Sex differences in aripiprazole sensitization from adolescence to adulthood

Aripiprazole withdrawal

Maintaining therapeutic plasma concentrations of an antipsychotic agent is essential in preventing relapse of symptoms in schizophrenia. Long-acting injectable (LAI) formulations provide extended exposure to antipsychotic therapy and have been useful in addressing treatment nonadherence. Aripiprazole is an atypical antipsychotic used in the treatment of schizophrenia and is available in 2 chemically different (aripiprazole monohydrate and aripiprazole lauroxil [AL]) and pharmaceutically different LAI formulations (aripiprazole once-monthly 400 mg [AOM 400] and AL). The pharmaceutical difference is that AL, unlike AOM 400, is a prodrug that requires additional metabolic steps to form the active drug aripiprazole. We present data demonstrating that aripiprazole plasma concentrations are similar for AOM 400 and the 882 mg dose of AL when administered once every 4 weeks and that both provide similar therapeutic plasma concentrations of aripiprazole when compared with therapeutic oral doses.

Objective To observe and explore the effect of aripiprazole(Ari) and olanzapine(Ola) on body weight and lipid metabolism in schizophrenia(SP) patients. Methods 96 patients with SP were randomly divided into two groups, 48 cases in the observation group and the control group.The control group was treated with Ola, while the observation group was treated with Ari.Before and 6 weeks after treatment, the height, body weight, blood glucose(FBG), insulin(INS), low-density lipoprotein(LDL), triglycerides(TG), total cholesterol(TC) levels in the two groups were detected, insulin resistance index(IRI) and BMI were calculated. Results The differences of body weight, BMI, FBG, INS, IRI, LDL, TG, TC before treatment between the two groups were not statistically significant(t=0.161, 0.564, 0.277, 0.078, 0.092, 0.124, 0.421, 0.245, all P>0.05). After 6 weeks treatment, FBG, INS, IRI in the observation group were (4.71±0.58)mmol/L, (21.85±12.36)μU/mL and (4.62±2.14), the differences were not statistically significant compared with before treatment(t=0.800, 0.571, 0.276, all P>0.05). Those in the control group were (5.14±0.56)mmol/L, (28.54±11.25)μU/mL and (6.23±3.82), which were significantly higher than those before treatment(t=4.898, 3.361, 2.628, all P 0.05), those in the control group were significantly higher than before treatment(t=2.601, 3.834, 5.773, 5.838, 4.375, all P<0.05), and were also significantly higher than those in the observation group(t=3.052, 3.265, 5.264, 5.496, 4.188, all P<0.05). Conclusion Ari treatment for SP has no significant effect on glucose and lipid metabolism and body weight in patients, and the effect of Ola treatment on patients' body weight and lipid metabolism is more significant. Key words: Schizophrenia; Aripiprazole; Olanzapine

Objective To investigate the drug utilization of hospitalized children in psychiatric hospital and analyze its the rationality. Methods A retrospective study was conducted to survey the utilization of psychotropic drugs in hospitalized children between January 2016 and June 2016, and according to drug instruction, its the rationality was analyzed. Results The top three used psychotropic drugs were aripiprazole, sertraline and sodium valproic sustained-release tablets.The types of drugs without safety data were at most and most frequently used.Diagnosis was not consistent with indications for totally 12 kinds of drugs, aripiprazole involved the most cases.A total of 5 drugs existed usage not matching drug instruction, and sodium valproic sustained-release tablets accounted for the most. Conclusion Irrational use of drugs in psychiatric hospital is still common at present.Clinical pharmacists can improve rationality of drug utilization of hospitalized children in psychiatric hospital by creating a drug database and carrying out pharmaceutical care. Key words: Department of psychiatry; Drug use for children; Rational use of drug

The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB) was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects.

Alcoholism is a chronic and recurrent disease. The studies on ethyl alcohol show a progressive deterioration of cognitive functions (motor hyperactivity, operating memory). The aim of the study was to establish whether combined single and chronic administration of aripiprazole (ARI) and fluoxetine (FLU) affects animal locomotor activity or modifies spatial memory functions in female rats exposed to ethyl alcohol. Female Wistar rats were studied in the Morris Water Maze (MWM) and locomotor activity test. Rats undergoing the MWM and locomotor activity test were injected with saline on day 1, 7, 14 and 21 of testing. Results showed a statistically significant mobility increase in the group of ethanol‑exposed females (CEt) (21 days) compared to the non-ethanol-exposed group (CNEt). Upon ARI administration to CEt, no statistically significant differences in animal mobility were found, either upon single or chronic administration. Chronic administration of FLU (21 days) as well as combined administration of ARI+FLU (14 and 21 days) caused a statistically significant reduction of the females' mobility compared to the control CEt group. Single and chronic administration of ARI (7x) both show a spatial memory improvement in CEt. No memory improvement was observed, however, after 14 and 21 days of ARI administration. FLU, likewise, improved spatial memory both upon single and chronic administration. Combined administration of ARI+FLU improved memory in CEt only upon single administration. Lack of effect upon chronic administration may be due to tolerance to memory improvement developing upon combined administration of ARI+FLU. It can be concluded that ARI (1.5 mg/kg), FLU (5 mg/kg), and combined administration of these drugs improves spatial memory in CEt.

Objective To systematically evaluate the efficacy of clozapine combined with other antipsychotic drugs in the treatment of refractory schizophrenia. Methods We searched Medline, EMBASE, and China Biology Medicine databases in both English and Chinese for randomized controlled trials, quasi-randomization controlled trials, and clinical controlled trials concerning the combinations of clozapine with other antipsychotic drugs for refractory schizophrenia. Quality assessment and data extraction were conducted with the Cochrane collaboration's RevMan 5.3 software. Results Totally 47 trials met the inclusion criteria, in which clozapine was combined with risperidone, aripiprazole, sulpiride, ziprasidone, modified electroconvulsive therapy, valproate, or lithium carbonate, respectively. Analysis showed that most combination strategies were superior to clozapoine alone (P<0.05), except for the combination with lithium carbonate(8 weeks: RR=1.27, 95%CI=0.82-1.97,P=0.28; 12 weeks: RR=1.53, 95% CI=0.45-5.13, P=0.49). Conclusion Reasonable combination of clozapine with other drugs may improve the therapeutic effectiveness and reduce adverse reactions and thus can be effectively used for treating refractory schizophrenia.

Here we provide, at least to our knowledge, the first evidence that aripiprazole (APPZ) in the water blunts the stress response of exposed fish in a concentration ten times lower than the concentration detected in the environment. Although the mechanism of APPZ in the neuroendocrine axis is not yet determined, our results highlight that the presence of APPZ residues in the environment may interfere with the stress responses in fish. Since an adequate stress response is crucial to restore fish homeostasis after stressors, fish with impaired stress response may have trouble to cope with natural and/or imposed stressors with consequences to their welfare and survival.

Partial regimen replacement with aripiprazole reduces serum prolactin in patients with a long history of schizophrenia: A case series.

The increase in prolactin (PRL) levels is a common adverse effect that occurs when using conventional and atypical antipsychotic drugs. Aripiprazole (ARI) is beneficial for antipsychotic-associated hyperprolactinemia but has been reported to decrease PRL secretion. Therefore, we investigated blood levels of PRL in patients who had taken ARI alone or in combination with other antipsychotics. Retrospective information was obtained from 25 psychiatric patients who were prescribed ARI, and the blood levels of PRL were measured. The incidence of hypoprolactinemia in the current study was 44.0% (11/25). Eighteen patients were treated with ARI alone and 7 received ARI in combination with other antipsychotics. The PRL value of patients who took ARI alone was significantly lower than those who were also taking other antipsychotics (5.45 ± 3.93 vs 10.85 ± 5.53, P = 0.02; mean ± SD). There was no significant correlation of the PRL levels and dose of ARI used in the 18 patients who had taken ARI alone. This was a retrospective study, and the data were obtained from a small number of psychiatric patients treated with ARI. Monitoring of PRL levels in patients treated with ARI may be useful in minimizing hypoprolactinemia, which has the potential to negatively impact patients. In particular, hypoprolactinemia as a consequence of taking ARI should be discussed with patients of childbearing age and those with immune deficiencies.

Many formulation and manufacturing processes can lead to morphological and crystalline transitions in many polycrystalline drugs, changing the properties of active pharmaceutical ingredients (APIs) such as solubility and physical stability which influence their therapeutic effects and safety and so limit their usefulness. Here, we report significant changes in crystal forms and morphology, including the shape and size of particles during the manufacture of off-white aripiprazole (APZ) dry powders used for long-acting and injectable suspensions. With the optimal top-down approach, powders were prepared by recrystallizing uniform monohydrous APZ (MA) and polycrystalline anhydrous APZ (AA) form III, characterized by thermal analysis, PXRD, and FT-IR. However, powders involving MA (MAP) with a lower mean size (2.126μm), narrower distribution (span = 1.90), and higher stability compared with AA dry powders (AAP) were found to exhibit dehydration behavior and morphological changes after completion of the preparation processes based on the results of thermal analysis. In the case of APZ powders, we wished to obtain more information to guide in the industrial production and experimental design of suspensions in the future.

Antioxidant properties of atypical antipsychotic drugs used in the treatment of schizophrenia

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

Background. Antipsychotic drugs (APDs) are used to manage traumatic brain injury (TBI)–induced behavioral disturbances, such as agitation and aggression. However, APDs exhibiting D2 receptor antagonism impede cognitive recovery after experimental TBI. Hence, empirical evaluation of APDs with different mechanistic actions is warranted. Aripiprazole (ARIP) is a D2 and 5-hydroxytryptamine1A (5-HT1A) receptor agonist; pharmacotherapies with these properties enhance cognition after TBI. Objective. To test the hypothesis that ARIP would increase behavioral performance and decrease histopathology after TBI. Methods. Adult male rats were subjected to either a controlled cortical impact (CCI) or sham injury and then randomly assigned to ARIP (0.1 or 1.0 mg/kg) or VEH (1.0 mL/kg, saline vehicle) groups. Treatments began 24 hours after surgery and were administered once daily for 19 days. Motor (beam-balance/beam-walk) and cognitive (Morris water maze) performance was assessed on postoperative days 1 to 5 and 14 to 19, respectively, followed by quantification of hippocampal CA1,3 neuron survival and cortical lesion volume. Results. Beam-balance was significantly improved in the CCI + ARIP (1.0 mg/kg) group versus CCI + ARIP (0.1 mg/kg) and CCI + VEH (P < .05). Spatial learning and memory retention were significantly improved in the CCI + ARIP (0.1 mg/kg) group versus the CCI + ARIP (1.0 mg/kg) and CCI + VEH groups (P < .05). Both doses of ARIP reduced lesion size and CA3 cell loss versus VEH (P < .05). Importantly, neither dose of ARIP impeded functional recovery as previously reported with other APDs. Conclusion. These findings support the hypothesis and endorse ARIP as a safer APD for alleviating behavioral disturbances after TBI.

Priapism Associated with Aripiprazole and Quetiapine in an 8-Year-Old Boy with Autism

Aripiprazole loaded poly(caprolactone) nanoparticles: Optimization and in vivo pharmacokinetics

Aripiprazole withdrawal

To investigate the mRNA expression of dopamine receptor D2 (DRD2) and dopamine transporter (DAT) in peripheral blood lymphocytes before and after treatment in children with tic disorder (TD). RT-PCR was used to measure the mRNA expression of DRD2 and DAT in peripheral blood lymphocytes before and after treatment in 60 children with TD. The correlations between mRNA expression of DRD2 and DAT and the severity of TD were analyzed. Sixty healthy children served as the control group. Before treatment, the children with TD had a significant increase in the mRNA expression of DRD2 and DAT compared with the control group (P<0.05). After 3 months of treatment with oral aripiprazole, the mRNA expression of DRD2 decreased significantly (P<0.05), while that of DAT showed no significant changes in children with TD. In the children with moderate or severe TD, the mRNA expression of DRD2 was positively correlated with Yale Global Tic Severity Scale (YGTSS) score (P<0.05). In the children with moderate TD, the mRNA expression of DAT was positively correlated with YGTSS score (P<0.05). In children with TD, the mRNA expression of DRD2 in peripheral blood lymphocytes can be used as one of the indicators for diagnosing TD, assessing the severity of TD, and evaluating clinical outcomes.

Clinical vignette – aripiprazol long acting injection monotherapy as long-term treatment for bipolar disease