Aripiprazole Research Articles

Reducing burst release and enhancing sustained release in SAIB-based implants: The role of polyphenol-modification.

Patients with bipolar disorder (BD) who also experience delayed sleep-wake phase (DSWP) disorder/syndrome may tend to be younger, have a higher risk of relapse, and exhibit more severe impairments in social functioning. However, few studies have explored this area, and there are currently no established treatment guidelines, prompting us to investigate this further through a case series. We report on a chart review of 15 patients diagnosed with bipolar disorder (BD) and delayed sleep-wake phase (DSWP) syndrome, who received Aripiprazole (APZ) monotherapy for 12 to 135 weeks. Efficacy was observed within the first two weeks, indicated by reductions in Clinical Global Impressions-Severity (CGI-S) scores and an advancement of the sleep-wake cycle. By the final visit, 93.3% (14/15) of participants had achieved clinical remission (defined as CGI-S < 3), with their social functioning returning to normal. The most common adverse events were extrapyramidal side effects and weight gain, but both were reversible. In summary, APZ monotherapy may be an effective and safe treatment option for BD patients with DSWP syndrome. Our chart review highlights the potential value of further systematic investigation through a clinical trial.

PurposeOASIS (NCT03919994) was a prospective, observational study designed to provide insights on real-world outcomes associated with atypical long-acting injectable (LAI) antipsychotic medications.Patients and MethodsOASIS (March 2019–January 2023) was conducted across 63 US sites. Adults (≥18 years) with schizophrenia who newly initiated one of four atypical LAI antipsychotics (aripiprazole lauroxil, aripiprazole monohydrate, paliperidone palmitate, or risperidone long-acting injection [microsphere formulation]) were enrolled and followed for up to 12 months in routine care. Treatment patterns (reasons for treatment initiation, duration of use, rates of switching/discontinuation) were assessed. Outcomes included Clinical Global Impression–Severity (CGI-S), Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) scale, and patient-reported Glasgow Antipsychotic Side-Effect Scale (GASS) scores. Results are summarized descriptively.ResultsOverall, 277 patients with schizophrenia enrolled and received ≥1 injection. Most common reasons for initiating atypical LAI antipsychotics at baseline were the presence of persistent psychotic symptoms (50%) and adherence challenges with oral antipsychotics (44%). Mean (SD) time on index treatment was 210.0 (145.3) days. Overall, 130 (47%) patients completed 12 months of follow-up; 74% of them remained on the treatment initiated until the end of study participation. Most study visits were conducted in person and were planned/scheduled versus crisis visits. Mean (SD) baseline CGI-S score was 4.2 (1.1), indicating moderate illness severity; individual CRDPSS symptom scores were mild (mean [SD] delusions score, 2.0 [1.4]; hallucinations, 1.9 [1.4]; negative symptoms, 1.6 [1.3]) at baseline and remained stable after treatment initiation. Antipsychotic side effects were generally absent or mild at baseline (mean [SD] GASS total score, 10.7 [10.3]) and over follow-up.ConclusionTreatment patterns in this observational study reinforced the real-world utility of atypical LAI antipsychotics in the treatment of schizophrenia. Results suggest that patients initiating treatment remained clinically stable with mostly absent or mild side effects for up to 12 months of follow-up.

BackgroundIn patients with remitted psychosis, the dosage of antipsychotics can be lowered without increased risk of relapse. Whether dose tapering can lead to improved cognition is unclear. We compared changes in cognitive performance between patients undergoing dose tapering and those receiving a fixed maintenance dose.MethodsA 2-year prospective trial of patients with stable schizophrenia-related psychotic disorders was conducted: one group received guided dose reduction (GDR) and one group received maintenance treatment. Cognitive function was assessed using the Wechsler Adult Intelligence Scale-Third Edition, Mandarin Chinese version, at baseline, 1, and 2 years. The relations between the ratio of reduced dose and the extent of cognitive improvement were examined by Spearman’s correlation coefficient. We also examined cognitive performance between aripiprazole (ARI) users and non-ARI users.ResultsGDR patients exhibited significantly greater improvements in total intellectual quotient (IQ), particularly working memory, and information and arithmetic subtest scores, with no significant difference in relapse rates between groups. Statistically significant dose–response correlations were found between the degree of dose reduction and improvements in total IQ (n = 72, r = 0.242, p = 0.041), Working Memory Index (n = 72, r = 0.284, p = 0.016), and Arithmetic subtest (n = 72, r = 0.295, p = 0.012). There were no differences in cognitive changes between ARI users and non-users.ConclusionsLowering antipsychotic dosage may ameliorate patient performance in several cognitive domains. This finding is worthy of consideration while evaluating the risk-to-benefit ratio of tapering antipsychotics in patients with remitted psychosis.

BackgroundThe number of patients with depression is increasing worldwide; however, current antidepressants need over two weeks for their effect. Around 30% of patients exhibit treatment resistance. Novel therapeutic strategies are required for these problems. Mutation in ODZ4, which encodes the Teneurin-4 (Tenm-4) protein, has been reported as a risk factor for mental disorders such as bipolar disorder and schizophrenia, accompanied by depressive syndrome. In addition, Tenm-4 could induce changes in synapse formation, axon guidance, or cell differentiation in oligodendrocytes. The prefrontal cortex (PFC) is involved in the regulation of depressive behaviors.Aims & ObjectivesTo reveal the relation of Tenm-4 with mental disorders, we generated PFC-specific knockdown (Tenm-4KD) mice and evaluated behavior phenotypes. To investigate neuropathological changes in PFC caused by Tenm4KD, the change in the amount of myelin sheath was evaluated with immunohistochemistry.MethodWe generated prefrontal Tenm-4KD mice with adeno-associated virus injection male C57BL6/J (6-7 week-old) with (Tenm-4KD, and Mock as control) vectors integrated with the CRISPR-Cas9 system. Four weeks after the AAV injection, behavioral tests, including the sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST), were conducted to assess depression-like behaviors. Additionally, aripiprazole (APZ), a dopamine D2/3 partial agonist and serotonin 5-HT1A partial agonist/5-HT2A antagonist, was administered to evaluate its antidepressant effects. Myelin alterations in the PFC were analyzed using immunofluorescence staining for myelin basic protein (MBP).ResultsTenm4KD mice exhibited significant reductions in sucrose preference (Tenm4KD mice=72.1% vs. Mock mice=85.8%, p < 0.05) in SPT. Tenm4KD mice showed increased immobility time in TST (164.7 sec vs. 130.1 sec, p < 0.05) and FST (218.7 sec vs. 179.2 sec, p < 0.01) compared to Mock mice. APZ treatment restored sucrose preference (80.5% vs. 58.6%, p < 0.05) in Tenm4KD mice compared to saline treatment. Furthermore, MBP staining revealed a significant reduction in myelin she in the PFC of Tenm4KD mice.Discussion & ConclusionsThese results suggest that PFC-specific Tenm4KD induces depression-like behaviors without affecting locomotor activity or recognition memory. The reversal of these behaviors after administration with APZ was recovered, therefore Tenm-4KD could involve dysfunction of dopamine and/or serotonin nervous. Additionally, the observed myelin reduction indicates that Tenm-4 deficiency would contribute to depression pathophysiology through glial dysfunction. Our results suggest PFC-specific Tenm-4KD mice could be a novel model for depression leading to the development of new antidepressant strategies.

Aripiprazole is a second-generation partial dopamine D₂ receptor agonist antipsychotic approved for the treatment of schizophrenia and maintenance treatment of bipolar I disorder. As the only partial dopamine D₂ receptor agonist available in both oral and long-acting injectable (LAI) formulations, it provides flexibility for tailoring treatment across different phases of the illness. Two LAI formulations of aripiprazole monohydrate are available: aripiprazole once-monthly 400 mg and aripiprazole 2-month ready-to-use 960 mg, offering options to accommodate patient needs and preferences and support adherence. The aripiprazole monohydrate LAIs are well-supported options for early intervention and maintenance treatment, with evidence demonstrating clinical effectiveness in reducing relapse and hospitalizations while supporting enhanced adherence. LAI antipsychotics, including aripiprazole monohydrate, offer practical benefits for patients with schizophrenia, particularly those at risk for nonadherence or recurrent episodes. However, these formulations are often underutilized due to lingering stigma and misperceptions, leading many clinicians to defer use of these agents until later in the treatment course. To support earlier and more informed use of aripiprazole monohydrate LAIs, a panel of psychiatric experts convened to review the latest evidence and share clinical strategies for integrating this agent into a comprehensive treatment plan. This Academic Highlights section presents the main points of their consensus recommendations, offering practical guidance for prescribers seeking to optimize outcomes in patients with schizophrenia.

Bipolar I disorder (BP-I) is a severe and chronic psychiatric condition characterized by recurrent episodes of mania and depression that significantly impact quality of life and functioning. Early recurrence, high relapse rates, and poor adherence to daily oral medications complicate long-term management and increase the risk of hospitalization and suicide. Long-acting injectable antipsychotics (LAIs) offer a potential solution to these challenges by promoting sustained medication delivery and efficacy, reducing pharmacokinetic variability, and improving treatment adherence. Among available LAIs, aripiprazole is the only partial dopamine D₂ receptor agonist, which may contribute to its favorable tolerability and mood-stabilizing properties. Despite the robust evidence for the efficacy and tolerability of aripiprazole monohydrate LAIs in patients with BP-I, this agent remains underutilized in this population. Misperceptions about efficacy and tolerability, coupled with systemic and prescriber-level barriers, have limited broader clinical adoption. To address these issues, a round table panel of experts in psychopharmacology, the clinical treatment of bipolar disorder, and antipsychotic prescribing was convened to evaluate the clinical rationale for earlier use of aripiprazole monohydrate LAIs in BP-I and to identify key challenges limiting its use. This article summarizes their consensus on the pharmacological distinctiveness, practical advantages, and potential of aripiprazole monohydrate LAIs in improving long-term outcomes in individuals with BP-I.

Predicting early treatment response in acute schizophrenia is critical yet challenging. This observational study aimed to determine whether improvements in specific symptom domains after 2 weeks predict overall response at 6 weeks in patients treated with aripiprazole (ARI) or brexpiprazole (BRE). We included 65 patients (34 antipsychotic-naïve and 31 antipsychotic-free recurrent) treated with flexible doses of ARI or BRE. Benzodiazepines were used in 41 patients (64.1%), and their use did not significantly impact prediction. The Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Improvement were used to assess responses. Receiver operating characteristic analysis revealed area under the curve values for PANSS total (PANSS-T), negative, excitement, cognitive, positive, and depressive/anxiety components of 0.788, 0.783, 0.603, 0.746, 0.738, and 0.735, respectively. Kendall's tau correlation and Cramer's V revealed significant predictive relationships for PANSS-T (0.413, P <0.001), negative (0.411, P <0.001), and therapeutic response dichotomized by this score (0.573, P <0.001), cognitive (0.364, P <0.001), positive (0.344, P <0.001), and depression/anxiety (0.344, P =0.001), but not for excitement (0.15, P =0.151). Benzodiazepine use did not significantly impact these predictive associations. This study is the first to evaluate the predictive validity of the PANSS 5-factor model in patients with acute schizophrenia treated with ARI/BRE. Early symptom improvements, particularly in negative domains, are stronger predictors of overall response, while excitement symptom improvements showed a weaker relationship. These findings underscore the importance of early, symptom-specific assessments to optimize treatment strategies for acute schizophrenia. Further studies with larger samples are necessary to validate these results.

TV-46000 [once monthly (q1m) or once every 2 months (q2m)] is a subcutaneously administered long-acting injectable antipsychotic (LAI) formulation of risperidone for the treatment of schizophrenia in adults. As second-generation LAIs become available, understanding comparative efficacy and safety is needed. We undertook a systematic literature review (SLR; January 1, 2020 to May 11, 2023) and network meta-analyses (NMAs) of randomized controlled clinical trials to compare the efficacy and safety of TV-46000 q1m and q2m with second-generation LAIs approved in Canada and used for treatment of schizophrenia [intramuscular aripiprazole monohydrate q1m, paliperidone palmitate q1m (PP1M), and paliperidone palmitate once every 3 months (PP3M)]. The primary efficacy outcome was relapse rate at 6 months, while safety outcomes were adverse event (AE)-related discontinuation, significant weight gain (≥7%), treatment-related AEs, and injection-site pain. Sixty-one records from 24 studies were included in the SLR, and 6 were included in the NMAs. For the relapse rate at 6 months, all treatments were significantly better than placebo, with relative risks (RRs) ranging from 0.23 for TV-46000 q1m to 0.46 for PP1M 50-150 mg eq and no significant differences among LAIs. There were no significant differences between TV-46000 and either placebo or PP1M 25-100 mg eq for AE-related discontinuation. TV-46000 q1m, PP1M 25-100 mg eq, and TV-46000 q2m were significantly less likely to cause weight gain≥7% than PP3M (RR: 0.09, 0.09, and 0.06, respectively) or PP1M 50-150 mg eq(0.08, 0.08, and 0.06, respectively). Treatment-related AEs were significantly less likely with PP1M 25-100 mg eq, TV-46000 q1m, and placebo than PP3M (RR: 0.48, 0.62, and 0.66, respectively). There were no significant differences in injection-site pain between groups. TV-46000 q1m and q2m demonstrated comparable efficacy and safety to second-generation LAIs approved in Canada and used for maintenance treatment of schizophrenia.

N-acetylcysteine enhances the antipsychotic effect of aripiprazole in the neurodevelopmental rat model of schizophrenia.

Introduction: Neurotransmitters (dopamine, serotonin, noradrenaline, and acetylcholine) play crucial roles in the regulation of various physiological processes. An imbalance in their levels can result in numerous neurological and psychiatric disorders, such as depression, anxiety, and schizophrenia. Numerous computational approaches enhance the efficiency of drug discovery, one of which is the design of analogs through bioisosteric replacement. Aripiprazole (APZ), a partial agonist of dopamine D2 receptors, is widely used in treating schizophrenia and bipolar disorder. However, prolonged APZ use can lead to side effects such as cardiovascular and liver toxicity. This study aims to in silico design APZ analogs with an improved pharmacological, drug-likeness, and reduced toxicity profile. Method: APZ analogs were generated using the MolOpt tool. Their pharmacokinetic and toxicological (ADMET) profiles were calculated using ADMETLab 3.0 online tool. Drug likeness (DL) and drug score (DS) were predicted using Osiris property explorer (PEO). Molecular docking studies were conducted against the protein (PDB ID: 7DFP) using Argus Lab 4.0.1. Result: A total of 983 APZ analogs were generated and 83 analogs were screened for molecular docking based on ADMET properties, DL, and DS. Docking analysis revealed that key interactions with Asp114 in the target protein were preserved in several bioisosteres, indicating potential pharmacological relevance. Conclusion: Based on ADMET analysis, DL scores, DS, and docking results, the APZ bioisosteres, particularly B104, B170, and C78, emerged as promising candidates for further investigation as potential antipsychotic agents. Further work is in progress in order to evaluate the potential of these analogs as antipsychotic agents.

Schizophrenia and bipolar I disorder (BP-I) are chronic, disabling psychiatric illnesses marked by high morbidity, elevated mortality, and functional deterioration, often exacerbated by poor adherence to oral antipsychotic medications. Long-acting injectable (LAI) antipsychotics were developed to address adherence challenges and have demonstrated clinical benefits including reduced non-adherence and relapse rates, fewer hospitalizations, and improved functioning and quality of life, and reduced mortality risk. Among available LAIs, aripiprazole offers a unique pharmacologic profile as the only partial dopamine agonist available in an LAI formulation. Aripiprazole monohydrate LAI is available as a once monthly and a once-every-two-month formulation. In this consensus panel report, five psychiatric experts convened to evaluate the pharmacokinetic properties, safety, efficacy, and clinical utility of aripiprazole monohydrate LAIs in the treatment of schizophrenia and BP-I. The panel focused particularly on the more recently approved once-every-2-month ready-to-use formulation. This article summarizes the evidence reviewed by the panel and highlights key considerations for optimizing the use of aripiprazole monohydrate LAIs in clinical practice to enhance treatment outcomes in patients with schizophrenia and BP-I.

Background/Objectives: Long-acting injections (LAIs) are innovative drug delivery systems that improve patient compliance by maintaining therapeutic drug levels over extended periods. Micro- and nanosuspensions are commonly used in LAIs to enhance bioavailability, but their thermodynamic instability poses challenges, including particle aggregation and growth. This study aimed to evaluate the impact of two helping processes—vehicle thermal treatment and high-shear homogenization—on the stability and manufacturing efficiency of aripiprazole monohydrate (AM) suspensions. Methods: AM suspensions containing sodium carboxymethyl cellulose (CMCNa), mannitol and disodium phosphate in water for injections (WFIs) were prepared using a combination of thermal treatment of the vehicle solution, high-shear homogenization and bead milling. Four manufacturing variants were tested to assess the influence of these processes on particle size distribution (PSD), viscosity and stability during a 3-month accelerated stability study. Molecular weight changes in CMCNa from thermal treatment were analyzed using size exclusion chromatography with multiangle scattering (SEC-MALS), and PSD was measured using laser diffraction. Results: Thermal treatment of the vehicle solution had minimal impact on CMCNa molecular weight, preserving its functionality. High-shear homogenization during bead milling significantly reduced particle aggregation, resulting in improved PSD and reduced viscosity. Synergistic effects of the two helping processes used in one manufacturing process were observed, which led to superior stability and minimal changes in PSD and viscosity during storage. Batches without the helping processes exhibited increased particle size and viscosity over time, indicating reduced suspension stability. Conclusions: Incorporating vehicle thermal treatment and high-shear homogenization during bead milling enhances the stability and manufacturing efficiency of AM suspensions. These findings underscore the importance of optimizing laboratory-scale processes to ensure the quality and safety of pharmaceutical suspensions.

Abstract Controlled drug release minimizes side effects by reducing dosage, and when biocompatible cryogels are combined with molecularly imprinted polymers, they provide an effective and targeted method for drug delivery. In this study, pHEMA-based cryogel patches were synthesized by molecularly imprinting aripiprazole (ARP), which is widely used in the treatment of neurological diseases. The synthesized cryogel patches were characterized using Fourier-transform infrared spectroscopy and scanning electron microscopy. The study demonstrated that the release behavior of ARP from cryogel patches was significantly influenced by factors such as cross-linker ratio, pH, and drug loading concentration. The cumulative drug release percentage reached 79% for an ARP loading concentration of 1.5 mg/mL. Additionally, cryogel patches showed biocompatibility, with over 80% cell viability at 48 h, confirming their potential for safe and effective drug delivery applications. The release kinetics were discussed, demonstrating the material’s potential suitability for future biomedical applications.

Abstract Introduction Post-COVID-19 conditions, also known as long COVID, encompass a range of symptoms, including fatigue, dyspnea, and cognitive dysfunction, that persist for at least two months following three months after the onset of COVID-19. The WHO estimates that approximately 10–20% of individuals infected with COVID-19 develop post-COVID-19 conditions. Among these patients, it has been reported that around 80% experience sleep disturbances, such as insomnia, hypersomnolence, or circadian rhythm disorders. These disruptions in sleep duration, whether reduced or prolonged, can adversely affect subjective health and quality of life. In adolescents, such disturbances may contribute to school absenteeism and impair social adaptation, emphasizing the need for effective management strategies. Aripiprazole (APZ), commonly prescribed for schizophrenia, has recently been shown to improve hypersomnolence symptoms when used at low doses. In this study, we report a case series of 10 adolescents with post-COVID-19 hypersomnolence. Administration of low-dose APZ effectively reduced sleep duration, providing insights into its potential utility as a therapeutic option for hypersomnolence associated with post-COVID-19 conditions. Methods Ten adolescent patients with post-COVID-19 hypersomnolence who visited our institution between 2019 and December 2024 were included if their sleep duration was prolonged compared to their pre-infection baseline. All participants displayed sleep patterns resembling those observed in delayed sleep phase syndrome (DSPS). After obtaining informed consent from the patients and their guardians, low-dose APZ (0.5–2.0 mg) was prescribed. Patients maintained sleep diaries documenting bedtime, wake-up time, and total sleep duration both before and after the initiation of APZ treatment. Sleep parameters were subsequently analyzed for changes in total sleep duration and wake-up times using statistical methods. Adverse effects were monitored throughout the treatment period. The Ethics Committee of Ibaraki Prefectural Medical Center of Psychiatry approved this study. Results Low-dose APZ effectively reduced total sleep duration and advanced wake-up times in adolescents with post-COVID-19 hypersomnolence, enabling some patients to return to their previous lifestyles. No significant adverse effects were reported. Conclusion Low-dose APZ effectively managed post-COVID-19 hypersomnolence in adolescents by reducing total sleep duration and advancing wake-up times. These findings suggest APZ as a promising therapeutic option for post-COVID-19 hypersomnolence, particularly in adolescents, warranting further investigation in larger studies. Support (if any)

Drug repurposing, which involves applying existing pharmaceuticals to new therapeutic areas, offers several advantages, including increased efficiency, reduced costs, and lower risks. The research aimed to investigate the molecular mechanisms underlying the new application of the antipsychotic drug aripiprazole (APZ) in the treatment of endometrial cancer (EC), as well as its synergistic efficacy when used in combination with progestin. The cell viability assay and proliferation assay demonstrated that APZ exerted a significant inhibitory effect on the proliferation of ISK and KLE cells. Moreover, APZ was found to induce cell apoptosis prominently by flow cytometry. Network pharmacology analysis indicated that the anti-EC effects of APZ were mediated via the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which was subsequently confirmed by Western blot analysis. Furthermore, APZ significantly enhanced the proliferation inhibitory effect of medroxyprogesterone acetate (MPA) against progestin-resistant KLE cells, displaying remarkable synergistic activity. These findings position APZ as a promising therapeutic candidate for EC, with potential utility both as a monotherapy and in combination with MPA, offering new avenues for EC treatment strategies.

The antipsychotic drug aripiprazole (ARP) can be determined at the trace level in biological samples employing an easy-to-use and very sensitive electrochemical approach. The cyclic voltammetric behavior of ARP at the gold (Au) electrode and the boron-doped diamond electrode (BDDE) was investigated and suggested that the ARP oxidation process is irreversible and adsorption-controlled. The morphology of ARP on the Au electrode surface was studied using optical microscopy and atomic force microscopy techniques. The various experimental parameters of the SW-AdSV method were optimized for the quantitative determination of ARP at the anodically pretreated BDDE (+2.4 V; 60 s). Under optimized conditions (pH 3.0; accumulation potential (Eacc) of 0.5 V and accumulation time (tacc) of 180 s), a linear concentration range was from 0.10 ng ml−1 to 16.91 ng ml−1, while the relative standard deviation did not exceed 4.6%, and the evaluated detection limit (LOD) was 0.03 ng ml−1. The interference study confirmed adequate selectivity of the proposed SW-AdSV method and BDDE towards ARP. During the analysis of ARP in spiked urine sample, good recovery and reproducibility were achieved, suggesting a good application capability and reliability of the developed voltammetric method for monitoring ARP in biological samples.

Methylphenidate (MPH) serves as a frequently utilized stimulant in the treatment of attention deficit hyperactivity disorder (ADHD). However, long-term administration of this medication has been linked to neurotoxic sequels such as cognitive decline and increased oxidative stress, especially in the hippocampus. In contrast, aripiprazole (ARP), an atypical antipsychotic, has shown promise in providing neuroprotection and reducing inflammation. This research seeks to investigate the protective role of ARP on MPH-induced neurotoxicity in rats. A total of 40 male Wistar rats participated in this study, which were organized into five groups. All the experimental groups received daily intraperitoneal injections of MPH at 10mg/kg, combined with varying doses of ARP at 3, 10, and 30mg/kg for 21days. Behavioral assessments included the open field test and forced swimming test to evaluate motor activity and depressive-like behaviors, as well as the inhibitory avoidance test for cognitive function. Seizure susceptibility was assessed using pentylenetetrazol (PTZ). Following these evaluations, hippocampal tissues were collected for biochemical analysis (oxidative stress markers and neurotrophicfactor)and histopathological studies. ARP at specific doses significantly mitigated locomotor activity impairment, depressive-like behaviors, and memory deficits induced by chronic MPH administration. Additionally, ARP reduced seizure susceptibility compared to the MPH-treated group. Biochemical analyses indicated that ARP decreased oxidative stress markers, including malondialdehyde (MDA) and myeloperoxidase (MPO), while enhancing levels of glutathione and the expression of brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2(NRF2), andprotein kinase B (Akt)in hippocampus. Aripiprazole reduces behavioral and biochemical deficits from chronic MPH use in rats, suggesting it may help mitigate adverse effects of long-term MPH treatment.

ObjectiveThe genetic architecture of antidepressant response is poorly understood. This study investigated whether polygenic risk scores (PRSs) for major psychiatric disorders and a personality trait (neuroticism) are associated with antidepressant treatment outcomes.MethodsWe analysed 148 participants with major depressive disorder (MDD) from the Canadian Biomarker Integration Network for Depression-1 (CAN-BIND-1) cohort. Participants initially received escitalopram (ESC) monotherapy for 8 weeks. Nonresponders at week 8 received augmentation with aripiprazole (ARI), while responders continued ESC until week 16. Primary outcomes were remission status and symptom improvement measured at weeks 8 and 16. At week 16, post-hoc stratified analyses were performed by treatment arm (ESC-only vs. ESC + ARI). Eleven PRSs derived from genome-wide association studies of psychiatric disorders (e.g., MDD and post-traumatic stress syndrome (PTSD)) and neuroticism, were analysed for associations with these outcomes using logistic and linear regression models.ResultsAt week 8, a higher PRS for PTSD was nominally associated with a lower probability of remission (odds ratio (OR) = 0.08 [0.014-0.42], empirical p-value = 0.017) and reduced symptom improvement (beta (standard error) = -29.15 (9.76), empirical p-value = 0.019). Similarly, a higher PRS for MDD was nominally associated with decreased remission probability (OR = 0.38 [0.18-0.78], empirical p-value = 0.044). However, none of the results survived multiple testing corrections. At week 16, the stratified analysis for the ESC-only group revealed that a higher PRS for MDD was associated with increased remission probability (empirical p-value = 0.034) and greater symptom improvement (empirical p-value = 0.02). In contrast, higher PRSs for schizophrenia (empirical p-value = 0.013) and attention-deficit hyperactivity disorder (empirical p-value = 0.032) were associated with lower symptom improvement. No significant associations were observed in the ESC + ARI group.ConclusionsThese findings suggest that PRSs may influence treatment outcomes, particularly in ESC monotherapy. Replication in larger studies is needed to validate these observations.

Objectives: There are currently no long-acting injectable antipsychotics (LAIAs) that are approved by the Food and Drug Administration for use in child and adolescent patients, however these agents are used off-label for the treatment of various psychiatric disorders. This study aims to describe the initiation and maintenance dosing strategies of LAIAs in child and adolescent psychiatry inpatients. Methods: This was a single-site retrospective chart review of patients less than 18 years of age initiated on an LAIA during an acute psychiatric hospitalization between October 1, 2015, and October 31, 2022. Patient demographics and hospital encounter information were collected and analyzed using descriptive statistics. Results: Of the 6402 unique pediatric patients discharged from the acute psychiatric hospital within the specified timeframe, 45 (0.7%) were newly initiated on an LAIA. The average age was 15.6 years (range 10-17), with a greater proportion of male (n = 26, 57.8%) and Black or African American (n = 27, 60%) patients. The LAIA agents prescribed included paliperidone palmitate (n = 21, 46.7%), aripiprazole monohydrate (n = 15, 33.3%), aripiprazole lauroxil (n = 7, 15.6%), haloperidol decanoate (n = 1, 2.2%), and risperidone microspheres (n = 1, 2.2%). Primary diagnosis via International Classification of Diseases-10 code at discharge included schizophrenia spectrum and other psychotic disorders (n = 19, 42.2%); bipolar disorder (n = 14, 31.1%); disruptive, impulse control, and conduct disorders (n = 6, 13.3%); autistic disorder (n = 5, 11.1%); and attention-deficit/hyperactivity disorder (n = 1, 2.2%). Seventeen patients (37.8%) received a loading dose regimen and/or a maintenance dose regimen that differed from adult package-insert dosing. The mean length of stay was 23.7 days, and 14 patients (31.1%) were readmitted to the psychiatric hospital within 6 months of discharge. The mean number of days to readmission was 71.9 days. Conclusions: This retrospective study is the first to focus on LAIA initiation and maintenance dosing strategies of multiple agents in both a child and adolescent patient population. Further research is required to evaluate the impact of LAIAs on clinical outcomes in this patient population.