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2.
Medicine (Baltimore) ; 99(42): e22823, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080761

RESUMO

INTRODUCTION/RATIONALE: Multiple sclerosis (MS) is associated with a higher prevalence of mood and psychiatric disorders, such as bipolar disorder (BD). While mania is most often associated with BD, MS can also induce manic symptoms. However, it is crucial to distinguish which condition is causing mania since medical management is different based on its etiology. Herein, we report a case of a manic episode in a middle-aged female with a prolonged history of BD who received a recent diagnosis of MS 1 year ago. PATIENT CONCERNS: A 56-year-old female presented with an episode of mania and psychosis while receiving a phenobarbital taper for chronic lorazepam use. She had a prolonged history of bipolar type 1 disorder and depression. She showed optic neuritis and was diagnosed with MS a year prior. DIAGNOSES: The patient was diagnosed with BD-induced mania based on the absence of increased demyelination compared to previous MRI and lack of new focal or lateralizing neurologic findings of MS. INTERVENTIONS: Lithium was given for mood stabilization and decreased dosage of prior antidepressant medication. Risperidone was given for ongoing delusions. OUTCOMES: After 8 days of hospitalization, patient's mania improved but demonstrated atypical features and ongoing delusions. She was discharged at her request to continue treatment in an outpatient setting. CONCLUSION/LESSON: In BD patients with an episode of mania, MS should be included in the differential, since both conditions can cause manic symptoms. The origin of mania should be delineated through a detailed neurological exam, neuroimaging, and thorough patient-family psychiatric history for appropriate clinical treatment.


Assuntos
Transtorno Bipolar/psicologia , Esclerose Múltipla/psicologia , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Pessoa de Meia-Idade , Risperidona/uso terapêutico
3.
Psychiatry Res ; 292: 113321, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32738553

RESUMO

Nowadays, adults with autism spectrum disorder (ASD) experience several comorbidities whose treatment implies a wide range of psychotropic prescriptions. This study aimed to evaluate medication-related safety, drug-drug interactions, and psychotropics prescription trends. We conducted an observational and multicentric pharmacovigilance study in subjects with ASD and Intellectual disability (ID, n = 83). Clinical information (diagnoses, ongoing medications, comorbidities [multimorbidity ≥ 4 chronic health conditions]) and psychotropic prescriptions (polypharmacy ≥ 4 chronic drugs, daily drug doses, co-prescription) were registered. Ethical approval for this study was obtained. Participants (30±10 years old, 86% men, BMI 27±6 kg/m2) displayed 37% multimorbidity (mean of 3, IQR 2-4), and 57% polypharmacy (13% out of dose recommended range). Most drugs prescribed were psychotropic risperidone which is related to nervous system comorbidities (18% epilepsy, 16% insomnia, and 14% psychotic agitations). Risperidone and quetiapine were co-prescribed in 60% of the cases without any monitoring adverse event routine. The rates of multimorbidity and polypharmacy, among our young adults with ASD and ID, are concerning. Data suggest the need to develop a pharmacovigilance monitoring system to evaluate prescription accuracy, long-term safety of ongoing medications, and the fixed doses in this autistic population with associated ID.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/epidemiologia , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/epidemiologia , Polimedicação , Psicotrópicos/uso terapêutico , Adulto , Estudos de Coortes , Comorbidade , Feminino , Humanos , Masculino , Multimorbidade , Farmacovigilância , Fumarato de Quetiapina/uso terapêutico , Risperidona/uso terapêutico , Adulto Jovem
4.
Nord J Psychiatry ; 74(8): 594-601, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32496921

RESUMO

Introduction: Cognitive impairment is a core feature of schizophrenia. The effects of atypical antipsychotics on the cognitive functions of patients with first-episode schizophrenia have not been comprehensively investigated so far. This study aims to compare neurocognitive effects of risperidone, olanzapine, and aripiprazole for first-episode schizophrenia.Methods: The study was a multicenter, randomized, open-label clinical trial. 546 patients were randomly divided into three medication groups, and followed up for 1 year. Cognitive performance was evaluated with a neuropsychological test battery. The Clinical trials.gov ID of the study is NCT01057849.Results: At 6 months, treatment resulted in significant improvements in all three groups in most cognitive domains except verbal learning and memory. At 12 months, three treatment groups had further improvements in three cognitive domains, but visual learning and memory performance dropped back to baseline.Conclusion: All three atypical antipsychotics tested in the study can potentially improve cognitive performance in first-episode schizophrenia, but no significant difference in the degree of improvement was found between drugs.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Humanos , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
5.
J Clin Psychiatry ; 81(4)2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32558403

RESUMO

People with bipolar I disorder experience an illness course marked by potentially disastrous manic episodes, disabling depressive episodes, and functional impairment. A frequent obstacle to wellness in these individuals is nonadherence to treatment. Long-acting injectable (LAI) antipsychotics have the potential to address nonadherence and thereby increase patients' chances at sustained recovery and normal psychosocial functioning. LAI formulations of 2 second-generation antipsychotics-aripiprazole monohydrate and risperidone-have received approval from the US Food and Drug Administration as monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adult patients. In a recent roundtable meeting, a panel of 4 experts discussed the use of these medications in bipolar I disorder. This Academic Highlights summarizes their discussion, which included the impact of functional impairment, the potential benefits of employing an LAI antipsychotic at earlier stages of bipolar illness, and the characteristics of patients who may be good candidates for treatment with an LAI antipsychotic.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Seleção de Pacientes , Risperidona/uso terapêutico , Aripiprazol/administração & dosagem , Análise Custo-Benefício , Preparações de Ação Retardada/uso terapêutico , Humanos , Injeções , Injeções Intramusculares , Adesão à Medicação , Guias de Prática Clínica como Assunto , Risperidona/administração & dosagem
6.
BMC Psychiatry ; 20(1): 199, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370778

RESUMO

BACKGROUND: Patients with a diagnosis of schizophrenia are at an increased risk for developing metabolic syndrome, which is associated with greater cardiovascular morbidity and mortality. Treatment with some commonly used antipsychotic medications may increase the risk of developing metabolic syndrome. The aim of the study was to evaluate the safety of lurasidone in patients who continued lurasidone or switched from risperidone to lurasidone. A secondary aim was assessment of the effect of long-term lurasidone on the Positive and Negative Syndrome Scale (PANSS). METHODS: The treatment sample in the current study consisted of clinically stable patients with schizophrenia (N = 223) who had completed a 12-month, double-blind study of lurasidone vs. risperidone. In the current extension study, all patients received 6 months of open-label treatment with lurasidone, either continuing lurasidone assigned during the preceding double-blind trial, or switching from double-blind risperidone to lurasidone. Safety and tolerability parameters included body weight, prolactin, and metabolic laboratory tests. RESULTS: Six months of OL treatment with lurasidone was generally well-tolerated, with a low incidence of parkinsonism (4.5%) and akathisia (3.1%). Overall, few adverse events were rated as severe (4.9%), and discontinuation due to an adverse event was low in the lurasidone continuation vs. risperidone switch groups (3.7% vs. 6.9%). In the lurasidone continuation versus risperidone switch groups, change from OL baseline to 6-month endpoint (observed case) was observed in mean body weight (- 0.6 vs. -2.6 kg), median total cholesterol (- 4.0 vs. + 4.5 mg/dL), triglycerides (- 4.5 vs. -5.5 mg/dL), glucose (0.0 vs. -3.0 mg/dL) and prolactin (males, + 0.15 vs. -11.2 ng/mL; females, + 1.3 vs. -30.8 ng/mL). Improvement in PANSS total score was maintained, from OL baseline to endpoint in the continuation vs. switch groups (+ 1.0 vs. -1.0; OC). CONCLUSIONS: In this 6-month extension study, lurasidone treatment was generally well-tolerated and associated with minimal effects on weight, metabolic parameters, and prolactin levels. Patients who switched from risperidone to lurasidone experienced reductions in weight, metabolic parameters and prolactin levels commensurate with increases in these safety parameters experienced during the previous 12 months of treatment with risperidone. TRIAL REGISTRATION: ClinicalTrials.gov NCT00641745 (Date of Registration: March 24, 2008).


Assuntos
Cloridrato de Lurasidona/administração & dosagem , Cloridrato de Lurasidona/uso terapêutico , Síndrome Metabólica/induzido quimicamente , Risperidona/administração & dosagem , Risperidona/uso terapêutico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Fatores de Tempo , Resultado do Tratamento
8.
J Clin Psychiatry ; 81(3)2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32237292

RESUMO

OBJECTIVE: To compare longitudinal metabolic effects of 7 antipsychotics, including body mass index (BMI), waist circumference (WC), blood pressure (BP), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); to investigate risk factors for metabolic syndrome (MetS); and to make recommendations on frequency and timing of monitoring metabolic measurements. METHODS: This randomized, open-label, pharmacologic trial was conducted among patients with schizophrenia (DSM-IV) in 32 hospitals across China. Patients were randomly assigned to 7 groups and assessed at baseline, 2, 4, and 6 weeks. Linear mixed-effect models were used to assess changes of metabolic measures over time. Multivariable logistic regression analysis was performed to investigate the risk factors for MetS. RESULTS: In total, 2,550 (718 drug-naïve) of 2,774 patients finished the study between July 6, 2010, and November 30, 2011. We found significant (P < .05) changes for BMI, WC, TG, and LDL-C, with TG and LDL-C reaching a plateau. Interactions between baseline metabolic condition and changes over time were observed for BMI (χ² = 43.11, P < .001), WC (χ² = 36.34, P < .001), systolic BP (χ² = 11.92, P = .002), glucose (χ² = 6.09, P = .01), and TG (χ² = 6.01, P = .01). Antipsychotics generally had greater adverse effects on patients who were initially screened as metabolically normal. After controlling for other associated factors, we found that antipsychotics resulted in differing risk for incident MetS, with a similar pattern to findings in other populations: olanzapine (odds ratio [OR] = 3.36, P < .001) > quetiapine (OR = 3.29, P < .001) > perphenazine (OR = 2.73, P = .007) > risperidone (OR = 2.21, P = .02) > aripiprazole (OR = 1.74, P = .15) ≈ haloperidol (OR = 1.75, P = .22) ≈ ziprasidone (OR = 1, reference). CONCLUSIONS: Metabolic traits should be monitored frequently in early stages of antipsychotic treatment due to rapid and substantial changes. Clinicians should not assume low risk for patients with normal metabolic parameters at baseline. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000934.


Assuntos
Antipsicóticos/efeitos adversos , Síndrome Metabólica/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Aripiprazol/efeitos adversos , Aripiprazol/uso terapêutico , Glicemia/efeitos dos fármacos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/uso terapêutico , Fatores de Risco , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Esquizofrenia/metabolismo , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Triglicerídeos/sangue
10.
Medicine (Baltimore) ; 99(15): e19694, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282724

RESUMO

BACKGROUND: To evaluate the association between risperidone use and interleukin-6 (IL-6) levels by conducting a meta-analysis of controlled before-and-after studies. METHODS: Studies were identified through a systematic search of PubMed and Embase. The mean and standardized differences were extracted to calculate the standardized mean differences. IL-6 levels were compared in patients with schizophrenia before and after risperidone treatment. RESULTS: Ten studies were included in the final meta-analysis. The primary findings from our study suggest that there was a significant decrease in serum IL-6 levels after risperidone treatment (P = .021). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated that the results were stable, and no publication bias was observed. CONCLUSIONS: The present meta-analysis provides evidence that risperidone can significantly reduce IL-6 levels in schizophrenia. IL-6 is a potential biomarker of the pathophysiology and clinical processes of schizophrenia.


Assuntos
Antipsicóticos/uso terapêutico , Interleucina-6/sangue , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia , Sensibilidade e Especificidade
11.
Clin Neuropharmacol ; 43(2): 39-45, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168067

RESUMO

OBJECTIVES: This study aimed to evaluate efficacy and safety of prednisolone as an adjunctive treatment to risperidone, in children with regressive autism spectrum disorder (ASD). METHODS: The current 12-week, randomized, single-blinded, placebo-controlled trial recruited 37 patients with regressive ASD. The participants were allocated to receive either 1 mg/kg per day prednisolone or matched placebo in addition to risperidone. The Aberrant Behavior Checklist-Community Edition (ABC-C) scale and Childhood Autism Rating Scale (CARS) were used to measure behavioral outcomes at weeks 0, 4, 8, and 12 of the study course. The primary outcome was the change in ABC-irritability subscale score, whereas the secondary outcomes were the change in scores of other ABC-C subscales, in CARS score, and in the level of inflammatory biomarkers. RESULTS: Twenty-six patients completed the 12 weeks of study period. Repeated-measures analysis demonstrated significant effect for time-treatment interaction in the CARS (F (1, 2.23) = 13.22, P < 0.001), as well as 4 subscales of the ABC-C including: irritability (F (1, 2.12) = 3.84, P = 0.026), hyperactivity (F (1, 2.09) = 3.56, P = 0.039), lethargy (F (1, 2.18) = 31.50, P < 0.001), and stereotypy (F (1, 1.89) = 4.04, P = 0.026). However, no significant time-treatment interaction was identified for inappropriate speech subscale (F (1, 2.03) = 1.71, P = 0.191). In addition, inflammatory biomarkers were significantly decreased after 3 months of prednisolone add-on. No significant adverse event was detected during the trial. CONCLUSIONS: Prednisolone, as an add-on to risperidone, could remarkably improve core features in children with regressive ASD.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno do Espectro Autista/tratamento farmacológico , Prednisolona/uso terapêutico , Risperidona/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
12.
PLoS One ; 15(2): e0228648, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017792

RESUMO

BACKGROUND: Antipsychotic medication, stress, gender, and age are factors that influence prolactin levels in patients with psychosis. The aim of the study was to investigate the level of prolactin response to antipsychotic treatment in acute patients, taking into account the total duration of psychosis. METHODS AND FINDINGS: The study was conducted on 170 acute patients with schizophrenia spectrum disorders and bipolar disorder. Subjects were divided into three subgroups according to the duration of the psychosis (less than 5 years, between 5 and 10 years and more than 10 years of disorder duration). The initial prolactin response under antipsychotic treatment was measured, while the severity of the psychiatric symptoms was assessed with the BPRS (Brief Psychiatric Rating Scale). Hyperprolactinemia was found in 120 (70.6%) patients, amongst which 80 (66.7%) were females and 40 (33.3%) were males. The average increase in prolactinemia was 2.46 times the maximum value in women, and 1.59 times in men. Gender (ß = 0.27, p<0.0001), type of antipsychotic medication according to potency of inducing hyperprolactinemia (ß = -0.23, p<0.003), and the duration of psychosis over 10 years (ß = -0.15, p = 0.04) significantly predicted prolactin levels, when age, diagnosis, antipsychotic category (conventional/atypical/combinations of antipsychotics), and BPRS total scores were controlled for. CONCLUSIONS AND RELEVANCE: Prolactin levels in patients treated with antipsychotic medication appeared to depend on patients' gender, on the type of antipsychotic medication according to potency of inducing hyperprolactinemia, and on the duration of the psychosis. An increase in prolactin levels was associated with female gender, while the use of prolactin sparing antipsychotics and a duration of psychosis over 10 years were associated with lower prolactin levels.


Assuntos
Antipsicóticos/farmacologia , Hiperprolactinemia/etiologia , Prolactina/efeitos dos fármacos , Transtornos Psicóticos/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Feminino , Humanos , Hiperprolactinemia/diagnóstico , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Prolactina/sangue , Transtornos Psicóticos/complicações , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Fatores Sexuais , Fatores de Tempo
13.
Clin Ther ; 42(1): 77-93, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31928831

RESUMO

PURPOSE: Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration-approved OAAs in a real-world setting. METHODS: This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up. FINDINGS: The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488-16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05-2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04-2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779-35,353] vs $23,851 [18,907-28,795]; medical, $19,343 [16,294-22,392] vs $12,013 [7488-16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694-11,795; P = 0.009) than in brexpiprazole users. IMPLICATIONS: Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.


Assuntos
Antipsicóticos/economia , Hospitalização/economia , Quinolonas/economia , Esquizofrenia/economia , Tiofenos/economia , Administração Oral , Adulto , Antipsicóticos/uso terapêutico , Aripiprazol/economia , Aripiprazol/uso terapêutico , Feminino , Custos de Cuidados de Saúde , Humanos , Cloridrato de Lurasidona/economia , Cloridrato de Lurasidona/uso terapêutico , Masculino , Medicaid/economia , Medicare/economia , Pessoa de Meia-Idade , Olanzapina/economia , Olanzapina/uso terapêutico , Palmitato de Paliperidona/economia , Palmitato de Paliperidona/uso terapêutico , Piperazinas/economia , Piperazinas/uso terapêutico , Fumarato de Quetiapina/economia , Fumarato de Quetiapina/uso terapêutico , Quinolonas/uso terapêutico , Risperidona/economia , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiazóis/economia , Tiazóis/uso terapêutico , Tiofenos/uso terapêutico , Estados Unidos
14.
J Pharmacol Exp Ther ; 373(1): 24-33, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31907305

RESUMO

Neurodevelopmental disorder with involuntary movements (Online Mendelian Inheritance in Man: 617493) is a severe, early onset neurologic condition characterized by a delay in psychomotor development, hypotonia, and hyperkinetic involuntary movements. Heterozygous de novo mutations in the GNAO1 gene cause neurodevelopmental disorder with involuntary movements. Gα o, the gene product of GNAO1, is the alpha subunit of Go, a member of the heterotrimeric Gi/o family of G proteins. Go is found abundantly throughout the brain, but the pathophysiological mechanisms linking Gα o functions to clinical manifestations of GNAO1-related disorders are still poorly understood. One of the most common mutant alleles among the GNAO1 encephalopathies is the c.626G>A or p.Arg209His (R209H) mutation. We developed heterozygous knock-in Gnao1 +/R209H mutant mice using CRISPR/Cas9 methodology to assess whether a mouse model could replicate aspects of the neurodevelopmental disorder with involuntary movements clinical pattern. Mice carrying the R209H mutation exhibited increased locomotor activity and a modest gait abnormality at 8-12 weeks. In contrast to mice carrying other mutations in Gnao1, the Gnao1 +/R209H mice did not show enhanced seizure susceptibility. Levels of protein expression in multiple brain regions were unchanged from wild-type (WT) mice, but the nucleotide exchange rate of mutant R209H Gα o was 6.2× faster than WT. The atypical neuroleptic risperidone has shown efficacy in a patient with the R209H mutation. It also alleviated the hyperlocomotion phenotype observed in our mouse model but suppressed locomotion in WT mice as well. In this study, we show that Gnao1 +/R209H mice mirror elements of the patient phenotype and respond to an approved pharmacological agent. SIGNIFICANCE STATEMENT: Children with de novo mutations in the GNAO1 gene may present with movement disorders with limited effective therapeutic options. The most common mutant variant seen in children with GNAO1-associated movement disorder is R209H. Here we show, using a novel Gnao1 +/R209H mouse, that there is a clear behavioral phenotype that is suppressed by risperidone. However, risperidone also affects wild-type mouse activity, so its effects are not selective for the GNAO1-associated movement disorder.


Assuntos
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Variação Genética/genética , Transtornos dos Movimentos/tratamento farmacológico , Transtornos dos Movimentos/genética , Risperidona/uso terapêutico , Animais , Sequência de Bases , Antagonistas de Dopamina/farmacologia , Antagonistas de Dopamina/uso terapêutico , Feminino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Risperidona/farmacologia
15.
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
16.
Artigo em Português | Coleciona SUS, CONASS, SES-GO | ID: biblio-1118711

RESUMO

Tecnologia: Palmitato de Paliperidona (PP) é um antipsicótico injetáveis de efeito prolongado (AIEP). Indicação: Tratamento sintomático da esquizofrenia. Objetivo: Comparar a eficácia, segurança e efetividade terapêutica entre PP e outros AIEP para o tratamento de esquizofrenia em adultos. Pergunta: O PP é mais eficaz e seguro que os outros AIEP (Decanoato de Haloperidol, Enantato de Flufenazina, Decanoato de Zuclopentixol, Risperidona-IEP) para o tratamento sintomático de esquizofrenia em adultos? Métodos: Levantamento bibliográfico, com estratégias estruturadas de busca, na base de dados PUBMED. Foi feita avaliação da qualidade metodológica das revisões sistemáticas (RS), ensaios clínicos randomizados (ECR) e dos estudos observacionais de efetividade no mundo real (EOEMR) com as ferramentas Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List e Newcastle-Ottawa Scale (NOS), respectivamente. Resultados: Foram selecionadas 3 RS, 1 ECR e 3 EOEMR. Conclusão: PP (de aplicação mensal) tem similar eficácia e segurança com a Risperidona-IEP para o tratamento de esquizofrenia, exceto que provoca menor incidência de sintomas extrapiramidais. PP e Decanoato de Haloperidol são similares na eficácia e segurança para o tratamento de esquizofrenia, inclusive no risco de sintomas extrapiramidais (discinesias tardias e parkinsonismo), exceto que PP tem menor incidência de acatisia. PP é similar aos outros AIEP nos vários desfechos de eficácia e segurança terapêutica, inclusive mortalidade


Technology: Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotics. Indication: Symptomatic treatment of schizophrenia. Objective: To compare the therapeutic efficacy, safety and effectiveness in the real world between PP and other LAI antipsychotics for the treatment of schizophrenia in adults. Question: Is PP more effective and safer than other LAI antipsychotics (Haloperidol Decanoate, Fluphenazine Enanthate, Zuclopentixol Decanoate, Risperidone-LAI), for the symptomatic treatment of schizophrenia? Methods: Bibliographic survey, with structured search strategies, in the PUBMED database. Na evaluation was made of the methodological quality of systematic reviews (SR), randomized clinical trials (RCT) and observational studies (OS) of effectiveness in the real world with Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List and Newcastle-Ottawa Scale (NOS) tools, respectively. Results: 3 SR, 1 RCT and 3 OE were included. Conclusion: PP (monthly dose presentation) has similar efficacy and safety with Risperidone-LAI for the treatment of schizophrenia, except that it causes a lower incidence of extrapyramidal symptoms. PP and Haloperidol Decanoate are similar in efficacy and safety for the treatment of schizophrenia, including the risk of extra-pyramidal symptoms (tardive dyskinesias and parkinsonism), except that PP has a lower incidence of akathisia. PP has similar outcomes of efficacy and safety to the other LAI antipsychotics, including mortality risk


Assuntos
Humanos , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Palmitato de Paliperidona/uso terapêutico , Clopentixol/uso terapêutico , Risperidona/uso terapêutico , Medicina Baseada em Evidências , Flufenazina/uso terapêutico , Haloperidol/uso terapêutico
17.
Int Immunopharmacol ; 79: 106093, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31863919

RESUMO

Clinical studies demonstrate alterations to immune measures in psychosis that can vary with illness stage and severity. For example, recent data show that changes to the JAK-STAT1 transcriptional signature, characteristic of an "M1" proinflammatory monocyte and macrophages phenotype, are related to illness duration. While antipsychotics have demonstrated immunomodulatory properties, their effects on this important immune signaling pathway are unknown. The primary aims of this study were to determine the effects of risperidone, a commonly prescribed antipsychotic drug, on the JAK-STAT1 transcriptional signature. Selected measures of JAK-STAT1 signature gene expression in peripheral blood mononuclear cells (PBMCs) from a clinical sample with psychosis were compared to examine differences induced by risperidone treatment. Additionally, the direct effects of risperidone on the JAK-STAT1 signature were investigated using a THP-1 human monocyte and macrophage cell model. Comparisons within the clinical sample demonstrated that the JAK-STAT1 signature was elevated in PBMCs from participants treated with risperidone who had a longer illness duration compared to untreated participants and those who were risperidone treated but had a shorter illness duration. Results of the in-vitro experiments showed a consistent potentiating effect of risperidone on expression of JAK-STAT1 signature genes in activated monocytes and monocyte-derived macrophages. Collectively these data indicate that risperidone may skew myeloid cells to a more proinflammatory phenotype, potentially contributing to increases in expression of JAK-STAT1 signature genes in participants with a longer illness duration.


Assuntos
Antipsicóticos/uso terapêutico , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Transtornos Psicóticos/tratamento farmacológico , Risperidona/uso terapêutico , Adulto , Citocinas/metabolismo , Feminino , Humanos , Janus Quinases/genética , Janus Quinases/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Células THP-1 , Células Th1/imunologia , Transcriptoma , Adulto Jovem
18.
J Dermatolog Treat ; 31(6): 602-605, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30270706

RESUMO

INTRODUCTION: The majority of patients with delusional infestation (DI) seek help from dermatologists as they consider their condition to be of cutaneous origin and deny referral to psychiatrists, with the prevalence of the condition arising. The objectives of our study were: (i) to assess whether there is a fixed delusional ideation in patients with DI, (ii) to assess the efficacy of managing such patients with combined dermatological and psychiatric treatment and (iii) to test any correlation between BABS scores and other variables. METHODS: All consecutive newly diagnosed patients with DI, from January 2014 to January 2015, seen in our specialist psychodermatology clinic were enrolled in our prospective observational study. Brown Assessment of Beliefs Scale (BABS) was used to assess the intensity of delusion. Correlation between BABS and other variables was also assessed. RESULTS: Forty-three patients were enrolled. There was a range of BABS scores pre- and post-treatment, indicative of the presence of a range of delusional ideation. A significant reduction in the BABS scores was noted post-treatment from 16.10 ± 5.53 to 11.66 ± 8.26 (p < .002). CONCLUSION: This is the first study to objectively demonstrate that delusional belief in patients with DI is not a binary phenomenon and to demonstrate an efficacious response to a combined multidisciplinary psychodermatological approach.


Assuntos
Delusões/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/uso terapêutico , Delusões/tratamento farmacológico , Delusões/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psicoterapia , Risperidona/uso terapêutico
19.
Pharmacopsychiatry ; 53(1): 21-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31390660

RESUMO

INTRODUCTION: Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia. MATERIALS AND METHODS: Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2-8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks. RESULTS: Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group. DISCUSSIONS: Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.


Assuntos
Antipsicóticos/uso terapêutico , Memantina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Doença Aguda , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Atenção/efeitos dos fármacos , Doença Crônica , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Memantina/administração & dosagem , Memantina/efeitos adversos , Memória/efeitos dos fármacos , Resolução de Problemas/efeitos dos fármacos , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Risperidona/administração & dosagem , Risperidona/efeitos adversos , Fatores Socioeconômicos , Aprendizagem Verbal/efeitos dos fármacos , Adulto Jovem
20.
Ann Pharmacother ; 54(5): 464-469, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31771334

RESUMO

Background: Risperidone dosing and safety data are limited in patients ≤2 years of age. Objective: To describe the dosing strategies, safety, and tolerability of risperidone in infants ≤2 years of age. Methods: An institutional review board-approved retrospective study was conducted in a 24-bed pediatric intensive care unit at an academic medical center in patients ≤2 years of age receiving risperidone for the management of ICU delirium. The primary outcome was mean initial daily dose of risperidone. Secondary outcomes included mean daily dose, dosing frequency, treatment duration, and adverse effects. Results: Seventeen patients who received at least 1 dose of risperidone were included in the study. The initial daily dose ranged from 0.1 to 0.25 mg (0.01-0.04 mg/kg), with a mean of 0.17 mg (0.02 mg/kg). Most patients were initiated on once-daily dosing (76.5%) versus twice-daily dosing (17.6%). More than 80% of patients required a dose increase during therapy. Median daily doses of fentanyl, morphine, ketamine, and midazolam were decreased following initiation of risperidone. No adverse events that led to discontinuation of risperidone were reported. Conclusion and Relevance: Risperidone was found to be safe and well tolerated at daily doses of risperidone of 0.1 to 0.25 mg in 1 or 2 doses per day in patients ≤2 years old for the management of ICU delirium. To our knowledge, these results provide the largest cohort describing dosing recommendations specific for risperidone in this age group. Further investigation on the effect of antipsychotic administration on other sedation and analgesic regimens is necessary.


Assuntos
Antipsicóticos/administração & dosagem , Cuidados Críticos/métodos , Delírio/tratamento farmacológico , Risperidona/administração & dosagem , Adolescente , Fatores Etários , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos Retrospectivos , Risperidona/efeitos adversos , Risperidona/uso terapêutico
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