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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 -
RSC Advances May 2024Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer...
Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer superlative properties of APIs. Previously, THEDESs of risperidone, fentanyl and levofloxacin with capric acid (CA) were developed by our group. These APIs share cyclic tertiary amine nuclei. Herein, DESs of two drugs bearing cyclic tertiary amine nucleus, namely, droperidol and aripiprazole, in the presence of CA, were investigated as model drugs. Comprehensive analyses were conducted using liquid-state 1D and 2D NMR and differential scanning calorimetry (DSC) to elucidate the regiochemistry and thermodynamic mechanisms bringing about those THEDESs. Everted gut sac technique was used to study the flux of the developed THEDESs. 1D and 2D NMR techniques analyses revealed the importance of cyclic tertiary amine nuclei in forming interactions with CA. This was confirmed by the downfield shift of the protons proximal to the tertiary amine groups compared to the individual drugs. Diffusion NMR analysis (DOSY) showed a significant reduction in the diffusion coefficient of CA in the mixed system compared with CA in isolation. Thermal analysis of the two drugs revealed that the drugs have a low tendency to recrystallise upon melting but rather vitrify from a melt to form an amorphous solid. Interestingly, the superior absorption and flux of the THEDES formulation of droperidol was demonstrated using the ERIS. Collectively, this work provides a green method to attain liquid formulations of APIs with enhanced pharmacokinetic features.
PubMed: 38716106
DOI: 10.1039/d4ra01469c -
Frontiers in Neuroscience 2024
PubMed: 38707592
DOI: 10.3389/fnins.2024.1371195 -
CNS Neuroscience & Therapeutics May 2024The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral...
AIMS
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.
Topics: Animals; Aripiprazole; Schizophrenia; Hippocampus; Antipsychotic Agents; Dizocilpine Maleate; Mice; Disease Models, Animal; Hyperkinesis; Male; Locomotion; Excitatory Amino Acid Antagonists; Mice, Inbred C57BL; Animals, Newborn; Neurons; Theta Rhythm
PubMed: 38702935
DOI: 10.1111/cns.14739 -
Indian Journal of Psychological Medicine May 2024
PubMed: 38699760
DOI: 10.1177/02537176231199210 -
European Journal of Pharmaceutical... Jul 2024Both biphasic dissolution and simultaneous dissolution-permeation (D-P) systems have great potential to improve the in vitro-in vivo correlation compared to simple...
Both biphasic dissolution and simultaneous dissolution-permeation (D-P) systems have great potential to improve the in vitro-in vivo correlation compared to simple dissolution assays, but the assay conditions, and the evaluation methods still need to be refined in order to effectively use these apparatuses in drug development. Therefore, this comprehensive study aimed to compare the predictive accuracy of small-volume (16-20 mL) D-P system and small-volume (40-80 mL) biphasic dissolution apparatus in bioequivalence prediction of five aripiprazole (ARP) containing marketed drug products. Assay conditions, specifically dose dependence were studied to overcome the limitations of both small-scale systems. In case of biphasic dissolution the in vivo maximum plasma concentration (C) prediction greatly improved with the dose reduction of ARP, while in case of the D-P setup the use of whole tablet gave just as accurate prediction as the scaled dose. With the dose reduction strategy both equipment was able to reach 100 % accuracy in bioequivalence prediction for C ratio. In case of the in vivo area under the curve (AUC) prediction the predictive accuracy for the AUC ratio was not dependent on the dose, and both apparatus had a 100 % accuracy predicting bioequivalence based on AUC results. This paper presents for the first time that not only selected parameters of flux assays (like permeability, initial flux, AUC value) were used as an input parameter of a mechanistic model (gastrointestinal unified theory) to predict absorption rate but the whole in vitro flux profile was used. All fraction absorbed values estimated by Predictor Software fell within the ±15 % acceptance range during the comparison with the in vivo data.
Topics: Aripiprazole; Therapeutic Equivalency; Solubility; Antipsychotic Agents; Permeability; Drug Liberation; Humans; Area Under Curve; Tablets
PubMed: 38697313
DOI: 10.1016/j.ejps.2024.106782 -
Journal of Integrative Neuroscience Apr 2024Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic... (Review)
Review
Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.
Topics: Humans; Antipsychotic Agents; Clozapine; Hallucinations; Parkinson Disease; Piperidines; Quetiapine Fumarate; Urea
PubMed: 38682215
DOI: 10.31083/j.jin2304080 -
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