Dissolution behavior of aripiprazole tablets based on near infrared spectroscopy / 药学实践杂志

Objective To establish a near infrared (NIR) quantitative model for the dissolution behavior of aripiprazole tablets. Methods The NIR spectra of aripiprazole tablets were collected and the dissolution tests were performed to determine the dissolution of each tablet at 3, 6, 9, 12, 15 and 30 min. The near infrared spectra regions of 4 000.00-4 396.90, 5 326.43-12 000.00 cm−1 were pretreated by Savitzky-Golay smoothing filter, and the dissolution behavior model was established by partial least squares method. Results The root mean square error of calibration (RMSEC) and the root mean square error of prediction (RMSEP) at different time points were analyzed. RMSEP was lower than 8%. The calibration correlation coefficient (RC) and the prediction correlation coefficient (RP) at different time points were above 0.95 (except for the point of 6 min). There was a good correlation between the NIR spectrum and the dissolution at each time point. Conclusion NIR spectroscopy could predict the dissolution behavior of aripiprazole tablets, which lays a foundation for online quality monitoring of tablets by NIR spectroscopy.

Aplicação da eletroforese capilar - espectrometria de massas para identificação dos produtos de degradação do aripiprazol em medicamentos / Application of capillary electrophoresis - mass spectrometry to identify aripiprazole degradation products in drugs

Diretrizes internacionais e nacionais como a FDA (Food and Drug Administration), ICH (International Council for Harmonisation) e ANVISA (Agência Nacional de Vigilância Sanitária) estabelecem a exigência de testes de estabilidade para entender melhor a qualidade de um medicamento. O estudo de estabilidade deve ser realizado usando métodos indicativos de estabilidade que possam qualificar e quantificar os insumos farmacêuticos do medicamento, bem como as impurezas e produtos de degradação nele contidos. O aripiprazol é um antipsicótico atípico de segunda geração aprovado para o tratamento de esquizofrenia, transtorno bipolar, depressão e transtornos do espectro do autismo. Os métodos oficiais descritos nas farmacopeias para avaliar o aripiprazol e suas impurezas utilizam a cromatografia líquida de alta eficiência (HPLC) como técnica principal. Nesta pesquisa, objetivou-se desenvolver um método indicativo de estabilidade por eletroforese capilar de zona (CZE) para o aripiprazol na forma farmacêutica de comprimidos, e identificação dos produtos de degradação por espectrometria de massas. O estudo de degradação forçada e a optimização do método desenvolvido por CZE foram realizados utilizando o conceito de delineamento de experimentos (DoE). A separação do aripiprazol de seus produtos de degradação foi conseguida usando uma coluna capilar de sílica fundida (30,2 cm x 75 µm ID), eletrólito de formiato de amônio 6 mmol/L (pH 3) com 5% de metanol sob um potencial de 15 kV e detecção em 214 nm. A capacidade indicativa de estabilidade do método foi investigada pela análise do aripiprazol após ser submetido a condições de estresse ácido, alcalino, térmico, fotolítico e oxidativo, de acordo com as diretrizes ICH. A oxidação foi a principal via de degradação entre as condições de estresse avaliadas. O aripiprazol foi separado dos seus produtos de degradação oxidativa em tempo de corrida abaixo de 5 minutos. O método por CZE mostrou ser linear na faixa de 60 - 140 µg/mL, R2 = 0,9980, precisão calculada como desvio padrão relativo (DPR) menor que 2% e exatidão calculada como recuperação média de 100,93 ± 0,77%. Os resultados obtidos demonstram que o método por HPLC-RP em modo gradiente, separou o aripiprazol e seus produtos de degradação em um tempo de corrida de 30 minutos. Quatro produtos de degradação foram detectados pelo método LC-MS e o principal produto de degradação oxidativo foi identificado. O aripiprazol mostrou-se suscetível à oxidação no grupo piperazina, gerando principalmente o composto aripiprazol-1-N-óxido

International and national guidelines such as the FDA (Food and Drug Administration), ICH (International Council for Harmonization) and ANVISA (National Health Surveillance Agency) establish the requirement for stability tests to better understand quality of a medicine. The stability study must be carried out using stability indicating methods that can qualify and quantify the pharmaceutical ingredients of the drug, as well as the impurities and degradation products contained therein. Aripiprazole is a second-generation atypic antipsychotic drug approved for the treatment of schizophrenia, bipolar disorder, depression, and autism spectrum disorders. The official method described in the pharmacopoeias to evaluate aripiprazole and its impurities is high performance liquid chromatography (HPLC) as the main technique. In this research, the objective was to develop an indicative method of stability by capillary zone electrophoresis (CZE) for aripiprazole in the pharmaceutical form of tablets, and identification of degradation products by mass spectrometry. The forced degradation study and the optimization of the method developed by CZE were carried out using the concept of design of experiments (DoE). The separation of aripiprazole from its degradation products was achieved using a fused silica capillary column (30,2 cm x 75 µm ID), 6 mmol/L ammonium formate electrolyte (pH 3) with 5% methanol under a potential of 15 kV and detection at 214 nm. The indicative stability of the method was investigated by analyzing aripiprazole after being subjected to acid, alkali, thermal, photolytic and oxidative stress conditions, according to the ICH guidelines. Oxidation was the main degradation pathway among the stress conditions evaluated. Aripiprazole was separated from its oxidative degradation products at run times below 5 minutes. The CZE method proved to be linear in the range of 60 - 140 µg/mL, R2 = 0,9980, precision calculated as a relative standard deviation (DPR) of less than 2% and accuracy calculated as a mean recovery of 100,93 ± 0,77%. The results obtained demonstrate that the HPLC-RP method in gradient mode separated aripiprazole and its degradation products in a run time of 30 minutes. Four degradation products were detected by the LC-MS method and the main oxidative degradation product was identified. Aripiprazole was shown to be susceptible to oxidation in the piperazine group, generating mainly the compound aripiprazole-1-N-oxide

Pathological Gambling Due to Aripiprazole: Two Cases

ABSTRACT Aripiprazole is an atypical antipsychotic agent which has a partial agonistic effect on dopamine D2 and D3 receptors. It is effective in the treatment of schizophrenia and bipolar disorder. Owing to its partial agonistic effect, hyperactivity of dopamine may occur in the mesolimbic pathway. In the literature, there are few case reports about pathological gambling due to aripiprazole. In this article, there are two case reports of patients who showed pathological gambling behaviour and alcohol abuse and who were under treatment with aripiprazole. The patient had a history of gambling in the past. With the use of aripiprazole, pathological gambling behaviour occurred quickly and with discontinuation of aripiprazole it ended completely. Aripiprazole causes pathological gambling by forming a hyperdopaminergic condition in the mesolimbic dopaminergic pathway. Aripiprazole should be recommended cautiously and carefully to patients who are impulsive and have a history of alcohol/substance abuse.

Sertraline combined with low-dose aripiprazole in the treatment of obsessive-compulsive disorder in children and adolescents： a randomized controlled study / 四川精神卫生

ObjectiveTo investigate the efficacy and safety of sertraline combined with low-dose aripiprazole in the treatment of obsessive-compulsive disorder in children and adolescents. MethodsA total of 62 cases pediatric patients aged 9~16 years who attended the outpatient clinic of a psychiatric hospital in Xiamen from June 2018 to May 2020 and met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for obsessive-compulsive disorder were enrolled in the study. The selected children were randomly classified into two groups for different treatments. Control group （n=30） received sertraline monotherapy， and study group （n=32） received sertraline combined with low-dose aripiprazole treatment. At the baseline and the end of the 2nd， 4th， 8th and 12th weeks of treatment， children were assessed using Children's Yale-Brown Obsessive Compulsive Scale （CY-BOCS） and Treatment Emergent Symptoms Scale （TESS）. Thereafter， the clinical efficacy and adverse reactions were compared between two groups. ResultsThe compulsive behavior dimensional score of CY-BOCS of study group was lower than that of control group at end of the 2nd and 4th weeks of treatment （t=-2.083， -2.176， P<0.05）. At the end of the 2nd week of treatment， the effective rate was 40.63% in study group， which was significantly higher than 3.33% in control group （χ2=12.317， P<0.01）. By the end of the 12th weeks of treatment， the incidence rate of side effects yielded no statistical difference between two groups （χ2=1.608， P=0.205）. ConclusionCompared with sertraline monotherapy， its combination with low-dose aripiprazole treatment can effectively accelerate the improvement of clinical symptoms in childrenand adolescents with obsessive-compulsive disorder， while the combination therapy and sertraline monotherapy have equivalent safety.

Effects of aripiprazole combined with duloxetine on the treatment effect and VEGF level in patients with refractory depression / 中国临床药理学与治疗学

AIM: To explore the effects of aripiprazole and duloxetine on refractory depression and the change of VEGF concentration during treatment. METHODS: Ninety patients with refractory depression who were treated at the Fourth People's Hospital of Jiande from February 2017 to February 2019 were selected, and 40 healthy volunteers were recruited as healthy control groups. Random numbers table was used to divide patients into aripiprazole combined with duloxetine treatment group (combined treatment group) and duloxetine treatment group (monotherapy group). After 4 weeks of treatment, the differences in efficacy and adverse reactions between the two groups were evaluated. The difference of VEGF level between each group was compared. RESULTS: The effective rate was 88.8% in the combined treatment group and 80.0% in the monotherapy group. The effective rate between the two groups was not statistically significant (P<0.05). After 4 weeks of treatment, the HAMD score in the combined treatment group was lower than that in the monotherapy group, the difference was statistically significant (P<0.05). The difference in adverse reactions between the two groups was not statistically significant (R=0.641, P=0.624). The level of VEGF before treatment in the two treatment groups was higher than that in the healthy control group, and the difference was statistically significant (P<0.01). After treatment, the VEGF level of the two groups decreased compared with before treatment, and the difference was statistically significant (P<0.01). The level of VEGF in the combined treatment group was lower than that in the monotherapy group, and the difference was statistically significant (P<0.05). Pearson correlation analysis showed that the level of VEGF before treatment was positively correlated with the HAMD score (R=0.403, P<0.01), and VEGF decline level is positively correlated with HAMD score reduction rate (R=0.330, P<0.01). CONCLUSION: Aripiprazole combined with duloxetine has a better effect on refractory depression than duloxetine alone, and can significantly reduce the level of VEGF in peripheral blood.

Efeitos citotóxicos do aripiprazol nas linhagens celulares MKN45 e NIH3T3 e efeitos genotóxicos nos linfócitos sanguíneos periféricos humanos / Cytotoxic effects of aripiprazole on mkn45 and nih3t3 cell lines and genotoxic effects on human peripheral blood lymphocytes

ABSTRACT BACKGROUND: Gastric cancer is known as the fourth most common cancer. Current treatments for cancer have damaged the sensitive tissues of the healthy body, and in many cases, cancer will be recurrent. Therefore, need for treatments that are more effective is well felt. Researchers have recently shifted their attention towards antipsychotic dopamine antagonists to treat cancer. The anticancer activities of aripiprazole remain unknown. OBJECTIVE: This study aimed to evaluate the efficacy and safety of aripiprazole on gastric cancer and normal cell lines. METHODS: In this regard, the cytotoxicity and genotoxicity of aripiprazole were investigated in MKN45 and NIH3T3 cell lines by methyl tetrazolium assay and on peripheral blood lymphocytes by micronucleus assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of aripiprazole and cisplatin were prepared. After cell incubation with different concentrations of aripiprazole (1, 10, 25, 50, 100 and 200 μL), methyl tetrazolium solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of aripiprazole (50, 100 and 200 μL) were added. RESULTS: The finding of present study showed that the IC50 of aripiprazole in the cancer cell line (21.36 μg/mL) was lower than that in the normal cell line (54.17 μg/mL). Moreover, the micronucleus assay showed that the frequency of micronuclei of aripiprazole at concentrations below 200 μM was much less than cisplatin. CONCLUSION: Aripiprazole can be a good cytotoxic compound and good candidate for further studies of cancer therapy.

RESUMO CONTEXTO: O câncer gástrico é conhecido como o quarto câncer mais comum. Os tratamentos atuais para o câncer danificaram os tecidos sensíveis do corpo saudável e, em muitos casos, o cancro será recorrente. Portanto, a necessidade de tratamentos que são mais eficazes é desejada. Recentemente, os pesquisadores mudaram sua atenção para os antagonistas antipsicóticos da dopamina para tratar o câncer. As atividades anticâncer de aripiprazol permanecem desconhecidas. OBJETIVO: Este estudo objetivou avaliar a eficácia e a segurança do aripiprazol no câncer gástrico e nas linhagens celulares normais. MÉTODOS: A este respeito, a citotoxicidade e a genotoxicidade do aripiprazol foram investigadas em linhas celulares MKN45 e NIH3T3 por ensaio de metil tetrazólio e em linfócitos periféricos de sangue por ensaio de micronúcleos. Para este efeito, as células foram cultivadas em 96 placas. As soluções de estoque de aripiprazol e cisplatina foram preparadas. Após incubação celular com diferentes concentrações de aripiprazol (1, 10, 25, 50, 100 e 200 μL), a solução de metil tetrazólio foi adicionada. Para o ensaio do micronúcleo o sangue fresco foi adicionado ao meio de cultura RPMI 1640 suplementado, e as concentrações diferentes de aripiprazole (50, 100 e 200 μL) foram adicionadas. RESULTADOS: O presente estudo mostrou que o IC50 de aripiprazol na linhagem celular cancerosa (21,36 μg/mL) foi menor do que na linha celular normal (54,17 μg/ mL). Além disso, o ensaio de micronúcleos demonstrou que a frequência de micronúcleos de aripiprazol em concentrações inferiores a 200 μM foi muito inferior à cisplatina. CONCLUSÃO: O aripiprazol pode ser um bom composto citotóxico e bom candidato para estudos adicionais da terapia do câncer.

Sex-differential effects of olanzapine vs. aripiprazole on glucose and lipid metabolism in first-episode schizophrenia

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients' type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole-induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.

The Potential Utility of Aripiprazole Augmentation for Major Depressive Disorder with Mixed Features Specifier: A Retrospective Study

OBJECTIVE: The present study aimed to observe potential benefit of aripiprazole augmentation in the treatment of major depressive disorder with mixed specifier (MDDM) in naturalistic treatment setting. METHODS: Data were collected from MDDM patients using a retrospective chart review for 8 weeks (week –8 and week 0) in routine practice. All patients were on current antidepressants upon starting of aripiprazole. Patients were treated without restriction of doses of aripiprazole. The primary endpoint was the mean change of Montgomery–Åsberg Depression Rating Scale (MADRS) total scores along with various secondary endpoint measures. RESULTS: In total 38 patients were analyzed. The changes of MADRS, Clinical Global Impression (CGI)-severity, Young Mania Rating Scale, Sheehan Disability Scale, and CGI-clinical benefit total scores from baseline to the endpoint were −7.1, −0.8, −4.9, −4.1, and −3.6, respectively (all p < 0.0001). At the endpoint, the responder and remitter rates by MADRS score criteria were approximately 32% and 21%, respectively. CONCLUSION: The present findings have clearly shown the effectiveness and tolerability of aripiprazole augmentation for MDDM patients in routine practice. The present study warrants subsequent, adequately-powered, well-controlled studies for generalizability near future.

Aripiprazole-induced Hepatitis: A Case Report

Aripiprazole is an atypical antipsychotic that acts as a partial agonist of dopamine type 2 receptors as well as 5-HT1A receptors. It is used in the treatment of schizophrenia and in type 1 bipolar disorder for mania. Because aripiprazole is well tolerated with few side effects it is used off-label in other psychotic disorders. The prevalence of abnormal liver function tests with antipsychotic use is 32%, with clinically significant effects in 4% of cases. No cases of aripiprazole-induced liver injury have been published. We report a 28-year-old female who presented with non-affective first-episode psychosis and who was treated with aripiprazole. Initially she was medicated with 10 mg per day, with an increase to 20 mg per day on the 12th day of hospitalization. Nine days after she became icteric, with nausea and had a vomiting episode. Laboratory analysis revealed a very high level of alanine aminotransferase, and minor to moderately high levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Aripiprazole was tapered and paliperidone was started with the improvement of clinical and laboratory findings.

Hypertension Induced by Aripiprazole Use in an Autistic Child Patient

Atypical antipsychotics in children and adolescents are widely used for aggression, emotional variability and psychosis treatment. Aripiprazole is also an atypical antipsychotic that increasingly used in children and adolescents with schizophrenia, autism and bipolar disorder. In this case report, a medically healthy patient with autism associated with behavioral problems is presented with the development of hypertension after the onset of aripiprazole and the return of blood pressure to normal levels after withdrawal of the drug. The purpose of this case study is to discuss and report the emergence of aripiprazole-induced hypertension as a side effect of drugs in children and adolescents.

Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats

OBJECTIVE: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. METHODS: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. RESULTS: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all). CONCLUSION: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.

Effect of aripiprazole on prolactinemia induced by antidepressants in patients with depression / 中国神经精神疾病杂志

Objective To investigate the effect and safety of different doses of aripiprazole on hyperprolactinemia (HPL) induced by antidepressants such as Selective Serotonin Reuptake Inhibitor (SSRIs). Methods One hundred and thirty-five depressive patients with SSRIs antidepressant-induced hyperprolactinemia were randomly divided into three groups and 95 cases who finished the study were included in the study. Thirty-three cases in group 1 were treated with aripiprazole 5 mg/d, thirty-two cases in group 2 were treated with aripiprazole 10 mg/d and thirty cases in control group were treated with SSRI alone. All three groups also received cognitive behavioral therapy in addition to antidepressants for 12 weeks. Serum prolactin levels were examined before admission and 4, 8 and 12 weeks after treatment. Hamilton Depression Scale (HAMD), Global Assessment Function (GAF) and Treatment Emergent Symptom Scale (TESS) were used to evaluate the efficacy and adverse reactions. Results At the end of the 4, 8 and 12 weeks, the serum prolactin level in group 1 and group 2 were significantly lower than those in control group (P<0.05). At the end of 8 and 12 weeks, the HAMD scores of group 1 and 2 group were significantly lower than those of the control group (P<0.01). At the end of 4, 8, and 12 weeks, the GAF scores of group 1 and 2 group were significantly higher than those of the control group (P< 0.01). However, there were no significant differences in prolactin levels, HAMD and GAF scores between group 1 and group 2 (P>0.05). There was no significant difference in the rate of adverse reaction among the three groups (P>0.05). Conclusion Aripiprazole can reduce the hyperprolactinemia caused by SSRIs antidepressants and synergistically enhance efficacy of antidepressant.

Augmentation of Aripiprazole versus Bupropion on Specific Symptoms of Depression in Older Adult Patients : A Post-Hoc, Multi-Center, Open-Label, Randomized Study / 생물치료정신의학

OBJECTIVES: The purpose of this study was to compare aripiprazole versus bupropion augmentation therapy in older adult patients with major depressive disorder unresponsive to selective serotonin reuptake inhibitors(SSRIs).METHODS: This is a post-hoc analysis of a 6-week, randomized prospective open-label multi-center study in thirty older adult patients with major depressive disorder. Participants were randomized to receive aripiprazole(N=16, 2.5–10mg/day) or bupropion(N=14, 150–300mg/day) for 6 weeks. Montgomery Asberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating scale(HAM-D17), Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores, and Clinical Global Impression-Severity (CGI-S) were obtained at baseline and after one, two, four, and six weeks. Changes on individual items of HAM-D17 were assessed as well as on composite scales(anxiety, insomnia and drive), and on four core subscales that capture core depression symptoms.RESULTS: There was a significantly greater decrease in MADRS scores in aripiprazole group compared to bupropion group at 4(p<0.05) and 6(p<0.05) weeks. There were significantly higher response rate at week 4(p<0.05) and 6(p<0.05) and remission rate at week 6 in aripiprazole group compared to bupropion group. Individual HAM-D17 items showing significantly greater change with adjunctive aripiprazole than bupropion: insomnia, late(ES=0.81 vs. −0.24, p=0.043), psychomotor retardation(ES=1.30 vs. 0.66, p=0.024), general somatic symptoms(ES=1.24 vs. 0.00, p=0.01). On three composite scales, adjunctive aripiprazole was significantly more effective than bupropion with respect to mean change for drive(p=0.005).CONCLUSION: Results of this study suggested that aripiprazole augmentation have superior efficacy in treating general and core symptoms of depression in older adult patients. Aripiprazole augmentation is associated with greater improvement in specific symptoms of depression such as psychomotor retardation, general somatic symptoms and drive.

First Manic Episode in a Young Woman with Schizophrenia after Initiation of Oral Aripiprazole and Aripiprazole Long-Acting Injection / 우울ㆍ조울병

A woman in her twenties with schizophrenia developed immediate-onset mania after taking oral aripiprazole and receiving aripiprazole long-acting injection (ALAI). The dosage of aripiprazole was rapidly increased due to inadequate stimulating effect of low-dosage aripiprazole, but her manic symptomatology worsened. Clinicians should therefore carefully monitor for the induction of mania by oral aripiprazole and ALAI. Her manic symptomatology improved after adding 20 mg of blonanserin, 3 mg of risperidone, and 300 mg of quetiapine.

Schizophrenia: effects of aripiprazole in metabolic syndrome

Schizophrenia, in general, is characterized by severe and disabling mental alterations, characterized by the impairment of one's mental, behavioral and social activities, developing certain clinical symptoms, relevant to the diagnosis. The drugs used for the reversion of the symptoms cause several adverse effects that affect the patient's health and well-being, such as motor, endocrine and cardiovascular damages. For a long time, little was known about the origin and the treatment of schizophrenia, which has become a curiosity for science, originating countless researches and theories that are background for several treatments. It is known that alterations in dopaminergic pathways are related to the development of the symptoms of the disease, and evaluating these symptoms, the diagnosis is made and the treatment is initiated. The insertion of new drugs with different characteristics and mechanisms tends to be an advance in the treatment of schizophrenia, as well as reducing the occurence of adverse effects or not worsening already existing cases. Aripiprazole is an innovative atypical antipsychotic employed in the pharmacotherapy of schizophrenia, which tends to attenuate the symptoms, inducing few adverse effects compared to other drugs that are already used, and promotes better quality of life to patients.

Aripiprazole-induced transient myopia: A rare entity

Aripiprazole is a new drug for the treatment of adults with schizophrenia. Ocular side effects of aripiprazole are very rare. Review of literature revealed few cases of aripiprazole-induced myopia. We report a rare case of aripiprazole-induced transient myopia. A 22-year-old female patient presented to the department of psychiatry with worsening of symptoms of schizophrenia and was started on aripiprazole. She presented with complaints of blurring of vision in both eyes for 1 week which started on the 3rd day following the use of aripiprazole. Anterior segment examination revealed a shallow anterior chamber and narrow angles. Intraocular pressure was normal. A diagnosis of aripiprazole-induced acute myopia was made and the treating psychiatrist was advised to stop the medication. At 2-week follow-up, the unaided visual acuity improved to 20/20 in both the eyes. Ophthalmologists should be aware of the myopic shift that may occur as an ocular side effect with aripiprazole.

Aripiprazol en dosis bajas para somnolencia diurna excesiva asociada a uso de haloperidol: un reporte de caso / Low dose aripiprazole for excessive daytime sleepiness associated with the use of haloperidol: A case report

La somnolencia diurna es un efecto adverso frecuentemente asociado al uso de antipsicóticos en pacientes con esquizofrenia. Presentamos el caso de una mujer de 43 años con esquizofrenia y tratamiento antipsicótico desde hace 24 años, que inicialmente, presentó mala respuesta a antipsicóticos clásicos de baja potencia, llegando a lograr estabilizar los síntomas psicóticos por más de 10 años con uso de haloperidol. Sin embargo, con este tratamiento presentó somnolencia diurna que llegó a ser un efecto adverso importante limitando su funcionalidad y calidad de vida. Luego de añadirse primero 3,75 mg y luego 7,5 mg de aripiprazol, mejoró hasta un 80% la somnolencia sin exacerbación de los síntomas psicóticos

Daily somnolence is a frequent adverse event associated to the use of antipsychotic medication in patients with schizophrenia. We present the case of a 43 years old women with schizophrenia and pharmacological treatment for 24 years, who, at the start of the treatment, showed inadequate response to low potency classical antipsychotics, achieving clinical stability for more than 10 years with the use of haloperidol. However, she presented severe daily somnolence which significantly limited her functionality and quality of life. After the addition of 3.75 mg and later 7.5 mg of aripiprazole the somnolence improved in nearly 80% without exacerbation of psychotic symptoms

A smart approach for delivery of aripiprazole via oro-soft palatal mucosal route for improved therapeutic efficacy

Effective management of schizophrenia, acute mania, mixed episodes associated with bipolar disorders, and depression can be managed with aripiprazole moiety. In the present research work an attempt was made to minimize the dose related side effects thus improving the quality life of the patients. A novel biopolymer was isolated from the fruits of Trachyspermum ammi. Ten optimized nanosized aripiprazole loaded formulations were prepared in 1-5% concentration of biopolymer (FA1-FA5) and sodium CMC (FM1-FM5) by solvent casting technique. The formulated flexy films were evaluated for thickness, folding endurance, weight uniformity, surface pH, mucoadhesivity, In-vitro drug release studies, In-vivo pharmacodynamic study and stability studies. The isolated biopolymer showed inbuilt fimability and mucoadhesivity and consists of carbonyl, hydroxyl and thiocarbonyl functional groups. All formulations showed folding endurance from 153 to 170, mucoadhesion time in the range of 24-48hrs., and in-vitro drug release was performed using dynamic Franz Diffusion cell and analyzed using BIT-SOFTWARE. The experimental animals showed improved activity score on actophotometer. The formulated nanosized aripiprazole loaded bio-flexy films showed pharmacotherapeutic response. Conclusion can be drawn that optimized formulation showed effective Pharmacodynamic activity and can be used as for improving therapeutic efficacy of aripiprazole through this platform.

Preparation and Evaluation of Aripiprazole Oral Disintegrating Tablets / 中国药师

Objective:To prepare aripiprazole oral disintegrating tablets , investigate the formula and evaluate the quality .Meth-ods:The formula of aripiprazole oral disintegrating tablets was investigated by a factorial experiment design .The aripiprazole particle size distribution ( X1 , D90/μm) , the ratio of mannitol to microcrystalline cellulose ( X2 ,％) and the amount of disintegration ( X3 ,％) were selected as the independent variables , and the tablet hardness ( Y1 , N) , the disintegration time ( Y2 , s) and the dissolution in 30 min ( Y3 ,％) were used as the dependent variables to ultimately determine the optimal formula .The dissolution profile of aripiprazole oral disintegrating tablets and the reference preparation in four dissolution media were compared by f2 similarity factor, and the stability of aripiprazole oral disintegrating tablets was investigated by accelerated stability testing .Results: The results of factorial experiment design of variance analysis showed that the filler ratio had significant effect on the tablet hardness (P<0.05), the amount of disinte-grant and the filler ratio had significant effect on the disintegration time (P<0.05), and the aripiprazole particle size had significant effect on the drug dissolution ( P<0.05 ) .The optimal formula of aripiprazole oral disintegrating tablets was as follows: the particle size D90 of aripiprazole was 20-40μm, the amount ratio of mannitol to microcrystalline cellulose was 2.5:1, and the amount of disinte-gration was 5.0％.Aripiprazole oral disintegrating tablets prepared with the optimal formula had higher hardness , shorter disintegration time and faster drug dissolution , and the dissolution profiles were similar with those of the reference preparation .The relevant sub-stances showed no significant increase during the accelerated stability testing , and the quality was satisfactory .Conclusion:The formu-la of aripiprazole oral disintegrating tablets is reasonable , the preparation process is feasible and the quality is controllable .

Effects of aripiprazole on clinical symptoms and serum neurotrophic factor levels in patients with schizophrenia / 中国神经精神疾病杂志

Objective To explore the effects of aripiprazole on clinical symptoms and neurotrophic factor levels in patients with schizophrenia. Methods Forty patients with schizophrenia and 40 normal controls were included in the study. The clinical symptoms of patients receiving aripiprazole only for 12 weeks were evaluated by using the Positive and Negative Syndrome Scale (PANSS). Stroop Color-Word Test (SCWT), Continuous Performance Test, Digit-Symbol Coding Test and Trail Making Test-A were used to evaluate the cognitive function both in patients and controls. Serum levels of Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin 3 (NT-3) were measured using enzyme linked immunosorbent assay. Results The clinical scores, cognitive function and levels of neurotrophic factors were different before and after treatment (P<0.01). And those were significantly lower in patients than in control group (P<0.05). Before treatment, BDNF was negatively correlated with PANSS negative symptom score (r=-0.362, P=0.022);NGF was related to the total score of PANSS (r=0.332, P=0.037) and positive symptoms (r=0.401, P=0.010); NT-3 was associated with negative symptom scores (r=-0.376, P=0.017) and SCWT-color words (r=0.332, P=0.037) in patient group. After treatment, the increase in BDNF was correlated with the reduction in PANSS total score (r=0.371, P=0.018), negative symptom score (r=0.345, P=0.029) and general pathology score (r=0.342, P=0.031). There was a correlation of the increase of NGF with the decrease of PANSS total scores (r=0.437, P=0.005) and with positive symptom scores (r=0.357, P=0.024). Conclusion Treatment with Aripiprazole can improve the clinical symptoms and cognitive functiona impairments in patients with schizophrenia, which may be related to the increase in serum levels of BDNF, NGF and NT-3.