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IBRO Neuroscience Reports Dec 2023Autism spectrum disorders (ASD) are a complex sequelae of neurodevelopmental disorders which manifest in the form of communication and social deficits. Currently, only...
Autism spectrum disorders (ASD) are a complex sequelae of neurodevelopmental disorders which manifest in the form of communication and social deficits. Currently, only two agents, namely risperidone and aripiprazole have been approved for the treatment of ASD, and there is a dearth of more drugs for the disorder. The exact pathophysiology of autism is not understood clearly, but research has implicated multiple pathways at different points in the neuronal circuitry, suggesting their role in ASD. Among these, the role played by neuroinflammatory cascades like the NF-KB and Nrf2 pathways, and the excitotoxic glutamatergic system, are said to have a bearing on the development of ASD. Similarly, the GPR40 receptor, present in both the gut and the blood brain barrier, has also been said to be involved in the disorder. Consequently, molecules which can act by interacting with one or multiple of these targets might have a potential in the therapy of the disorder, and for this reason, this study was designed to assess the binding affinity of taurine, a naturally-occurring amino acid, with these target molecules. The same was scored against these targets using docking studies, with Risperidone and Aripiprazole being used as standard comparators. Encouraging docking scores were obtained for taurine across all the selected targets, indicating promising target interaction. But the affinity for targets actually varied in the order Given the potential implication of these targets in the pathogenesis of ASD, the drug might show promising results in the therapy of the disorder if subjected to further evaluations.
PubMed: 37711998
DOI: 10.1016/j.ibneur.2023.08.2191 -
Frontiers in Psychiatry 2024Hyperprolactinemia is a common antipsychotic-induced adverse event in psychiatric patients, and the quality of clinical studies investigating the best treatments has... (Review)
Review
BACKGROUND
Hyperprolactinemia is a common antipsychotic-induced adverse event in psychiatric patients, and the quality of clinical studies investigating the best treatments has varied. Thus, to better summarize the clinical evidence, we performed an umbrella review of overlapping systematic reviews and meta-analyses for the treatment of antipsychotic-induced hyperprolactinemia.
METHODS
The PubMed, Cochrane Library, PsycINFO, Scopus and EMBASE were searched, and reviews and meta-analyses meeting our inclusion criteria were selected. Relevant data were extracted, and an umbrella review was conducted of all included meta-analyses. The quality of included meta-analyses was assessed by using PRISMA scores and AMSTAR 2 quality evaluation. Finally, the clinical evidence for appropriate treatments was summarized and discussed.
RESULTS
Five meta-analyses published between 2013 and 2020 met the requirements for inclusion in this umbrella review. The PRISMA scores of the included meta-analyses ranged from 19.5-26. AMSTAR 2 quality evaluation showed that 2 of the 5 included meta-analyses were of low quality and 3 were of very low quality. The included meta-analyses provide clinical evidence that adding aripiprazole or a dopamine agonist can effectively and safely improve antipsychotic-induced hyperprolactinemia. Two meta-analyses also showed that adjunctive metformin can reduce serum prolactin level, but more clinical trials are needed to confirm this finding.
CONCLUSION
Adjunctive dopamine agonists have been proven to be effective and safe for the treatment of antipsychotic-induced hyperprolactinemia. Among the researched treatments, adding aripiprazole may be the most appropriate.
PubMed: 38505795
DOI: 10.3389/fpsyt.2024.1337274 -
Therapeutic Advances in... 2023Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising... (Review)
Review
Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication - 5, 2.5 and 1.25 mg for the three regimens, respectively - is required for ALAI to complete full cessation to prevent too rapid a reduction in D occupancy. Oral medication should probably be maintained at a consistent dose for 3-6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication.
PubMed: 37719449
DOI: 10.1177/20451253231198463 -
Advanced Biomedical Research 2023Sexual desire and sexual activity are natural needs of human beings, which can be problematic and lead to various sexual disorders, if not used in the right way,...
BACKGROUND
Sexual desire and sexual activity are natural needs of human beings, which can be problematic and lead to various sexual disorders, if not used in the right way, including hypersexuality. The present study aimed to compare the effect of dialectical behavior therapy (DBT) and aripiprazole drug on marital instability in patients with hypersexuality.
MATERIALS AND METHODS
This experimental case--control Pretest--Posttest Control Group Design with follow up was done on 27 male and female patients with hypersexuality having at least a higher education degree selected from four hospitals and psychiatric centers including Khorshid Hospital, Asgariyeh Specialized Hospital, Farhangian Clinic and Imam Reza Medical Center in Isfahan and were randomly assigned to two groups of treatment (nine patients in every group) and one group of control (nine patients) after adjusting the age and gender. Pretest phase was done for both three groups using Marital Instability Index (MII). The first treatment group underwent DBT intervention for eight sessions of 2 hours (once a week), and the second experimental group was prescribed aripiprazole for 2 months. Afterwards, the posttest and follow-up were performed for all the three groups. The data were analyzed using SPSS 24 and multivariate analysis of covariance (MANCOVA).
RESULTS
The findings showed that DBT and aripiprazole had little effect on the problem of marital instability in patients with hypersexuality ( > 0.05); also, there was no significant difference between the effect of DBT and aripiprazole ( > 0.05).
CONCLUSION
DBT and the drug aripiprazole cannot have a significant effect on the marital instability in patients.
PubMed: 37694240
DOI: 10.4103/abr.abr_161_22 -
Brain Research Bulletin Jul 2023The onset of schizophrenia is associated with both genetic and environmental risks during brain development. Environmental factors during pregnancy can represent risk...
BACKGROUND
The onset of schizophrenia is associated with both genetic and environmental risks during brain development. Environmental factors during pregnancy can represent risk factors for schizophrenia, and we have previously reported that several microRNA and mRNA expression changes in fetal brains exposed to haloperidol during pregnancy may be related to the onset of this disease. This study aimed to replicate that research and focused on apoptotic-related gene expression changes.
METHODS
Haloperidol (1 mg/kg) or aripiprazole (1 mg/kg) was injected into pregnant mice. Using RNA sequencing for the hippocampus of each offspring born from pregnant mice exposed to haloperidol, we analyzed genes identified as changed in our previous report and validated two apoptosis-related genes (Cdkn1a and Apaf1) using quantitative polymerase chain reaction (qPCR) methods. Furthermore, we attempted to elucidate the direct effects of haloperidol and aripiprazole on those mRNA expressions in in vitro experiments.
RESULTS
RNA sequencing successfully replicated 16 up-regulated and 5 down-regulated genes in this study. Of those, up-regulations of Cdkn1a and Apaf1 mRNA expression were successfully validated by direct quantification. Moreover, haloperidol and aripiprazole dose-dependent upregulation of both mRNA expressions were confirmed in a Neuro2a cell line.
CONCLUSIONS
In the hippocampus of offspring, intraperitoneal injection of haloperidol to pregnant mice induced up-regulation of apoptotic genes that representing the phenotypic change without apoptosis. These findings will be useful for understanding the molecular biological mechanisms underlying the effects of antipsychotics on the fetal brain.
Topics: Mice; Animals; Haloperidol; Aripiprazole; Piperazines; Quinolones; Antipsychotic Agents; Hippocampus; RNA, Messenger
PubMed: 37150328
DOI: 10.1016/j.brainresbull.2023.110662 -
Prague Medical Report 2024Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder,... (Review)
Review
Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder, and related psychiatric conditions. The plasma concentration of antipsychotic drugs is a valid measure of the drug at its primary target structure in the brain, and therefore determines the efficacy and safety of these drugs. However, despite the well-known high variability in pharmacokinetics of these substances, psychiatric medication is usually administered in uniform dosage schedules. Therapeutic drug monitoring (TDM), as the specific method that can help personalised medicine in dose adjustment according to the characteristics of the individual patient, minimizing the risk of toxicity, monitoring adherence, and increasing cost-effectiveness in the treatment, thus seems to be an elegant tool to solve this problem. Non-response to therapeutic doses, uncertain adherence to medication, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM of SGAs. This review aims to summarize an overview of the current knowledge and evidence of the possibilities to tailor the dosage of selected SGAs using TDM, including the necessary pharmacokinetic parameters for personalised pharmacotherapy.
Topics: Humans; Drug Monitoring; Antipsychotic Agents; Schizophrenia
PubMed: 38761044
DOI: 10.14712/23362936.2024.10 -
International Journal of Circumpolar... Dec 2023This nationwide retrospective cross-sectional study examines the prevalence of antipsychotic polypharmacy (APP) and demographic, forensic, and clinical factors...
This nationwide retrospective cross-sectional study examines the prevalence of antipsychotic polypharmacy (APP) and demographic, forensic, and clinical factors associated with its practice among Greenlandic forensic psychiatric patients. We collected data from electronic patient files, court documents, and forensic psychiatric assessments. We defined APP as two or more concurrent prescriptions of antipsychotic medication. The study population of 74 patients had a mean age of 41.4 years, and 61 were men. All included patients had either schizophrenia or another ICD-10 F2-diagnosis. We used unpaired t-tests and Chi or Fisher's exact test. The prevalence of APP was 35% ( = 26), and there was a significant association between APP and a prescription of clozapine (Chi, = 0.010), olanzapine (Fisher's test, = 0.003), and aripiprazole (Fisher's test, = 0.013). Furthermore, we found a significant association between APP and prescription of a first-generation antipsychotic (FGA) (Chi, = 0.011). Despite recommendations in guidelines, the use of APP is common practice. The majority of forensic psychiatric patients suffer from severe psychiatric disorders, often with other comorbidities, including substance use disorder. The severity and complexity in mental health render forensic psychiatric patients at high risk of APP treatment. Further knowledge on APP use is crucial to secure and further improve the psychopharmacological treatment for this group of patients.
Topics: Male; Humans; Adult; Female; Antipsychotic Agents; Polypharmacy; Retrospective Studies; Cross-Sectional Studies; Clozapine
PubMed: 37300837
DOI: 10.1080/22423982.2023.2218654 -
The Journal of Clinical Psychiatry Feb 2024Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (AL) plus 30-mg oral aripiprazole was efficacious... (Comparative Study)
Comparative Study Randomized Controlled Trial
Safety and Tolerability of Starting Aripiprazole Lauroxil With Aripiprazole Lauroxil NanoCrystal Dispersion in 1 Day Followed by Aripiprazole Lauroxil Every 2 Months Using Paliperidone Palmitate Monthly as an Active Control in Patients With Schizophrenia: A Post Hoc Analysis of a Randomized...
Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (AL) plus 30-mg oral aripiprazole was efficacious and well tolerated in a 25-week, randomized, double-blind phase 3 trial in adults with acute schizophrenia. This post hoc analysis further characterized the safety of AL 1064 mg administered every 2 months and that of active control paliperidone palmitate (PP) 156 mg monthly based on occurrence, timing, and severity of adverse events (AEs) associated with antipsychotic medications. This study was conducted between November 2017 and March 2019. AL or PP was initiated during an inpatient stay of ≥ 2 weeks with transition to outpatient treatment thereafter. Rates of AEs of clinical interest, including injection site reactions (ISRs), motor AEs, sedation, hypotension, prolactin level increase, weight gain, and suicidal ideation/behavior, were summarized through weeks 4, 9, and 25 for each treatment. Of 200 patients who received ≥ 1 dose of study treatment, 99 (49.5%) completed the study (AL, 57%; PP, 43%). Mean (SD) baseline Positive and Negative Syndrome Scale total scores were 94.1 (9.04) and 94.6 (8.41) in the AL and PP treatment groups, respectively. AEs were reported by 69/99 (70%) patients administered AL and 72/101 (71%) administered PP; most AEs were mild or moderate in severity. ISRs (AL, 18.2%; PP, 26.7%) occurred primarily on days 1 and 8. All akathisia/restlessness AEs (AL, 10.1%; PP, 11.9%) occurred during the first 4 weeks; <10% of patients (either treatment) experienced hypotension, sedation, or suicidal ideation/behavior events. Weight gain of ≥ 7% from baseline occurred in 9.3% of AL- and 23.8% of PP-treated patients. Median prolactin concentrations changed by -4.60 and -3.55 ng/mL among AL-treated males and females, respectively, and did not exceed 2 times normal levels in any AL-treated patients. In PP-treated patients, changes were 21.20 and 80.40 ng/mL and concentrations exceeded 2 times normal in 38% and 88% of males and females, respectively. No new early- or late-emerging safety concerns were observed through 25 weeks of treatment with AL 1064 mg every 2 months following initiation using AL plus 30-mg oral aripiprazole. Results were consistent with known safety profiles of AL and PP and support the safety of AL 1064 mg every 2 months initiated using AL plus 30-mg oral aripiprazole. ClinicalTrials.gov identifier: NCT03345979.
Topics: Adult; Female; Humans; Male; Antipsychotic Agents; Aripiprazole; Delayed-Action Preparations; Hypotension; Nanoparticles; Noncommunicable Diseases; Paliperidone Palmitate; Prolactin; Schizophrenia; Treatment Outcome; Weight Gain; Double-Blind Method
PubMed: 38416865
DOI: 10.4088/JCP.23m15095 -
Pharmaceuticals (Basel, Switzerland) Jan 2024Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure,...
Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants and or antipsychotics and according to the latest state-of-the-art international dosing recommendations for and metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.
PubMed: 38399366
DOI: 10.3390/ph17020151 -
Neuropsychiatric Disease and Treatment 2023There is a need when optimizing antipsychotic treatment to know the plasmatic levels (PLs) achieved with the different doses and their relationship with effectiveness...
Plasmatic Levels and Response to Variable Doses of Monthly Aripiprazole and Three-Month Paliperidone in Patients with Severe Schizophrenia. Treatment Adherence, Effectiveness, Tolerability, and Safety.
INTRODUCTION
There is a need when optimizing antipsychotic treatment to know the plasmatic levels (PLs) achieved with the different doses and their relationship with effectiveness and toxicity, especially in patients with poor clinical progress. This study investigates the dose-PL-response relationship of monthly aripiprazole (AOM) and three-month paliperidone (PP3M).
METHODS
Observational, 52-week prospective study of patients with severe schizophrenia (CGI-S ≥ 5) treated with PP3M or AOM for at least one year before their inclusion in the study (N=68). Dose-PL relationship was determined. Subjects were included in standard-dose and high-dose (above labeled) and standard/therapeutic range-PLs and high-PLs (above range) groups. Treatment adherence, effectiveness (hospitalizations, severity), tolerability and safety were assessed. PLs and clinical response were evaluated.
RESULTS
No clear linear relationship was found between doses and PLs. In a considerable number of cases, standard doses achieved PLs above the therapeutic range. A significant clinical improvement was related to high PLs, without less safety, tolerability, or treatment compliance being involved. Clinical severity decreased more frequently in patients who received high doses and reached high PLs. Hospital admissions decreased significantly in those patients with high PLs.
CONCLUSION
Taking into account the absence of a linear relationship between doses and PLs, the effectiveness in people with severe schizophrenia of AOM and PP3M depends on reaching high PLs, achieved with high doses, but also with standard doses in some cases, without leading to worse treatment tolerability, safety, or adherence.
PubMed: 37818449
DOI: 10.2147/NDT.S425516