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2.
Medicine (Baltimore) ; 99(33): e21639, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872027

RESUMO

INTRODUCTION: Anabolic steroids are commonly used by athletes, body builders, and young adults to improve muscle strength. Deleterious effects of anabolic steroids on physical health are well-established. Psychiatric aspects are of particular importance and include psychosis, delirium, mania, depression, and aggression. We describe the case of a young gentleman who was managed as a case of androgenic steroid induced delirium. PATIENT CONCERN: A 33-year-old gentleman presented with increased aggression, hostility, and destructive impulses. He was a regular user of testosterone propionate, testosterone cyprionate and trenbolone acetate up to 200 mg daily in injectable form. His mental status examination showed labile effect, flight of ideas and persecutory delusions. Physical examination was positive for atrophic testes. Laboratory results showed a decreased plasma testosterone level of 9.59 nmol/l (10.4-37.4 nmol/l). Sex Hormone Binding Globulin was 23.8 nmol/l (18.3-54.1 nmol/l) and bioavailable testosterone was 5.110 nmol/l (4.36-14.30 nmol/l). DIAGNOSIS: He was diagnosed as a case of anabolic steroids induced delirium. INTERVENTIONS AND OUTCOME: Patient was treated with regular haloperidol and quetiapine after which his sensorium, speech and behavior improved. He was discharged on haloperidol 7.5 mg and quetiapine 700 mg daily. CONCLUSION: The purpose of this case report is to emphasize on the neuropsychiatric effects and management of anabolic steroids manifested by delirium, increased aggression, hostility, and destructive impulses.


Assuntos
Delírio/induzido quimicamente , Congêneres da Testosterona/efeitos adversos , Adulto , Agressão/efeitos dos fármacos , Antipsicóticos/administração & dosagem , Delírio/tratamento farmacológico , Haloperidol/administração & dosagem , Humanos , Masculino , Fumarato de Quetiapina/administração & dosagem , Testosterona/sangue , Congêneres da Testosterona/administração & dosagem
3.
Psiquiatr. biol. (Internet) ; 27(2): 74-77, mayo-ago. 2020.
Artigo em Espanhol | IBECS | ID: ibc-193251

RESUMO

El síndrome de Usher (SU) es una enfermedad caracterizada por una alteración importante de la audición y de la visión. Se trata de la causa hereditaria más frecuente de presentación de sordera junto con ceguera, pudiendo afectar también al equilibrio. Se ha observado la asociación con diversas enfermedades mentales, destacando entre ellas la esquizofrenia. Presentamos el caso clínico de un paciente de 50 años de edad con SU tipo II, sin antecedentes personales de enfermedad psiquiátrica, que presenta desorganización conductual, alteraciones sensoperceptivas y del contenido y forma del pensamiento. La aparición de psicosis está descrita con frecuencia en estos pacientes, siendo su identificación precoz, esencial para un abordaje integral


Usher syndrome is an illness mainly characterized by a significant impairment of hearing and vision. It is the most common inherited cause of deafness along with blindness, and it may also affect balance. An association with various mental disorders has been observed, particularly with schizophrenia. We are reporting the case of a 50-year-old patient with Usher syndrome type II, without previous history of psychiatric disorder, who presents with behavioural disorganization, sensory-perceptual disturbances and alterations in form and content of thought. Psychosis is often described in patients Usher syndrome, and its early detection is essential to a comprehensive approach


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/complicações , Síndromes de Usher/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Palmitato de Paliperidona/administração & dosagem , Antipsicóticos/administração & dosagem
4.
Lancet Psychiatry ; 7(9): 749-761, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32828165

RESUMO

BACKGROUND: Most individuals with schizophrenia-spectrum disorders have relapses, which increase the risk of morbidity and mortality. Because non-adherence to antipsychotic maintenance treatment could affect more than half of individuals with schizophrenia-spectrum disorders, psychosis relapse can often be confounded by unnoticed treatment interruption. Research of relapse during confirmed antipsychotic exposure has basic clinical and neurobiological implications, but data are scarce. We aimed to generate reliable estimates of incidence and predictors of relapse during assured antipsychotic treatment. METHODS: We did a systematic review and individual participant data (IPD) meta-analysis of clinical trials of long-acting injectable antipsychotics (LAIs) for psychosis relapse-prevention, following IPD-PRISMA guidelines. Datasets were identified by searching relevant repositories from inception to Aug 1, 2019. Each LAI group was reanalysed as a separate cohort, further identifying subcohorts of individuals with and without prospectively determined symptom remission (PSR). Summary incidence rate of relapse, incidence rate ratios (IRRs) of relapse between individuals with and without PSR, hazard ratios (HRs) of covariates on risk of relapse, and standardised mean difference (SMDs) in changes in overall functioning associated with relapse were generated by pooling results from the harmonised reanalysis of each study. This study is registered with PROSPERO, number CRD42019137439. FINDINGS: 19 treatment cohorts consisting of 5130 individuals (2938 with PSR, 2192 without PSR), with 3959·53 observed participant-years, were meta-analysed. Pooled incidence of relapse was 22·97 per 100 participant-years (14·76 per 100 participant-years for the PSR subcohort, 31·51 per 100 participant-years for the non-PSR subcohort), with an IRR of 0·19 (95% CI 0·07 to 0·54). Relapse was associated with functional decline (overall SMD -0·76, 95% CI -1·14 to -0·37; PSR SMD -0·52, 95% CI -0·80 to -0·21; non-PSR SMD -0·72, 95% CI -1·18 to -0·26). The strongest predictor of relapse was tardive dyskinesia at treatment onset (HR 2·39, 95% CI 1·05 to 5·42). INTERPRETATION: Despite the established efficacy of antipsychotics in preventing relapse, these data indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Tardive dyskinesia in particular might have pathophysiological implications for relapse. FUNDING: Northwell Health.


Assuntos
Antipsicóticos/administração & dosagem , Transtornos Psicóticos/prevenção & controle , Esquizofrenia/tratamento farmacológico , Ensaios Clínicos como Assunto , Preparações de Ação Retardada , Humanos , Injeções , Esquizofrenia/prevenção & controle , Prevenção Secundária
5.
Expert Opin Pharmacother ; 21(15): 1793-1798, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32735148

RESUMO

INTRODUCTION: Schizophrenia has a prevalence of approximately 1% in the general population, with 15.2 per 100,000 persons affected. Iloperidone is a second-generation antipsychotic drug approved for the treatment of schizophrenia in adults. It acts primarily by D2/5HT2a receptor antagonism, with greater affinity for the 5HT2a receptor than for the D2 receptor. AREAS COVERED: This article discusses iloperidone and aims to provide useful information for clinicians to determine which circumstances would best suit the use of iloperidone to treat schizophrenic patients. In this review, the authors briefly discuss schizophrenia and its treatment, before they discuss properties of iloperidone, its indications, approval process, and adverse effects. Finally, the authors review the specific strengths and weaknesses of the medication. EXPERT OPINION: Iloperidone would be an attractive option in patients who are particularly prone to EPS, or who are showing prominent negative symptoms, as well as cognitive deficits. Its availability only in an oral formulation makes it a better option for patients with good medication adherence, and though it could be useful in patients prone to weight gain or hepatic dysfunction on other second generation antipsychotics, it should be used with caution in patients prone to side effects related to alpha adrenergic blockade.


Assuntos
Antipsicóticos/uso terapêutico , Isoxazóis/uso terapêutico , Piperidinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Humanos , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Receptor 5-HT2A de Serotonina/metabolismo , Receptores de Dopamina D2/metabolismo , Esquizofrenia/metabolismo , Ganho de Peso/efeitos dos fármacos
6.
Med Care ; 58(9): 763-769, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32732784

RESUMO

BACKGROUND: Increases in prescription drug cost-sharing may decrease adherence to treatment among persons with schizophrenia and lead to discontinuation of use and an increased risk of hospitalization. OBJECTIVE: The objective of this study was to investigate the impact of new deductible and increased drug copayments implemented on antipsychotic and other drug purchases and on rates of hospitalizations and primary care contacts among persons with schizophrenia in Finland. RESEARCH DESIGN: Interrupted time series analysis. SUBJECTS: All persons with schizophrenia in Finland who were alive at the beginning of 2015 (N=41,017). MEASURES: We measured the rates of antipsychotic, other psychotropic and cardiometabolic drug purchasers, hospitalizations, and primary care contacts during 2015 and 2016 with data collected from several nationwide health care registers. RESULTS: During 2016, the proportion of antipsychotic purchasers decreased by -0.26 percentage points per month [95% confidence interval (CI): -0.47 to -0.05] compared with 2015. The trend of other psychotropic purchasers decreased to -0.13 percentage points per month in 2016 (95% CI: -0.22 to -0.04) compared with 2015 and cardiometabolic drug purchases to -0.17 percentage points per month (95% CI: -0.29 to -0.05) compared with 2015. The decreasing trend of psychiatric hospitalizations in 2015 halted in 2016. There were no other significant differences in health care utilization. CONCLUSIONS: In our nationwide time-series analysis, we observed decreases in the slopes of antipsychotic and other drug purchases of persons with schizophrenia after prescription drug cost-sharing increase implementation on January 1, 2016. Policymakers need to be aware of the unintended consequences of increasing cost-sharing among people with severe mental disorders.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/economia , Custo Compartilhado de Seguro/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Antipsicóticos/uso terapêutico , Feminino , Finlândia , Hospitalização/estatística & dados numéricos , Humanos , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Psicotrópicos/administração & dosagem , Psicotrópicos/economia
8.
J Clin Psychiatry ; 81(4)2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32609958

RESUMO

The goals of schizophrenia treatment are to control symptoms, prevent relapse, and improve functioning and quality of life. For many patients, these goals are not being met. This report highlights information provided by experts on the reasons for, impact of, and means to reduce relapse in patients with schizophrenia; on patient-centered and patient-reported assessment; on the benefits and risks of medication options, including long-acting injectable (LAI) antipsychotics; and on psychosocial interventions that may improve adherence and help prevent relapse in individuals living with schizophrenia. Modifiable risk factors for poor outcomes in patients with schizophrenia include longer duration of untreated illness, comorbid substance abuse, early nonresponse to an antipsychotic, and the number of relapses that are related to nonadherence. Recommendations include 1) adopting a patient-centered approach that incorporates the use of patient-reported outcome measures; 2) selecting medications based on a balanced risk-benefit assessment, including a focus on addressing symptoms for which the agents were superior to placebo and/or active controls; 3) considering LAIs as an alternative to oral medications, as they offer benefits such as reliable drug delivery, uncovering nonadherence and pseudo-resistance, and reduced relapse risk and mortality; and 4) implementing psychosocial interventions that have been proven to be effective in improving adherence and overall outcomes.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Terapia Combinada/métodos , Preparações de Ação Retardada/uso terapêutico , Humanos , Injeções Intramusculares , Adesão à Medicação , Psicoterapia , Esquizofrenia/terapia , Prevenção Secundária
9.
J Clin Psychiatry ; 81(4)2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32609960

RESUMO

OBJECTIVE: INP105 is a drug-device combination of olanzapine and technology that delivers a powder formulation of olanzapine to the vascular-rich upper nasal space. This study evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of single ascending doses of INP105, olanzapine intramuscular (OLZ IM), and olanzapine oral disintegrating tablet (OLZ ODT). METHODS: This was a phase 1, active and double-blind placebo comparator-controlled, ascending-dose, 2-period, incomplete-block, 1-way crossover study in 40 healthy subjects, randomized to single doses of OLZ IM (5 or 10 mg) or OLZ ODT (10 mg) in Period 1 and then 1 of 3 doses (5 mg, 10 mg, or 15 mg) of INP105 or placebo in Period 2 between July and October 2018. Sedation and attention were evaluated by visual analog scale (VAS), the Agitation/Calmness Evaluation Scale (ACES), and the Digit Symbol Substitution Test (DSST). RESULTS: At equivalent doses, INP105 provided similar area under the drug concentration-time curve (AUC) from time 0 to the last measurable concentration, AUC from time 0 to infinity, and maximum observed concentration (Cmax) as OLZ IM and greater Cmax than but similar AUCs to OLZ ODT. Median time to maximum concentration was less for INP105 (15, 10, and 9.5 min for 5 mg, 10 mg, and 15 mg, respectively) than for OLZ IM (20 and 15 min for 5 mg and 10 mg, respectively) or OLZ ODT (120 min). Effects as measured with the VAS, ACES, and DSST with INP105 5 mg were comparable to those with OLZ IM 5 mg, with earlier onset for INP105 10 mg and 15 mg and greater effects than placebo and OLZ ODT. The incidence of treatment-emergent adverse events with INP105 5 mg, 10 mg, and 15 mg was 80%, 66.7%, and 75%, respectively, compared to 90% and 100% for OLZ IM 5 mg and 10 mg, respectively, and 83.3% for OLZ ODT; most common were dizziness, hypotension, and orthostatic symptoms. CONCLUSIONS: INP105 has rapid absorption and pharmacodynamic effects and may represent an effective, convenient, noninvasive, and well-tolerated alternative for treating acutely agitated patients by self- or caregiver administration in the home, community, or hospital environments. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03624322.


Assuntos
Olanzapina/efeitos adversos , Olanzapina/farmacocinética , Administração Intranasal , Administração Oral , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Antipsicóticos/farmacologia , Atenção/efeitos dos fármacos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Hipnóticos e Sedativos/farmacologia , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Olanzapina/administração & dosagem , Olanzapina/farmacologia , Adulto Jovem
10.
Encephale ; 46(3S): S126-S127, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32475694
12.
Eur J Endocrinol ; 183(3): C11-C13, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508315

RESUMO

There can potentially be a number of clinical interactions that could adversely affect patient outcomes in a patient with a prolactinoma and psychiatric disease that might require antipsychotic and dopamine agonist treatment. Dopamine agonists stimulate the dopamine D2 receptor, resulting in a decrease in prolactin (PRL) levels and in prolactinoma size but action on dopamine receptors in the meso-limbic system may rarely cause psychosis and more commonly cause impulse control disorders. The psychiatric benefits of antipsychotic agents involve blocking the D2 and other dopamine receptors but this blockade often also causes hyperprolactinemia. In patients with macroprolactinomas and psychosis, observation, estrogen/progestin replacement, and surgery can be considered in addition to dopamine agonists. In those who require dopamine agonists for PRL and tumor size control, the introduction of antipsychotics may blunt this effect, so that higher doses of the dopamine agonists may be needed. Alternatively, antipsychotics that have less of a blocking effect at the D2 receptor, such as aripiprazole, can be tried, if appropriate. For patients already on antipsychotic drugs who are found to have a macroprolactinoma for which dopamine agonists are required, dopamine agonists can be initiated at low dose and the dose escalated slowly. However, such patients require careful monitoring of psychiatric status to avoid the rare complication of exacerbation of the underlying psychosis. Again, if appropriate, use of antipsychotics that have less of a blocking effect at the D2 receptor may allow lower doses of dopamine agonists to be used in this situation.


Assuntos
Antipsicóticos/efeitos adversos , Agonistas de Dopamina/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Antipsicóticos/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Interações Medicamentosas , Humanos , Hiperprolactinemia/induzido quimicamente , Transtornos Mentais/induzido quimicamente , Prolactina/metabolismo , Prolactinoma/patologia , Receptores de Dopamina D2/efeitos dos fármacos
13.
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
14.
BMC Psychiatry ; 20(1): 290, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517724

RESUMO

BACKGROUND: Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible pharmacologic mechanisms supporting or refuting the propensity of clozapine to induce hypothermia, as well as risk factors for clozapine-induced hypothermia, and a comparison to clozapine-induced hyperthermia. CASE PRESENTATION: A 70 year-old African American female with treatment-refractory schizoaffective disorder developed hypothermia with a nadir temperature of 89 °F (31.7 °C) after 7 days on clozapine, on a total dose of 50 mg twice daily. Accompanying symptoms included bradycardia, hypotension, QTc prolongation, tachypnea, hypoxemia, and an absence of shivering. The patient was transferred to the ICU, and rewarmed within 10 h with the discontinuation of her clozapine, ziprasidone, and carvedilol. Broad spectrum antibiotics were initiated, but discontinued shortly after, as the patient had no leukocytosis, and blood cultures were negative. DISCUSSION: While hypoglycemia, hypothyroidism, sepsis, and stroke were effectively ruled out, alternative drug-disease (including chronic kidney disease), and drug-drug interactions were considered possible contributing features. Benzodiazepines, valproic acid, ziprasidone, and the numerous antihypertensive agents the patient was taking were considered as either primary or compounding factors for hypothermia. After exclusion or inclusion of these alternative causes, we calculated a score of 4 (possible) for clozapine-induced hypothermia on the Naranjo Scale. CONCLUSIONS: Clozapine-induced hypothermia may occur more commonly than clinicians believe. Practitioners should be cognizant of this potentially fatal phenomenon, and monitor for temperature dysregulations while on clozapine, especially during initial titration, in those with multiple comorbid factors, and on additional medications that may contribute to hypothermia.


Assuntos
Antipsicóticos/efeitos adversos , Regulação da Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Clozapina/administração & dosagem , Clozapina/efeitos adversos , Hipotermia/induzido quimicamente , Idoso , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Pacientes Internados
15.
J Clin Psychiatry ; 81(3)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32412702

RESUMO

Individuals with schizophrenia can achieve the ultimate goal of treatment-recovery. However, patients are often nonadherent to prescribed medication regimens, leading to relapses and significantly decreasing their chances of ever reaching this goal. By implementing patient-centered assessment and evidence-based pharmacologic and psychosocial interventions, such as LAI antipsychotics, cognitive-behavioral therapy, and motivational interviewing, clinicians can improve medication adherence and enhance the potential for functional recovery.


Assuntos
Antipsicóticos/uso terapêutico , Tomada de Decisão Compartilhada , Assistência Centrada no Paciente , Esquizofrenia/terapia , Antipsicóticos/administração & dosagem , Terapia Cognitivo-Comportamental , Terapia Combinada , Preparações de Ação Retardada , Humanos , Entrevista Motivacional , Medidas de Resultados Relatados pelo Paciente , Assistência Centrada no Paciente/métodos , Esquizofrenia/tratamento farmacológico
18.
PLoS One ; 15(5): e0233684, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470000

RESUMO

White matter abnormalities are well-established in adult patients with psychosis. Less is known about abnormalities in the rarely occurring adolescent early onset psychosis (EOP). In particular, whether antipsychotic medication might impact white matter microstructure is not known. Using 3T diffusion weighted imaging, we investigated differences in white matter microstructure and the impact of antipsychotic medication status in medicated (n = 11) and unmedicated (n = 11) EOP patients relative to healthy controls (n = 33), aged between 12-18 years. Using Tract-based Spatial Statistics, we calculate case-control differences in scalar diffusion measures, i.e. fractional anisotropy (FA), axial diffusion (AD) and radial diffusion (RD), and investigated their association with antipsychotic medication in patients. We found significantly lower FA in the left genu of the corpus callosum, the left anterior corona radiata (ACR) and the right superior longitudinal fasciculus in EOP patients relative to healthy controls. AD values were also lower in the left ACR, largely overlapping with the FA findings. Mean FA in the left ACR was significantly associated with antipsychotic medication status (Cohen's d = 1.37, 95% CI [0.01, 2.68], p = 0.008), showing higher FA values in medicated compared to unmedicated EOP patients. The present study is the first to link antipsychotic medication status to altered regional FA in the left ACR, a region hypothesized to contribute to the etiology of psychosis. Replications are warranted to draw firm conclusions about putatively enhancing effects of antipsychotic medication on white matter microstructure in adolescent-onset psychosis.


Assuntos
Antipsicóticos/administração & dosagem , Imagem de Tensor de Difusão , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/tratamento farmacológico , Substância Branca/diagnóstico por imagem , Adolescente , Anisotropia , Criança , Feminino , Humanos , Masculino
19.
AAPS PharmSciTech ; 21(5): 141, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32419084

RESUMO

Current study is focused to enhance the solubility of poorly soluble drug olanzapine (OLZ) by nanogels drug delivery system, as improved solubility is one of the most important applications of nanosystems. Poor solubility is a major issue, and 40% of marketed and about 75% of new active pharmaceutical ingredients are poorly water soluble which significantly affect the bioavailability and therapeutic effects of these drugs. In this study, nanogels, a promising system for solubility enhancement, were developed by free-radical polymerization technique. Different formulations were synthesized in which poloxamer-407 was cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with the help of cross-linker methylene bisacrylamide (MBA). The chemically cross-linked nanogels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermos gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), zeta size, swelling, sol-gel analysis, drug loading, solubility, and in vitro drug release studies. In order to determine the biocompatibility and cytotoxicity of nanogels to biological system, toxicity study on rabbits was also carried out. It was confirmed that the developed nanogels was thermally stable, safe, effective, and compatible to biological system, and the solubility of olanzapine (OLZ) was enhanced up to 38 folds as compared with reference product.


Assuntos
Antipsicóticos/administração & dosagem , Reagentes para Ligações Cruzadas , Nanogéis , Olanzapina/administração & dosagem , Poloxâmero/química , Acrilamidas , Animais , Antipsicóticos/química , Antipsicóticos/toxicidade , Disponibilidade Biológica , Liberação Controlada de Fármacos , Excipientes , Radicais Livres , Olanzapina/química , Olanzapina/toxicidade , Tamanho da Partícula , Coelhos , Solubilidade
20.
J Clin Psychiatry ; 81(3)2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32433835

RESUMO

OBJECTIVE: Evaluate efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) with 1-day initiation during hospitalization for acute exacerbation of schizophrenia followed by transition to outpatient care. METHODS: The phase 3b double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study was conducted from November 2017 to March 2019. Adults with acute schizophrenia according to DSM-5 criteria were randomized (1:1) to AL (AL NanoCrystal Dispersion + oral aripiprazole 30 mg, day 1; AL 1,064 mg, day 8 and every 8 weeks [q8wk]) or paliperidone palmitate (PP 234 mg, day 1; PP 156 mg, day 8 and then q4wk) for 25 weeks. Patients remained hospitalized ≥ 2 weeks after randomization per protocol. Primary endpoint was within-group change in Positive and Negative Syndrome Scale total score (PANSST) from baseline to week 4. Secondary analyses included within- and between-group changes from baseline at various time points. Adverse events (AEs) and laboratory data were monitored. RESULTS: A total of 200 patients were randomized (AL, n = 99; PP, n = 101); 56.6% and 42.6%, respectively, completed the study. For AL, the mean baseline PANSST was 94.1; scores were significantly reduced from baseline at week 4 (-17.4; P < .001) and were also reduced at weeks 9 (-19.8) and 25 (-23.3). With PP, PANSST also improved significantly from baseline (94.6) at week 4 (-20.1; P < .001) and also improved at weeks 9 (-22.5) and 25 (-21.7). The 3 most common AEs over 25 weeks in the AL group were injection site pain (17.2%), increased weight (9.1%), and akathisia (9.1%). The same AEs were the most common in the PP group (injection site pain [24.8%], increased weight [16.8%], and akathisia [10.9%]). CONCLUSIONS: AL and PP were efficacious and well-tolerated for initiating treatment of schizophrenia in the hospital and continuing outpatient treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03345979.


Assuntos
Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Assistência Ambulatorial , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Aripiprazol/administração & dosagem , Aripiprazol/efeitos adversos , Preparações de Ação Retardada , Método Duplo-Cego , Hospitalização , Humanos , Injeções Intramusculares , Pessoa de Meia-Idade , Palmitato de Paliperidona/administração & dosagem , Palmitato de Paliperidona/efeitos adversos , Palmitato de Paliperidona/uso terapêutico , Alta do Paciente , Adulto Jovem
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