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1.
Nervenarzt ; 91(1): 34-42, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31919550

RESUMO

BACKGROUND: Schizophrenia is a severe psychiatric disorder with variable therapeutic responses, the etiology and pathophysiology of which require further elucidation. OBJECTIVE: To review which pharmacological options are effective and safe and for which treatment goals in schizophrenia. MATERIAL AND METHODS: Narrative review of the pharmacological therapy of adults diagnosed with schizophrenia. RESULTS: Despite heterogeneous therapeutic responses, to date only dopamine antagonists or partial agonists are approved for the treatment of schizophrenia. The efficacy of antipsychotic agents differs only gradually, with the exception of clozapine for treatment-resistant schizophrenia, whereas undesired adverse effects are more variable. Those antipsychotic agents that show gradual efficacy advantages in meta-analyses of acute and maintenance treatment (clozapine, amisulpride, olanzapine, risperidone) are also those where at least one undesired adverse effect is most severely expressed. Antipsychotic adverse effects occur in subgroups of patients and are generally tolerable or treatable, whereas the "side effect" of untreated schizophrenia affects almost all patients, including relapses, psychosocial deterioration, secondary treatment resistance and increased mortality. Therefore, in patients with a confirmed diagnosis of schizophrenia, a lifelong continuous therapy is currently most likely indicated, ideally with antipsychotic agents for which adherence is directly measurable and improved. In the case of treatment resistant clozapine is the agent of choice, followed by electroconvulsive therapy, which also has the best evidence as augmentation treatment in cases of clozapine resistance. CONCLUSION: New therapeutic agents with improved efficacy and tolerability as well as effectiveness for negative symptoms and cognitive disturbance are needed.


Assuntos
Antipsicóticos , Esquizofrenia , Adulto , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Humanos , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
2.
Medicine (Baltimore) ; 98(38): e17237, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567988

RESUMO

INTRODUCTION: With the second-generation antipsychotics (SGAs) widely applied to treat patients with schizophrenia, adverse effects, especially the metabolic syndrome (MetS), were paid more attention following by the efficacy of SGAs. Several studies have suggested that acupuncture could be an effective and safe intervention for MetS. Here, we present a study protocol to investigate the effect of electroacupuncture on MetS due to olanzapine and risperidone. METHODS: This study is a prospective, randomized, single-centered, patient-assessor-blinded, parallel-controlled clinical pilot trial. In all, 36 patients will be randomized to an experimental group or control group by a 1:1 ratio. All patients will receive lifestyle interventions. The experimental group will receive electroacupuncture treatment. The control group will receive sham electroacupuncture treatment. The primary outcomes are body mass index (BMI) and waist circumference (WC). The secondary outcome measures include blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), leptin, and adiponectin. We will assess at baseline, 8 weeks after intervention and at the end of 3 months' follow-up. DISCUSSION: The results of this trial are expected to provide data on the efficacy and safety of electroacupuncture on MetS due to olanzapine and risperidone, and potential biochemical mechanism.


Assuntos
Antipsicóticos/efeitos adversos , Eletroacupuntura , Síndrome Metabólica/terapia , Olanzapina/efeitos adversos , Risperidona/efeitos adversos , Antipsicóticos/uso terapêutico , Protocolos Clínicos , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Humanos , Síndrome Metabólica/induzido quimicamente , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
3.
Actas esp. psiquiatr ; 47(5): 190-201, sept.-oct. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-185171

RESUMO

El trastorno esquizoafectivo (TEA) es un trastorno psicótico que ha entrañado cierta controversia nosológica, junto a esta dificultad encontramos muy pocos estudios que aborden su tratamiento como una entidad diferente a la esquizofrenia. Estas dos dificultades dan como resultado la falta de evidencia específica sobre el tratamiento. Actualmente, el mismo, se basa principalmente en el empleo de antipsicóticos, aunque no existen guías específicas de manejo terapéutico. Esta revisión tiene el objetivo de conocer cuáles son los fármacos que actualmente cuentan con estudios de mayor calidad científica que avalen su empleo según variables clínicas de efectividad, seguridad, adherencia y tolerancia, así como su papel en los diferentes subtipos de TEA y situaciones clínicas. Para ello, se realizó una revisión exhaustiva de estudios experimentales y observacionales que incluyeran pacientes con diagnóstico de TEA. Se concluyó que son necesarios más ensayos clínicos realizados en pacientes con diagnóstico exclusivo de TEA. La paliperidona, el único fármaco con uso autorizado en el TEA es el fármaco que cuenta con mayor cantidad y calidad de estudios que avalen su uso. Risperidona, olanzapina, aripiprazol y ziprasidona también tienen ensayos clínicos aleatorizados que apoyan su eficacia y seguridad. En pacientes refractarios, hay estudios observacionales que señalan la utilidad de la clozapina. Así mismo, hay evidencia de estudios observacionales que señalan la utilidad de litio y carbamazepina durante la fase de mantenimiento. Es necesario establecer el papel del tratamiento combinado con regula-dores del humor y/o antidepresivos


Schizoaffective disorder (SAD) is a psychotic disorder which has presented a certain nosological controversy. Apart from these difficulties, very few studies focused in SAD as a distinct condition from schizophrenia have been found. This lack of specifical studies on SAD results in a lack of specific evidence about treatment. Currently, its treatment is based mainly on the use of antipsychotics, although there are no specific treatment guidelines for SAD. The objective of this review is to establish which are the most recommended treatments according to evidence avail-able, considering clinical variables such as efficacy, safety, adherence, and tolerance as well as the role of these factors in different subtypes of SAD. This exhaustive review exam-ines experimental and observational studies involving patients with a diagnosis of SAD. It was concluded that more clinical trials performed exclusively on patients affected by SAD are needed. Paliperidone, the only drug with authorized use in SAD, is the one that has the highest quality of studies to support its use. Risperidone, olanzapine, aripiprazole and ziprasidone also have randomized clinical trials supporting their efficacy and safety. In treatment-refractory patients, there are observational studies indicating the usefulness of clozapine. Like-wise, there is evidence from observational studies showing the usefulness of lithium and carbamazepine during the treatment maintenance phase. It is necessary to establish the role of combined treatment with mood stabilizers and/or antidepressants


Assuntos
Humanos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Psicofarmacologia , Resultado do Tratamento , Medicina Baseada em Evidências , Transtornos Psicóticos/tratamento farmacológico , Risperidona/uso terapêutico , Olanzapina/uso terapêutico , Aripiprazol/uso terapêutico , Clozapina/uso terapêutico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico
4.
Iran J Allergy Asthma Immunol ; 18(3): 262-268, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31522433

RESUMO

A growing body of evidence suggests the existence of abnormalities in the immune system of schizophrenic patients. The current study examined serum levels of interleukin (IL) -1ß, IL-6, IL-2,interferon(IFN) -γ, and tumor necrosis factor(TNF)-α in schizophrenic patients before and after treatment with risperidone and correlated levels of these cytokines with symptomatology. The study group consisted of 24 schizophrenic patients as defined by Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria and 24 healthy controls. Serum cytokine levels were examined using enzyme-linked immunosorbent assay (ELISA). Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) questionnaire. The serum levels of TNF-α, IL-1ß and IL-6 were significantly higher in participants before treatment compared with the healthy controls and after treatment (p<0.001). IFN-γ and IL-2 levels were significantly lower in participants after treatment compared with before treatment and the healthy controls (p<0.001). Except for IL-6 (p<0.05), there was no significant difference in the levels of TNF-α and IL-1ß between the patients receiving treatment and the healthy subjects. Moreover, there was no significant difference in levels of IFN-γ and IL-2 between patients before treatment and the healthy subjects. There were no significant correlations between the concentration of cytokines studied and the PANSS. Positive intercorrelations between the production of IFN-γ and IL-2 were detected for sums of all groups(r=0.33, p=0.005). Clinical improvement of treated patients was associated with a reduction in the studied cytokines. It seems that changes in the cytokines level may play a significant role in the psychopathology of these patients.


Assuntos
Antipsicóticos/uso terapêutico , Citocinas/sangue , Risperidona/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Risperidona/administração & dosagem , Risperidona/efeitos adversos , Esquizofrenia/diagnóstico , Esquizofrenia/imunologia , Células Th1/imunologia , Células Th1/metabolismo
5.
Int J Mol Sci ; 20(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540405

RESUMO

Compelling evidence from preclinical and clinical studies has shown that mild hypothermia is neuroprotective against ischemic stroke. We investigated the neuroprotective effect of post-risperidone (RIS) treatment against transient ischemic injury and its mechanisms in the gerbil brain. Transient ischemia (TI) was induced in the telencephalon by bilateral common carotid artery occlusion (BCCAO) for 5 min under normothermic condition (37 ± 0.2 °C). Treatment of RIS induced hypothermia until 12 h after TI in the TI-induced animals under uncontrolled body temperature (UBT) compared to that under controlled body temperature (CBT) (about 37 °C). Neuroprotective effect was statistically significant when we used 5 and 10 mg/kg doses (p < 0.05, respectively). In the RIS-treated TI group, many CA1 pyramidal neurons of the hippocampus survived under UBT compared to those under CBT. In this group under UBT, post-treatment with RIS to TI-induced animals markedly attenuated the activation of glial cells, an increase of oxidative stress markers [dihydroethidium, 8-hydroxy-2' -deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE)], and a decrease of superoxide dismutase 2 (SOD2) in their CA1 pyramidal neurons. Furthermore, RIS-induced hypothermia was significantly interrupted by NBOH-2C-CN hydrochloride (a selective 5-HT2A receptor agonist), but not bromocriptine mesylate (a D2 receptor agonist). Our findings indicate that RIS-induced hypothermia can effectively protect neuronal cell death from TI injury through attenuation of glial activation and maintenance of antioxidants, showing that 5-HT2A receptor is involved in RIS-induced hypothermia. Therefore, RIS could be introduced to reduce body temperature rapidly and might be applied to patients for hypothermic therapy following ischemic stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Risperidona/uso terapêutico , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Gerbillinae , Hipocampo/metabolismo , Hipocampo/patologia , Hipotermia/induzido quimicamente , Hipotermia Induzida/métodos , Masculino , Estresse Oxidativo/efeitos dos fármacos
6.
Artigo em Inglês | MEDLINE | ID: mdl-31413891

RESUMO

Background: Trends in the use of antipsychotics and alpha agonists for the treatment of tic disorders in Canadian children, and how closely these trends align with evidence-based guidelines on the pharmacotherapy of tic disorders, have not been explored. Methods: IQVIA's Canadian Disease and Therapeutic Index, a survey-based data set, was used to identify prescription patterns by physicians. Respondents recorded all patient visits during a 48-hour period in each quarter of the year, including patient age, gender, drug recommendation and therapeutic indication. Recommendations for alpha agonists and antipsychotics from 2012 to 2016 were analysed for children and adolescents with tic disorders. Results: Risperidone and clonidine were the most commonly recommended medications for tic disorders over the study period, with 36,868 and 35,500 recommendations in 2016, respectively. Recommendations for clonidine increased over the study period, whereas those for risperidone decreased. Guanfacine (approved in Canada in 2013) was used less frequently than clonidine. Clonidine was more frequently recommended than antipsychotics in children younger than 6, in whom antipsychotic recommendations were uncommon. Aripiprazole was the second most commonly recommended antipsychotic for tic disorders, with 22,892 recommendations in 2016. Of the first-generation antipsychotics, pimozide was most commonly recommended (11,334 recommendations in 2016); haloperidol was infrequently recommended. Discussion: The trends observed are in line with guideline recommendations reflected in the decreasing use of risperidone, and the growing use of clonidine and guanfacine. The growing use of aripiprazole is likely due to emerging evidence from clinical trials supporting its efficacy for tics. Recommendations for pimozide and haloperidol were limited, likely due to the greater adverse effects associated with these medications.


Assuntos
Antipsicóticos/uso terapêutico , Prescrições/estatística & dados numéricos , Transtornos de Tique/tratamento farmacológico , Síndrome de Tourette/tratamento farmacológico , Adolescente , Aripiprazol/uso terapêutico , Criança , Pré-Escolar , Feminino , Guanfacina/uso terapêutico , Humanos , Lactente , Masculino , Farmacoepidemiologia , Risperidona/uso terapêutico , Transtornos de Tique/epidemiologia
7.
J Autism Dev Disord ; 49(11): 4595-4602, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31468273

RESUMO

Using a dataset involving 415 individuals with irritability, aggression, agitation and self-injury (IAAS) behaviors from the fragile X syndrome (FXS) FORWARD database, we describe the psychopharmacologic management of IAAS and features of the population of persons with FXS treated with drug therapy for IAAS. Among those with FXS exhibiting IAAS, individuals with FXS receiving drug treatment of IAAS were older, more predominantly male, have more significant intellectual disability, more like to have comorbid autism, hyperarousal, and social impairments. The most commonly utilized medications for IAAS in FXS are antipsychotic medications, specifically aripiprazole and risperidone (37% and 27%, respectively). The majority of subjects (63%) experienced no side effects noted from the use of their psychopharmacologic medications.


Assuntos
Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Síndrome do Cromossomo X Frágil/tratamento farmacológico , Humor Irritável/efeitos dos fármacos , Agitação Psicomotora/tratamento farmacológico , Comportamento Autodestrutivo/tratamento farmacológico , Adolescente , Adulto , Agressão/fisiologia , Agressão/psicologia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antipsicóticos/farmacologia , Criança , Comorbidade , Estudos Transversais , Feminino , Síndrome do Cromossomo X Frágil/epidemiologia , Síndrome do Cromossomo X Frágil/psicologia , Humanos , Humor Irritável/fisiologia , Masculino , Pessoa de Meia-Idade , Agitação Psicomotora/epidemiologia , Agitação Psicomotora/psicologia , Risperidona/farmacologia , Risperidona/uso terapêutico , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Adulto Jovem
8.
Psychiatry Res ; 276: 203-209, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31102885

RESUMO

Autism spectrum disorder (ASD) is a group of life-long neurodevelopmental conditions with a prevalence of 1.5% in developed countries. Beside core symptomatology, ASD people are frequently affected by psychiatric comorbidities and behavioral problems. To date, only risperidone and aripiprazole have been approved for the pharmacological treatment of ASD-associated irritability in children and adolescents, while no guidelines exist for adults. The present cross-sectional study examined the prevalence and predictors of psychotropic medication use in 195 autistic subjects, aged between 14 and 58, treated in two Italian tertiary care centers. 58.5% of the sample were taking at least one medication; one third of the sample were on polypharmacotherapy. Antipsychotics were prescribed to 40% of the sample. Nearly 30% of the sample were on anticonvulsants/mood stabilizers. Both antidepressants and benzodiazepines were prescribed to approximately 16% of the subjects. IQ, epilepsy and psychiatric comorbidities were regarded as independent predictors of both mono- and polypharmacotherapy, while severity of repetitive behaviors predicted only polypharmacotherapy. Our data highlighted that medications prescribed to adolescents and adults with ASD are heterogeneous and often rely only on clinicians' experience. Future research should investigate the effectiveness of psychotropic drugs in this specific population, to promote the development of appropriate treatment guidelines.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Psicotrópicos/uso terapêutico , Adolescente , Adulto , Aripiprazol/uso terapêutico , Transtorno do Espectro Autista/psicologia , Benzodiazepinas/uso terapêutico , Criança , Comorbidade , Estudos Transversais , Feminino , Humanos , Humor Irritável/efeitos dos fármacos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Risperidona/uso terapêutico , Adulto Jovem
9.
Clin Neuropharmacol ; 42(4): 117-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31045590

RESUMO

BACKGROUND: Introduction of old and new generations of antipsychotics leads to significant improvements in the positive symptoms of schizophrenia. However, negative symptoms remain refractory to conventional trials of antipsychotic therapy. Recently, there were several open clinical human trials with curcumin. Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including antioxidative and neuroprotective effects. The studies showed that curcumin improved the negative symptoms of schizophrenia. The purpose of our study was to examine the efficacy of curcumin as an add-on agent to regular antipsychotic medications in patients with chronic schizophrenia. METHODS: Thirty-eight patients with chronic schizophrenia were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 3000 mg/d curcumin or placebo combined with antipsychotics from January 2015 to February 2017. The outcome measures were the Positive and Negative Symptoms Scale (PANSS) and the Calgary Depression Scale for Schizophrenia. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. There was a significant response to curcumin within 6 months in total PANSS (P = 0.02) and in the negative symptoms subscale (P = 0.04). There were no differences in the positive and general PANSS subscales, and the Calgary Depression Scale for Schizophrenia scores between the treatment and placebo groups. No patient complained of any adverse effect. CONCLUSIONS: The promising results of curcumin as an add-on to antipsychotics in the treatment of negative symptoms may open a new and safe therapeutic option for the management of schizophrenia. However, these results should be replicated in further studies.ClinicalTrials.gov Identifier: NCT02298985.


Assuntos
Antipsicóticos/uso terapêutico , Curcumina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Risperidona/uso terapêutico
10.
Artigo em Russo | MEDLINE | ID: mdl-31089091

RESUMO

AIM: To conduct a routine therapeutic drug monitoring (TDM) and analyze its results for the optimization of pharmacotherapy. MATERIAL AND METHODS: Fifty-six inpatients (in total 68 samples) with various forms of schizophrenia were enrolled. High performance liquid chromatography with mass-spectrometric detection was used for quantitative determination of risperidone and 9-hydroxyrisperidone in the serum. RESULTS: Concentrations of risperidone and 9-hydroxyrisperidone were correlated with drug dose. Total concentrations in the blood at doses from 2 to 8 mg per day were distributed as follows: 44.1% were in the therapeutic, 29.4% in sub-therapeutic (<20 ng/mL) and 26.5% in conditionally toxic range (>60 ng/mL). CONCLUSIONS: Concentrations of risperidone and 9-hydroxyrisperidone did not follow the normal distribution. The results showed that monitoring of the total concentration of risperidone and its metabolite 9-hydroxyrisperidone was an effective tool for testing and quality control for the purpose of individualization of pharmacotherapy.


Assuntos
Antipsicóticos , Monitoramento de Medicamentos , Risperidona , Esquizofrenia , Antipsicóticos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Humanos , Isoxazóis , Palmitato de Paliperidona/uso terapêutico , Pirimidinas , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
11.
J Clin Pharm Ther ; 44(4): 543-552, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31056781

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Dopamine D2 receptor (DRD2) polymorphisms are inconsistently associated with elevated prolactin levels related to risperidone treatment. The aim of this systematic review and meta-analysis was to investigate whether DRD2 polymorphisms could modulate prolactin levels in patients treated with risperidone. METHODS: Three electronic databases (PubMed, EMBASE and the Cochrane Library) were searched for studies investigating the effect of DRD2 polymorphisms on prolactin levels in patients treated with risperidone until May 2018. Summary standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated with Hedges' g tests for effect estimates using random effects models. The heterogeneity, sensitivity, univariable meta-regression, subgroup analyses and publication biases were calculated. RESULTS AND DISCUSSION: After initially identifying 886 studies, 772 patients from eight studies were included. Summary SMDs indicated that compared with A1 non-carriers, Taq1A A1 carriers did not have different risperidone-related prolactin levels (SMD: 0.13; 95% CI: -0.18 to 0.43; P = 0.423) among patients with schizophrenia (SCZ; SMD: 0.07; 95% CI: -0.14 to 0.29; P = 0.505) or among those without SCZ (SMD: 0.16; 95% CI: -0.39 to 0.71; P = 0.562). There was no significant difference between Del carriers and Del non-carriers with regard to risperidone-related prolactin levels (SMD: -0.00; 95% CI: -0.59 to 0.58; P = 0.996). In an Asian subgroup analysis, we also noted that compared with Taq1A A1A2 carriers, Taq1A A1A1 carriers had lower prolactin levels (SMD: -0.34; 95% CI: -0.66 to -0.02; P = 0.040). However, there was no significant difference in prolactin levels between A1A1 carriers and A2A2 carriers (SMD: -0.27; 95% CI: -0.60 to 0.05; P = 0.098), or between A2 carriers and A2 non-carriers (SMD: 0.29; 95% CI: -0.01 to 0.59; P = 0.059). Based on univariable meta-regression analyses, the effects of publication year, study design, ethnicity, comparison groups and study quality could bias the identified association of DRD2 Taq1A with risperidone-related prolactin levels. WHAT IS NEW AND CONCLUSION: The findings of this study suggest that there is no significant difference between Taq1A A1 carriers and non-A1 carriers with regard to risperidone-related prolactin levels. As there were few A1 homozygotes, large prospective studies with robust designs are still needed to investigate whether A1A1 could affect risperidone-related prolactin levels in the Asian population.


Assuntos
Polimorfismo Genético/genética , Prolactina/metabolismo , Receptores de Dopamina D2/genética , Risperidona/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Humanos
12.
Int Clin Psychopharmacol ; 34(3): 124-130, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30870237

RESUMO

High-dose antipsychotic(s) can induce dopamine supersensitivity psychosis in schizophrenia patients. The precise relationship between a drug's blood concentration and the occurrence of dopamine supersensitivity psychosis has not been established. We divided 36 patients with schizophrenia who had undergone treatment mainly with risperidone into two groups: one with normal metabolizing activity of CYP2D6 (n = 15), and the other with lower activity of its variant, CYP2D6*10 (n = 21). The patients' blood concentrations of risperidone and 9-OH-risperidone were measured, and we compared the occurrence of dopamine supersensitivity psychosis episodes between the groups. There was no significant difference in any concentration of risperidone, 9-OH-risperidone, or active moiety between the groups although the with-CYP2D6*10 group had greater variabilities of these parameters compared to the without-CYP2D6*10 group. There was a lower rate of dopamine supersensitivity psychosis episodes in the without-CYP2D6*10 group (4/15, 26.7%) compared to the with-CYP2D6*10 group (11/21, 52.4%), but the difference was not significant. Although our findings were negative, largely because of the small sample size, these results suggest that (1) patients with an impaired functional allele of CYP2D6 may have higher concentrations of risperidone and its active metabolite and that (2) these patients may experience more frequent dopamine supersensitivity psychosis episodes.


Assuntos
Citocromo P-450 CYP2D6/metabolismo , Dopamina/fisiologia , Psicoses Induzidas por Substâncias/tratamento farmacológico , Risperidona/metabolismo , Esquizofrenia/tratamento farmacológico , Alelos , Antipsicóticos/uso terapêutico , Citocromo P-450 CYP2D6/genética , Genótipo , Humanos , Palmitato de Paliperidona/sangue , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/tratamento farmacológico , Risperidona/sangue , Risperidona/uso terapêutico , Esquizofrenia/genética
13.
Neuropharmacology ; 150: 1-14, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30831160

RESUMO

Methylazoxymethanol (MAM)-treated pregnant rat at gestation day (GD) 17 has been shown to be a valuable developmental animal model for schizophrenia. Yet, this model remains to be established in mice. In the present study, we examined behavioral, cytoarchitectural, and neurochemical changes in the offspring of MAM-treated mice and validated the model's face, construct and predictive validities. We found that in contrast to a single injection of MAM to dams at GD 15, 16 or 17, its daily administration from GD 15 to 17 led to deficits in prepulse inhibition (PPI) of startle in the post-pubertal offspring. In addition, we observed behavioral deficits in working memory and social interactions, as well as an increase in locomotor activity induced by the NMDA antagonist MK-801 in GD15-17 MAM offspring. These animals also showed a reduction in the volume of the prefrontal cortex (PFC) and hippocampus, neuroanatomical changes such as discontinuities and heterotopias in the hippocampus, and an increase of DA level and DOPAC/DA ratio in the medial PFC. Atypical antipsychotic drugs clozapine, risperidone, and aripiprazole, but not the typical drug haloperidol, reversed the deficit in PPI and social withdrawal in the offspring of MAM-treated dams. In contrast, MK-801-induced hyperactivity in MAM mice was reversed by both and typical or atypical antipsychotic drugs. Taken together, the treatment of pregnant mice with MAM during GD 15-17 offers a new approach to study neurobiological mechanisms involved in the pathogenesis of schizophrenia.


Assuntos
Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Acetato de Metilazoximetanol/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Esquizofrenia/fisiopatologia , Animais , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Aripiprazol/farmacologia , Aripiprazol/uso terapêutico , Clozapina/farmacologia , Clozapina/uso terapêutico , Modelos Animais de Doenças , Feminino , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Camundongos , Atividade Motora/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Inibição Pré-Pulso/efeitos dos fármacos , Risperidona/farmacologia , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
14.
Asia Pac Psychiatry ; 11(3): e12354, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30912222

RESUMO

OBJECTIVE: The efficacy and safety of lurasidone in schizophrenia has been demonstrated in multiple controlled trials, primarily in US and European populations. The aim of the current study was To evaluate lurasidone for the treatment of schizophrenia among patients in Japan, Korea, and Taiwan. METHODS: Hospitalized patients (N = 460) with schizophrenia were randomized to 6 weeks of fixed-dose lurasidone 40 mg/d, lurasidone 80 mg/d, risperidone 4 mg/d, or placebo. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). RESULTS: No significant endpoint differences in PANSS total score were found for lurasidone or risperidone vs placebo. Lurasidone was safe and well tolerated, with minimal effects on weight and metabolic parameters. DISCUSSION: The current study was inconclusive regarding the efficacy of lurasidone in schizophrenia but further confirmed its safety and tolerability.


Assuntos
Antipsicóticos/uso terapêutico , Cloridrato de Lurasidona/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Cloridrato de Lurasidona/efeitos adversos , Masculino , Pessoa de Meia-Idade , Risperidona/efeitos adversos , Resultado do Tratamento , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-30852126

RESUMO

BACKGROUND: Schizophrenia is associated with progressive white matter changes, but it is unclear whether antipsychotic medications contribute to these. Our objective was to characterize effects of short-term treatment with risperidone on white matter diffusion indices. METHODS: We recruited 42 patients with schizophrenia (30 never treated and 12 currently untreated) and 42 matched healthy control subjects in this prospective case-control neuroimaging study. Patients received a 6-week trial of risperidone. Using diffusion tensor imaging, we assessed microstructural (fractional anisotropy, mean diffusivity, and radial diffusivity) and macrostructural (radial fiber trophy) white matter integrity deficits in unmedicated patients compared with control subjects and change in white matter integrity in patients before and after antipsychotic treatment (mean risperidone dose at end point was 3.73 ± 1.72 mg). RESULTS: At baseline, fractional anisotropy was decreased in the left medial temporal white matter (cluster extent: 123 voxels; Montreal Neurological Institute peak coordinates: x = -51, y = -44, z = -7; α < .05), and mean diffusivity was increased in the fusiform/lingual gyrus white matter extending to the hippocampal part of the cingulum (cluster extent: 185 voxels; peak coordinates: x = -27, y = -49, z = 2; α < .04) in patients compared with control subjects. Radial diffusivity and macrostructure were not abnormal. None of the diffusion indices showed a significant change after 6 weeks of treatment with both voxelwise and whole-brain white matter analyses. CONCLUSIONS: We demonstrate microstructural white matter integrity abnormalities in the absence of macrostructural impairment in unmedicated patients with primarily early-stage schizophrenia. In our data, we found no significant white matter changes after short-term treatment with risperidone.


Assuntos
Antipsicóticos/uso terapêutico , Encéfalo/patologia , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Substância Branca/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Esquizofrenia/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos dos fármacos , Adulto Jovem
16.
Clin Neuropharmacol ; 42(3): 97-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829883

RESUMO

Levetiracetam is an antiepileptic agent that is used for partial and generalized epilepsy. Although it is well tolerated in most cases, behavioral and nonbehavioral adverse effects may be observed. Among behavioral symptoms, depression, hostility, and agitation have been frequently reported. However, mania or mania-like symptoms are relatively rare, especially in children and adolescents. Hereby, we report mania-like symptoms with levetiracetam use in a 15-year-old boy. Mania-like symptoms emerged 3 weeks after starting levetiracetam and disappeared after adding risperidone to ongoing levetiracetam treatment.


Assuntos
Anticonvulsivantes/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Levetiracetam/efeitos adversos , Adolescente , Humanos , Masculino , Risperidona/uso terapêutico
17.
Eur Psychiatry ; 58: 1-9, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30738380

RESUMO

BACKGROUND: Negative symptoms in schizophrenia are heterogeneous and multidimensional; effective treatments are lacking. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, was significantly more effective than risperidone in treating negative symptoms in a prospectively designed trial in patients with schizophrenia and persistent, predominant negative symptoms. METHODS: Using post hoc analyses, we evaluated change from baseline at week 26 in individual items of the Positive and Negative Syndrome Scale (PANSS) and PANSS-derived factor models using a mixed-effects model for repeated measures (MMRM) in the intent-to-treat (ITT) population (cariprazine = 227; risperidone = 227). RESULTS: Change from baseline was significantly different in favor of cariprazine versus risperidone on PANSS items N1-N5 (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking) (P < .05), but not on N6 (lack of spontaneity/flow of conversation) or N7 (stereotyped thinking). On all PANSS-derived negative symptom factor models evaluated (PANSS-Factor Score for Negative Symptoms, Liemburg factors, Khan factors, Pentagonal Structure Model Negative Symptom factor), statistically significant improvement was demonstrated for cariprazine versus risperidone (P < .01). Small and similar changes in positive/depressive/EPS symptoms suggested that negative symptom improvement was not pseudospecific. Change from baseline was significantly different for cariprazine versus risperidone on PANSS-based factors evaluating other relevant symptom domains (disorganized thoughts, prosocial function, cognition; P < .05). CONCLUSIONS: Since items representing different negative symptom dimensions may represent different fundamental pathophysiological mechanisms, significant improvement versus risperidone on most PANSS Negative Subscale items and across all PANSS-derived factors suggests broad-spectrum efficacy for cariprazine in treating negative symptoms of schizophrenia.


Assuntos
Sintomas Comportamentais/tratamento farmacológico , Piperazinas/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Sintomas Comportamentais/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Resultado do Tratamento
18.
Brain Dev ; 41(6): 501-506, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30795919

RESUMO

OBJECTIVE: We aimed to clarify the current status of pharmacotherapy for tic disorders and comorbidities in Japan. We used a systematic survey to collate the consensus of Japanese experts and compare it with the recent international evidence. METHODS: We devised a questionnaire on pharmacotherapy for tics and comorbidities and sent it to Japanese experts on tic disorders. Based on the response to the first survey, we revised the questionnaire and conducted a second survey to determine the consensus among the experts on a 4-point Likert scale by the Delphi method. RESULTS: The first survey revealed variability in preferred medications and dosages among the experts in Japan. However, we were able to build a general consensus on pharmacotherapy for tic disorders and comorbidities based on the second survey. Aripiprazole and risperidone were the first- and second-line medication for tic disorders, respectively. Agonists of α-2 adrenergic receptors were seldom prescribed. Fluvoxamine was the first-line medication for comorbid obsessive-compulsive disorder, and atomoxetine for comorbid attention deficit/hyperactivity disorder. CONCLUSIONS: This study will help Japanese physicians choose medications for tic disorders more judiciously and will improve the quality of tic pharmacotherapy in Japan.


Assuntos
Transtornos de Tique/tratamento farmacológico , Transtornos de Tique/epidemiologia , Adulto , Idoso , Aripiprazol/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Comorbidade , Consenso , Tratamento Farmacológico/métodos , Prova Pericial , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Médicos , Risperidona/uso terapêutico , Inquéritos e Questionários , Tiques/tratamento farmacológico , Tiques/etiologia , Síndrome de Tourette/tratamento farmacológico , Síndrome de Tourette/epidemiologia
19.
J Affect Disord ; 246: 861-866, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30795492

RESUMO

BACKGROUND: Risperidone, an atypical antipsychotic medication, is recommended as a first line treatment for acute mania in patients with bipolar disorder I (BD I). It is unknown if continuing treatment with risperidone adjunct to lithium or valproate after remission of the manic episode offers additional benefit in prevention of mood episode relapse. METHODS: A post-hoc subgroup analysis was conducted using data from a 52-week, double-blind, placebo controlled trial involving 93 patients treated with oral risperidone adjunct to mood stabilizer, randomized to arms discontinuing risperidone at entry ("0-week arm"), 24 weeks after entry ("24-week arm") or continuing risperidone ("52-week arm"). Time to any episode, manic episode, and depressive episode was compared between arms using Cox regression models. RESULTS: Time to any mood episode was longer in the 24-week arm versus the 0-week arm (HR: 0.57, 95% CI: 0.31-1.05, P = 0.07) and shorter in the 52-week arm versus 24-week arm (HR: 1.85, 95% CI: 1.00-3.41, P = 0.05), though these results were not significant. Time to relapse into manic episode was significantly longer in the 24-week arm versus 0-week arm (HR: 0.14, 95% CI: 0.03, 0.65, P = 0.01). No other significant differences were observed between arms. LIMITATIONS: The sample size was modest, as the original dataset was powered to study optimal duration for two atypical antipsychotics. CONCLUSIONS: Adjunctive risperidone treatment was observed to reduce the risk of manic episodes during the first 24 weeks, but not after 24 weeks. Treatment did not appear to reduce the risk of depressive episodes.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/prevenção & controle , Lítio/uso terapêutico , Risperidona/uso terapêutico , Prevenção Secundária/métodos , Ácido Valproico/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Transtorno Bipolar/tratamento farmacológico , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
20.
Expert Opin Pharmacother ; 20(5): 571-583, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30702354

RESUMO

INTRODUCTION: Conduct disorder (CD) is a common mental health disorder of childhood and adolescence. CD's complexity, with its heterogenous clinical manifestations and overlapping comorbidities makes the application of evidence-based management approaches challenging. This article aims to combine a systematic review of the available literature, with a consensus opinion from both child and adolescent psychiatrists and developmental pediatricians on the clinical and pharmacological management of children and adolescents with conduct disorder (CD). AREAS COVERED: The authors review the CD population and provide a systematic review and meta-analysis of the effectiveness and safety of pharmacotherapies using preferred reporting items for systematic review and meta-analysis (PRISMA) and strength of evidence recommendation taxonomy (SORT) guidelines. The authors then provide an expert clinical opinion for the use of different pharmacotherapies to address aggressive and disruptive behavior in children. EXPERT OPINION: Atypical antipsychotics (e.g. risperidone) demonstrate evidence for efficacy in CD. Other pharmacotherapies (e.g. mood stabilizers, anticonvulsants, psychostimulants and selective norepinephrine reuptake inhibitors) have a low level of evidence for CD alone, however, can sometimes be effective in managing the symptoms of CD when other psychiatric disorders are also present.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno da Conduta/tratamento farmacológico , Adolescente , Agressão/efeitos dos fármacos , Anticonvulsivantes/uso terapêutico , Antimaníacos/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Humanos , Risperidona/uso terapêutico
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