Effects Of Aripiprazole Research Articles

Administration of Aripiprazole Alleviates Memory Impairment and Restores Damaged Glutamatergic System in 5xFAD Mice.

Many patients with Alzheimer's disease (AD) also have psychosis, and it has been reported that these patients have more severely impaired cognitive functions than patients without psychosis. The glutamatergic system in the brain is known to play an important role in memory and learning in the neural circuits. However, there has been limited research on how antipsychotic drugs affect the glutamatergic system of AD. Therefore, we aimed to investigate the effects of aripiprazole on the glutamatergic system in an animal model of AD using functional molecular imaging. In this study, 5xFAD mice were used as the animal model. At the age of 5months, the mice were divided into wild-type, vehicle control, and aripiprazole-treated groups (n = 6 per group). The aripiprazole-treated group was administered aripiprazole for 2months at a dose of 1mg·kg-1·day-1. At 7months of age, the animals underwent behavioral tests and glutamate positron emission tomography (PET) scans. The aripiprazole-treated group exhibited alleviated memory impairment in a novel object recognition test. Moreover, this group displayed 7-8% higher binding in the glutamate PET scan than the vehicle-treated 5xFAD group. Postmortem examination confirmed the recovery of glutamatergic damage. The administration of aripiprazole alleviated memory impairment and restored the damaged glutamatergic system in 5xFAD mice. Although the use of aripiprazole in AD patients may be a constraint in terms of safety, we confirmed the possibility that the administration of antipsychotic drugs can be effective in AD.

Aripiprazole cognitive effects on attention deficit hyperactivity disorder (ADHD) in experimental mouse model

Background: Attention deficit hyperactivity disorder (ADHD) is one of children's neurodevelopmental psychological disorders with ideal therapy obscure. Aripiprazole is an antipsychotic medication with a unique mechanism of action that enhances dopamine activity in the prefrontal cortex in turn it might executive function in ADHD patients. This study aimed to clarify the impact of aripiprazole on ADHD using a socially isolated (SI) mice model. Methods: In the current study we used early-life SI mice as models for ADHD and tested three different doses of aripiprazole on attention set-shifting performance. The socially Isolated mice are known to have impairment in attentional set-shifting. Socially housed and isolated reared mice across different doses of aripiprazole for each stage were cross-matched for comparison. Results: Socially isolated mice showed selective great deficits in interdimen¬sional discriminations and extradimensional discriminations. Aripiprazole at 3 and 6mg/kg did greatly mitigate the cognition deficits in comparison with placebo and 1 mg/kg of aripiprazole. Conclusion: The current study results emphasise the positive effect of aripiprazole on cognition. Aripiprazole has the potential to be a treatment for ADHD with a psychostimulatory effect.

Effect of aripiprazole on neural tube development in early chick embryos

IntroductionAripiprazole (ARI) is a recently developed antipsychotic medication that belongs to the second generation of antipsychotics. The literature has contradictory information regarding ARI, which has been classified as pregnant use category C by the FDA. Methods125 pathogen-free fertilized eggs were incubated for 28 h and divided into five groups of 25 eggs each (including the control group), and 18 eggs with intact integrity were selected from each group. After the experimental groups were divided, ARI was administered subblastodermally with a Hamilton micro-injector at 4 different doses (1 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg). At the 48th hour of incubation, all eggs were hatched and embryos were removed from the embryonic membranes. And then morphologic (position of the neural tube (open or closed), crown-rump length, number of somites, embryological development status), histopathologic (apoptosis (caspase 3), cell proliferation (PCNA), in situ recognition of DNA breaks (tunnel)), genetic (BRE gene expression) analyzes were performed. ResultsAccording to the results of the morphological analysis, when the frequency of neural tube patency was evaluated among the experimental groups, a statistically significant difference was determined between the control group and all groups (p < 0.001). In addition, the mean crown-rump length and somite number of the embryos decreased in a dose-dependent manner compared to the control group. It was determined that mRNA levels of the BRE gene decreased in embryos exposed to ARI compared to the control group (p < 0.001). ConclusionMorphologically, histopathologically, and genetically, aripiprazole exposure delayed neurogenesis and development in early chick embryos. These findings suggest its use in pregnant women may be teratogenic. We note that these results are preliminary for pregnant women, but they should be expanded and studied with additional and other samples.

Prenatal Immune Challenge Differentiates the Effect of Aripiprazole and Risperidone on CD200-CD200R and CX3CL1-CX3CR1 Dyads and Microglial Polarization: A Study in Organotypic Cortical Cultures.

Microglia are the primary innate immune cells of the central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity of microglia may be associated with several neuropsychiatric disorders, including schizophrenia. Therefore, we examined whether aripiprazole and risperidone could influence the expression of the Cd200-Cd200r and Cx3cl1-Cx3cr1 axes, which are crucial for the regulation of microglial activity and interactions of these cells with neurons. Additionally, we evaluated the impact of these drugs on microglial pro- and anti-inflammatory markers (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 and Tgf-β) and cytokine release (IL-6, IL-10). The research was executed in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those exposed to maternal immune activation (MIA OCCs), which allows for the exploration of schizophrenia-like disturbances in animals. All experiments were performed under basal conditions and after additional stimulation with lipopolysaccharide (LPS), following the "two-hit" hypothesis of schizophrenia. We found that MIA diminished the mRNA level of Cd200r and affected the OCCs' response to additional LPS exposure in terms of this parameter. LPS downregulated the Cx3cr1 expression and profoundly changed the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Risperidone increased Cd200 expression in MIA OCCs, while aripiprazole treatment elevated the gene levels of the Cx3cl1-Cx3cr1 dyad in control OCCs. The antipsychotics limited the LPS-generated increase in the expression of proinflammatory factors (Il-1β and Il-6) and enhanced the mRNA levels of anti-inflammatory components (Cd206 and Tgf-β) of microglial polarization, mostly in the absence of the MIA procedure. Finally, we observed a more pronounced modulating impact of aripiprazole on the expression of pro- and anti-inflammatory cytokines when compared to risperidone in MIA OCCs. In conclusion, our data suggest that MIA might influence microglial activation and crosstalk of microglial cells with neurons, whereas aripiprazole and risperidone could beneficially affect these changes in OCCs.

Aripiprazole as protector against COVID-19 mortality

The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79–0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.

The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.

Anti-inflammatory and protective effects of Aripiprazole on TNBS-Induced colitis and associated depression in rats: Role of kynurenine pathway

BackgroundThe prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Inflammatory cytokines and the kynurenine pathway (KP) play important roles in IBD and associated depression. Aripiprazole (ARP), an atypical antipsychotic, shows various anti-inflammatory properties and may be useful in treating major depressive disorder. This study aimed to evaluate the protective effects of ARP on TNBS-induced colitis and subsequent depression in rats, highlighting the role of the KP. Material and MethodsFifty-six male Wistar rats were used, and all groups except for the normal and sham groups received a single dose of intra-rectal TNBS. Three different doses of ARP and dexamethasone were injected intraperitoneally for two weeks in treatment groups. On the 15th day, behavioral tests were performed to evaluate depressive-like behaviors. Colon ulcer index and histological changes were assessed. The tissue levels of inflammatory cytokines, KP markers, lipopolysaccharide (LPS), nuclear factor-kappa-B (NF-κB), and zonula occludens (ZO-1) were evaluated in the colon and hippocampus. ResultsTNBS effectively induced intestinal damages and subsequent depressive-like symptoms in rats. TNBS treatment significantly elevated the intestinal content of inflammatory cytokines and NF-κB expression, dysregulated the KP markers balance in both colon and hippocampus tissues, and increased the serum levels of LPS. However, treatment with ARP for 14 days successfully reversed these alterations, particularly at higher doses. ConclusionARP could alleviate IBD-induced colon damage and associated depressive-like behaviors mainly via suppressing inflammatory cytokines activity, serum LPS concentration, and affecting the NF-κB/kynurenine pathway.

Inhibition of voltage-gated potassium channel by aripiprazole in rabbit coronary arterial smooth muscle cells

Aripiprazole, a third-generation antipsychotic, has been widely used to treat schizophrenia. In this study, we evaluated the effect of aripiprazole on voltage-gated potassium (Kv) channels in rabbit coronary arterial smooth muscle cells using the patch clamp technique. Aripiprazole reduced the Kv current in a concentration-dependent manner with a half-maximal inhibitory concentration of 0.89 ± 0.20 μM and a Hill coefficient of 1.30 ± 0.25. The inhibitory effect of aripiprazole on Kv channels was voltage-dependent, and an additional aripiprazole-induced decrease in the Kv current was observed in the voltage range of full channel activation. The decay rate of Kv channel inactivation was accelerated by aripiprazole. Aripiprazole shifted the steady-state activation curve to the right and the inactivation curve to the left. Application of a repetitive train of pulses (1 and 2 Hz) promoted inhibition of the Kv current by aripiprazole. Furthermore, the recovery time constant from inactivation increased in the presence of aripiprazole. Pretreatment of Kv1.5 subtype inhibitor reduced the inhibitory effect of aripiprazole. However, pretreatment with Kv 7 and Kv2.1 subtype inhibitors did not change the degree of aripiprazole-induced inhibition of the Kv current. We conclude that aripiprazole inhibits Kv channels in a concentration-, voltage-, time-, and use (state)-dependent manner by affecting the gating properties of the channels.

Male gynecomastia linked to antipsychotics: a case report

IntroductionGynecomastia refers to the abnormal development of breast tissue in males, often posing a concerning symptom. Often, gynecomastia is associated with multiple factors, including the use of various drugs, notably certain atypical antipsychotics. Gynecomastia is a significant side effect that affects the quality of life of male patients taking antipsychotic medications. Among these, risperidone and paliperidone have been identified as the most prone to causing gynecomastia, although aripiprazole has garnered attention for its superior profile in controlling prolactin and gynecomastia. The relationship between these drugs and the development of gynecomastia lies in their ability to elevate prolactin levels, a hormone that regulates reproductive function and is involved in milk production. Several studies have shown that prolactin levels are more commonly elevated with risperidone and paliperidone prescription, thus triggering gynecomastia.ObjectivesThe study aims to investigate the management of gynecomastia in male patients receiving antipsychotic medications.MethodsThis research employs a retrospective analysis of patient records to examine the association between specific antipsychotic drugs, prolactin levels, and the development of gynecomastia, while also evaluating the effectiveness of aripiprazole as an alternative treatment.ResultsWe present the case of a 21-year-old male with no prior medical history who initiated treatment with oral paliperidone and later switched to 100 mg of long-acting injectable paliperidone once monthly during his initial admission for psychotic symptoms. After six months, he developed gynecomastia, which was ruled out as breast tissue and was determined to be an increase in adipose tissue. Since his hospital discharge, he has gained 25 kg (30%) in body weight, and his baseline prolactin level has decreased. This weight gain, a common side effect of several antipsychotics, was linked to gynecomastia. However, a promising approach for gynecomastia antipsychotic-associated treatment is aripiprazole, which has a milder impact on prolactin levels. In this case, during the next appointment, a switch to 400 mg of long-acting injectable aripiprazole once-monthly was made, which led to weight loss, a reduction in breast size and blood prolactin levels in the following weeks.ConclusionsThe detection and management of gynecomastia in these patients are crucial to improving their quality of life and treatment adherence. This management encompasses changes in medication, hormonal therapy, or surgery in severe cases. Physicians must be aware of this potential complication when prescribing antipsychotics and closely monitor at-risk patients. In summary, antipsychotic-associated gynecomastia in men represents a medical challenge that requires careful attention and an individualized treatment strategy for each affected patient.Disclosure of InterestNone Declared

Effects of Aripiprazole on Olanzapine Population Pharmacokinetics and Initial Dosage Optimization in Schizophrenia Patients.

Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug-drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients. In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five schizophrenia patients were enrollmented for analysis using population pharmacokinetic model by means of nonlinear mixed effect (NONMEM). Weight and combined use of aripiprazole significantly affected olanzapine clearance. Without aripiprazole, for once-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-70, and 70-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-60, and 60-100 kg schizophrenia patients, respectively. With aripiprazole, for once-daily olanzapine administration dosages, 0.4, 0.3 mg/kg/day were recommended for 40-53, and 53-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.4 mg/kg/day was recommended for 40-100 kg schizophrenia patients, respectively. Aripiprazole significantly affected olanzapine clearance, and when schizophrenia patients use aripiprazole, the olanzapine dosages need adjust. Meanwhile, we firstly recommended the optimal initial dosages of olanzapine in schizophrenia patients.

Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study

BackgroundWe conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. MethodsSeventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. ResultsThe overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LimitationsThe small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. ConclusionThe results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Effects of aripiprazole on resting-state functional connectivity of large-scale brain networks in first-episode drug-naïve schizophrenia patients

Aripiprazole modulates functional connectivity (FC) between several brain regions in first-episode schizophrenia patients, contributing to improvement in clinical symptoms. However, the effects of aripiprazole on abnormal connections among extensive brain networks in schizophrenia patients remain unclear. We aimed to investigate the effects of 12 weeks of aripiprazole treatment on the FC of large-scale brain networks. Forty-five first-episode drug-naïve schizophrenia patients and 45 healthy controls were recruited for this longitudinal study. Resting-state functional magnetic resonance imaging (fMRI) data were collected at baseline and after 12 weeks of aripiprazole treatment. The patients were classified into those in response (SCHr group) and non-response (SCHnr group) according to the improvement of clinical symptoms after 12-weeks treatment. The FC were evaluated for seven large-scale brain networks. In addition, correlation analysis was performed to investigate associations between changes FC of large-scale brain networks and clinical symptoms. Before aripiprazole treatment, schizophrenia patients showed decreased FC of extensive brain networks compared to healthy controls. The 12-week aripiprazole treatment significantly prevented the constantly decreased FC of subcortical network, default mode network and other brain networks in patients with SCHr, in association with the improvement of clinical symptoms. Taken together, these findings have revealed the effects of aripiprazole on FC in large-scale networks in schizophrenia patients, which could provide new insight on interpreting symptom improvement in SCH.

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model.

The available antipsychotics for schizophrenia (SZ) only reduce positive symptoms and do not significantly modify SZ neurobiology. This has raised the question of the robustness and translational value of methods employed during drug development. Electroencephalography (EEG)-based measures like evoked and spontaneous gamma oscillations are considered robust translational biomarkers as they can be recorded in both patients and animal models to probe a key mechanism underlying all SZ symptoms: the excitation/inhibition imbalance mediated by N-methyl-D-aspartate receptor (NMDAr) hypofunction. Understanding the effects of commercialized atypical antipsychotics on such measures could therefore contribute to developing better therapies for SZ. Yet, the effects of such drugs on these EEG readouts are unknown. Here, we studied the effect of the atypical antipsychotic aripiprazole on the gamma-band auditory steady-state response (ASSR), spontaneous gamma oscillations and behavioral features in a SZ rat model induced by the NMDAr antagonist MK-801. Interestingly, we found that aripiprazole could not normalize MK-801-induced abnormalities in ASSR, spontaneous gamma oscillations or social interaction while it still improved MK-801-induced hyperactivity. Suggesting that aripiprazole is unable to normalize electrophysiological features underlying SZ symptoms, our results might explain aripiprazole's inefficacy towards the social interaction deficit in our model but also its limited efficacy against social symptoms in patients.

Effects of aripiprazole on prolactin levels and differences in effectiveness in patients with schizophrenia: a post-hoc analysis of the real-world data of a multicenter study.

To investigate the effect of aripiprazole on prolactin levels in patients with schizophrenia and analyze whether varying baseline prolactin levels affect the effectiveness and safety of aripiprazole, in a real-life diagnostic and therapeutic setting in a post-hoc analysis. In this post-hoc analysis, patients with schizophrenia in the acute phase were divided into an elevated-prolactin group and a normal-prolactin group. After 8 weeks of aripiprazole treatment, changes in the proportion of patients with an abnormal prolactin level were analyzed in both groups, and the efficacy and safety of aripiprazole were compared between the two groups. The elevated-prolactin group had more women, a longer duration of disease, and lower Positive and Negative Syndrome Scale (PANSS) total and subscale scores at baseline compared with the normal-prolactin group (all P < 0.05), and there was no significant difference in the proportion of patients with prior use of antipsychotic medication between the two groups. Regardless of previous antipsychotic use, patients in both groups developed hyperprolactinemia (23/168 [13.7%] in those who had taken antipsychotics vs. 43/375 [11.4%] in those who had not). After 8 weeks of aripiprazole treatment, the proportion of patients with abnormal prolactin in the elevated-prolactin group significantly decreased with prolonged treatment (P < 0.001), and aripiprazole had no significant effect on the normal-prolactin group (P = 0.250). Normal-prolactin group showed better efficacy than the elevated-prolactin group, and the differences in efficacy between the two groups was observed from week 4 to the endpoint (all p<0.05). In total, 87.2% (68/78) patients experienced mild to moderate adverse events in the elevated-prolactin group, which was significantly more frequent compared with the normal-prolactin group 71.0% (365/514). In this real-world study, for patients with acute schizophrenia, aripiprazole was effective in lowering the proportion of patients with abnormal prolactin levels, while it had no significant effect on patients with normal baseline prolactin. After adjusting for factors such as sex, age, prior antipsychotic drugs use history and disease severity, effectiveness and safety of aripiprazole in patients with normal baseline prolactin was significantly better than that in patients with elevated baseline prolactin.

Investigating the effects and side effects of two antipsychotic drugs in the treatment of children and adolescents with Tourette syndrome: a semi-experimental research.

Due to the high prevalence of Tourette's disorder among children and adolescents and its negative consequences, an appropriate and effective medical treatment with minimal complications is necessary. Therefore, this study was conducted to compare the effects of Aripiprazole and Risperidone on Tourette's disorders in children and adolescents. The statistical population of this semi-experimental study was children and adolescents aged seven to eighteen years old. They were diagnosed with Tourette's disorder based on the DSM-V criteria by the clinical interview of a child and adolescent psychiatrist in the child Psychiatry clinic of Ibn-e-Sina's Psychiatric Hospital (Mashhad-Iran) in 2018. A total of forty participants were selected by the convenience sampling method, and they were randomly divided into two groups treated with medicines, Risperidone or Aripiprazole, for two months. Then, the demographic information questionnaire was completed. The Y-GTSS Scale was completed. The clinical Effect Rating Scale (CGI-Tics Scale) was completed. Calculation of body mass index and medical side effects complications were completed. The evaluation was carried out at the beginning and on the second, fourth, and eighth weeks, and the results were compared. The data were analyzed using SPSS software. 14, descriptive statistics, Chi-square, and variance analysis. The two groups were homogeneous in terms of demographic variables and body mass index. Despite the positive effect of both medicines, no significant difference was observed among the general scores of such disorders, the overall score of severity, Tourette's recovery, and BMI of these two groups at the intervals and the end of treatments. (p <0.05). Due to the low number of complications reported, statistical comparisons of the medical side effects were not made. According to the results, the two medicines, Aripiprazole and Risperidone, effectively improved the symptoms of Tourette's disorder and its overall severity. However, there were no significant statistical differences between them. Furthermore, in terms of the medical side effects, the statistical comparison between the two medicines was impossible due to the small number of complications.

(014) Fighting the Fire: Anti-Inflammatory Effects of Aripiprazole as Mechanism for Improvement in Medical Catatonia?

(014) Fighting the Fire: Anti-Inflammatory Effects of Aripiprazole as Mechanism for Improvement in Medical Catatonia?

Therapeutic Dosage of Antipsychotic Drug Aripiprazole Induces Persistent Mitochondrial Hyperpolarisation, Moderate Oxidative Stress in Liver Cells, and Haemolysis.

Aripiprazole has fewer metabolic side effects than other antipsychotics; however, there are some severe ones in the liver, leading to drug-induced liver injury. Repeated treatment with aripiprazole affects cell division. Since this process requires a lot of energy, we decided to investigate the impact of aripiprazole on rat liver cells and mitochondria as the main source of cellular energy production by measuring the mitochondrial membrane potential, respiration, adenosine triphosphate (ATP) production, oxidative stress, antioxidative response, and human blood haemolysis. Here, we report that mitochondrial hyperpolarisation from aripiprazole treatment is accompanied by higher reactive oxygen species (ROS) production and increased antioxidative response. Lower mitochondrial and increased glycolytic ATP synthesis demand more glucose through glycolysis for equal ATP production and may change the partition between the glycolysis and pentose phosphate pathway in the liver. The uniform low amounts of the haemolysis of erythrocytes in the presence of aripiprazole in 25 individuals indicate lower quantities of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH+H+), which is in accordance with a decreased activity of glucose 6-phosphate dehydrogenase and the lower dehydrogenase activity upon aripiprazole treatment. The lower activity of glucose 6-phosphate dehydrogenase supports a shift to glycolysis, thus rescuing the decreased mitochondrial ATP synthesis. The putative reduction in NADPH+H+ did not seem to affect the oxidised-to-reduced glutathione ratio, as it remained equal to that in the untreated cells. The effect of aripiprazole on glutathione reduction is likely through direct binding, thus reducing its total amount. As a consequence, the low haemolysis of human erythrocytes was observed. Aripiprazole causes moderate perturbations in metabolism, possibly with one defect rescuing the other. The result of the increased antioxidant enzyme activity upon treatment with aripiprazole is increased resilience to oxidative stress, which makes it an effective drug for schizophrenia in which oxidative stress is constantly present because of disease and treatment.

Effect of aripiprazole on promoting cognitive function and enhancing clinical efficacy in patients with first-episode depression on escitalopram: A randomized controlled trial

ObjectivesTo explore the effect of escitalopram combined with aripiprazole on cognitive function in patients with major depressive disorder (MDD), and to evaluate the clinical efficacy of the combination therapy. MethodA total of 70 patients with first-episode MDD were randomly divided into the study group or the control group, receiving escitalopram combined with aripiprazole (5 mg/day) or escitalopram monotherapy respectively for 8 weeks. The severity of illness was assessed by using the Hamilton Rating Scale for Depression (HAMD) at baseline, at the end of 4th and 8th week, and cognitive function was assessed by using the THINC integrated tool (THINC-it), the Wisconsin Card Sorting Test (WCST), and the Continuous Performance Test (CPT). Rating Scale for Extrapyramidal Side Effects (RSESE) was applied to assess adverse reactions. ResultsThe average HAMD-17 and HAMA scores decreased over time in both the control and the study groups, but the reductions were not statistically different between two groups with the passage of time. In WCST, total number of response (TR) of the study group decreased relative to the baseline at the end of the eighth week, but the control group did not significantly change during whole eight weeks. Perseverative errors (PE) in the control group eventually decreased at the end of Week 8 compared to that at Week 4, but in the study group, it was a continuous trend of decrease. In CPT, the decrease of leakage responses (LR) in the study group was higher than that of the control group in 2-digit number, and LR of the control group was higher than that of the study group at the end of Week 8 in 4-digit number. The downtrend of LR in 4-digit number kept for the whole period in study group, while in the control group, the LR did not decrease significantly until the end of Week 8 compared to that at baseline. ConclusionEscitalopram combined with a low-dose of aripiprazole, and escitalopram monotherapy could both enhance cognitive function of MDD patients, while the improvements of combination therapy might happen relatively earlier. The combined use of escitalopram and aripiprazole might be more beneficial to the domains of executive function (EF) and continuous attention compared to escitalopram monotherapy. There was no significant differences between two treatment options in alleviating depressive and anxiety symptoms.

Comparative effectiveness of aripiprazole and olanzapine on neurocognitive profile of patients with schizophrenia.

Schizophrenia causes significant neurocognitive impairment. Treatment with antipsychotics leads to improvement in psychopathology and neurocognitive functions. To see comparative effectiveness of aripiprazole and olanzapine on neurocognitive profile of patients with schizophrenia. This was a comparative, prospective, and interventional study. Patients with schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), were assessed on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests at baseline. Patients were randomly assigned to aripiprazole (10-30 mg per day, orally) and olanzapine (5-20 mg per day, orally) groups on the basis of computer-generated random table number. Patients were reassessed at 10 weeks. A total of 40 patients completed the study duration of 10 weeks. At baseline, the majority of patients showed significant impairment in one or more domains of neurocognition. Both aripiprazole and olanzapine led to improvement in psychiatric symptoms as well as neurocognitive profile. Aripiprazole treatment leads to significant improvement in mental speed as compared to olanzapine. A highly significant decrease in the value of the Stroop effect indicates improvement (P = 0.000**) with aripiprazole and visual-spatial constructive ability (P < 0.001). The olanzapine group showed highly significant improvement in performance of category fluency (P < 0.01) and verbal fluency (P < 0.01). The study concludes that aripiprazole and olanzapine have strong potential to improve specific domains of neurocognitive profile.

Efficacy and Side Effects of Aripiprazole and Olanzapine in Patients with Psychotic Disorders: A Randomized Controlled Trial.

In clinical experience, selecting atypical antipsychotics optimally balancing their benefits and potential side effects is seen to improve treatment adherence in patients. This study aimed to compare the effectiveness and side effect profiles of aripiprazole and olanzapine in patients with psychotic disorders. In this double-blind clinical trial, the subjects were patients with psychotic disorders treated with aripiprazole and olanzapine. The subjects were randomly divided into two equally sized groups. One group was treated with olanzapine and the other group with aripiprazole. All participants were assessed using the positive and negative syndrome scale and side effects were monitored over a two-month follow-up period. The participants comprised N = 76 patients (65 male; 11 female). Treatments with both aripiprazole (n = 38) and olanzapine (n = 38) were associated with a significant decrease in the severity of psychotic symptoms over the two-month treatment period. This decrease was achieved faster in the olanzapine group. There were no significant differences in the changes in body mass index, waist circumference, blood sugar, triglyceride, or cholesterol between the two groups. A qualitative difference between the groups was found in their total sleep duration. Olanzapine was more effective than aripiprazole in reducing psychotic symptoms. There were no significant differences between the overall side effect profiles of the two drugs.