomipramine, imipramine, chlorpromazine and promethazine on isolated liver mitochondria of rats were examined. All the drugs tested accelerated state 4 respiration. Their stimulative potency at concentrations below 100 microM was in the order of chlorpromazine greater than clomipramine greater than imipramine, promethazine. On state 3 respiration, the chlorine containing drugs had an inhibitive effect at high concentrations, while the other drugs seemed to have a slightly stimulative effect. These drugs stimulated latent ATPase activity of mitochondria. Clomipramine and chlorpromazine inhibited 2, 4-dinitrophenol-stimulated ATPase activity in a dose-dependent fashion. Imipramine also inhibited 2, 4-dinitrophenol-stimulated ATPase activity at high concentrations. Promethazine, however, had almost no effect. All the drugs induced potassium release from mitochondrial vesicles, and their potency was in the order of clomipramine greater than chlorpromazine greater than imipramine greater than promethazine. These results suggest that clomipramine, imipramine, chlorpromazine and promethazine cause impediments in both mitochondrial respiration and ion compartmentation, and that the chlorine containing drugs are more toxic than others on the functions of the mitochondrial membrane.

  4. Effect of chlorpromazine or sulpiride and alcohol on psychomotor skills related to driving.

    Science.gov (United States)

    Seppälä, T

    1976-10-01

    A double-blind cross-over trial was conducted with 20 healthy paid volunteers for the evaluation of the subacute effects of chlorpromazine (CPZ) and sulpiride, in oral doses used for anxious outpatients, on psychomotor skills related to driving. Psychomotor performance was measured on the 7th and 14th days of treatment at 30, 90 and 150 min after the intake of 0.5 g/kg of an alcoholic or placebo drink. After the neuroleptics alone, reaction and coordination skills, but not attention, were slightly impaired, CPZ differing significantly from the placebo on the 14th day. Both drugs interacted additively with alcohol. The combined administration of CPZ and alcohol led to inaccuracy, a slowing of reactions and impaired proprioception and coordination. The combination of sulpiride and alcohol increased the error rate in the choice reaction test and impaired coordination in the coordination test driven at a free speed. It is concluded that the psychomotor decrement that occurs after 2 weeks of treatment with small doses of CPZ may effect the ability to control a motor vehicle. The concurrent administration of alcohol during treatment with CPZ or sulpiride may cause some extra risk in traffic or occupational life.

  5. Chlorpromazine transformation by exposure to ultraviolet laser beams in droplet and bulk.

    Science.gov (United States)

    Andrei, Ionut Relu; Tozar, Tatiana; Dinache, Andra; Boni, Mihai; Nastasa, Viorel; Pascu, Mihail Lucian

    2016-01-01

    Multiple drug resistance requires a flexible approach to find medicines able to overcome it. One method could be the exposure of existing medicines to ultraviolet laser beams to generate photoproducts that are efficient against bacteria and/or malignant tumors. This can be done in droplets or bulk volumes. In the present work are reported results about the interaction of 266nm and 355nm pulsed laser radiation with microdroplets and bulk containing solutions of 10mg/ml Chlorpromazine Hydrochloride (CPZ) in ultrapure water. The irradiation effects on CPZ solution at larger time intervals (more than 30min) are similar in terms of generated photoproducts if the two ultraviolet wavelengths are utilized. The understanding of the CPZ parent compound transformation may be better evidenced, as shown in this paper, if studies at shorter than 30minute exposure times are made coupled with properly chosen volumes to irradiate. We show that at exposure to a 355nm laser beam faster molecular modifications of CPZ in ultrapure water solution are produced than at irradiation with 266nm, for both microdroplet and bulk volume samples. These effects are evidenced by thin layer chromatography technique and laser induced fluorescence measurements.

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

    Science.gov (United States)

    Tesfaye, Siranesh; Debencho, Nigussie; Kisi, Teresa; Tareke, Minale

    2016-01-01

    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.

  7. 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.

  8. 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.

  9. 利培酮对首发精神分裂症患者血清α-肿瘤坏死因子的影响%Effect of risperidone and chlorpromazine on plasma level of TNF-α in patients with first-episode schizophrenia.

    Institute of Scientific and Technical Information of China (English)

    田博; 陆晓姿

    2011-01-01

    目的 探讨抗精神病药物对首发精神分裂症患者血清α-肿瘤坏死因子(TNF -α)的影响,并探讨TNF -α与精神病理之间的关系.方法 90例首发精神分裂症患者随机分为利培酮组(45例)和氯丙嗪组(45例),进行8周治疗,采用酶联免疫吸附法对治疗前后α-肿瘤坏死因子(TNF-α)进行检测,以40例健康志愿者为对照.同时采用阳性和阴性症状量表(PANSS)评估患者精神症状及其变化.结果 精神分裂症患者治疗前TNF -α水平显著高于对照组(t=3.08,P<0.01),治疗后4周末及8周末与对照组比较均无显著性差异(t=0.11,0.52,P>0.05),均较治疗前显著降低(P <0.05,P<0.01).治疗前及治疗后4周末血清TNF -α水平与对应PANSS总分及各因子分无显著相关(P>0.05),治疗后8周末TNF -α与阳性症状分及总分呈正相关.利培酮组患者TNF -α水平治疗后4周末无显著变化,治疗后8周末显著低于治疗前(P<0.05);氯丙嗪组患者治疗后4周末及8周末均显著低于治疗前(P<0.01).治疗后4周末血清TNF -a变化率与氯丙嗪日剂量呈显著正相关(P<0.05),利培酮日剂量与TNF -α变化率无相关,8周末两药日剂量与TNF - α变化率均无相关.结论 抗精神病药物对首发精神分裂症患者血TNF -α有抑制作用,血清TNF -α水平与精神病理之间有着一定关系.%Objective To explore the effect of antipsychotic drugs on plasma level of tumor necrosis factor-α (TNF-α ) in patients with first - episode schizophrenia, and to explore the relationship between TNF-a and the psychopathology of schizophrenia. Methods 90 patients with first - episode schizophrenia were randomized into risperidone group (45 cases) and chlorpromazine group (45 cases) treated with risperidone or chlorpromazine respectively for 8 weeks. Plasma level of TNF-a of patients was measured with ELISA at baseline and endpoint of the treatment, then was compared with that of 40 healthy volunteers

  10. Is aripiprazole the only choice of treatment of the patients who developed anti-psychotic agents-induced leucopenia and neutropenia? A case report.

    Science.gov (United States)

    Yalcin, Demet Ozen; Goka, Erol; Aydemir, M Cigdem; Kisa, Cebrail

    2008-05-01

    Leucopenia and neutropenia could be side effects of anti-psychotic drugs, especially clozapine. However, there is evidence that other anti-psychotics can cause leucopenia and neutropenia. We present the clinical follow-up and treatment process of a patient, who had initially developed quetiapine and amisulpride related neutropenia, but not with aripiprazole.

  11. 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.

  12. Are there schizophrenics for whom drugs may be unnecessary or contraindicated?

    Science.gov (United States)

    Rappaport, M; Hopkins, H K; Hall, K; Belleza, T; Silverman, J

    1978-01-01

    This study reports that there are schizophrenics who do relatively well long term without the routine or continuous use of antipsychotic medication. Specially selected young males undergoing an acute schizophrenic episode were followed, after hospitalization, for up to three years. While hospitalized they were assigned randomly to either placebo or chlorpromazine treatment. Many unmedicated-while-in-hospital patients showed greater long-term improvement, less pathology at follow-up, fewer rehospitalizations and better overall function in the community than patients who were given chlorpromazine while in the hospital. Factors related to post-hospital outcome were good premorbid history and short-lived paranoid characteristics. Considerations which may have an effect on the successful management of acute schizophrenic patients not on medication are mentioned. The findings underline the need for further study of how to utilize antipsychotic medication more selectively in the treatment of schizophrenia.

  13. 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.

  14. Advances in detection of antipsychotics in biological matrices.

    Science.gov (United States)

    Patteet, Lisbeth; Cappelle, Delphine; Maudens, Kristof E; Crunelle, Cleo L; Sabbe, Bernard; Neels, Hugo

    2015-02-20

    Measuring antipsychotic concentrations in human matrices is important for both therapeutic drug monitoring and forensic toxicology. This review provides a critical overview of the analytical methods for detection and quantification of antipsychotics published in the last four years. Focus lies on advances in sample preparation, analytical techniques and alternative matrices. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used most often for quantification of antipsychotics. This sensitive technique makes it possible to determine low concentrations not only in serum, plasma or whole blood, but also in alternative matrices like oral fluid, dried blood spots, hair, nails and other body tissues. Current literature on analytical techniques for alternative matrices is still limited and often requires a more thorough validation including a comparison between conventional and alternative results to determine their actual value. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) makes it possible to quantify a high amount of compounds within a shorter run time. This technique is widely used for multi-analyte methods. Only recently, high-resolution mass spectrometry has gained importance when a combination of screening of (un)known metabolites, and quantification is required.

  15. Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action

    OpenAIRE

    Mocci, Giuseppe; Jiménez-Sánchez, Laura; Adell, Albert; Cortés, Roser; Artigas, Francesc

    2013-01-01

    The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially target cortical serotonin (5-HT) receptors. The brain networks involved in the therapeutic action of atypical drugs are not fully understood. Previous work indicated that medial PFC (mPFC) pyramidal neur...

  16. 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.

  17. 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

  18. Movement disorders in adults with intellectual disability and behavioral problems associated with use of antipsychotics

    NARCIS (Netherlands)

    Scheifes, A.; Walraven, S.; Stolker, J.J.; Nijman, H.L.I.; Tenback, D.E.; Egberts, A.C.G.; Heerdink, E.R.

    2016-01-01

    Background: Antipsychotic drugs are prescribed to approximately 30% to 40% of adults with intellectual disability (ID) and behavioral problems despite lack of evidence of effectiveness and potential adverse effects, including movement disorders. Aims: The aim of this study was to examine the prevale

  19. Effect of Aripiprazole on Hyperprolactinemia in Patients with Senile Schizophrenia Induced by Antipsychotic Drugs%阿立哌唑对抗精神病药物所致的老年精神分裂症患者高催乳素血症的影响分析

    Institute of Scientific and Technical Information of China (English)

    孙伟; 马世发; 高天飞

    2015-01-01

    目的:探讨阿立哌唑对抗精神病药物所致的老年精神分裂症患者高催乳素血症的影响。方法根据治疗方法对该院于2012年5月-2014年10月收治的患者进行分组,两组患者均继续沿用原有抗精神病药物,在此基础上给予观察组患者阿立哌唑。分别测定两组治疗前、治疗4、8周末血清催乳素水平,同时采用精神病评定量表(BPRS)对精神病症状进行评定,比较两组药物不良反应。结果观察组患者治疗4周、8周末血清催乳素水平显著降低,与对照组比较,差异有统计学意义(P0.05);两组患者药物不良反应发生率差异无统计学意义(P>0.05)。结论阿立哌唑能够有效降低抗精神病药物所致的老年精神分裂症患者高催乳素血症状,且未出现严重药物不良反应,具有有效性和安全性,可作为治疗用药。%Objective To investigate the effect of aripiprazole on hyperprolactinemia in patients with senile schizophrenia induced by antipsychotic drugs. Methods The patients from 2012 May to 2014 October in our hospital were divided according to the meth-ods of treatment. All the patients continued to use original antipsychotic drugs, based on which patients in the observation group were given aripiprazole. Serum prolactin level before the operation, four weeks after operation, 8 weeks after operation of the two groups was detected respectively;and psychiatric symptoms were assessed by Brief Psychiatric Rating Scale (BPRS), and adverse drug reaction of the two groups was compared. Results In the observation group, serum prolactin level after 4 weeks treatment and that after 8 weeks treatment both decreased significantly, and compared with those of the control group, there were significant dif-ferences (P0.05; No obvious sig-nificant difference was found in the rate of adverse drug reactions of the two groups,P>0.05. Conclusion Without serious adverse drug reactions, and with efficacy and

  20. The orexin-1 receptor antagonist SB-334867 blocks the effects of antipsychotics on the activity of A9 and A10 dopamine neurons: implications for antipsychotic therapy.

    Science.gov (United States)

    Rasmussen, Kurt; Hsu, Mei-Ann; Yang, Yili

    2007-04-01

    Antipsychotic drugs alter the activity of dopamine neurons in the ventral tegmental area (A10) and substantia nigra pars compacta (A9). As there is a dense projection of orexin neurons from the lateral hypothalamus to A10 dopaminergic neurons, and some antipsychotics have been shown to increase the expression of c-fos in orexin-containing cells in the hypothalamus, we hypothesized that stimulation of orexin receptors plays a role in the effects of antipsychotics on the activity of A9 and A10 dopamine cells. Single-unit recordings in anesthetized rats demonstrated the central effects of the selective orexin-1 receptor antagonist SB-334867 (2 mg/kg, intravenous), as it reversed the excitatory effects of orexin-A administration (6 microg, intracerebroventricular) on the activity of locus coeruleus (LC) cells. Recordings from midbrain dopamine neurons showed that acute administration of SB-334867 alone did not alter the number of spontaneously active A9 or A10 cells, but did reverse: (1) the increase in the number of spontaneously active A9 and/or A10 dopamine cells caused by the acute administration of haloperidol (1 mg/kg, subcutaneous) or olanzapine (10 mg/kg, s.c.) and (2) the decrease in the number of spontaneously active A9 and/or A10 dopamine cells caused by the chronic administration of haloperidol (1 mg/kg/day x 21 days, s.c.) or olanzapine (10 mg/kg/day x 21 days, s.c.). However, SB-334867 did not block a different electrophysiological effect of olanzapine, as it did not block the olanzapine-induced activation of LC cells. These results indicate that activation of orexin-1 receptors plays an important role on the effects of antipsychotic drugs on dopamine neuronal activity and may play an important role in the clinical effects of antipsychotic drugs.

  1. The Effects of Nicotine on MK-801-induced Attentional Deficits: An Animal Model of Schizophrenia

    Science.gov (United States)

    2002-01-01

    antipsychotic effects when used in schizophrenic patients. Chlorpromazine (Thorazine) is a “conventional antipsychotic ,” or a neuroleptic - a class of...drugs that also includes Haloperidol (Haldol) (Dixon, Lehman, & Levine, 1995; Love, 1996; Stahl, 2000). Conventional antipsychotics are rarely...prescribed now because of their negative side effects including: cognitive and neurologic deficits (such as sedation, confusion, and tardive dyskinesia

  2. Drug interference in the Bradford and 2,2'-bicinchoninic acid protein assays.

    Science.gov (United States)

    Marshall, T; Williams, K M

    1991-11-01

    The interference of a range of drugs and related substances has been investigated in the Bradford Coomassie brilliant blue (CBB) protein dye-binding assay and the 2,2'-bicinchoninic acid (BCA) protein assays. Chlorpromazine was the only substance to interfere in the CBB assay but the interference was slight. In contrast, the BCA reagent interacted strongly with chlorpromazine, the penicillins, vitamin C, and paracetamol and the mode of interference varied with the test substance. The chlorpromazine produced turbidity and an atypical color. The penicillins show a slow but normal color response while vitamin C and paracetamol gave an immediate and intense response.

  3. Chlorpromazine as permeabilizer and reagent for detection of microbial peroxidase and peroxidaselike activities.

    Science.gov (United States)

    Galeazzi, L; Turchetti, G; Grilli, G; Groppa, G; Giunta, S

    1986-01-01

    Chlorpromazine was used to perform a test for the detection of microbial peroxidase activities. The compound acts as both a cell permeabilizer and a reagent in the procedure developed which allows the detection of peroxidase and peroxidase like reactions both semiquantitatively in whole cell determinations and quantitatively in cell-free supernatants. PMID:3539020

  4. New prospects for antipsychotic treatment - the role of the kynurenine pathway

    Directory of Open Access Journals (Sweden)

    Hanna Karakuła-Juchnowicz

    2014-12-01

    Full Text Available The mechanism of action of antipsychotic drugs is mainly associated with changes in dopaminergic system. The application of antipsychotic agents simultaneously produces changes in concentrations of metabolites (e.g. kynurenic acid – KYNA, 3-hydroxykynurenine – 3-OHKYN, kynurenine – KYN of the kynurenine pathway, the pathway engaged in glutamatergic transmission. The increase in KYNA levels in certain areas of the central nervous system results in inhibition of glutamatergic transmission. Pharmacologically induced elevation of KYNA levels produces effects similar to those observed after administering ketamine or phencyclidine (the noncompetitive NMDA receptor antagonist, concerning increased activity of mesolimbic dopamine neurons, as well as reduction in dopamine release from the prefrontal cortex. Recent research results confirm the predictive value of changes in concentrations of kynurenine pathway metabolites for assessment of effectiveness of antipsychotic treatment. Significant relationships were found 1 in schizophrenia between the reduction of psychopathological symptoms and variations in 3-OHKYN levels as well as changes in KYNA/3-OHKYN and KYN/KYNA ratios, 2 in mania between varying tryptophan concentrations and the reduction in manic symptoms achieved with antipsychotic treatment. The research as well presented the possibilities of kynurenine pathway modifications, raising high hopes for their future application as target points for the action of novel antipsychotic agents.

  5. Phosphodiesterase 4B genetic variants are not associated with antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

    Souza, Renan P; Remington, Gary; Meltzer, Herbert Y; Lieberman, Jeffrey A; Kennedy, James L; Wong, Albert H C

    2010-09-01

    Phosphodiesterase 4B (PDE4B) has been evaluated as a genetic risk factor for schizophrenia. Selective PDE4 inhibitor drugs have antipsychotic-like effects and reduce tardive dyskinesia-like movements in animal models. We investigated whether PDE4B genetic variants are associated with antipsychotic-induced tardive dyskinesia incidence and severity in schizophrenia patients. Our sample consisted of 169 Caucasian patients taking typical antipsychotic medication for at least 1 year. We found two PDE4B gene variants to be nominally associated with tardive dyskinesia (rs1338719 and rs7528545) in the overall population and two other variants nominally associated with the presence of tardive dyskinesia and severity in female patients (rs1890196 and rs783036). None of these results survived correction for multiple testing. Overall, our results do not support a genetic association between tardive dyskinesia and PDE4B.

  6. Drug: D02642 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02642 Drug Butaperazine (USAN) C24H31N3OS 409.2188 409.5874 D02642.gif Antipsychot...PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AB Phenothiazines with piperazine structure N05AB09 Butaperazine D02642 Butaper

  7. 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.

  8. 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.

  9. [Antipsychotic-induced weight gain--pharmacogenetic studies].

    Science.gov (United States)

    Olajossy-Hilkesberger, Luiza; Godlewska, Beata; Marmurowska-Michałowskal, Halina; Olajossy, Marcin; Landowski, Jerzy

    2006-01-01

    Drug-naive patients with schizophrenia often present metabolic abnormalities and obesity. Weight gain may be the side effect of treatment with many antipsychotic drugs. Genetic effects, besides many other factors, are known to influence obesity in patients with schizophrenia treated with antipsychotics. Numerous studies of several genes' polymorphisms have been performed. -759C/T polymorphism of 5HT2C gene attracted most attention. In 5 independent studies of this polymorphism the association between T allele with the lower AP-induced weight gain was detected. No associations could be detected between weight gain and other polymorphisms of serotonergic system genes as well as histaminergic system genes. Studies of adrenergic and dopaminergic system have neither produced any unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene) confirmed the role of genetic factors in AP-induced weight gain. It is worth emphasising, that the studies have been conducted in relatively small and heterogenic groups and that various treatment strategies were used.

  10. 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

  11. Antipsychotic treatment of schizophrenia: an update.

    Science.gov (United States)

    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.

  12. Response of Ehrlich carcinoma and the small intestine of mouse to combined treatment with chlorpromazine and X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Rao, K.R. (Zurich Univ. (Switzerland). Strahlenbiologisches Inst.)

    1991-05-01

    The effect of combined treatment with chlorpromazine (20 mg/kg body weight) and X-rays at different dose levels was tested on the growth of Ehrlich carcinoma tumor in solid or ascites form in mice. The radiation response of murine gut was also examined separately but under similar experimental conditions. The results obtained indicate that chlorpromazine did not influence the radiation response of all the test systems used in this study. The relevant literature, reviewed in short, shows that the interaction between chlorpromazine and X-rays can result in enhanced radiation response, non-interference or increased radiation tolerance. Therefore any combined effect of chlorpromazine and X-ray observed cannot be generalised. (orig.).

  13. FMRI, antipsychotics and schizophrenia. Influence of different antipsychotics on BOLD-signal.

    Science.gov (United States)

    Röder, Christian H; Hoogendam, Janna Marie; van der Veen, Frederik M

    2010-01-01

    In the last decade, functional Magnetic Resonance Imaging (FMRI) has been increasingly used to investigate the neurobiology of schizophrenia. This technique relies on changes in the blood-oxygen-level-dependent (BOLD) - signal, which changes in response to neural activity. Many FMRI studies on schizophrenia have examined medicated patients, but little is known about the effects of antipsychotic medication on the BOLD-signal. In this review we investigated to what extent studies in patients with schizophrenia (SC), who were treated with different antipsychotics, could give insight in the effects of antipsychotics on the BOLD-signal. A PubMed search was performed using the search items "schizophrenia", "FMRI", "antipsychotics" and "schizophrenia", "BOLD", "antipsychotics". Only articles in which there were at least two groups of patients with different treatments or in which patients were scanned twice with different treatments were selected. 18 articles, published between 1999 and 2009, fulfilled these criteria. Paradigms and results of these studies were compared regarding differences induced by the administered antipsychotics. This analysis showed no general effect of antipsychotics on the BOLD-signal. However, there is some evidence that the extent of blockade of the dopamine (DA) D(2) receptor does influence the BOLD-signal. Higher affinity to the dopamine D2 receptor, as expressed by a higher/lower inhibition constant (Ki) seems to cause a decrease in BOLD-signal.

  14. Osteoporosis Associated with Antipsychotic Treatment in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Haishan Wu

    2013-01-01

    Full Text Available Schizophrenia is one of the most common global mental diseases, with prevalence of 1%. Patients with schizophrenia are predisposed to diabetes, coronary heart disease, hypertension, and osteoporosis, than the normal. In comparison with the metabolic syndrome, for instance, there are little reports about osteoporosis which occurs secondary to antipsychotic-induced hyperprolactinaemia. There are extensive recent works of literature indicating that osteoporosis is associated with schizophrenia particularly in patients under psychotropic medication therapy. As osteoporotic fractures cause significantly increased morbidity and mortality, it is quite necessary to raise the awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia. In this paper, we will review the relationship between schizophrenia, antipsychotic medication, hyperprolactinaemia, and osteoporosis.

  15. Treatment of antipsychotic-induced hyperprolactinemia: an update on the role of the dopaminergic receptors D2 partial agonist aripiprazole.

    Science.gov (United States)

    De Berardis, Domenico; Fornaro, Michele; Serroni, Nicola; Marini, Stefano; Piersanti, Monica; Cavuto, Marilde; Valchera, Alessandro; Mazza, Monica; Girinelli, Gabriella; Iasevoli, Felice; Perna, Giampaolo; Martinotti, Giovanni; Di Giannantonio, Massimo

    2014-01-01

    Hyperprolactinemia is an unwanted adverse effect present in several typical and atypical antipsychotics. Aripiprazole is a drug with partial agonist activity at the level of dopamine receptors D2, which may be effective for antipsychotic- induced hyperprolactinemia. Therefore, we analyzed the literature concerning the treatment of antipsychoticinduced hyperprolactinemia with aripiprazole by updating a previous paper written on the same topic. More recent studies were reviewed. They showed that there are two options for the treatment of antipsychotic-induced hyperprolactinemia with aripiprazole. The safest strategy may require the addition of aripiprazole to ongoing treatments, in the case patients had previously responded to antipsychotic drugs and then developed hyperprolactinemia. However, it is advisable to monitor the patients in case relapses and/or side effect, although rare, might occur. Switching drugs should be considered when a patient does not appear to be responding to the previous antipsychotic, thus developing hyperprolactinemia. A cross-taper switch should always be considered, but the risk of a relapse in the disorder may occur more frequently and the patients should be closely monitored. However, limitations must be considered and further studies are needed to definitely elucidate this important issue. Some relevant patents are also described in this review.

  16. 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

  17. 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...

  18. Progress in treatment based on syndrome differentiation of traditional Chinese medicine for hyperp-rolactinemia caused by antipsychotic drugs%抗精神病药物所致高血清催乳素血症的中医分型辨证治疗进展

    Institute of Scientific and Technical Information of China (English)

    李玉欣; 韩彦超; 李林

    2014-01-01

    抗精神病药物所致高血清催乳素血症是抗精神病治疗中最常见的一种不良反应,严重影响了精神病患者的服药依从性,从而导致治疗中断,目前西医没有可靠的治疗方法。综合近年来研究成果表明,抗精神病药物所致高血清催乳素血症的病机主要是郁、湿、痰、虚、瘀五个方面。但治疗时要着眼于整体,尤其必须抓住化瘀通经这一环节,再根据辨证分型,配以清化湿热、豁痰化浊、理气畅达等方药,标本同治,正本清源。研究表明,中医药治疗催乳素血症疗效肯定,不良反应少于西药,减轻了患者的痛苦,提高了患者服药的依从性。%The hyperprolactinemia is the most common adverse reactions of Antipsychotic drugs. It seriously impacts the medication compliance, causing interruption of treatment of psychiatric patients. In this regard the current western medicine can not provide reliable therapeutical method. Researches in re-cent years show that the pathomechanism of hyperprolactinemia caused by antipsychotic drugs are generally attributed to five respects:stagnation of qi, dampness, phlegm, deficiency, blood stasis. The treatment for this should focus on the overall, specifically catching the important link that is dispersing blood stasis to promote menstruation. Then based on pattern differentiation, prescriptions with the functions of clearing a-way heat and eliminating dampness, reducing phlegm, and regulating the flow of qi. Research shows:that Chinese medicine treatment on hyperprolactinemia is effective. Its adverse reactions are less than western medicine ,and can alleviate the suffering of patients and improve patient medication compliance.

  19. 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

  20. Positive predictive value of a case definition for diabetes mellitus using automated administrative health data in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid study

    Directory of Open Access Journals (Sweden)

    Bobo William V

    2012-08-01

    Full Text Available Abstract Background We developed and validated an automated database case definition for diabetes in children and youth to facilitate pharmacoepidemiologic investigations of medications and the risk of diabetes. Methods The present study was part of an in-progress retrospective cohort study of antipsychotics and diabetes in Tennessee Medicaid enrollees aged 6–24 years. Diabetes was identified from diabetes-related medical care encounters: hospitalizations, outpatient visits, and filled prescriptions. The definition required either a primary inpatient diagnosis or at least two other encounters of different types, most commonly an outpatient diagnosis with a prescription. Type 1 diabetes was defined by insulin prescriptions with at most one oral hypoglycemic prescription; other cases were considered type 2 diabetes. The definition was validated for cohort members in the 15 county region geographically proximate to the investigators. Medical records were reviewed and adjudicated for cases that met the automated database definition as well as for a sample of persons with other diabetes-related medical care encounters. Results The study included 64 cases that met the automated database definition. Records were adjudicated for 46 (71.9%, of which 41 (89.1% met clinical criteria for newly diagnosed diabetes. The positive predictive value for type 1 diabetes was 80.0%. For type 2 and unspecified diabetes combined, the positive predictive value was 83.9%. The estimated sensitivity of the definition, based on adjudication for a sample of 30 cases not meeting the automated database definition, was 64.8%. Conclusion These results suggest that the automated database case definition for diabetes may be useful for pharmacoepidemiologic studies of medications and diabetes.

  1. The effect of 4% Lignocaine gel, 5% Amiloride HCl and 10% Chlorpromazine on E.faecalis

    Directory of Open Access Journals (Sweden)

    Udayakumar Jayasimha Raj

    2011-01-01

    Full Text Available Introduction : Thorough disinfection of the root canal system is essential for the success of root canal therapy. Enterococcus faecalis is the most frequently found species in persistent/secondary intracanal infection associated endodontic treatment failure. The aim of this study was to evaluate the disinfection of dentinal tubules using 10% Chlorpromazine, 4% Lignocaine gel, 5% Amiloride hydrochloride in comparison with 2% chlorhexidine gel. Materials and Methods : The antibacterial efficacy of the four medicaments against Enterococcus faecalis was assessed in vitro using extracted human first and second mandibular premolar teeth at the depths of 200 ΅m and 400 ΅m. Results : The overall percentage inhibition of bacterial growth was 100% with 2% chlorhexidine gel followed by 10% chlorpromazine (88.8%, 4% lignocaine gel (76.4% and 5% amiloride hydrochloride (71.4%. Conclusion : 2% chlorhexidine gel was most effective against E. faecalis followed by the newer non- antibiotic medicament 10% chlorpromazine when compared to the other medicaments tested.

  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

    Background Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. Aims of the Study To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Methods Using 2011 data from Pennsylvania’s Medicaid program, IMS Health’s HCOS™ database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to ≥10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. Results There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Discussion Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians

  3. Drug: D00793 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available eration/Typical Fluphenazine D00793 Fluphenazine decanoa...ne structure N05AB02 Fluphenazine D00793 Fluphenazine decanoate (JAN/USP) USP drug classification [BR:br08302] Antipsychotics 1st Gen

  4. Drug: D02100 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02100 Drug Ziprasidone mesylate (USAN); Ziprasidone mesylate hydrate; Geodon (TN) ...C21H21ClN4OS. CH4SO3. 3H2O 562.1323 563.0871 D02100.gif Antipsychotic [central D2 and 5HT2 receptor antagoni... N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AE Indole derivatives N05AE04 Ziprasidone D02100 Ziprasidone mesyl...ate (USAN) USP drug classification [BR:br08302] Antipsychotics 2nd Generation/Atypical Ziprasidone D02100 Zi...prasidone mesylate (USAN) Bipolar Agents Bipolar Agents, Other Ziprasidone D02100

  5. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    O'Sullivan, David; Green, Laura; Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS.

  6. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose

    Science.gov (United States)

    Seeman, P

    2016-01-01

    Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects. PMID:27754480

  7. Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences.

    Science.gov (United States)

    Maguire, Gerald A

    2002-01-01

    Antipsychotic agents differ in efficacy and side effects such as movement disorders and prolactin elevation because of varying mechanisms of action. A revised nomenclature for antipsychotic agents, which categorizes the drugs according to efficacy, risk of movement disorders, and risk of prolactin elevation, is described. Prolactin elevation, a potential side effect of some antipsychotic medications, is underdiagnosed but can have serious short-term and long-term consequences. Short-term problems include menstrual irregularities, sexual dysfunction, and depression. Long-term problems related to prolactin elevation include decreased bone density and osteoporosis, relapse of psychosis because of poor compliance due to sexual dysfunction or depression, and perhaps cancer, although more research in this area is needed. Despite the serious nature of these effects, prolactin elevation is seldom detected because clinicians often fail to inquire about sexual function or other symptoms that signal that a patient's prolactin may be elevated. These are problems that patients may not bring up with clinicians unless they are asked. Therefore, when patients are taking antipsychotic medications, clinicians should regularly inquire about sexual dysfunction, depression, menstrual disturbances, galactorrhea, and gynecomastia.

  8. Nonhuman primates: translational models for predicting antipsychotic-induced movement disorders.

    Science.gov (United States)

    Porsolt, Roger D; Castagné, Vincent; Hayes, Eric; Virley, David

    2013-12-01

    Repeated haloperidol treatment administered to nonhuman primates (NHPs) over several months or even years leads to the gradual appearance of drug-induced dystonic reactions in the orofacial region (mouth opening, tongue protrusion or retraction, bar biting) and in the whole body (writhing of the limbs and trunk, bar grasping). The propensity of antipsychotics to induce dystonia in NHPs is not correlated with their propensity to induce catalepsy in rodents, suggesting that the two types of effects are dissociated and may represent distinct aspects of the extrapyramidal symptoms induced by antipsychotics. In view of the clear homology to clinically observed phenomena, antipsychotic-induced dystonias in antipsychotic-primed NHPs would appear to possess a high degree of translational validity. These NHP phenomena could therefore serve as a useful model for predicting the occurrence of similar abnormal movements with novel substances developed for the treatment of schizophrenia or other psychotic disorders. Moreover, the NHP dystonia model could possibly serve as a biomarker for substances that will eventually cause tardive dyskinesia in patients.

  9. Borderline personality disorder: bipolarity, mood stabilizers and atypical antipsychotics in treatment.

    Science.gov (United States)

    Belli, Hasan; Ural, Cenk; Akbudak, Mahir

    2012-10-01

    In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics.

  10. What is the role of sedating antidepressants, antipsychotics, and anticonvulsants in the management of insomnia?

    Science.gov (United States)

    McCall, Catherine; McCall, W Vaughn

    2012-10-01

    Psychiatric medications such as antidepressants, antipsychotics, and anticonvulsants are commonly prescribed by physicians for the off-label use of improving sleep. Reasons for preferential prescription of these medications over FDA-approved insomnia drugs may include a desire to treat concurrent sleep problems and psychiatric illness with a single medication, and/or an attempt to avoid hypnotic drugs due to their publicized side effects. However, there have been few large studies demonstrating the efficacy and safety of most off-label medications prescribed to treat insomnia. In addition, many of these medications have significant known side effect profiles themselves. Here we review the pertinent research studies published in recent years on antidepressant, antipsychotic, and anticonvulsant medications frequently prescribed for sleep difficulties. Although there have been few large-scale studies for most of these medications, some may be appropriate in the treatment of sleep issues in specific well-defined populations.

  11. 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.

  12. Effect of GLP-1 Receptor Agonist Treatment on Body weight in Obese Antipsychotic-treated Patients with Schizophrenia

    DEFF Research Database (Denmark)

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

    2016-01-01

    AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like obesity...

  13. 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...

  14. 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

  15. Schizophrenia, antipsychotics and risk of hip fracture

    DEFF Research Database (Denmark)

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

    2013-01-01

    -morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture...

  16. Switch to quetiapine in antipsychotic agent-related hyperprolactinemia.

    Science.gov (United States)

    Keller, R; Mongini, F

    2002-12-01

    Novel antipsychotics (clozapine, risperidone, olanzapine, quetiapine) are effective in treating psychotic symptoms, also in neurological disease. Hyperprolactinemia is a side effect related to antipsychotics that can cause galactorrhea, gynecomastia, amenorrhea, anovulation, impaired spermatogenesis, decreased libido and sexual arousal, impotence, and anorgasmia, consequent to removal of tonic dopaminergic inhibition of prolactin secretion via hypothalamic dopaminergic receptor blockade in the tuberoinfundibolar tract. Hyperprolactinemia occurs more frequently during treatment with risperidone and olanzapine compared with clozapine and quetiapine. The therapeutic algorithm to antipsychotic-relatedhyperprolactinemia is the following: reduction in antipsychotic dose, addition of cabergoline, bromocriptine, amantadine, and/or switch to another antipsychotic. We propose switching to quetiapine in symptomatic hyperprolactinemia related to antipsychotics and describe five cases.

  17. The impact of side-effects of antipsychotic agents on life satisfaction of schizophrenia patients: a naturalistic study.

    Science.gov (United States)

    Ritsner, Michael; Ponizovsky, Alexander; Endicott, Jean; Nechamkin, Yakov; Rauchverger, Boris; Silver, Henry; Modai, Ilan

    2002-02-01

    This study compared the impact of side-effects of antipsychotic treatment, clinical and psychosocial factors on the subjective quality of life (QOL) of hospitalized patients. We surveyed 161 patients meeting DSM-IV criteria for schizophrenia stabilized on conventional and atypical antipsychotic drugs using standardized measures of adverse events, psychopathology, psychosocial variables, and perceived QOL. We found that patients with adverse events reported less satisfaction with life domains of subjective feelings and general activities than asymptomatic patients. Patients treated with conventional and novel antipsychotic agents had comparable QOL ratings. Multiple regression analysis showed total variance in QOL ratings as follows: psychosocial factors, 20.9%; clinical symptoms and associated distress, 10.1%; adverse effects, 3.2%. Thus, medication side-effects influence subjective quality of life of schizophrenia inpatients significantly less than other clinical and psychosocial factors. Patient's subjective response to these events rather than their number is more predictive of QOL.

  18. 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?

    OpenAIRE

    O’Callaghan, Matthew J; Bay-Richter, Cecilie; O’Tuathaigh, Colm MP; Heery, David M.; Waddington, John L.; Moran, Paula M.

    2014-01-01

    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 antipsycho...

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

    DEFF Research Database (Denmark)

    Coello, Klara; Broberg, Brian Villumsen; 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...

  20. Antipsychotic-Induced Neuroleptic Malignant Syndrome After Cardiac Surgery.

    Science.gov (United States)

    Moll, Vanessa; Ward, Ceressa T; Zivot, Joel B

    2016-07-01

    We report a case of neuroleptic malignant syndrome (NMS) in a postoperative cardiac surgery patient after the administration of typical and atypical antipsychotics for the treatment of delirium. On postoperative day 8, the patient's temperature peaked at 40.6°C. Agitation, rigidity, elevation in creatine kinase, and leukocytosis were associated findings. NMS was suspected on postoperative day 10. All antipsychotics were discontinued; dantrolene infusions and fluid therapy were initiated. After 2 days of NMS treatment, the patient's symptoms resolved. The temporal relationship between discontinuation of all antipsychotics, initiation of dantrolene, and clinical improvement supports the diagnosis of antipsychotic-induced NMS.

  1. Treatment of Antipsychotic Drug-induced Phlegm Dampness Type Amenorrhea by Wuji Powder and a Small Dose Aripiprazole: a Clinical Study%五积散与小剂量阿立哌唑治疗抗精神病药物所致痰湿型闭经的临床研究

    Institute of Scientific and Technical Information of China (English)

    夏时炎; 张颖然; 虞洪; 孟旭; 张鹏; 刘军

    2014-01-01

    Objective To assess the efficacy and safety of Wuji Powder (WP) and a small dose aripiprazole in treatment of antipsychotic drug-induced phlegm dampness type amenorrhea.Methods Seventy female schizophrenic patients with antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS) were recruited and randomly assigned to the treatment group and the control group,35 in each group.All patients received antipsychotic drug therapy.Patients in the treatment group additionally took WP,while those in the control group took aripiprazole (at the daily dose of 5 mg,once daily).The therapeutic course for all was 4 weeks.Prolactin levels and obesity indices [body weight、waist aircumstance、body mass index(BMI) and waist-hit ratio (WHR)] were determined before and after treatment.The efficacy was evaluated.Results The treatment course was completed in 95.71% of patients.The total effective rate of the 33 patients of the treatment group was 93.94% (31/33),while it was 91.18%(31/34) in the 34 patients of the control group.There was no difference in the total effective rate between the two groups (P >0.05).Prolactin levels in both group after treatment were significantly lower than those of the baseline (P <0.01).There was no significant difference in prolactin levels between the two groups after treatment (P >0.05).Compared with before treatment,body weight,BMI,waist circumstance,and waist-hip ratio obviously decreased after treatment,showing significant difference when compared with the control group (P <0.05).There was no significant difference in body weight,BMI,waist circumstance,and waist-hip ratio in the control group between before and after treatment (P >0.05).Conclusions Both WP and aripiprazole could lower high prolactin levels of schizophrenics with phlegm dampness type amenorrhea.They showed equivalent efficacy.But WP showed more obvious effect in reducing obesity indices.%目的 探讨五积散与小剂量阿立哌唑治疗抗精神病药物所

  2. 抗精神病新药鲁拉西酮的药理与临床研究进展%Progress in pharmacological and clinical studies of antipsychotic drug:lurasidone

    Institute of Scientific and Technical Information of China (English)

    封宇飞

    2011-01-01

    Lurasidone is a novel psychotropic agent with high affinity for dopamine D2 and serotonin 5-HT2A receptors. Lurasidone has received accelerated approval from the FDA for the treatment of schizophrenia. A literature search was conducted using Medline with the key word lurasidone. Its pharmacology, pharmacokinetics and drug interactions, clinical study and safety were reviewed in this paper.%鲁拉西酮是一种新型抗精神病药,对多巴胺D和5-HT受体具有高度的亲和性.FDA批准其用于精神分裂症的治疗.文中通过Medline对鲁拉西酮进行文献检索,并对其药理作用、药动学、药物相互作用、临床研究和安全性进行了综述.

  3. 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.

  4. 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

  5. UP LC-MS/MS法测定3种兽药制剂中违禁药物氯丙嗪%Determination of Chlorpromazine Illegally Added in 3 Kinds of Veterinary Preparations by UPLC-MS/MS

    Institute of Scientific and Technical Information of China (English)

    李波平; 花锦; 李涵; 陈谷峰; 刘能盛; 肖前; 李丹; 赵泉; 单利君

    2015-01-01

    建立了3种兽药制剂中违禁药物氯丙嗪的超高效液相色谱-串联质谱( UP LC-MS/MS )检测方法。用无水乙醇超声提取试样中违禁药物氯丙嗪,采用Waters ACQUITY UPLC BEH C18柱(50 mm×2.1 mm,1.7μm),乙腈和10 mmol/L乙酸铵+0.1%甲酸溶液流动相,梯度洗脱,电离喷雾电离方式(ESI+),多反应监测(MRM)定量。该方法线性关系良好,相关系数r2达到0.9956,回收率在88.3%~96.7%之间,相对标准偏差( RSD)介于3.7%~8.1%。方法的检出限为0.003 mg/kg。本方法适用于兽药制剂中氯丙嗪违法添加的定性、定量分析。%A method of determination of chlorpromazine illegally added in 3 kinds of veterinary preparations by ultra-performance liquid chromatography -tandem mass spectrometry ( UPLC -MS/MS ) was developed. Chlorpromazine was extracted with ethanol by ultrasonic wave and separated on the Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7μm) using the mobile phase of acetonitrile/mixture of 10 mmol/L ammonium acetate and 0.1%formic acid with gradient elution. Chlorpromazine was detected in electrospray ionization ( ESI+) mode using multiple reaction monitoring ( MRM ) . There was a good linear relationship with the correlation rate more than 0. 9956. The average recoveries ranged from 88. 3% to 96. 7%. The standard deviation was between 3.7% and 8.1%. The limit of detection was 0.003 mg/kg. The method was rapid, simple, sensitive and accurate. It was suitable for qualitative and quantitative analysis of the illicit drug chlorpromazine in veterinary preparations.

  6. Gene expression changes in peripheral mononuclear cells from schizophrenic patients treated with a combination of antipsychotic with fluvoxamine.

    Science.gov (United States)

    Chertkow, Yael; Weinreb, Orly; Youdim, Moussa B H; Silver, Henry

    2007-10-01

    Antipsychotic treatment combined with Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant can improve negative symptoms in schizophrenic patients that are unresponsive to antipsychotic drugs alone. The mechanism of this therapeutic effect is not clear. The current study examined molecular changes induced by the combined treatment in human peripheral mononuclear cells (PMC) in order to get insight into its mechanism of action. Gene expression profile of PMC from antipsychotic-treated patients was examined before addition of the SSRI fluvoxamine, and 3 and 6 weeks after. Gene expression patterns screened with a cDNA array, comprising 1176 genes, revealed homologous changes in a range of transcripts related to G-protein coupled receptors (GPCR). Genes related to GPCR-family were assayed using customized cDNA array and the results verified by real-time RT-PCR. The mRNA expression of chemokine receptors, IL8RA and CCR1, and of RGS7 was significantly down-regulated following fluvoxamine augmentation. The clinical assessments showed improvement in negative symptoms following the combined treatment. The transcriptional analysis suggests that the therapeutic mechanism of the combined antipsychotic-fluvoxamine treatment may involve genes associated with G-protein coupled receptors (GPCR). Our findings suggest that gene expression changes in PMC may be useful in investigating the mechanism of drug action in schizophrenia.

  7. 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

  8. Applicability of gene expression and systems biology to develop pharmacogenetic predictors; antipsychotic-induced extrapyramidal symptoms as an example.

    Science.gov (United States)

    Mas, Sergi; Gassó, Patricia; Lafuente, Amelia

    2015-11-01

    Pharmacogenetics has been driven by a candidate gene approach. The disadvantage of this approach is that is limited by our current understanding of the mechanisms by which drugs act. Gene expression could help to elucidate the molecular signatures of antipsychotic treatments searching for dysregulated molecular pathways and the relationships between gene products, especially protein-protein interactions. To embrace the complexity of drug response, machine learning methods could help to identify gene-gene interactions and develop pharmacogenetic predictors of drug response. The present review summarizes the applicability of the topics presented here (gene expression, network analysis and gene-gene interactions) in pharmacogenetics. In order to achieve this, we present an example of identifying genetic predictors of extrapyramidal symptoms induced by antipsychotic.

  9. 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

  10. Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics.

    Science.gov (United States)

    Munro, Janet; Skrobot, Olivia; Sanyoura, May; Kay, Victoria; Susce, Margaret T; Glaser, Paul E A; de Leon, Jose; Blakemore, Alexandra I F; Arranz, Maria J

    2012-03-01

    People with schizophrenia have an increased risk of metabolic syndrome, with consequent elevated morbidity and mortality, largely due to cardiovascular disease. Metabolic disorders comprise obesity, dyslipidemia and elevated levels of triglycerides, hypertension, and disturbed insulin and glucose metabolism. The elevated risk of metabolic syndrome in individuals suffering from schizophrenia is believed to be multifactorial, related to a genetic predisposition, lifestyle characteristics and treatment with antipsychotic medications. Relaxin 3 (RLN3, also known as INSL7) is a recently identified member of the insulin/relaxin superfamily that plays a role in the regulation of appetite and body weight control. RLN3 stimulates relaxin-3 receptor 1 (relaxin/insulin-like family peptide receptor 3, RXFP3) and relaxin receptor 2 (relaxin/insulin-like family peptide receptor 4, RXFP4). We have investigated the role of ten polymorphisms in these genes (RLN3 rs12327666, rs1982632, and rs7249702, RLN3R1 rs42868, rs6861957, rs7702361, and rs35399, and RLN3R2 rs11264422, rs1018730 and rs12124383) in the occurrence of metabolic syndrome phenotypes (obesity, diabetes, hypercholesterolemia, hypertrigyceridemia, and hypertension) in a cross-sectional cohort of 419 US Caucasian patients treated with antipsychotic drugs. We found several associations between relaxin polymorphisms and hypecholesterolemia, obesity and diabetes, suggesting a role for the relaxin/insulin pathway in the development of metabolic disturbance observed in patients treated with antipsychotics.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis.

    Science.gov (United States)

    Boks, Marco P M; Liddle, Peter F; Russo, Sascha; Knegtering, Rikus; van den Bosch, Robert Jan

    2003-07-15

    First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of antipsychotic medication does not influence NSS, but that atypical antipsychotics are associated with less dyskinesia in the early stages of treatment.

  14. 氯氮平与氯丙嗪对精神分裂症患者听觉感觉门控的比较:前瞻性病例对照研究%Comparison of the effects of clozapine and chlorpromazine on auditory sensory gating in patients with schizophrenia:a prospective case-control study

    Institute of Scientific and Technical Information of China (English)

    苏亮; 施慎逊; 王继军; 李惠; 王立伟; 张明园

    2011-01-01

    精神分裂症患者听觉感觉门控(以下简称感觉门控)P50受损,各种抗精神病药物对该P50的作用仍有争议.假设第二代抗精神病药物氯氮平治疗的精神分裂症患者比氯丙嗪治疗患者的感觉门控P50的改善明显.方法 前瞻性对照研究纳入刚住院的精神分裂症患者,由治疗医师决定氯氮平治疗者26例(研究组),氯丙嗪治疗者30例(对照组).氯氮平组有23例完成8周研究纳入分析,氯丙嗪组为20例.检测P50的方法为双短声刺激[听觉条件(S1)-测试刺激(S2)范式],检测时点为基线、治疗第4周和第8周.临床症状用阳性与阴性综合征量表(Positive and Negative Syndrome Scale,PANSS)评定.结果 两组年龄、性别、教育程度、病程和基线PANSS总分差异均无统计学意义.氯丙嗪组平均(标准差)治疗剂量为389(96)mg/d,氯氮平组为345(117)mg/d.重复测量的方差分析显示,氯氮平组颅顶中央脑区(central zone,Cz)P50比值(S2/S1)的下降比氯丙嗪组明显[基线为108%比106%,第4周94%比102%,第8周84%比95%,F=4.91,P=0.029],而S1和S2波幅差异无统计学意义.两组间S1和S2的波幅无明显差异.氯氮平组治疗后P50比值较治疗前下降(F=4.39,P=0.014),氯丙嗪组治疗前后P50比值没有明显变化.结论氯氮平治疗可以减轻精神分裂症患者感觉门控的受损程度;与氯丙嗪治疗相比,氯氮平治疗者的改善程度较明显.%Background: Patients with schizophrenia have deficits in their P5O auditory sensory gating but the effect of different antipsychotic medications on patients' P50 sensory gating remains controversial.Hypothesis: The improvement in P50 auditory sensory gating of patients with schizophrenia is greater when they are treated with the second generation antipsychotic clozapine than when treated with the first generation antipsychotic chlorpromazine.Methods: This prospective case-control study of inpatients with schizophrenia enrolled at the time of

  15. 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.

  16. Chlorpromazine increases the lowered response to antidiuretic hormone in rats with lithium-induced diabetes insipidus.

    Science.gov (United States)

    Kristensen, A R; Hammer, M; Christensen, S

    1985-01-01

    The interaction between chlorpromazine (CPZ) and lithium on renal concentrating ability was studied in rats fed a Li-containing diet for 8 weeks (plasma-Li 0.6-0.7 mmol/l). CPZ (15 mg/kg daily orally) reduced the polydipsia and increased the ability to concentrate the urine upon water deprivation in rats treated with lithium. CPZ also reduced systolic blood pressure, but had no effect on the glomerular filtration rate or plasma levels of arginine vasopressin (AVP) in hydrated rats treated with lithium. However, CPZ prevented the rise in plasma AVP levels observed in lithium-polyuric rats in response to dehydration. During anaesthesia CPZ partially restored the impaired anti-diuretic response to exogenous AVP in rats treated with lithium. CPZ had no influence on plasma-Li levels in rats treated with lithium. It is suggested that CPZ by unknown mechanisms interferes with the effects of lithium on the water permeability response to AVP.

  17. Long-term adverse effects of novel antipsychotics.

    Science.gov (United States)

    Masand, P S; Gupta, S

    2000-11-01

    The introduction of novel antipsychotics for the treatment of patients with serious psychiatric illness has alleviated the burden of managing some of the side effects of conventional agents. However, the novel agents may also cause adverse events. The long-term adverse events of concern include weight gain, diabetes, tardive dyskinesia (TD), and those associated with hyperprolactinemia. Recent studies with the novel agents have prompted clinicians to revisit antipsychotic-induced weight gain. Clinically significant weight gain puts patients at risk for coronary heart disease, hypertension, type II diabetes, dyslipidemia, and some types of cancer. More recently, case reports of glucose abnormalities and diabetes have emerged, indicating that some novel antipsychotics may be associated with altered glucose metabolism or insulin sensitivity. The novel antipsychotics may also have a lower propensity for causing TD than the conventional antipsychotics. Side effects associated with hyperprolactinemia include galactorrhea, gynecomastia, and menstrual and sexual dysfunction. All of these adverse events can cause patients to become non-compliant and may thus predispose them to relapse. In this review, the authors summarize the literature on the long-term side effects of the novel antipsychotics and examine the severity of the problem, with recommendations for management. When selecting treatments, clinicians should consider the side-effect profiles of the various antipsychotic agents.

  18. 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

  19. Efficacy and safety of blonanserin versus other antipsychotics: a review

    Directory of Open Access Journals (Sweden)

    Anant D. Patil

    2013-12-01

    Full Text Available Although many atypical antipsychotics are available, there is a need of an atypical antipsychotic effective in all symptom domains of schizophrenia and well tolerated especially for side effects like extrapyramidal side effects, weight gain and blood prolactin elevation. Blonanserin is an atypical antipsychotic which blocks dopamine D2 and serotonin 5HT2A receptors. Its efficacy and safety has been studied in patients with schizophrenia and delirium. Blonanserin is found to be effective and well tolerated in both conditions. This article has reviewed efficacy and tolerability of blonanserin in these two psychiatry diseases. [Int J Basic Clin Pharmacol 2013; 2(6.000: 689-692

  20. [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.

  1. Indications of atypical antipsychotics in the elderly.

    Science.gov (United States)

    McKean, Andrew; Monasterio, Erik

    2015-01-01

    Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.

  2. Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

    Directory of Open Access Journals (Sweden)

    Eduardo Henrique Teixeira

    2013-01-01

    Full Text Available Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA. All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.

  3. 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.

  4. (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.

  5. 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.

  6. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

    NARCIS (Netherlands)

    Bakker, Ilse C A; Schubart, Chris D; Zelissen, Pierre M J

    2016-01-01

    In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and

  7. Homology modeling and structural analysis of the antipsychotic drugs receptorome

    OpenAIRE

    López Muñoz, Laura

    2010-01-01

    Tradicionalmente se asumía que los fármacos terapéuticamente efectivos actuaban interaccionando con un único receptor. Actualmente está ampliamente reconocido que el efecto farmacológico de la mayoría de los fármacos es más complejo y abarca a un conjunto de receptores, algunos asociados a los efectos terapéuticos y otros a los secundarios y toxicidad. Los fármacos antipsicóticos son un ejemplo de compuestos eficaces que se caracterizan por unirse a varios receptores simultáneamente (principa...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE To i...

  9. Would I take antipsychotics, if I had psychotic symptoms? Examining determinants of the decision to take antipsychotics.

    Science.gov (United States)

    Berna, Fabrice; Göritz, Anja S; Llorca, Pierre-Michel; Vidailhet, Pierre; Fond, Guillaume; Moritz, Steffen

    2017-03-22

    Poor adherence to treatment in schizophrenia is mainly associated to patients-related factors. However, social negative representations of schizophrenia and its treatment may also contribute to patients' decision to take or not to take antipsychotics. A web-based study on 1807 participants was conducted during which participants imagined that they had a particular chronic illness based on clinical vignettes (mental illnesses: schizophrenia, depression; somatic illnesses: multiple sclerosis, rheumatoid arthritis). Participants rated their subjective distress and perceived social stigma associated with each illness. They also rated the perceived treatability of the illness, their belief in the effectiveness of treatment, and their treatment preference regarding medication. Results show that schizophrenia was considered more distressful, less treatable and associated with higher social stigma than somatic illnesses. Medication was less preferred for treating schizophrenia compared to somatic illnesses. Perceived treatability of illness and belief in the effectiveness of pharmacological treatment were the factors driving preference for medication in schizophrenia and depression respectively; these factors had weaker influence on preference for medication in somatic illnesses. Our study points out more severe negative representations of mental illnesses in general, and their treatment, particularly schizophrenia. These attitudes are not confined to patients, and may influence patients' decisions to take psychotropic drugs.

  10. Antipsychotics, mood stabilisers, and risk of violent crime

    OpenAIRE

    Fazel, Seena; Zetterqvist, Johan; Larsson, Henrik; Långström, Niklas; Lichtenstein, Paul

    2014-01-01

    Summary Background Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden. Methods We used linked Swedis...

  11. 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

  12. 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

  13. [Effect of chlorpromazine and amphetamine on incidental memory and its relation to the introvert-extravert structure of personality].

    Science.gov (United States)

    Zaimov, K; Kokoshkarova, A

    1978-10-01

    A total of fifty-four test subjects divided into one control group and two experimental groups were used to study the effects of chlorpromazine and amphetamine upon the incidental memory, its accuracy, and possible dependence on the introversive or extroversive personality structure, respectively. It has been found that chlorpromazine tends to lessen the incidental memory in extent and increase the number of allomnesias or instances of inaccurate remembrance, whereas amphetamine has the effects of increasing the extent of the incidental memory and reducing the number of allomnesias. A comparison of the extent of the incidental memory with the structure of personality in respect of introversion or extroversion in the control group also showed significant differences, the incidental memory being of smaller extent in the case of introversion and greater extent in the case of extroversion.

  14. Drug: D08137 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08137 Drug Lithium sulfate; Lithionit (TN) SO4. 2Li 109.9837 109.9446 D08137.gif A...SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D08137 Lithium sulfate USP drug c...lassification [BR:br08302] Bipolar Agents Mood Stabilizers Lithium D08137 Lithium

  15. Drug: D04750 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04750 Drug Lithium hydroxide (USP) LiHO. H2O 42.0293 41.9636 D04750.gif Antimanic ...CHOLEPTICS N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D04750 Lithium hydroxide (USP) USP drug classif...ication [BR:br08302] Bipolar Agents Mood Stabilizers Lithium D04750 Lithium hydro

  16. Drug: D08136 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08136 Drug Lithium gluconate; Lithioderm (TN) C6H11O7. Li 202.0665 202.0883 D08136...RVOUS SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D08136 Lithium gluconate US...P drug classification [BR:br08302] Bipolar Agents Mood Stabilizers Lithium D08136 Lithium

  17. Antipsychotics from theory to practice: integrating clinical and basic data.

    Science.gov (United States)

    Tandon, R; Milner, K; Jibson, M D

    1999-01-01

    The recent introduction of the atypical antipsychotics into the treatment arena for psychoses and related disorders comes with justifiable excitement. These newer antipsychotics offer several clinical benefits over the conventional antipsychotics, which have been the mainstays of care thus far. The primary advantage of these atypical agents is their superior side effect profiles, particularly with regard to extrapyramidal side effects (EPS). The implications from a reduction in EPS touch on virtually every aspect of pathology in schizophrenic illness, including short- and long-term movement disorders, negative symptoms, noncompliance, cognitive dysfunction, and dysphoria. It should be emphasized that while atypical antipsychotics share many clinical attributes, there are also substantial differences among them. This review will examine the pharmacology, clinical efficacy, and side effect profiles of the atypical antipsychotics and attempt to relate the attributes observed in clinical practice and clinical trials to their basic pharmacologic profiles. There is a fair, but not perfect, correspondence between the pharmacologic profiles of the different atypical antipsychotics and their respective clinical attributes. After a comparative overview of their receptor-binding profiles, a brief pharmacokinetic summary will be provided. Finally, the clinical profiles of these agents will be summarized with regard to both their efficacy and adverse effects.

  18. 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

    Science.gov (United States)

    Wang, Yu-Xi; Xiang, Yu-Tao; Su, Yun-Ai; Li, Qian; Shu, Liang; Ng, Chee H; Ungvari, Gabor S; Chiu, Helen FK; Nin, Yu-Ping; Wang, Gao-Hua; Bai, Pei-Shen; Li, Tao; Sun, Li-Zhong; Shi, Jian-Guo; Chen, Xian-Sheng; Mei, Qi-Yi; Li, Ke-Qing; Yu, Xin; Si, Tian-Mei

    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 of antipsychotic 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 (χ2 = 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., Level-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

  19. A Facile Electrochemical Preparation of Reduced Graphene Oxide@Polydopamine Composite: A Novel Electrochemical Sensing Platform for Amperometric Detection of Chlorpromazine

    Science.gov (United States)

    Palanisamy, Selvakumar; Thirumalraj, Balamurugan; Chen, Shen-Ming; Wang, Yi-Ting; Velusamy, Vijayalakshmi; Ramaraj, Sayee Kannan

    2016-01-01

    We report a novel and sensitive amperometric sensor for chlorpromazine (CPZ) based on reduced graphene oxide (RGO) and polydopamine (PDA) composite modified glassy carbon electrode. The RGO@PDA composite was prepared by electrochemical reduction of graphene oxide (GO) with PDA. The RGO@PDA composite modified electrode shows an excellent electro-oxidation behavior to CPZ when compared with other modified electrodes such as GO, RGO and GO@PDA. Amperometric i-t method was used for the determination of CPZ. Amperometry result shows that the RGO@PDA composite detects CPZ in a linear range from 0.03 to 967.6 μM. The sensor exhibits a low detection limit of 0.0018 μM with the analytical sensitivity of 3.63 ± 0.3 μAμM–1 cm–2. The RGO@PDA composite shows its high selectivity towards CPZ in the presence of potentially interfering drugs such as metronidazole, phenobarbital, chlorpheniramine maleate, pyridoxine and riboflavin. In addition, the fabricated RGO@PDA modified electrode showed an appropriate recovery towards CPZ in the pharmaceutical tablets. PMID:27650697

  20. Antipsychotic Drugs Rechallenge in Multi-antipsychotic Drug Induced Atypical Neuroleptic Malignant Syndrome: A Case of Cotard’s Syndrome

    Directory of Open Access Journals (Sweden)

    Helin Yılmaz

    2017-03-01

    Full Text Available Neuroleptic malignant syndrome (NMS is an uncommon but potentially fatal idiosyncratic reaction to neuroleptics and characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. Cotard’s syndrome is characterized by the appearance of nihilistic delusions concerning one’s own body or life. By presenting this case, we aim to discuss the differential diagnosis and treatment plan of a patient with catatonia and Cotard’s syndrome, which were noted after NMS, in light of the literature.

  1. Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes.

    Science.gov (United States)

    Greenbaum, Lior; Lerer, Bernard

    2015-01-01

    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 motor symptoms in 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 motor 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 could 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 might 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.

  2. 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.

  3. In vitro interaction between psychotropic drugs and alcohol dehydrogenase activity.

    Science.gov (United States)

    Roig, M G; Bello, F; Burguillo, F J; Cachaza, J M; Kennedy, J F

    1991-03-01

    A series of CNS-stimulating and -depressant drugs have been studied for their in vitro interaction with horse liver alcohol dehydrogenase (ADH) activity. The depressant drugs studied included barbital, phenobarbital, thiopental, nitrazepam, chlorpromazine, sulpiride, clomethiazole, Li2CO3, diazepam, phenytoin, ethosuximide, morphine, and codeine. The stimulant drugs were theophylline, caffeine, amphetamine, imipramine, chlorimipramine, amitriptyline, and tranylcypromine. The results were as follows. First, ADH activity was inhibited by the action of chlorpromazine, tranylcypromine, imipramine, chlorimipramine, amitriptyline, sulpiride, amphetamine, codeine, ethosuximide, morphine, clomethiazole, nitrazepam, Li2CO3, theophylline, and phenobarbital, in descending order of inhibitory effect. Second, inhibition followed by activation of ADH activity was observed for imipramine and chlorimipramine. Third, activation of ADH activity was observed for phenytoin. Finally, the following drugs were not seen to exert any effect on ADH activity: barbital, thiopental, diazepam, and caffeine.

  4. 苯二氮卓类药物与氯氮平或氯丙嗪治疗失眠的对照研究%Treatment of insomnia with benzodiazepines and clozapine or chlorpromazine:a comparative study

    Institute of Scientific and Technical Information of China (English)

    杨如良

    2014-01-01

    目的:了解氯氮平和氯丙嗪治疗失眠的疗效。方法将52例精神疾病伴失眠的患者随机分氯氮平和氯丙嗪组(观察组)26例,苯二氮艹卓类组(对照组)26例,依据匹兹堡睡眠质量表(PSQI)对失眠程度进行评估。结果氯氮平和氯丙嗪组有效率88.46%,苯二氮艹卓组有效率96.15%,2组疗效无统计学差异(P>0.05)。结论苯二氮艹卓类药物与氯丙嗪和氯氮平治疗精神疾病失眠疗效相当,为了防止苯二氮艹卓类药物滥用,选用替代药物也是一种很好的选择。%Objective To understand the curative effect of clozapine and chlorpromazine in the treatment of insomnia . Methods 52 patients with mental illness associated with insomnia were randomly divided into a clozapine /chlorpromazine group and a benzodiazepines group ,each with 26 cases.The degree of insomnia was evaluated according to the Pittsburgh sleep quality index (PSQI).Results The effective rate of Clozapine/chlorpromazine group was 88.46% and that of benzodiaz-epines group was 96.15%.The curative effect of the two groups was almost the same .There was no statistical differences ( P>0.05).Conclusion The effectiveness of the two groups of drugs in the treatment of mental illness insomnia is basically e -qual.In order to prevent drug abuse of benzodiazepines , it is also a good choice to choose alternative medicines .

  5. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agnoist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study - the TAO study

    DEFF Research Database (Denmark)

    Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen;

    Background and aim: 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-associated obesity are limited and insufficient. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of type 2 diabetes, but their bodyweight lowering effects have also been recognized in non-diabetic patients. The purpose of this trial is to examine if treatment...... with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Materials and methods: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs...

  6. Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study

    DEFF Research Database (Denmark)

    Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen;

    Introduction: 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-associated obesity are limited and insufficient. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of type 2 diabetes, but their bodyweight lowering effects have also been recognized in non-diabetic patients. The purpose of this trial is to examine if treatment...... with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised...

  7. May the best friend be an enemy if not recognized early: possible role of omega-3 against cardiovascular abnormalities due to antipsychotics in the treatment of autism.

    Science.gov (United States)

    Cysneiros, Roberta M; Terra, Vera C; Machado, Hélio R; Arida, Ricardo M; Schwartzman, José Salomão; Cavalheiro, Esper A; Scorza, Fulvio A

    2009-09-01

    Autism spectrum disorders (ASD) are neurodevelopment disorders that cause severe and pervasive impairment in socialization, communication, and behavior. Although the availability of antipsychotic treatment in ASD has expanded, we will be very careful with side effects of these pharmacological agents. Following this reasoning, emerging data indicate that some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation), suggesting that this could be correlated to sudden death. Quite interesting, substantial evidence from epidemiological and case-control studies indicates that omega-3 reduces the risk of cardiovascular mortality, particularly sudden cardiac death. In accordance to the above mentioned findings, as omega-3 fatty acids per se have a direct cardiovascular protective role, our paper hypothesized that omega-3 fatty acids supplementation in ASD patients treated with atypical antipsychotic drugs may reduce cardiac arrhythmias and hence sudden cardiac death.

  8. The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment of Psychiatric Disorders.

    Science.gov (United States)

    De Berardis, Domenico; Orsolini, Laura; Iasevoli, Felice; Prinzivalli, Emiliano; de Bartolomeis, Andrea; Serroni, Nicola; Mazza, Monica; Valchera, Alessandro; Fornaro, Michele; Vecchiotti, Roberta; Carano, Alessandro; Sepede, Gianna; Vellante, Federica; Matarazzo, Ilaria; Pompili, Maurizio; Perna, Giampaolo; Conti, Chiara; Segura-García, Cristina; Martinotti, Giovanni; Di Giannantonio, Massimo

    2016-01-01

    Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants. The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A systematic search was conducted on PubMed/Medline/ Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords. Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics. Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs.

  9. Dual inhibitor of PDE7 and GSK-3-VP1.15 acts as antipsychotic and cognitive enhancer in C57BL/6J mice.

    Science.gov (United States)

    Lipina, Tatiana V; Palomo, Valle; Gil, Carmen; Martinez, Ana; Roder, John C

    2013-01-01

    Cognitive deficit is a core of schizophrenia and it is not effectively treated by the available antipsychotic drugs, hence new and more effective therapy is needed. Schizophrenia is considered as a pathway disorder where Disrupted-In-Schizophrenia-1 (DISC1) is important molecular player that regulates multiple cellular cascades. We recently reported synergistic action between phosphodiesterase-4 (PDE4) and glycogen synthase kinase-3 (GSK-3) as DISC1 interacting proteins. In the current study we characterized behavioural effects of a newly developed compound, VP1.15 that inhibits both PDE7 and GSK-3 with main focus on its antipsychotic and cognitive capacities. VP1.15 reduced ambulation in C57BL/6J mice in a dose-dependent manner (7.5 mg/kg and 3 mg/kg, respectively) and, hence, lower dose was chosen for the further analysis. VP1.1.5 facilitated pre-pulse inhibition (PPI), reversed amphetamine- but not MK-801-induced PPI deficit. The drug was able to ameliorate the disrupted latent inhibition (LI) induced by the increased number of conditioning trials and reversed amphetamine-induced LI deficit, supporting further its antipsychotic effects. The drug also significantly improved episodic memory in the spatial object recognition test, facilitated working memory in Y-maze and enhanced cued fear memory, but had no effect on executive function in the Puzzle box and contextual fear conditioning. Taken together, VP1.15 elicited antipsychotic effects and also facilitated cognitive domains in mice, suggesting that multitarget drugs, affecting molecular substrates from the same pathway, perhaps could be antipsychotics of new-generation that open a new possibilities in drug discoveries. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  10. Effects of Controlled Discontinuation of Long-Term Used Antipsychotics on Weight and Metabolic Parameters in Individuals With Intellectual Disability

    NARCIS (Netherlands)

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

    2013-01-01

    Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of antipsychot

  11. Drug: D00794 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00794 Drug Loxapine succinate (USP); Loxitane (TN) C18H18ClN3O. C4H6O4 445.1404 44...EPTICS N05A ANTIPSYCHOTICS N05AH Diazepines, oxazepines and thiazepines N05AH01 Loxapine D00794 Loxapine suc...cinate (USP) USP drug classification [BR:br08302] Antipsychotics 1st Generation/Typical Loxapine D00794 Loxapi...coupled receptors Rhodopsin family Dopamine dopamine D2-receptor [HSA:1813] [KO:K04145] Loxapine [ATC:N05AH01] D00794 Loxapi

  12. Drug: D02340 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02340 Drug Loxapine (USAN/INN); Adasuve (TN) C18H18ClN3O 327.1138 327.808 D02340.g...LEPTICS N05A ANTIPSYCHOTICS N05AH Diazepines, oxazepines and thiazepines N05AH01 Loxapine D02340 Loxapine (U...SAN/INN) USP drug classification [BR:br08302] Antipsychotics 1st Generation/Typical Loxapine D02340 Loxapine...eceptors Rhodopsin family Dopamine dopamine D2-receptor [HSA:1813] [KO:K04145] Loxapine [ATC:N05AH01] D02340 Loxapi

  13. Drug: D02609 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02609 Drug Prochlorperazine edisylate (USP); Compazine syrup (TN) C20H24ClN3S. C2H...6O6S2 563.0985 564.1381 D02609.gif Anti-emetic; Antipsychotic ATC code: N05AB04 Phenothiazine derivatives do...HOTICS N05AB Phenothiazines with piperazine structure N05AB04 Prochlorperazine D02609 Prochlorperazine edisy...late (USP) USP drug classification [BR:br08302] Antiemetics Antiemetics, Other Prochlorperazine D0260...9 Prochlorperazine edisylate (USP) Antipsychotics 1st Generation/Typical Prochlorperazine D0260

  14. 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

    avoidance response behaviour in rodents, correlate with clinically relevant plasma exposure for the classical antipsychotic drug haloperidol and four second generation antipsychotics: sertindole, clozapine, risperidone and olanzapine, including selected metabolites. In order to confirm the validity...... receptor occupancy required to suppress conditioned avoidance response behaviour according to EC50 measurements to be sertindole (+dehydrosertindole)=dehydrosertindole=paliperidone (the metabolite of risperidone)=haloperidol=olanzapine>risperidone>clozapine. Overall, a good agreement was observed between...... for sertindole (+dehydrosertindole) and olanzapine were 3-4-fold too high whereas for haloperidol, clozapine and risperidone the predicted steady-state EC50 in conditioned avoidance responding rats correlated well with the therapeutically effective plasma levels observed in patients. Accordingly, the proposed PK...

  15. CYP2D6 genotype predicts antipsychotic side effects in schizophrenia inpatients: a retrospective matched case-control study

    DEFF Research Database (Denmark)

    Kobylecki, Camilla J; Jakobsen, Klaus D; Hansen, Thomas;

    2009-01-01

    OBJECTIVE: The aim of the present retrospective pilot study was to examine the clinical impact of the cytochrome P450 (CYP) enzyme CYP2D6 poor metabolizer (PM) genotype in patients taking antipsychotic medication. The impaired metabolic capacity of the PM genotype results in higher steady...... and consultant psychiatrist, who was blinded to the results of the genotyping. RESULTS: We found that extrapyramidal syndrome or tardive dyskinesia (EPS/TD) was significantly more frequent among PM patients than among the matched IM and EM control subjects. This finding was further supported by the significantly...... of drug metabolism through CYP2D6 can predict antipsychotic side effects and prompts the question of whether genotyping early in the course of illness to facilitate adjustment of pharmacotherapy will improve treatment outcomes and reduce side effects....

  16. 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.

  17. 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.

  18. Clinical Observation of 4 Kinds of the Second-generation Antipsychotic Drugs in the Treatment of Acute Phase of Schizophrenia%4种第二代抗精神病药物治疗精神分裂症急性期的临床观察

    Institute of Scientific and Technical Information of China (English)

    赵晶媛; 黄光彪; 顾小静; 艾小青; 杨淑珍; 华婷婷; 吕路线

    2016-01-01

    OBJECTIVE:To investigate clinical efficacy and adverse reactions(ADRs)of 4 kinds of the second-generation anti-psychotic drugs in the treatment of acute phase of schizophrenia. METHODS:159 patients with schizophrenia were randomly divid-ed into risperidone group(40 cases),olanzapine group(40 cases),aripiprazole group(39 cases)and ziprasidone group(40 cas-es). All groups were given routine dosage of relevant medicine by routine usage for 6 weeks. Mental status of patients were mea-sured by PANSS before treatment and after 2,4 and 6 weeks of treatment. At the same time,blood glucose,blood lipid,prolac-tion and other metabolic and biological indicators were all detected. RSESE,BARS and UKU were adopted to evaluate ADR. RE-SULTS:A total of 100 patients completed the study. Compared with aripiprazole group and ziprasidone group,risperidone and olan-zapine inhibited symptom more rapidly,with statistical significance (P<0.05). After treatment,body mass index and abdominal circumference of olanzapine group were significantly higher than those of other 3 groups,with statistical significance (P<0.05). Low density lipoprotein of olanzapine group was increased significantly,there was statistical significance compared to ziprasidone group and aripiprazole group(P<0.05). Prolactin level of risperidone group was significantly higher than those of other 3 groups, while that of aripiprazole group was significantly lower than those of other 3 groups,with statistical significance(P<0.05). ADRs of 4 drugs were mild or moderate,most of whom could be alleviated by symptomatic treatment. CONCLUSIONS:In the treatment of acute phase schizophrenia,4 drugs of the second-generation have similar curative effect in symptoms control,among which ris-peridone and olanzapine inhibit positive symptom more rapidly while more ADRs that related to lipid and glucose metabolism and prolactin also show. Aripiprazole and ziprasidone induce less ADRs relatively,and patients show better tolerability

  19. 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

  20. Representation of people with intellectual disabilities in randomised controlled trials on antipsychotic treatment for behavioural problems

    NARCIS (Netherlands)

    Scheifes, A.; Stolker, J.J.; Nijman, H.L.I.; Egberts, A.C.G.; Heerdink, E.R.

    2011-01-01

    Background Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems

  1. 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.

  2. Neuroleptic malignant syndrome-like reaction precipitated by antipsychotics in a patient with gamma-butyrolactone withdrawal.

    Science.gov (United States)

    Eiden, Céline; Capdevielle, Delphine; Deddouche, Charlotte; Boulenger, Jean-Philippe; Blayac, Jean-Pierre; Peyrière, Hélène

    2011-12-01

    We report the case of a patient with chronic abuse of gamma-butyrolactone (GBL, 3 bottles per week for 4 months), who in the course of the management of acute agitation and hallucinations developed symptoms compatible with both neuroleptic malignant syndrome and GBL withdrawal symptoms.Some GHB withdrawal symptoms are similar to those of neuroleptic malignant syndrome, and the administration of antipsychotics might worsen the neurological condition of patients. So, it seems important to rapidly detect drugs taken by patients with mental agitation, to optimize management and minimize complications related to drugs.

  3. 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...

  4. 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.

  5. Predictors of effect of atypical antipsychotics on speech

    Directory of Open Access Journals (Sweden)

    Preeti Sinha

    2015-01-01

    Full Text Available Background: Most of the studies have looked into the effect of typical antipsychotics on speech secondary to tardive dyskinesia. Aims: This study was aimed to explore the factors predicting the effect of atypical antipsychotic medications on the production of speech. Materials and Methods: One hundred and forty patients on stable regimen of three or more months on risperidone (92, olanzapine (28, aripiprazole (14, and clozapine (6 were recruited for the study. Speech was assessed by maximum phonation duration task, s/z ratio, diadochokinetic task, acoustic analysis and Frenchay Dysarthria Assessment (FDA. Extrapyramidal symptoms (EPS were assessed by Simpson Angus scale. Statistical Analysis: Spearman correlation analysis was carried out to find the association between speech parameters and continuous variables. Effect of EPS, duration and dose of antipsychotic treatment on speech parameters was compared using Mann-Whitney test. Results: The risperidone group differ from other antipsychotics groups significantly in s/z ratio (0.07, FDA-total (0.23 and FDA-reflex (0.25. People who took antipsychotic for more than 2 years had lower score of FDA-palate (P = 0.042, and FDA-respiratory (P = 0.04 and higher values in noise-harmonic ratio (P = 0.011 and maximum /fundamental frequency (MFF for males (P = 0.02. Effect of EPS was seen on MFF for males (spearman correlation coefficient = 0.34 and on almost all sections of FDA (spearman correlation coefficients = -0.2 to -0.33. Conclusion: Both duration of use and propensity of atypical antipsychotics to cause EPS can influence the speech performance of the patients. This information can be useful, particularly in people with the requirement of high quality speech.

  6. Initiation of antipsychotic treatment by general practitioners. A case-control study

    NARCIS (Netherlands)

    Boonstra, Geartsje; Grobbee, Diederick E; Hak, Eelko; Kahn, René S; Burger, Huibert

    2011-01-01

    RATIONALE, AIMS AND OBJECTIVES: Antipsychotics are approved treatment for severe conditions and have serious side effects. Antipsychotics are often prescribed off-label. Although a substantial proportion of antipsychotics are prescribed in primary care, it is largely unknown what motivates the gener

  7. Antipsychotics for the management of psychosis in Parkinson's disease: systematic review and meta-analysis

    OpenAIRE

    Jethwa, Ketan Dipak; Onalaja, Oluwademilade A.

    2015-01-01

    Background Antipsychotics can exacerbate motor symptoms in Parkinson's disease psychosis. Aims To systematically review the literature on the efficacy and acceptability of antipsychotics for Parkinson's disease psychosis. Method Randomised controlled trials comparing an antipsychotic with placebo were systematically reviewed. Results The final selection list included nine studies using quetiapine (3), clozapine (2), olanzapine (3) and pimavanserin (1). A narrative synthesis and meta-analyses ...

  8. Antipsychotic Medication Prescription Patterns in Adults with Developmental Disabilities Who Have Experienced Psychiatric Crisis

    Science.gov (United States)

    Lunsky, Yona; Elserafi, Jonny

    2012-01-01

    Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics…

  9. Effects of dopamine D2 receptor partial agonist antipsychotic aripiprazole on dopamine synthesis in human brain measured by PET with L-[β-11C]DOPA.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ito

    Full Text Available Dopamine D(2 receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2 receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11C]raclopride and L-[β-(11C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2 receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2 receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

  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. Ecological Assessment of Clinicians’ Antipsychotic Prescription Habits in Psychiatric Inpatients: A Novel Web- and Mobile Phone–Based Prototype for a Dynamic Clinical Decision Support System

    Science.gov (United States)

    Barrigón, Maria Luisa; Brandt, Sara A; Nitzburg, George C; Ovejero, Santiago; Alvarez-Garcia, Raquel; Carballo, Juan; Walter, Michel; Billot, Romain; Lenca, Philippe; Delgado-Gomez, David; Ropars, Juliette; de la Calle Gonzalez, Ivan; Courtet, Philippe; Baca-García, Enrique

    2017-01-01

    Background Electronic prescribing devices with clinical decision support systems (CDSSs) hold the potential to significantly improve pharmacological treatment management. Objective The aim of our study was to develop a novel Web- and mobile phone–based application to provide a dynamic CDSS by monitoring and analyzing practitioners’ antipsychotic prescription habits and simultaneously linking these data to inpatients’ symptom changes. Methods We recruited 353 psychiatric inpatients whose symptom levels and prescribed medications were inputted into the MEmind application. We standardized all medications in the MEmind database using the Anatomical Therapeutic Chemical (ATC) classification system and the defined daily dose (DDD). For each patient, MEmind calculated an average for the daily dose prescribed for antipsychotics (using the N05A ATC code), prescribed daily dose (PDD), and the PDD to DDD ratio. Results MEmind results found that antipsychotics were used by 61.5% (217/353) of inpatients, with the largest proportion being patients with schizophrenia spectrum disorders (33.4%, 118/353). Of the 217 patients, 137 (63.2%, 137/217) were administered pharmacological monotherapy and 80 (36.8%, 80/217) were administered polytherapy. Antipsychotics were used mostly in schizophrenia spectrum and related psychotic disorders, but they were also prescribed in other nonpsychotic diagnoses. Notably, we observed polypharmacy going against current antipsychotics guidelines. Conclusions MEmind data indicated that antipsychotic polypharmacy and off-label use in inpatient units is commonly practiced. MEmind holds the potential to create a dynamic CDSS that provides real-time tracking of prescription practices and symptom change. Such feedback can help practitioners determine a maximally therapeutic drug treatment while avoiding unproductive overprescription and off-label use. PMID:28126703

  12. Antipsychotic-induced life-threatening 'esophageal dyskinesia'.

    Science.gov (United States)

    Horiguchi, J; Shingu, T; Hayashi, T; Kagaya, A; Yamawaki, S; Horikawa, Y; Kitadai, Y; Inoue, M; Nishikawa, T

    1999-03-01

    We report two patients with lingual dyskinesia and complaints of food regurgitation following long-term antipsychotic therapy. Esophageal contrast radiography revealed dyskinetic movements extending from the pharynx to the upper portion of the esophagus. The elevation of intraesophageal pressure was confirmed by esophageal manometry. The dyskinetic movements almost disappeared along with improvement of lingual dyskinesia following the administration of sulpiride in one patient. Another patient suddenly died due to asphyxiation of foods before the beginning of treatment. We termed this life-threatening movement, 'esophageal dyskinesia'. It should be emphasized that 'esophageal dyskinesia' associated with lingual dyskinesia is a potentially fatal adverse reaction to antipsychotic therapy.

  13. 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.

  14. Changes in Tissue Metals After Cadmium Intoxication and Intervention With Chlorpromazine in Male Rats 

    Institute of Scientific and Technical Information of China (English)

    YANGXIAO-FANG; WANGSHU-YI; 等

    2000-01-01

    Cadmium(Cd),one of the most dangerous heavy metals,has a very similar ionic radius to calcium(Ca),The interference of cadmium in calcium homeostasis may play an important role in cadmium toxicity.Recent reports indicate that calmodulin(CaM) inhibitors such as trifluoperazine and chlorpromazine(CPZ) could protect rodents against cadmium toxicity,It was also reported that pretreatment of mice with zine(Zn)could reduce the adverse effects induced by cadmium.The aim of this study is to determine whether Cd changes the balance of other essential metals such as Zn and copper(Cu) in rat tissues,and whether CPZ can reverse these changes which are induced by cadmium intoxication.Adult male Sprague-Dawley(SD) rats were injected intraperitoneally(ip) with cadmium chloride(CdCl2)(0.2,0.4,0.8mg Cd/kg body wight) alone and 0.4mg Cd/kg in association with CPZ(5mg/kg) daily for a week.The control animals were injected with normal saline only.The results showed that the cadmium content in the liver,kidney,and testis increased significantly with a dose-response relationship.Cadmium treatment markedly increased the Zn and Ca content in some of the tissues,Hepatic and renal metallothionein(MT) increased significantly after cadmium intoxication,CPZ treatment,howerver,reduced cadmium content in liver,but not blood and kidney.CPZ seemed to decrease the content of MT in liver and significantly increase the amounts of MT in kidney.These data suggest that the intervention of cadmium with tissue essential metals may play a role in cadium toxicity in rats,and calmodulin inhibitors to some extent can reduce the adverse effect of cadmium by decreasing the cadmium load in tissues and reversing the unbalance of essetial metals.

  15. The Pharmacokinetics of Second-Generation Long-Acting Injectable Antipsychotics: Limitations of Monograph Values.

    Science.gov (United States)

    Lee, Lik Hang N; Choi, Charles; Collier, Abby C; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

    2015-12-01

    Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.

  16. Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

    Directory of Open Access Journals (Sweden)

    P Roberto Bakker

    Full Text Available OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

  17. Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

    Science.gov (United States)

    Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

    2006-01-01

    Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

  18. Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder

    Directory of Open Access Journals (Sweden)

    Azekawa T

    2011-11-01

    Full Text Available Takaharu Azekawa, Shizuko Ohashi, Akira ItamiShioiri Mental Clinic, Yokosuka-shi, Kanagawa-ken, JapanBackground: Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting.Methods: Using a retrospective cohort study design, we screened all outpatients (n = 7936 who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703 diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic.Results: Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant.Conclusion: Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.Keywords: retrospective study, second-generation antipsychotics, effectiveness, treatment continuation, schizophrenia, aripiprazole

  19. Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

    Science.gov (United States)

    Yin, You; Liu, Yan; Zhuang, Jianhua; Pan, Xiao; Li, Peng; Yang, Yuechang; Li, Yan-Peng; Zhao, Zheng-Qing; Huang, Liu-Qing; Zhao, Zhong-Xin

    2015-01-01

    Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

  20. Gradual vs. wait-and-gradual discontinuation in antipsychotic switching: A meta-analysis.

    Science.gov (United States)

    Takeuchi, Hiroyoshi; Thiyanavadivel, Sadhana; Agid, Ofer; Remington, Gary

    2017-02-24

    To address whether wait discontinuation (i.e., introducing the new antipsychotic while maintaining the first for a period before initiating its discontinuation) is superior to non-wait discontinuation (i.e., initiating the first antipsychotic's discontinuation when introducing the new antipsychotic) in antipsychotic switching, we conducted a meta-analysis of randomized controlled trials comparing gradual vs. wait-and-gradual antipsychotic discontinuation in patients with schizophrenia. The meta-analysis of 5 studies (n=410) demonstrated no significant differences in any clinical outcomes, including study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events, between the two groups. These findings indicate either strategy can be used in clinical practice.

  1. Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use.

    Directory of Open Access Journals (Sweden)

    David Pickar

    Full Text Available Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively, mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs.

  2. Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use.

    Science.gov (United States)

    Pickar, David; Vinik, Jessie; Bartko, John J

    2008-09-10

    Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs.

  3. 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

  4. Antipsychotic-Induced Hyperprolactinemia and Testosterone Levels in Boys

    NARCIS (Netherlands)

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

    2012-01-01

    Aims: This cross-sectional study investigates the effect of antipsychotic (AP)-induced hyperprolactinemia on testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, and puberty in boys with mainly autism spectrum disorders (ASD). Method: One hundred and four physically

  5. Antipsychotic-induced hyperprolactinemia and testosterone levels in boys.

    NARCIS (Netherlands)

    Roke, Y.; Harten, P.N. van; Buitelaar, J.K.; Tenback, D.E.; Rijke, Y.B. de; Boot, A.M.

    2012-01-01

    AIMS: This cross-sectional study investigates the effect of antipsychotic (AP)-induced hyperprolactinemia on testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, and puberty in boys with mainly autism spectrum disorders (ASD). METHOD: One hundred and four physically

  6. The spectrum of subjective effects of antipsychotic medication

    NARCIS (Netherlands)

    Wolters, HA; Knegtering, R; Wiersma, D; van den Bosch, RJ

    2003-01-01

    Background: This study examined the spectrum of subjective experiences which patients attribute to the use of antipsychotic medication. Methods: We collected interview data and answers to structured questions based on a comprehensive checklist in 77 patients using various types of classical or atypi

  7. Antipsychotic induced parkinsonism in the elderly: assessment, causes and consequences

    NARCIS (Netherlands)

    Knol, W.

    2011-01-01

    Elderly people are prone to develop antipsychotic induced parkinsonism (AIP), and there are notable variations in occurrence of this adverse effect in individual elderly people. Factors that influence the variation in occurrence of AIP have not been well elucidated. The main objectives of this thesi

  8. 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…

  9. Drug: D02603 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02603 Drug Diethazine hydrochloride C18H22N2S. HCl 334.127 334.9066 D02603.gif map...07028 Antipsychotics map07029 Phenothiazines CAS: 341-70-8 PubChem: 17396773 LigandBox: D02603 ATOM 22 1 C8y

  10. Drug: D07311 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07311 Drug Veralipride (INN); Agreal (TN) C17H25N3O5S 383.1515 383.4625 D07311.gif...N NERVOUS SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AL Benzamides N05AL06 Veralipride D07311 Veralipride

  11. Drug: D07310 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07310 Drug Amisulpride (INN); Deniban (TN); Solian (TN) C17H27N3O4S 369.1722 369.4...n [BR:br08303] N NERVOUS SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AL Benzamides N05AL05 Amisulpride D07310 Amisulpride

  12. Drug: D08133 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available me as: C15473 ATC code: N05AN01 Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] N NERVOUS SYSTEM N05 PSYCHOLEPTICS... N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D08133 Lithium USP drug classific

  13. Drug: D08135 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ntidepressant ATC code: N05AN01 Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] N NERVOUS SYSTEM N05 PSYCHOLEPTICS... N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D08135 Lithium bromide USP drug c

  14. Drug: D02621 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02621 Drug Fluanisone (INN) C21H25FN2O2 356.19 356.4338 D02621.gif ATC code: N05AD...M N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AD Butyrophenone derivatives N05AD09 Fluanisone D02621 Fluanisone

  15. Drug: D09216 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09216 Drug Thiopropazate (INN) C23H28ClN3O2S 445.1591 446.0053 D09216.gif ATC code...N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AB Phenothiazines with piperazine structure N05AB05 Thiopropazate D09216 Thiopropaz

  16. Abnormalities of cingulate cortex in antipsychotic-naïve chronic schizophrenia.

    Science.gov (United States)

    Liu, Xiaoyi; Wang, Xijin; Lai, Yunyao; Hao, Chuanxi; Chen, Lei; Zhou, Zhenyu; Yu, Xin; Hong, Nan

    2016-05-01

    While several morphometric studies have postulated a critical contribution of the cingulate cortex (CC) to the pathophysiology of schizophrenia based on abnormalities in CC volume, other studies have been inconclusive. Most such studies have focused only on changes in cortical volume, whereas other morphometric parameters such as surface area and cortical thickness could be more relevant and possibly account for these discrepancies. Furthermore, factors such as antipsychotic drug use and treatment duration may also influence cortical morphology. To clarify the association between schizophrenia and CC deficits, we investigated morphometric abnormalities of the CC in antipsychotic drug (AD)-naïve chronic schizophrenia patients by comparing T1-weighted magnetic resonance images (T1WI-MRI) from patients (n=17) to healthy controls (n=17) using the surface-based morphometry program FreeSurfer. Partial correlations were examined between abnormal morphometric measures and both clinical variables and cognitive performance scores. Compared to healthy controls, drug-naïve schizophrenia patients exhibited significantly lower volumes in both left rostral anterior CC (rACC) and left posterior CC (PCC). These reductions in CC volume resulted from reduced surface area rather than reduced cortical thickness. There was also a significant relationship between left PCC volume and working memory in patients. No significant correlations were observed between CC volume and clinical variables. The results suggest that abnormalities in the CC as manifested by reduced surface area may contribute to cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled SI: PSC and the brain.

  17. Drug: D02682 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02682 Drug Remoxipride (USAN) C16H23BrN2O3 370.0892 371.2694 D02682.gif Antipsycho...TICS N05A ANTIPSYCHOTICS N05AL Benzamides N05AL04 Remoxipride D02682 Remoxipride (USAN) Target-based classif...A:1813] [KO:K04145] Remoxipride [ATC:N05AL04] D02682 Remoxipride (USAN) Opioid si...gma1-opioid receptor [HSA:10280] Remoxipride [ATC:N05AL04] D02682 Remoxipride (USAN) CAS: 80125-14-0 PubChem

  18. Stability Indicating HPLC Method for Simultaneous Quantification of Trihexyphenidyl Hydrochloride, Trifluoperazine Hydrochloride and Chlorpromazine Hydrochloride from Tablet Formulation

    Directory of Open Access Journals (Sweden)

    P. Shetti

    2010-01-01

    Full Text Available A new, simple, precise, rapid, selective and stability indicating reversed-phase high performance liquid chromatographic (HPLC method has been developed and validated for simultaneous quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and chlorpromazine hydrochloride from combined tablet formulation. The method is based on reverse-phase using C-18 (250×4.6 mm, 5 μm particle size column. The separation is achieved using isocratic elution by methanol and ammonium acetate buffer (1% w/v, pH 6.5 in the ratio of 85:15 v/v, pumped at flow rate 1.0 mL/min and UV detection at 215 nm. The column is maintained at 30 °C through out the analysis. This method gives baseline resolution. The total run time is 15 min. Stability indicating capability is established buy forced degradation experiment. The method is validated for specificity, accuracy, precision and linearity as per International conference of harmonisation (ICH. The method is accurate and linear for quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and Chlorpromazine hydrochloride between 5 - 15 μg/mL, 12.5- 37.5 μg/mL and 62.5 - 187.5 μg/mL respectively.

  19. 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...... 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....

  20. A Novel Melt-Dispersion Technique for Simplistic Preparation of Chlorpromazine-Loaded Polycaprolactone Nanocapsules

    Directory of Open Access Journals (Sweden)

    Thiresen Govender

    2015-06-01

    Full Text Available The aim of this study was to design, synthesize and optimize chlorpromazine hydrochloride (CPZ-loaded, poly-ε-caprolactone (PCL based nanocapsules, intended for site specific delivery to the frontal lobe, using a novel melt-dispersion technique that is non-arduous, inexpensive and devoid of any hazardous organic solvents. Experimental trials using a central composite design were performed on 13 statistically derived formulations of various combinations of PCL (1000–3000 mg and Polysorbate 80 (2%–5% v/v on the physicochemical and physicomechanical properties and interactive effects on PCL nanocapsule formulation. Differential scanning calorimetry (DSC, Temperature modulated differential scanning calorimetry (TMDSC and Fourier transform infrared spectroscopy (FTIR revealed that there was no thermodegardation of the constituents utilized in the melt dispersion technique. Nanocapsule yields achieved were very high however entrapment of CPZ proved to be relatively low due to the highly hydrophilic nature of CPZ and the processing of the nanocapsules post synthesis. Nanocapsule sizes were in the nanotherapeutic range and varied from 132.7 ± 6.8 nm to 566.6 ± 5.5 nm. Zeta potential ranged from 15.1 ± 0.65 mV to 28.8 ± 0.84 mV revealing capsules that were of incipient to moderate stability. Transmission electron microscopy revealed nanocapsules that were spherical shape, well individualized with a moderate degree of flocculation. In vitro CPZ release was biphasic for all formulations with an initial burst release followed by pseudo-steady controlled release over 30 days. The cytotoxicity of the optimized nanocapsule system on a PC12 neuronal cell line proved to be minimal. Following incorporation of the optimized nanocapsules within a polymeric membrane, in vivo implantation of the device in a New Zealand Albino rabbit model proved the efficacy of the system in achieving prolonged more targeted CPZ levels to the brain. Extensive in vitro

  1. Psychiatrists' decision making between branded and generic drugs.

    Science.gov (United States)

    Hamann, Johannes; Mendel, Rosmarie; Kissling, Werner; Leucht, Stefan

    2013-07-01

    To study psychiatrists' decision making between generic and branded antipsychotics or antidepressants a hypothetical decision scenario involving decisions between branded and generic drugs was presented to a sample of German psychiatrists. Factors influencing this decision were identified using a regression analysis. n=410 Psychiatrists participated in the survey. Psychiatrists were more likely to choose branded drugs when imagining choosing the drug for themselves (vs. recommending a drug to a patient). In addition, psychiatrists were more likely to choose generic antidepressants than generic antipsychotics. Additional predictors for choosing a generic drug were a higher share of outpatients, less negative attitudes toward generics and higher uncertainty tolerance. In conclusion, psychiatrists' decision making in choosing between branded or generic antidepressants or antipsychotics is to a large extent influenced by vague attitudes towards properties of generics and branded drugs as well as by "non-evidence based" factors such as uncertainty tolerance.

  2. 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.

  3. Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis.

    Science.gov (United States)

    Dixit, Tejashree S; Sharma, Ajaykumar N; Lucot, James B; Elased, Khalid M

    2013-04-10

    Recent studies indicate a high comorbidity between type-2 diabetes mellitus (T2DM) and neurological disorders. Many are associated with abnormalities in dopamine neurotransmission such as schizophrenia. Because most of the antipsychotic drugs aggravate pre-existing insulin resistance in type-2 diabetics, there is a need to search for alternative antipsychotics. Glucagon like peptide-1 (GLP-1) is a gut hormone primarily involved in glucose homeostasis. GLP-1 agonist (liraglutide) and dipeptidyl peptidase-IV (DPP-IV) inhibitor (sitagliptin) are the US-FDA approved medications for the management of T2DM. However, little is known about their role in dopamine mediated neurological disorders like schizophrenia. To address this, we used apomorphine-induced cage climbing behavior as a murine model for psychosis and examined for potential antipsychotic-like effect of liraglutide and sitagliptin. While acute liraglutide treatment (50 μg/kg; i.p.) significantly attenuated apomorphine (3 mg/kg, s.c.) induced cage climbing, sitagliptin (50mg/kg; i.p.) failed to elicit such effect. This is the first preclinical evidence for antipsychotic-like effect of GLP-1 receptor agonist. These results open an opportunity to explore GLP-1 analogs for their potential to modulate spectrum of dopamine-mediated neurological disorders.

  4. Effects of antipsychotic drugs on pain threshold and motor behavior in a rat model of schizophrenia%抗精神病药物对精神分裂症大鼠模型痛阈和运动行为的影响

    Institute of Scientific and Technical Information of China (English)

    李刚; 纪蒙蒙; 杨帅; 崔东红; 曹焕军; 于剑锋

    2011-01-01

    Background:Previous investigations have suggested that patients with schizophrenia have decreased pain sensitivity that is partially reversed with antipsychotic treatment.One way to assess this hypothesis is to test it in animal models of schizophrenia.Objective: Determine whether or not rats that manifest the expected behavioral changes of a ketamine-induced rat model of schizophrenia have an increased pain threshold,and test whether or not pretreatment with antipsychotic medication reverses this increase in the pain threshold.Methods: 30 male Wistar rats were randomly assigned to five groups:three groups received intraperitoneal anti-pscyhotics [risperidone (0.3mg/kg),risperidone (0.9mg/kg) or haloperidol (1mg/kg)] 30 minutes prior to receiving intraperitoneal ketamine (100mg/kg);one group received normal saline followed by intraperitoneal ketamine;and a control group received two injections of normal saline.The threshold values for pressure pain and thermal pain were assessed at baseline and at 5,15,30 and 45 minutes after the second injection.The behaviors of another 30 rats treated in the same manner were assessed using the open field test for 120 minutes after receiving the second injection.Results: Compared to the control group,rats in the ketamine group (without pretreatment with antipsychotics) had decreased thresholds for pressure pain and increased thresholds for thermal pain at all time periods after administration of ketamine.Pretreatment with haloperidol significantly diminished the ketamine-induced decreased pressure pain threshold at all time periods but low-or high-dose risperidone had no effect on pressure pain thresholds.Pretreatment with low-dose risperidone reduced the ketamine-induced increase in thermal pain threshold 5 minutes after the ketamine injection but not at 15-45 minutes after the ketamine injection;high-dose risperidone and haloperidol had no significant effect on thermal pain thresholds.In the open field test the groups pretreated

  5. The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse.

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    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.

  6. 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; Pae, Chi-Un

    2016-09-01

    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.

  7. Synthesis, computational studies and preliminary pharmacological evaluation of 2-[4-(aryl substituted piperazin-1-yl]-N-benzylacetamides as potential antipsychotics

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    Sushil Kumar

    2016-11-01

    Full Text Available A series of 2-[4-(aryl substituted piperazin-1-yl]-N-benzylacetamides were synthesized and the target compounds (3a–j were evaluated for atypical antipsychotic activity by studying apomorphine induced climbing behavior, 5-HTP induced head twitches behavior and catalepsy in mice. The physicochemical similarity of the target compounds with respect to standard drugs clozapine, ketanserin and risperidone was assessed by calculating from a set of physicochemical properties using software programs. The test compounds (3a–j demonstrated good similarity values with respect to the standard drugs. Among them, compound 3b has emerged as an important lead compound showing potential atypical antipsychotic-like profile.

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

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    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.

  9. Methamphetamine psychosis, the efficacy of atypical antipsychotics

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    Amir Rezaei Ardani

    2014-12-01

    Full Text Available Worldwide growing methamphetamine abuse is one of the most serious health problems with several different consequences for victims, especially in developing countries. Chronic methamphetamine abuse is associated with several psychiatric problems in all countries which are faced to epidemic methamphetamine abuse. Methamphetamine-induced psychosis is a major medical challenge for clinical practitioner from both diagnostic and therapeutic viewpoints. Stimulant psychosis commonly occurs in people who abuse stimulants, but it also occurs in some patients taking therapeutic doses of stimulant drugs under medical supervision. The main characteristic of meth psychosis is the presence of prominent hallucinations and delusions. Other drugs, such as cocaine and marijuana, can trigger the onset of psychosis in someone who is already at increased risk because they have “vulnerability”.The current literature review attends to explain several aspects of MIP epidemiologically and clinically. Investigators proposed pharmacologically treatment based on recently published data.

  10. Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study

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    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.

  11. Haloperidol-loaded polysorbate-coated polymeric nanocapsules increase its efficacy in the antipsychotic treatment in rats.

    Science.gov (United States)

    Benvegnú, Dalila M; Barcelos, Raquel C S; Boufleur, Nardeli; Reckziegel, Patrícia; Pase, Camila S; Ourique, Aline F; Beck, Ruy Carlos R; Bürger, Marilise E

    2011-02-01

    Haloperidol is an antipsychotic drug associated with the development of movement disorders. We evaluated the effect of its nanoencapsulation on its pharmacological activity and motor side effects. Haloperidol-loaded polysorbate-coated nanocapsules (H-NC) showed nanometric size, negative zeta potential and low polydispersity indices and high encapsulation efficiency (>95%). Rats received a single dose of H-NC (0.2mg/kg ip) and four doses of D,L-amphetamine, AMPH (8.0mg/kg ip), injected every 3h (0, 3, 6 and 9h). The AMPH-induced stereotyped movements were quantified in the intervals of 15 min after each of four doses of AMPH, demonstrating greater pharmacological efficacy of the H-NC over free haloperidol (FH). The acute motor side effects were evaluated 1h after a single dose of H-NC or its free solution (0.2mg/kg ip). The group treated with H-NC presented lower extrapyramidal effects (catalepsy and oral dyskinesia) than those treated with FH. In the last experimental set, rats sub-chronically treated with a daily dose of H-NC (0.2mg/kg ip) for 28 days showed a lower incidence of extrapyramidal effects than those treated with the free drug (0.2mg/kg ip). Our findings showed the potential of using H-NC in the development of a nanomedicine aimed at increasing the efficacy of this antipsychotic drug and reducing its side effects.

  12. Drug utilization study of psychotropic drugs in outdoor patients in a tertiary care hospital attached with a medical college

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    Chintan Madhusudan Doshi

    2015-12-01

    Conclusion: Overall, the drugs were prescribed rationally. Benzodiazepine should be prescribed only for short-term duration. Use of central acting anticholinergic drugs with all antipsychotic drugs was not justified. [Int J Basic Clin Pharmacol 2015; 4(6.000: 1220-1223

  13. The muscarinic acetylcholine receptor agonist BuTAC mediates antipsychotic-like effects via the M4 subtype.

    Science.gov (United States)

    Watt, Marla L; Rorick-Kehn, Linda; Shaw, David B; Knitowski, Karen M; Quets, Anne T; Chesterfield, Amy K; McKinzie, David L; Felder, Christian C

    2013-12-01

    The generation of muscarinic acetylcholine receptor (mAChR) subtype-selective compounds has been challenging, requiring use of nonpharmacological approaches, such as genetically engineered animals, to deepen our understanding of the potential that members of the muscarinic receptor subtype family hold as therapeutic drug targets. The muscarinic receptor agonist 'BuTAC' was previously shown to exhibit efficacy in animal models of psychosis, although the particular receptor subtype(s) responsible for such activity was unclear. Here, we evaluate the in vitro functional agonist and antagonist activity of BuTAC using an assay that provides a direct measure of G protein activation. In addition, we employ the conditioned avoidance response paradigm, an in vivo model predictive of antipsychotic activity, and mouse genetic deletion models to investigate which presynaptic mAChR subtype mediates the antipsychotic-like effects of BuTAC. Our results show that, in vitro, BuTAC acts as a full agonist at the M2AChR and a partial agonist at the M1 and M4 receptors, with full antagonist activity at M3- and M5AChRs. In the mouse conditioned avoidance response (CAR) assay, BuTAC exhibits an atypical antipsychotic-like profile by selectively decreasing avoidance responses at doses that do not induce escape failures. CAR results using M2(-/-), M4(-/-), and M2/M4 (M2/M4(-/-)) mice found that the effects of BuTAC were near completely lost in M2/M4(-/-) double-knockout mice and potency of BuTAC was right-shifted in M4(-/-) as compared with wild-type and M2(-/-) mice. The M2/M4(-/-) mice showed no altered sensitivity to the antipsychotic effects of either haloperidol or clozapine, suggesting that these compounds mediate their actions in CAR via a non-mAChR-mediated mechanism. These data support a role for the M4AChR subtype in mediating the antipsychotic-like activity of BuTAC and implicate M4AChR agonism as a potential novel therapeutic mechanism for ameliorating symptoms associated with

  14. Menstrual disturbance and galactorrhea in people taking conventional antipsychotic medications.

    Science.gov (United States)

    Thangavelu, Karthik; Geetanjali, S

    2006-11-01

    Endocrine disturbances are emerging as major side effects of antipsychotic medications. Of particular note is the profile of menstrual disturbance and galactorrhea as a consequence of hyperprolactinemia (A. Weick & P. M. Haddad, 2003), a sequela of antidopaminergic action at the hypothalamopituitary axis. Research into the clinical aspects of this sensitive issue is sparse. The authors completed a cross-sectional descriptive study of 50 patients on conventional antipsychotic medications. The prevalence of menstrual disturbance was 54%, and the prevalence of amenorrhea was 12%. Symptoms of galactorrhea were present in 32% of patients. A history of pregnancy and childbirth was noted to be significantly associated with the development of galactorrhea (p = .01). The authors hypothesized that pregnancy and lactation might sensitize the hypothalamopituitary axis for further development of hyperprolactinemia due to medications.

  15. Drug: D04749 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04749 Drug Lithium citrate (USP); Lithonate (TN) C6H5O7. 4H2O. 3Li 282.0938 281.98...N NERVOUS SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D04749 Lithium citrate ...(USP) USP drug classification [BR:br08302] Bipolar Agents Mood Stabilizers Lithium D04749 Lithium

  16. Drug: D00801 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00801 Drug Lithium carbonate (JP16/USP); Eskalith (TN); Lithobid (TN) CO3. 2Li 74....ing central nervous system 117 Psychotropics 1179 Others D00801 Lithium carbonate...TICS N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D00801 Lithium carbonate (JP16/USP) USP drug classifi...cation [BR:br08302] Bipolar Agents Mood Stabilizers Lithium D00801 Lithium carbon

  17. Drug: D08134 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08134 Drug Lithium acetate; Quilonorm (TN) C2H3O2. Li 66.0293 65.985 D08134.gif An...YSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AN Lithium N05AN01 Lithium D08134 Lithium acetate USP drug cl...assification [BR:br08302] Bipolar Agents Mood Stabilizers Lithium D08134 Lithium

  18. Drug: D08636 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08636 Drug Trifluoperazine (INN); Apo-trifluoperazine (TN) C21H24F3N3S 407.1643 40...e structure N05AB06 Trifluoperazine D08636 Trifluoperazine (INN) USP drug classification [BR:br08302] Antips...ychotics 1st Generation/Typical Trifluoperazine D08636 Trifluoperazine (INN) Targ... D2-receptor [HSA:1813] [KO:K04145] Trifluoperazine [ATC:N05AB06] D08636 Trifluoperazine (INN) CAS: 117-89-5

  19. Drug: D00799 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00799 Drug Trifluoperazine hydrochloride (JAN/USP); Stelazine (TN) C21H24F3N3S. 2H...azine structure N05AB06 Trifluoperazine D00799 Trifluoperazine hydrochloride (JAN/USP) USP drug classificati...on [BR:br08302] Antipsychotics 1st Generation/Typical Trifluoperazine D00799 Trifluopera...ptors Rhodopsin family Dopamine dopamine D2-receptor [HSA:1813] [KO:K04145] Trifluoperazine [ATC:N05AB06] D00799 Trifluopera

  20. Two cases of neuroleptic malignant syndrome in elderly patients taking atypical antipsychotics

    Institute of Scientific and Technical Information of China (English)

    Yuhui FENG; Xianhong YANG; Yanyan HUANG

    2013-01-01

    Summary: Neuroleptic malignant syndrome (NMS) is a rare, life-threatening adverse reaction to antipsychotic medication that typically includes high-fever, extrapyramidal symptoms, autonomic nervous system dysfunction and disturbances in consciousness. Though reported to be more common following use of the older, first generation antipsychotic medications, it can also occur in patients taking the newer, second generation antipsychotic medications. This report discusses the clinical presentation, possible etiology, pathogenesis and treatment of two cases of NMS that occurred in elderly patients after taking atypical antipsychotics. With the increasing use of atypical antipsychotic medication in elderly patients - who may be more susceptible to this adverse reaction - there is a need to increase clinical vigilance about this condition, particularly among internists and gerontologists who may be unfamiliar with this rare complication to antipsychotic medication.

  1. Severe tardive dystonia on low dose short duration exposure to atypical antipsychotics: Factors explored

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    Nilanjan C Chandra

    2017-01-01

    Full Text Available Tardive dystonia (TD is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine. The goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features, hyperthymic temperament, or borderline intellectual functioning suggestive of organic brain damage, who are more prone to develop adverse effects such as TD and monitor the onset of TD in patients taking atypical antipsychotics.

  2. Severe Tardive Dystonia on Low Dose Short Duration Exposure to Atypical Antipsychotics: Factors Explored

    Science.gov (United States)

    Chandra, Nilanjan C.; Sheth, Shabina A.; Mehta, Ritambhara Y.; Dave, Kamlesh R.

    2017-01-01

    Tardive dystonia (TD) is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine. The goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features, hyperthymic temperament, or borderline intellectual functioning suggestive of organic brain damage, who are more prone to develop adverse effects such as TD and monitor the onset of TD in patients taking atypical antipsychotics.

  3. Thalamic shape abnormalities in antipsychotic naïve schizophrenia

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    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.

  4. Changes of the rats’ heart rate variability caused by chlorpromazine modulation of central noradrenergic neurotransmission during prolonged stress

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    O. Z. Мelnikova

    2012-03-01

    Full Text Available It’s established that under the prolonged stress there were changes of geometric and spectral indices of the rats’ heart rate variability (HRV, manifestations of which depended on duration of stressful factors acting and represented the stress reaction development from the stage of anxiety to the exhaustion phase. Application of chlorpromazine at the beginning and against the background of stress blocked the central alpha adrenoceptors and contributed to renewal of the most HRV indices into the limits of control values at the end of experiment. The results of research show that the modulation of functional state of central noradrenergic system plays a great role in the changes of HRV during prolonged stress.

  5. 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

  6. The impact of antipsychotic polytherapy costs in the public health care in Sao Paulo, Brazil.

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    Denise Razzouk

    Full Text Available Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce.To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil.A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider's perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated.147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs.Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially

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

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    Montemagni C

    2016-04-01

    Full Text Available 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-generation antipsychotic LAIs (SGA-LAIs combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL. Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other

  8. 酵母细胞壁的盐酸氯丙嗪微囊的制备和稳定性考察%Preparation of chlorpromazine hydrochloride microcapsules with yeast cell wall and evaluation on their stability

    Institute of Scientific and Technical Information of China (English)

    江涛; 李伟; 谭力清; 邓春兰; 李明; 于明安

    2012-01-01

    目的 以酵母细胞壁为囊材,制备盐酸氯丙嗪微囊,并观察其稳定性.方法 以载药量为评价指标,采用正交试验设计确定制备盐酸氯丙嗪微囊最佳处方和工艺,并对微囊含量的检测方法进行精密度、稳定性及准确性验证.光学显微镜观察微囊形态,考察其体外释放、高湿度和强光照射的稳定性.结果 在40℃,盐酸氯丙嗪与酵母细胞壁质量比为1∶3,时间为6h,微囊的平均载药量可达41.76%.改进的含量检测方法精密度、稳定性、准确性良好.光学显微镜下可见微囊囊壁完整,呈球形或椭球形,形态均一.盐酸氯丙嗪微囊500 min体外累积释放为94.89%.盐酸氯丙嗪微囊对湿度和光度稳定性显著增加.结论 酵母细胞壁可作为囊材用于制备微囊,且能增加药物的稳定性.%Objective To prepare chlorpromazine hydrochloride microcapsules by using yeast cell wall and observe their sta-bility. Methods The formula and procedure were optimized by orthogonal design, serving drug-loading rate as an index for evalua-tion. The method for determination of drug-loading was verified for precision and stability. The microcapsules were observed for mor-phology by optical microscopy, and evaluated for drug release in vitro as well as the drug stabilities to high humidity and highlight exposure. Results The optimal temperature, ratio of chlorpromazine hydrochloride to yeast cell wall and time for preparation of micro-capsules were 40℃, 1:3 and 6 h respectively. The drug-loading rate of microcapsules prepared under the optimal condition was 41. 76%. The modified method for determination of drug-load showed high precision, stability and accuracy. Optical microscopy showed that the microcapsules were in even sphere or oval shape, with intact walls. A portion of 94. 89% of total drug in the micro-capsules were released in vitro within 500 min. The drug stability in microcapsules to humidity and light increased. Conclusion

  9. Binding of lurasidone, a novel antipsychotic, to rat 5-HT7 receptor: analysis by [3H]SB-269970 autoradiography.

    Science.gov (United States)

    Horisawa, Tomoko; Ishiyama, Takeo; Ono, Michiko; Ishibashi, Tadashi; Taiji, Mutsuo

    2013-01-10

    Lurasidone is a novel antipsychotic agent with high affinity for dopamine D(2) and serotonin 5-HT(7), 5-HT(2A), and 5-HT(1A) receptors. We previously reported that in addition to its antipsychotic action, lurasidone shows beneficial effects on mood and cognition in rats, likely through 5-HT(7) receptor antagonistic actions. In this study, we evaluated binding of lurasidone to 5-HT(7) receptors in the rat brain by autoradiography using [(3)H]SB-269970, a specific radioligand for 5-HT(7) receptors. Brain slices were incubated with 4 nM [(3)H]SB-269970 at room temperature and exposed to imaging plates for 8 weeks before phosphorimager analysis. Using this method, we first investigated 5-HT(7) receptor distribution. We found that 5-HT(7) receptors are abundantly localized in brain limbic structures, including the lateral septum, thalamus, hypothalamus, hippocampus, and amygdala. On the other hand, its distribution was moderate in the cortex and low in the caudate putamen and cerebellum. Secondly, binding of lurasidone, a selective 5-HT(7) receptor antagonist SB-656104-A and an atypical antipsychotic olanzapine to this receptor was examined. Lurasidone, SB-656104-A (10–1000 nM), and olanzapine (100–10,000 nM) showed concentration-dependent inhibition of [(3)H]SB-269970 binding with IC(50) values of 90, 49, and 5200 nM, respectively. Similar inhibitory actions of these drugs were shown in in vitro [(3)H]SB-269970 binding to 5-HT(7) receptors expressed in Chinese hamster ovary cells. Since there was no marked species difference in rat and human 5-HT(7) receptor binding by lurasidone (K(i) = 1.55 and 2.10 nM, respectively), these findings suggest that binding to 5-HT(7) receptors might play some role in its beneficial pharmacological actions in schizophrenic patients.

  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. Interactions between six psychotherapeutic drugs and plastic containers. Influence of plastic material and infusion solutions.

    Science.gov (United States)

    Airaudo, C B; Gayte-Sorbier, A; Bianchi, C; Verdier, M

    1993-06-01

    The interactions of chlorpromazine, clomipramine, maprotiline and viloxazine hydrochlorides, and of clorazepate dipotassium salt and diazepam with polyvinyl chloride (PVC) and Stedim 6 infusion bags were studied. Stedim 6, is anew multilayer film whose inner layer is made of polyethylene. The drugs were in 5% dextrose and 0.9% sodium chloride isotonic solutions and the influence of these was also considered. The remaining concentrations of each drug were determined at regular time intervals in a 24-h period, by a spectrofluorometric method for chlorpromazine hydrochloride and by ultraviolet spectrophotometric methods for the other drugs. No binding was observed for viloxazine and maprotiline hydrochlorides whatever the infusion solution and the plastic container. A slight retention in PVC bags, but not in Stedim 6 ones, was noted for clomipramine hydrochloride and clorazepate dipotassium salt. This was more marked in the sodium chloride solution than in the dextrose one. Diazepam and chlorpromazine hydrochloride were bound both in PVC and Stedim 6 bags, but more in the former and more again in the sodium chloride solution than in the dextrose one. The results were explained in terms of the degree of crystallinity of the plastic material and the degree of lipophilicity of the drugs. Practical consequences are discussed.

  12. 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…

  13. 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

    of the striatum, suggesting a role for muscarinic M4 receptors in the motor side effects of antipsychotics, and in the alleviation of these side effects by anticholinergics. Here we investigated the potential role of the muscarinic M4 receptor in catalepsy induced by antipsychotics (haloperidol and risperidone...

  14. Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis

    NARCIS (Netherlands)

    Boks, MPM; Liddle, PF; Russo, S; Knegtering, R; van den Bosch, RJ

    2003-01-01

    First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of

  15. Antipsychotic Medication and People with Intellectual Disabilities: Their Knowledge and Experiences

    Science.gov (United States)

    Crossley, Rachel; Withers, Paul

    2009-01-01

    Background: Antipsychotics are the most frequently prescribed psychotropic medication for people with intellectual disabilities. Many people are prescribed this medication for "challenging behaviours" without having had a formal diagnosis of a psychiatric disorder. Antipsychotics have been reported to have severe side-effect profiles, which can…

  16. Comparative study among acepromazine, chlorpromazine and methotrimeprazine in different doses, through bispectral index, term and pressure algimetry, in dogs / Estudo comparativo entre a acepromazina, clorpromazina e levomepromazina em diferentes doses, através do exame bispectral, termo e pressoalgimetria, em cães

    Directory of Open Access Journals (Sweden)

    Lidia Mitsuko Matsubara

    2009-12-01

    Full Text Available The study’s objective was to realize comparisons among different acepromazine, chlorpromazine and methotrimeprazine doses, evaluate parametric changes, test analgesia using press and term algimetry, and evaluate bispectral condition. 90 mongrel dogs were used, male and female, adult, weighting 10 to 15 Kg as a rule, distributed in 9 groups with 10 animals each. At first, second and third groups acepromazine was used at 0,1; 0,05 e 0,025 mg/Kg, respectively. At forth, fifth and sixth groups, chlorpromazine was used at 1,0; 0,5 and 0,25 mg/Kg, respectively. At seventh, eighth and ninth groups, methotrimeprazine at 1,0; 0,5 and 0,25 mg/Kg was used, respectively. All drugs were administered intravenously. Objects of study: heart rate (HR, non invasive blood pressure (SAP, MAP, DAP, respiratory rate (f, capnography (ETCO2, pulse oxymetry (SatO2, mouth and rectal temperature, bispectral index (BIS, electromyography (EMG%, press and term algimetry. Somatic analgesia was evaluated by animal’s response to nociceptives stimulus. We concluded that chlorpromazine had more hypotension. Dogs showed higher hypnosis level at chlorpromazine group, with evident myorelaxation. All groups showed analgesia to thermic and mechanic stimulus. Acepromazine group showed high duration to both pain stimuli. Bispectral index was shorten at chlorpromazine group at 1,0 mg/kg doses, showing higher hypnosis index, and acepromazine was the less depressing considering the bispectral index.Objetivou-se comparar, em diferentes doses, a acepromazina, a clorpromazina e a levomepromazina com relação às alterações paramétricas, à analgesia avaliada através da presso e termoalgimetria e a condição bispectral em 90 cães sem raça definida alocados em nove grupos. No primeiro, segundo e terceiro grupo foi empregada a acepromazina nas doses de 0,1; 0,05 e 0,025 mg/kg, respectivamente. No quarto, quinto e sexto grupo foi empregada a clorpromazina nas doses de 1,0; 0,5 e 0

  17. Bitropic D3 Dopamine Receptor Selective Compounds as Potential Antipsychotics.

    Science.gov (United States)

    Luedtke, Robert R; Rangel-Barajas, Claudia; Malik, Mahinder; Reichert, David E; Mach, R H

    2015-01-01

    Neuropsychiatric disorders represent a substantial social and health care issue. The National Institutes of Health estimates that greater than 2 million adults suffer from neuropsychiatric disorders in the USA. These individuals experience symptoms that can include auditory hallucinations, delusions, unrealistic beliefs and cognitive dysfunction. Although antipsychotic medications are available, suboptimal therapeutic responses are observed for approximately one-third of patients. Therefore, there is still a need to explore new pharmacotherapeutic strategies for the treatment of neuropsychiatric disorders. Many of the medications that are used clinically to treat neuropsychiatric disorders have a pharmacological profile that includes being an antagonist at D2-like (D2, D3 and D4) dopamine receptor subtypes. However, dopamine receptor subtypes are involved in a variety of neuronal circuits that include movement coordination, cognition, emotion, affect, memory and the regulation of prolactin. Consequently, antagonism at D2-like receptors can also contribute to some of the adverse side effects associated with the long-term use of antipsychotics including the a) adverse extrapyramidal symptoms associated with the use of typical antipsychotics and b) metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes mellitus, dyslipidemia and gynecomastia) associated with atypical antipsychotic use. Preclinical studies suggest that D3 versus D2 dopamine receptor selective compounds might represent an alternative strategy for the treatment of the symptoms of schizophrenia. In this review we discuss a) how bitropic Nphenylpiperazine D3 dopamine receptor selective compounds have been developed by modification of the primary (orthosteric) and secondary (allosteric or modulatory) pharmacophores to optimize D3 receptor affinity and D2/D3 binding selectivity ratios and b) the functional selectivity of these compounds. Examples of how these compounds might be

  18. Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, D

    2014-01-01

    effectiveness studies in children and adolescents are limited in number and size, and only a few meta-analyses based on conventional methodologies have been conducted. METHODS AND ANALYSES: We will conduct a network meta-analysis of all randomised controlled trials (RCTs) that evaluate antipsychotic therapies...... for EOS to determine which compounds are efficacious, and to determine the relative efficacy and safety of these treatments when compared in a network meta-analysis. Unlike a contrast-based (standard) meta-analysis approach, an arm-based network meta-analysis enables statistical inference from combining...

  19. 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......, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when...... 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...

  20. Anti-inflammatory drugs and psychosis

    NARCIS (Netherlands)

    Laan, W.

    2008-01-01

    This thesis focuses on the disorder we know as schizophrenia. Although there is treatment for schizophrenia in the form of anti-psychotic drugs, not all patients respond well to this treatment. A large part of patients will have remaining symptoms for the rest of their lives. A number of hypotheses

  1. Side effects of clozapine and some other psychoactive drugs.

    Science.gov (United States)

    Flanagan, Robert J

    2008-05-01

    The recognition, management, and if possible prevention, of major cardiovascular, central nervous system, haematological, and metabolic adverse effects, including diabetes mellitus and weight gain, of antipsychotics and some other drugs used to treat mental illness is a topic of much debate. However, a wide range of other adverse effects, some of which may be life-threatening, may also be encountered. Side-effects reviewed here include: gastrointestinal-associated effects (constipation, hypersalivation, oropharyngeal lesions, nasal congestion, nausea, nocturnal enuresis, and urinary retention), metabolic effects (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), neuromuscular effects (extrapyramidal side effects, myoclonus, and neuroleptic malignant syndrome, and pleurothotonus), thermoregulatory effects, effects on the liver, pancreas, and kidney, sexual side effects, and effects on skin and bone. Metabolic factors affecting the incidence of adverse effects to clozapine especially are also discussed. The increasing use of atypical (second generation) antipsychotics and indeed of selective serotonin reuptake inhibitors has led to a greater appreciation of not only the benefits of these drugs, but also of the spectrum of toxicity that may occur in clinical practice. The adverse effects of antipsychotics are a major factor in promoting poor adherence to, and even discontinuation of, antipsychotic treatment on the one hand, and increasing the risk of cardiovascular and metabolic disease on the other. As such they merit recognition and either harm minimization strategies (use of the minimum effective dose, or use of lower doses of combinations of antipsychotics), or in extreme cases discontinuation of the offending drug(s).

  2. Effects of tricyclic compounds and other drugs having a membrane stabilizing action on analgesia, tolerance to and dependence on morphine.

    Science.gov (United States)

    Contreras, E; Tamayo, L; Quijada, L

    1977-08-01

    Several drugs affecting nerve cell excitability, by opposing ion movements in membranes, were tested in mice rendered tolerant to or dependent on morphine. The purpose of the study was to investigate whether these drugs share the ability to attenuate morphine tolerance and dependence exhibited by tricyclic antidepressants. Tolerance to morphine was decreased by the administration of imipramine, doxepin, promethazine, propranolol, lidocaine and quinidine. Chlorpromazine and carbamazepine were ineffective. The intensity of the abstinence syndrome provoked by naloxone was decreased by chlorpromazine, imipramine, doxepin, lidocaine, quinidine and propranolol. Diphenyl. hydantion and carbamazepine had no effect. The results are discussed in relation with the blockade of ion conductance and their interference with the release of neurotransmitters produced by the drugs assayed.

  3. 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

  4. STUDY OF IDENTIFICATION AND ASSESSMENT OF DRUG - DRUG INTERACTIONS

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    Shekar

    2014-02-01

    Full Text Available INTRODUCTION : Drugdrug interactions can be defined as pharmacological or clinical respons e to the administration of drug combination s that is different from its known effects of two or more than two medicines. It frequently conjures images of a sudden catastrophic and even fatal outcome. While such an event can occur and it is important to prevent in the clinical set up. Drug interactio ns can occur by pharmacokinetic & pharmacodynamic interactions. The antipsychotics are known to have more drug interactions compared to any other class of drugs hence we aimed for the identification of drug interactions of psychiatric drugs. METHODOLOGY : T he data was collected from medication chart of inpatients in the psychiatric department and analyzed the interactions using Stockley’s drug interactions , Dipiro etc. RESULTS AND DISCUSSION : The study includes 508 samples out of which 368 case were found to have interactions. The cobalamine and panto prazole interactions were found to be 36.14% and the combination of antipsychotics , anticonvulsants with anxiolytics and anticonvulsants were 10.22 %

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

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    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

  6. Histamine H3-receptor inverse agonists as novel antipsychotics.

    Science.gov (United States)

    Ito, Chihiro

    2009-06-01

    Schizophrenia (SZ) that is resistant to treatment with dopamine (DA) D2 antagonists may involve changes other than those in the dopaminergic system. Recently, histamine (HA), which regulates arousal and cognitive functions, has been suggested to act as a neurotransmitter in the central nervous system. Four HA receptors-H1, H2, H3, and H4-have been identified. Our recent basic and clinical studies revealed that brain HA improved the symptoms of SZ. The H3 receptor is primarily localized in the central nervous system, and it acts not only as a presynaptic autoreceptor that modulates the HA release but also as a presynaptic heteroreceptor that regulates the release of other neurotransmitters such as monoamines and amino acids. H3-receptor inverse agonists have been considered to improve cognitive functions. Many atypical antipsychotics are H3-receptor antagonists. Imidazole-containing H3-receptor inverse agonists inhibit not only cytochrome P450 but also hERG potassium channels (encoded by the human ether-a-go-go-related gene). Several imidazole H3-receptor inverse agonists also have high affinity for H4 receptors, which are expressed at high levels in mast cells and leukocytes. Clozapine is an H4-receptor agonist; this agonist activity may be related to the serious side effect of agranulocytosis caused by clozapine. Therefore, selective non-imidazole H3-receptor inverse agonists can be considered as novel antipsychotics that may improve refractory SZ.

  7. Clinical effectiveness of atypical antipsychotics in elderly patients with psychosis.

    Science.gov (United States)

    Masand, Prakash

    2004-11-01

    The elderly represent a unique patient group in the sense that they have a high prevalence of psychotic symptoms that are a manifestation of a variety of psychiatric, neurological and organic disorders. Treatment is complicated by several factors including comorbid diagnoses (psychiatric and medical), polypharmacy, age-related changes in pharmacokinetics and pharmacodynamics and high susceptibility to adverse events. Elderly patients require pharmacological interventions that are effective in reducing symptoms but also are well tolerated, improve everyday functioning, subjective well-being and treatment adherence and reduce family/career burden. The ability of an antipsychotic to fulfil these requirements determines its clinical effectiveness. To date, few studies have investigated the clinical effectiveness of atypical antipsychotics in elderly patients. However, clear differences exist between the available agents, particularly with regard to tolerability profiles, which have a major impact on the clinical outcome of patients. Clinicians should select an agent that is not only effective in reducing psychotic symptoms but, more importantly, one that has a low incidence of adverse events, such as extrapyramidal symptoms (EPS) and neurocognitive problems, which are of concern in the elderly.

  8. 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.

  9. 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.

  10. 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.

  11. Pathogenesis of drug induced acneform eruptions

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    Lobo Audrey

    1992-01-01

    Full Text Available To determine the pathogenesis of drug induced acneform eruption (DAE, 44 patients were evaluated clinically and representative samples histologically. INAH and corticosteroids were the main offenders in 38.6 percent and 36.4 percent patients respectively. Chloroquin precipitated lesions in 9.1 percent of the patients. There were significant differences in the duration of drug-intake before onset, morphology and severity of lesions. Histological differences with different drugs were also noted. Based on clinical and histological findings, pathogenesis of lesions caused by different drugs could be suggested. Keratinization of follicular epithelium was the main effect with corticosteroids and INAH. Suppuration of follicular epithelium was an additional early event with corticosteroids. Type III allergic reaction was responsible for iodine lesions and delayed hypersensitivity for chlorpromazine and chloroquine induced lesions.

  12. An fMRI study of visual attention and sensorimotor function before and after antipsychotic treatment in first-episode schizophrenia.

    Science.gov (United States)

    Keedy, Sarah K; Rosen, Cherise; Khine, Tin; Rajarethinam, Rajaprabhakaran; Janicak, Philip G; Sweeney, John A

    2009-04-30

    While much is known about receptor affinity profiles of antipsychotic medications, less is known about their impact on functional brain systems in patients with schizophrenia. We conducted functional magnetic resonance imaging (fMRI) studies with first-episode schizophrenia patients as they made saccades to unpredictable visual targets before and after 4-6 weeks of antipsychotic treatment. Matched healthy individuals were scanned at similar time intervals. Pretreatment, patients had less activation in frontal and parietal eye fields and cerebellum. After treatment these disturbances were not present, suggesting improved function in attentional and sensorimotor systems. Other pretreatment abnormalities were noted in sensory and ventromedial prefrontal cortex, but after treatment these abnormalities were absent or less prominent, in line with improved function in attentional systems. In addition, although not abnormal at baseline, there was reduced activity after treatment in dorsal prefrontal cortex, dorsal striatum, and dorsomedial thalamus, suggesting a potential adverse effect of treatment on frontostriatal systems, perhaps related to dopamine blockade in the caudate. These findings provide evidence for a complex impact of antipsychotic medication on functional brain systems in schizophrenia and illustrate the potential of neuroimaging biomarkers for both adverse and beneficial drug effects on functional brain systems.

  13. Drug: D02608 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02608 Drug Perazine fendizoate (JAN) (C20H14O4)2. C20H25N3S 975.3553 976.1431 D0260...08303] N NERVOUS SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AB Phenothiazines with piperazine structure N05AB10 Perazine D0260...8 Perazine fendizoate (JAN) PubChem: 17396778 LigandBox: D0260

  14. Drug: D08549 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08549 Drug Sultopride (INN) C17H26N2O4S 354.1613 354.4643 D08549.gif Neuroleptic S...:br08303] N NERVOUS SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AL Benzamides N05AL02 Sultopride D08549 Sultopride...ily Dopamine dopamine D2-receptor [HSA:1813] [KO:K04145] Sultopride [ATC:N05AL02] D08549 Sultopride

  15. Drug: D08343 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available st [HSA:4988] [KO:K04215] hsa04080(4988) Neuroactive ligand-receptor interaction map07028 Antipsychotics map07039 Opioid analgesic...3327 D08343.gif Opioid analgesic Same as: C07128 ATC code: N02AB02 Synthesis opioid mu-opioid receptor agoni...D08343 Drug Pethidine (INN); Meperidine; Pethidine DBL (TN) C15H21NO2 247.1572 247.

  16. Drug: D02643 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02643 Drug Butaperazine maleate (USAN) C24H31N3OS. (C4H4O4)2 641.2407 641.7318 D02...NERVOUS SYSTEM N05 PSYCHOLEPTICS N05A ANTIPSYCHOTICS N05AB Phenothiazines with piperazine structure N05AB09 Butaperazine D02643 Butap...erazine maleate (USAN) CAS: 1063-55-4 PubChem: 17396813

  17. Drug: D08585 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08585 Drug Thioproperazine (INN) C22H30N4O2S2 446.181 446.6292 D08585.gif Neurolep... ANTIPSYCHOTICS N05AB Phenothiazines with piperazine structure N05AB08 Thioproperazine D08585 Thioproperazin...ine dopamine D2-receptor [HSA:1813] [KO:K04145] Thioproperazine [ATC:N05AB08] D08585 Thiopropera

  18. Voltammetric Determination of Homocysteine Using Multiwall Carbon Nanotube Paste Electrode in the Presence of Chlorpromazine as a Mediator

    Directory of Open Access Journals (Sweden)

    Fathali Gholami-Orimi

    2012-01-01

    Full Text Available We propose chlorpromazine (CHP as a new mediator for the rapid, sensitive, and highly selective voltammetric determination of homocysteine (Hcy using multiwall carbon nanotube paste electrode (MWCNTPE. The experimental results showed that the carbon nanotube paste electrode has a highly electrocatalytic activity for the oxidation of Hcy in the presence of CHP as a mediator. Cyclic voltammetry, double potential step chronoamperometry, and square wave voltammetry (SWV are used to investigate the suitability of CHP at the surface of MWCNTPE as a mediator for the electrocatalytic oxidation of Hcy in aqueous solutions. The kinetic parameters of the system, including electron transfer coefficient, and catalytic rate constant were also determined using the electrochemical approaches. In addition, SWV was used for quantitative analysis. SWV showed wide linear dynamic range (0.1–210.0 μM Hcy with a detection limit of 0.08 μM Hcy. Finally, this method was also examined as a selective, simple, and precise electrochemical sensor for the determination of Hcy in real samples.

  19. DRUG UTILIZATION STUDY OF PSYCHOTROPIC DRUGS PRESCRIBED IN PSYCHIATRY OPD OF L. N. MEDICAL COLLEGE ASSOCIATED J. K. HOSPITAL, BHOPAL DISTRICT, MADHYA PRADESH

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    Richa

    2016-06-01

    Full Text Available BACKGROUND Utilization pattern of drugs varies from place to place and is influenced by differing patient characteristics, type of disease prevalent, cultural and environmental influences, socioeconomic states, availability of newer drugs and prescribing habit of physicians. Psychiatric disorders are one of the major causes of morbidity. Development of newer drugs like SSRIs and atypical antipsychotics has altered the treatment paradigms. Various factors like cost of drugs, local paradigms, etc. play a role in the selection of drug therapy and hence affect the outcome. Keeping this in mind, we conducted a study to delineate the various drugs used in psychiatric disorders. Psychotropic drugs have had a remarkable impact in psychiatric practice. However, their utilization in actual clinical practice, effectiveness and safety in real life situation needs continuous studies. So our aim to study the prevalence of psychiatric morbidity and analyse drug prescribing pattern in various psychiatric illnesses. METHODOLOGY A prospective cross sectional study was carried out for 6 months (Dec. 2014 - May. 2015 in psychiatry OPD of L. N. Medical College, Bhopal. Patients of all ages and both sexes were included in the study and 600 prescriptions were randomly selected. RESULT Antipsychotic drugs (75.33% were most frequently prescribed psychotropic drugs in various psychiatric disorders followed by Anti-Depressants (48.33% and Anxiolytics (26%. CONCLUSION This study shows that antipsychotics are the most common antipsychotic drugs prescribed in patients with psychotic illness. Depression is the most common disease. Prescription rate was higher in men between 21-40 yrs. age

  20. The role of in vivo molecular imaging with PET and SPECT in the elucidation of psychiatric drug action and new drug development.

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    Talbot, Peter S; Laruelle, Marc

    2002-12-01

    This paper reviews the contribution of human PET and SPECT neuroreceptor occupancy studies to the understanding of drug action in psychiatric illness, and how they can aid the development of new drugs. All effective antipsychotics show significant D(2) receptor occupancy. However, at least for atypical antipsychotics, there is no clear relationship between occupancy and clinical response. The mechanisms underlying antipsychotic efficacy, and the minimal effective D(2) occupancy, remain to be elucidated, particularly for drugs with modest or transient occupancy. The low liability of some atypical antipsychotics for extrapyramidal side effects does not appear to be explained by their 5-HT(2A) antagonism, and the muscarinic receptor occupancy of some drugs may be partly explanatory. Previous reports of apparent 'limbic selectivity' of atypical antipsychotics may be in error, and may be due to technical differences in radiotracers. For SSRIs, high occupancies at the serotonin transporter (SERT) are achieved at therapeutic doses, although the minimum SERT occupancy required for therapeutic response remains undefined. Previous attempts to augment the antidepressant effect of SSRIs by pindolol have generally used daily doses which result in inadequate 5-HT(1A) receptor occupancy. For benzodiazepines, clinical doses would appear to leave a wide margin of unoccupied receptors. For methylphenidate and cocaine, typical doses occupy more than 50% of dopamine transporters, and their profiles are extremely similar. In therapeutic drug development, these techniques may be used to assess receptor occupancy profiles, likely drug dosages and dosing intervals which cannot be reliably assessed in humans by other methods.

  1. The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain?

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    Deng, Chao; Weston-Green, Katrina; Huang, Xu-Feng

    2010-02-01

    Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of schizophrenia, with a low risk of extra-pyramidal side-effects. However a major downfall to their use is metabolic side-effects particularly weight gain/obesity, which occurs by unknown mechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in the mechanisms of atypical antipsychotic-induced weight gain, with a focus on the histaminergic H1 and H3 receptors. Olanzapine and clozapine have a high affinity for the H1 receptor, and meta-analyses show a strong correlation between risk of weight gain and H1 receptor affinity. In addition, olanzapine treatment decreases H1 receptor binding and mRNA expression in the rat hypothalamus. Furthermore, a complex role is emerging for the histamine H3 receptor in the control of hunger. The H3 receptor is a pre-synaptic autoreceptor that inhibits the synthesis and release of histamine, and a heteroreceptor that inhibits other neurotransmitters such as serotonin (5-HT), noradrenaline (NA) and acetylcholine (ACh), which are also implicated in the regulation of food intake. Thus, the H3 receptor is in a prime position to regulate food intake, both through its control of histamine and its influence on other feeding pathways. We proposed that a mechanism for atypical antipsychotic-induced weight gain may be partly through the H3 receptor, as a drug-induced decrease in H1 receptor activity may decrease histamine tone through the H3 autoreceptors, compounding the weight gain problem. In addition, atypical antipsychotics may affect food intake by influencing 5-HT, NA and ACh release via interactions with the H3 heteroreceptor.

  2. Delayed drug interactions in psychiatry: armodafinil and risperidone as a potential case in point.

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    Andrade, Chittaranjan

    2015-12-01

    Modafinil or armodafinil (ar/mod) augmentation of antipsychotic medication in schizophrenia patients may be considered with a view to reduce negative symptoms associated with the illness or excessive daytime drowsiness due to any cause. The available data suggest that there is no role for ar/mod in reducing negative symptom burden. A recent pharmacokinetic (PK) study suggested that armodafinil (250 mg/d) reduces key PK parameters of risperidone by about 50%, and key PK parameters of 9-hydroxyrisperidone (paliperidone) by about 20%-30%, probably through induction of CYP3A4. Ar/mod augmentation is therefore best avoided in patients receiving risperidone or paliperidone (and most other atypical antipsychotic drugs, as well, because most atypical antipsychotics are metabolized by enzymes that ar/mod induce). If the ar/mod-antipsychotic drug combination is necessary, for whatever reason, then the dose of the atypical antipsychotic drug may need to be appropriately raised. If this is not done, relapse may occur; because the relapse may postdate the introduction of ar/mod by many months, the causal role of a metabolic drug interaction may not be suspected, and physicians may attribute the relapse to the natural course of the illness. Physicians need to be aware that any agent that induces the metabolism of psychotropic drugs that are used in maintenance therapy may, through lowered psychotropic drug levels, result in a delayed drug interaction that is characterized by illness relapse.

  3. Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics

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    Ludovic Samalin

    2016-11-01

    Full Text Available The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg. Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs, and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

  4. Schizophrenia, antipsychotics and risk of hip fracture: a population-based analysis.

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

    2013-08-01

    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-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture (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 consumption was found (IRR=1.13 95% CI 1.07-1.19) and both prolactin-increasing and non-prolactin-increasing antipsychotics contributed to the effect. In conclusion, several factors, including complex psychopharmacological treatment, contribute in the prediction of hip fracture in large populations. Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics.

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

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    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.

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

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    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

  7. Overlapping of Serotonin Syndrome with Neuroleptic Malignant Syndrome due to Linezolid-Fluoxetine and Olanzapine-Metoclopramide Interactions: A Case Report of Two Serious Adverse Drug Effects Caused by Medication Reconciliation Failure on Hospital Admission

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    Akram, Shahzad; Haider, Nafis; Ahmed, Rafeeque

    2016-01-01

    Antipsychotic and antidepressant are often used in combination for the treatment of neuropsychiatric disorders. The concomitant use of antipsychotic and/or antidepressant with drugs that may interact can lead to rare, life-threatening conditions such as serotonin syndrome and neuroleptic malignant syndrome. We describe a patient who has a history of taking two offending drugs that interact with drugs given during the course of hospital treatment which leads to the development of serotonin syndrome overlapped with neuroleptic malignant syndrome. The physician should be aware that both NMS and SS can appear as overlapping syndrome especially when patients use a combination of both antidepressants and antipsychotics. PMID:27433163

  8. Overlapping of Serotonin Syndrome with Neuroleptic Malignant Syndrome due to Linezolid-Fluoxetine and Olanzapine-Metoclopramide Interactions: A Case Report of Two Serious Adverse Drug Effects Caused by Medication Reconciliation Failure on Hospital Admission

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    Faizan Mazhar

    2016-01-01

    Full Text Available Antipsychotic and antidepressant are often used in combination for the treatment of neuropsychiatric disorders. The concomitant use of antipsychotic and/or antidepressant with drugs that may interact can lead to rare, life-threatening conditions such as serotonin syndrome and neuroleptic malignant syndrome. We describe a patient who has a history of taking two offending drugs that interact with drugs given during the course of hospital treatment which leads to the development of serotonin syndrome overlapped with neuroleptic malignant syndrome. The physician should be aware that both NMS and SS can appear as overlapping syndrome especially when patients use a combination of both antidepressants and antipsychotics.

  9. A placebo controlled trial on add-on modafinil on the anti-psychotic treatment emergent hyperglycemia and hyperlipidemia

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    Pathapati Lakshmi Prasuna

    2014-01-01

    Full Text Available Modafinil is non stimulant drug which is marketed for mainly Narcolepsy and daytime drowsiness. The clinical experience and Summary of Product Characteristics (SPC of the drug also mentions Anorexia as one of the side effects. Anorexia can have a direct impact on the carbohydrate and fat intake, which may, in turn, regulate antipsychotic induced dyslipidemia and Hyperglycaemia. Aim: To compare the effects of Modafinil- ADDON with Placebo add on with olanzapine, Clozapine and Risperidone in drug naive subjects and people who were started on the drugs within 15days of assessment. Materials and Methods: Randomized, Double blind, Placebo controlled study, which was conducted at two centres, one at department of Psychiatry, S.V Medical College, Tirupati and the other at Asha hospitals, Hyderabad. Seventy two patient were randomised, sixty three patients have completed the total study period of three months.The dose of Modafinil was 200 mgs constantly as Flexible doses of Olanzapine, Clozapine and Risperidone as per clinical need was given. A baseline, three week and twelve week assessments of Fasting blood Glucose and fasting Serum cholesterol were made and the groups were compared on these parameters. Results: From baseline to week 3 there was a significant raise in Fasting serum cholesterol followed by a fall from week 3 to week 12 in the Modafinil addon group, though it could not be considered a drug for hypercholesteremia like Statins in controlling hyperlipidaemia. The implications of these findings were discussed.

  10. Entorhinal cortex volume in antipsychotic-naïve schizophrenia

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    Sam P Jose

    2012-01-01

    Full Text Available Background: Entorhinal cortex (ERC, a multimodal sensory relay station for the hippocampus, is critically involved in learning, emotion, and novelty detection. One of the pathogenetic mechanistic bases in schizophrenia is proposed to involve aberrant information processing in the ERC. Several studies have looked at cytoarchitectural and morphometric changes in the ERC, but results have been inconsistent possibly due to the potential confounding effects of antipsychotic treatment. Materials and Methods In this study, we have examined the entorhinal cortex volume in antipsychotic-naïve schizophrenia patients (n=40; M:F=22:18 in comparison with age, sex, and handedness, matched (as a group with healthy subjects (n=42; M:F=25:17 using a valid method. 3-Tesla MR images with 1-mm sections were used and the data was analyzed using the SPSS software. Results: Female schizophrenia patients (1.25±0.22 mL showed significant volume deficit in the right ERC in comparison with female healthy controls (1.45±0.34 mL (F=4.9; P=0.03, after controlling for the potential confounding effects of intracranial volume. However, male patients did not differ from male controls. The left ERC volume did not differ between patients and controls. Conclusions: Consistent with the findings of a few earlier studies we found a reduction in the right ERC volume in patients. However, th