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Pharmaceuticals (Basel, Switzerland) Apr 2024Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder...
Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10-30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 mg/kg, i.p.). BTBR mice pretreated with APG (20 mg/kg) or ARP (1 mg/g, i.p.) displayed significant improvements in the marble-burying test (MBT), cotton-shredding test (CST), and self-grooming test (SGT) (all < 0.05). However, a lower dose of APG (10 mg/kg, i.p.) failed to modulate behaviors in the MBT or SGT, but significantly attenuated the increased shredding behaviors in the CST of tested mice. Moreover, APG (10-30 mg/kg, i.p.) and ARP (1 mg/kg) moderated the disturbed levels of oxidative stress by mitigating the levels of catalase (CAT) and superoxide dismutase (SOD) in the hippocampus and cerebellum of treated BTBR mice. In patch clamp studies in hippocampal slices, the potency of choline (a selective agonist of α7-nAChRs) in activating fast inward currents was significantly potentiated following incubation with APG. Moreover, APG markedly potentiated the choline-induced enhancement of spontaneous inhibitory postsynaptic currents. The observed results propose the potential therapeutic use of APG in the management of ASD. However, further preclinical investigations in additional models and different rodent species are still needed to confirm the potential relevance of the therapeutic use of APG in ASD.
PubMed: 38675442
DOI: 10.3390/ph17040482 -
PloS One 2024To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVES
To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD).
METHODS
We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events.
RESULTS
Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies.
CONCLUSIONS
A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies.
Topics: Aripiprazole; Bupropion; Humans; Depressive Disorder, Major; Randomized Controlled Trials as Topic; Depressive Disorder, Treatment-Resistant; Treatment Outcome; Drug Therapy, Combination
PubMed: 38669232
DOI: 10.1371/journal.pone.0299020 -
Gels (Basel, Switzerland) Mar 2024Aripiprazole (ARZ) is a medication used for the treatment of various diseases such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette's...
Aripiprazole (ARZ) is a medication used for the treatment of various diseases such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette's syndrome. Despite its therapeutic benefits, ARZ is characterized by a poor water solubility which provoked the development of various delivery systems in order to enhance its solubility. In the present work, a nanoscale drug delivery system based on N,N-dimethylacrylamide (DMAA) and β-cyclodextrin triacrylate (β-CD-Ac) as potential aripiprazole delivery vehicles was developed. The nanogels were synthesized by free radical polymerization of DMAA in the presence of β-CD-Ac as a crosslinking agent and then loaded with ARZ via host-guest inclusion complexation. The blank- and drug-loaded nanogels were evaluated using different methods. Fourier transform infrared (FTIR) spectroscopy was employed to confirm the incorporation of β-CD moieties into the polymer network. Dynamic light scattering (DLS) was used to study the size of the developed systems. The samples exhibited a monomodal particle size distribution and a relatively narrow dispersity index. The hydrodynamic diameter (D) of the gels varied between 107 and 129 nm, with a tendency for slightly larger particles as the β-CD-Ac fraction increased. Loading the drug into the nanocarrier resulted in slightly larger particles than the blank gels, but their size was still in the nanoscopic range (166 to 169 nm). The release profiles in PBS were studied and a sustained release pattern with no significant burst effect was observed. A cytotoxicity assessment was also conducted to demonstrate the non-toxicity and biocompatibility of the studied polymers.
PubMed: 38667636
DOI: 10.3390/gels10040217 -
Annales Pharmaceutiques Francaises Apr 2024The current pandemic, in addition to putting a strain on healthcare systems and global economies, has exacerbated psychiatric problems and undermined the mental health...
BACKGROUND
The current pandemic, in addition to putting a strain on healthcare systems and global economies, has exacerbated psychiatric problems and undermined the mental health of many individuals. In an Italian cohort, this phenomenon has been assessed through a retrospective study aimed at evaluating the consumption and costs of antipsychotic drugs between 2020 and 2022.
METHODS
All dispensations made in local pharmacies accessible to the public have been extracted from a database called 'Sistema Tessera Sanitaria', which covers a population of approximately one million people residents in the ASL Napoli 3 Sud. Consumption data expressed in defined daily dose (DDD) and expenditure data expressed in Euro have been extrapolated.
RESULTS
The results in the years 2020-2021 were relatively consistent, with consumption and expenditure decreasing slightly from 2020 to 2021. In 2022, the results showed a decrease in consumption and expenditure (2,706,951.07 DDD and €1,700,897.47) representing the reduced accessibility of patients to the healthcare facilities due to the pandemic. However, it should be noted that the antipsychotic drug aripiprazole showed an upward trend, registering an increase in consumption.
CONCLUSION
Despite expectations of increased consumption of antipsychotic medications, real-world evidence indicated a different phenomenon, with the pandemic seemingly not affecting the consumption of these drugs. The difficulty in accessing care and medical appointments has probably influenced this data, masking the therapeutic needs of citizens. It will be necessary to assess in the coming years, as normal clinical activity resumes, whether there will be a growing consumption of these medications, which represent one of the main expenditure categories for the National Healthcare System.
PubMed: 38663841
DOI: 10.1016/j.pharma.2024.04.007 -
European Journal of Pharmacology Jun 2024Aripiprazole, a third-generation antipsychotic, has been widely used to treat schizophrenia. In this study, we evaluated the effect of aripiprazole on voltage-gated...
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.
Topics: Animals; Aripiprazole; Rabbits; Potassium Channels, Voltage-Gated; Myocytes, Smooth Muscle; Coronary Vessels; Potassium Channel Blockers; Male; Antipsychotic Agents; Dose-Response Relationship, Drug
PubMed: 38663541
DOI: 10.1016/j.ejphar.2024.176610 -
Psychiatry Research Jun 2024Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated...
Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated with considerable side effects, such as weight gain, and increasing evidence has also indicated that its use impacts gut microbiota (GM), although this connection is still little understood. To assess APs effects on the GM of patients starting or ongoing treatment, a systematic review was carried out in PubMed and Scopus databases. Twelve articles were considered eligible for the review, which investigated the effects of risperidone (5 studies), quetiapine (3), amilsupride (1), olanzapine (1), and unspecified atypical drugs (2). Eleven reported changes in GM in response to APs, and associations between the abundance of bacterial groups and different metabolic parameters were described by most of them. However, the studies were noticeably heterogeneous considering design, methods, and results. In this way, the effects of APs on GM composition and diversity were inconclusive. Despite the uncertain interactions, a more comprehensive understanding on how microbiota is affected by APs may help to optimize treatment, potentially minimizing side effects and improving adherence to treatment.
Topics: Humans; Gastrointestinal Microbiome; Antipsychotic Agents
PubMed: 38663221
DOI: 10.1016/j.psychres.2024.115914 -
Rivista Di Psichiatria 2024Treatment with long-acting injection (LAI) antipsychotics, such as paliperidone palmitate, has improved the quality of life in terms of symptoms and prevention of... (Review)
Review
Treatment with long-acting injection (LAI) antipsychotics, such as paliperidone palmitate, has improved the quality of life in terms of symptoms and prevention of relapses in patients with schizophrenia. Although there are plenty of evidences about the efficacy and safety of paliperidone palmitate 3-monthly injection (PP3M) in adults with schizophrenia, literature appears lacking about the use of LAIs during pregnancy. We hereby describe the clinical case of a pregnant woman affected by schizophrenia (DSM-5-TR), taking pharmacological treatment of PP3M. Considering the inadequate evidence regarding the use of PP3M in pregnancy in agreement with the patient, we switched PP3M to an oral therapy with aripiprazole. The switch to oral aripiprazole allowed the patient to improve her sense of autonomy and strengthen the therapeutic relationship. To our knowledge, this is the first case report monitoring an entire pregnancy of a women affected by schizophrenia in treatment with PP3M injection and oral aripiprazole. No obstetrical or fetal complications were reported. As the research in this field is very demanding, it would be precipitous to derive final conclusions from the current case report, but we hope to build a growing number of data that would allow us to make more appropriate and safe therapeutic choices in such a vulnerable phase as the peripartum.
Topics: Humans; Female; Aripiprazole; Paliperidone Palmitate; Pregnancy; Antipsychotic Agents; Schizophrenia; Adult; Administration, Oral; Delayed-Action Preparations; Pregnancy Complications; Drug Substitution; Injections, Intramuscular
PubMed: 38651776
DOI: 10.1708/4259.42361 -
Therapeutic Drug Monitoring Apr 2024This study comprehensively examined the demographic and clinical characteristics of patients undergoing valproic acid therapy and explored their potential impact on...
Retrospective Analysis of Steady-State Sodium Valproate Plasma Concentrations in Chinese Patients With Bipolar Disorder: Impact of Demographic and Clinical Characteristics.
BACKGROUND
This study comprehensively examined the demographic and clinical characteristics of patients undergoing valproic acid therapy and explored their potential impact on plasma valproic acid concentrations. All enrolled patients were administered the extended-release formulation. An in-depth investigation of factors, including dose, age, sex, body mass index, co-administered medications, and laboratory test findings, was conducted to evaluate their potential influence on study outcomes.
METHODS
In total, 164 patients met the inclusion criteria and were included in the analysis. The patient age ranged from 13 to 60 years, with a median age of 25.71 years. Most patients (89%) received a daily dose of 1 g valproic acid. Co-administered psychiatric medications included aripiprazole, quetiapine, and lorazepam. Laboratory test results, such as hemoglobin and transaminase levels, were also collected as part of the study.
RESULTS
The average plasma valproic acid plasma concentration was 79.8 mg/L. The dose significantly affected valproic acid concentrations, as a higher percentage of measurements exceeded the therapeutic range at a daily dose of 1 g. Furthermore, females exhibited significantly higher valproic acid concentrations compared with males at the same dose (P < 0.05). However, different age groups showed no statistically significant differences in valproic acid concentrations (P > 0.05). The co-administered antipsychotic and antidepressant medications significantly affected valproate concentrations, as reflected in the multiple regression model (P < 0.01).
CONCLUSIONS
This study offers valuable insights into the demographic and clinical characteristics of patients undergoing valproic acid therapy. It highlights the influence of dose, sex, and concomitant medications on plasma valproic acid concentrations. Overall, these findings can help guide dose adjustments and implement personalized treatment strategies in valproic acid therapy.
PubMed: 38648661
DOI: 10.1097/FTD.0000000000001199 -
Molecular Pharmaceutics May 2024The main purpose of our studies is to demonstrate that commercially available mesoporous silica (MS) can be used to control the physical state of aripiprazole (ARP). The...
The main purpose of our studies is to demonstrate that commercially available mesoporous silica (MS) can be used to control the physical state of aripiprazole (ARP). The investigations performed utilizing differential scanning calorimetry and broadband dielectric spectroscopy reveal that silica can play different roles depending on its concentration in the system with amorphous ARP. At low MS content, it activates recrystallization of the active pharmaceutical ingredient and supports forming the III polymorphic form of ARP. At intermediate MS content (between ca. 27 and 65 wt %), MS works as a recrystallization inhibitor of ARP. At these concentrations, the formation of III polymorphic form is no longer favorable; therefore, it is possible to use this additive to obtain ARP in either IV or X polymorphic form. At the same time, employing MS in concentrations >65 wt % amorphous form of ARP with high physical stability can be obtained. Finally, regardless of the polymorphic form it crystallizes into, each composite is characterized by the same temperature dependence of relaxation times in the supercooled and glassy states.
Topics: Aripiprazole; Silicon Dioxide; Calorimetry, Differential Scanning; Porosity; Crystallization; Dielectric Spectroscopy; X-Ray Diffraction
PubMed: 38644570
DOI: 10.1021/acs.molpharmaceut.3c01095 -
Journal of Clinical PsychopharmacologyThe augmentative antidepressant effects of dopamine partial agonists (aripiprazole, brexpiprazole, and cariprazine) for treatment-resistant depression have been compared... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The augmentative antidepressant effects of dopamine partial agonists (aripiprazole, brexpiprazole, and cariprazine) for treatment-resistant depression have been compared in a previous network meta-analysis. However, the comparative efficacy of the dose-responses of these drugs remains unclear. Therefore, we aimed to estimate the dose-response relationships and compare the effects of each dopamine partial agonist doses.
METHODS
We conducted a systematic review of the Cochrane Library, PubMed, CINHAL, and ClinicalTrials.gov databases until January 1, 2023. Double-blind, randomized, placebo-controlled trials evaluating aripiprazole, brexpiprazole, and cariprazine for treatment-resistant depression were included. A random-effect dose-response model-based network meta-analysis was conducted. This study was registered in PROSPERO (CRD42023393035).
RESULTS
The maximum effective doses were 5.5 mg for aripiprazole, 1.6 mg for brexpiprazole, and 1.5 mg for cariprazine, respectively. Although all doses of the 3 drugs were significantly more effective than placebo, aripiprazole ranging from 5.5 to 12.5 mg was significantly more effective than brexpiprazole 0.5 mg and cariprazine ranging from 0.5 to 1 mg. Moreover, aripiprazole ranging from 7.5 to 12.5 mg was significantly more effective than all doses of cariprazine. In addition, brexpiprazole ranging from 1 to 3 mg was significantly more effective than cariprazine 0.5 mg and brexpiprazole ranging from 1.6 to 2.5 mg was significantly superior to cariprazine 1 mg. There were no doses at which brexpiprazole overcame aripiprazole, and cariprazine overcame aripiprazole or brexpiprazole.
CONCLUSIONS
Aripiprazole, brexpiprazole, and cariprazine may be effective in treatment-resistant depression in that order, with the maximum effective doses at 5.5 mg, 1.6 mg, and 1.5 mg, respectively.
Topics: Humans; Network Meta-Analysis; Depressive Disorder, Treatment-Resistant; Aripiprazole; Dopamine Agonists; Dose-Response Relationship, Drug; Piperazines; Randomized Controlled Trials as Topic; Quinolones; Thiophenes; Antidepressive Agents; Treatment Outcome
PubMed: 38639435
DOI: 10.1097/JCP.0000000000001862