-
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 -
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 -
CNS Drugs Jun 2024Adequate antipsychotic treatment intensity is required before diagnosing resistant schizophrenia and initiating clozapine treatment. We aimed to investigate potential...
INTRODUCTION
Adequate antipsychotic treatment intensity is required before diagnosing resistant schizophrenia and initiating clozapine treatment. We aimed to investigate potential rapid drug metabolism underlying low dose-adjusted serum concentration (CD) of non-clozapine atypical antipsychotics preceding clozapine treatment.
METHODS
Patients using non-clozapine, atypical antipsychotics (aripiprazole, risperidone, olanzapine, or quetiapine) within 1 year before starting clozapine were included in this study from a therapeutic drug monitoring service in Oslo, Norway, between 2005 and 2023. Patients were assigned into low CD (LCD) and normal CD (NCD) subgroups. Using a reference sample with 147,964 antipsychotic measurements, LCD was defined as CDs below the 25th percentile, while patients with NCD exhibited CDs between the 25th and 75th percentile of the respective reference measurements. Metabolic ratios, doses, and frequency of subtherapeutic levels of non-clozapine antipsychotics were compared between LCD and NCD groups.
RESULTS
Preceding clozapine treatment, 110 out of 272 included patients (40.4%) were identified with LCD. Compared with the NCD group, LCD patients exhibited higher metabolic ratios of olanzapine (1.5-fold; p < 0.001), quetiapine (3.0-fold; p < 0.001), and risperidone (6.0-fold; p < 0.001). Metabolic ratio differences were independent of smoking and CYP2D6 genotype for olanzapine (p = 0.008) and risperidone (p = 0.016), respectively. Despite higher doses of olanzapine (1.25-fold; p = 0.054) and quetiapine (1.6-fold; p = 0.001) in LCD versus NCD patients, faster metabolism among the former was accompanied by higher frequencies of subtherapeutic levels of olanzapine (3.3-fold; p = 0.044) and quetiapine (1.8-fold; p = 0.005).
CONCLUSION
LCD and associated rapid metabolism of non-clozapine antipsychotics is frequent before starting clozapine treatment. For olanzapine and quetiapine, this is associated with significantly increased risk of having subtherapeutic concentrations.
Topics: Humans; Antipsychotic Agents; Clozapine; Female; Male; Adult; Retrospective Studies; Middle Aged; Drug Monitoring; Norway; Schizophrenia; Schizophrenia, Treatment-Resistant; Quetiapine Fumarate
PubMed: 38635089
DOI: 10.1007/s40263-024-01079-y -
Journal of Medical Case Reports Apr 2024Significant elevation of creatine kinase levels (above three digits) and leucocytosis in the absence of muscle rigidity, tremors, or autonomic dysfunction can pose a...
BACKGROUND
Significant elevation of creatine kinase levels (above three digits) and leucocytosis in the absence of muscle rigidity, tremors, or autonomic dysfunction can pose a real challenge in the context of antipsychotic treatment as an early herald of neuroleptic malignant syndrome.
CASE PRESENTATION
We present here two cases of adult male patients of Black British heritage, ages 51 years and 28 years, respectively. Both received a diagnosis of schizoaffective disorder and presented with massive increase of creatine kinase blood level after aripiprazole depot administration, one with pernicious increase associated with silent neuroleptic malignant syndrome, and the second with asymptomatic benign enzyme elevation.
CONCLUSION
Though aripiprazole use is less likely to cause neuroleptic malignant syndrome, on rare occasions it can produce massive symptomatic or asymptomatic increase in serum creatine kinase enzyme levels, raising the need for close monitoring, especially at the initial doses of the drug.
Topics: Adult; Humans; Male; Aripiprazole; Neuroleptic Malignant Syndrome; Antipsychotic Agents; Psychotic Disorders; Creatine Kinase
PubMed: 38632633
DOI: 10.1186/s13256-024-04508-0 -
Journal of Psychiatric Research Jun 2024Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and... (Review)
Review
Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and risperidone are two commonly prescribed antipsychotics, metabolized primarily through CYP2D6. Here, we aimed to provide an overview of the effect of CYP2C19 and CYP2D6 on side-effects of aripiprazole and risperidone, and expand on existing literature by critically examining methodological issues associated with pharmacogenetic studies. A PRISMA compliant search of six electronic databases (Pubmed, PsychInfo, Embase, Central, Web of Science, and Google Scholar) identified pharmacogenetic studies on aripiprazole and risperidone. 2007 publications were first identified, of which 34 were included. Quality of literature was estimated using Newcastle-Ottowa Quality Assessment Scale (NOS) and revised Cochrane Risk of Bias tool. The average NOS score was 5.8 (range: 3-8) for risperidone literature and 5 for aripiprazole (range: 4-6). All RCTs on aripiprazole were rated as high risk of bias, and four out of six for risperidone literature. Study populations ranged from healthy volunteers to inpatient individuals in psychiatric units and included adult and pediatric samples. All n = 34 studies examined CYP2D6. Only one study genotyped for CYP2C19 and found a positive association with neurological side-effects of risperidone. Most studies did not report any relationship between CYP2D6 and any side-effect outcome. Heterogeneity between and within studies limited the ability to synthesize data and draw definitive conclusions. Studies lacked statistical power due to small sample size, selective genotyping methods, and study design. Large-scale randomized trials with multiple measurements, providing robust evidence on this topic, are suggested.
Topics: Humans; Aripiprazole; Cytochrome P-450 CYP2D6; Risperidone; Cytochrome P-450 CYP2C19; Antipsychotic Agents
PubMed: 38631139
DOI: 10.1016/j.jpsychires.2024.04.001 -
Clinical Psychopharmacology and... May 2024: This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine...
OBJECTIVE
: This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice.
METHODS
: Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved.
RESULTS
: The changes of primary endpoint HAMA (t = 5.731, -4.6, = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, -3.4, < 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, -0.9, t = 1.821, = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, -0.4, < 0.001) scores were also significantly improved during the study. No significant adverse events were observed.
CONCLUSION
: This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.
PubMed: 38627084
DOI: 10.9758/cpn.23.1106 -
General Psychiatry 2024Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of...
BACKGROUND
Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.
AIMS
We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.
METHODS
A total of 2985 patients with schizophrenia were randomised into seven groups. Each group received one of seven antipsychotic treatments and was assessed at 2, 4 and 6 weeks. Clinical symptoms were evaluated using the positive and negative syndrome scale (PANSS). Additionally, we measured blood cell counts and metabolic parameters, such as blood lipids. Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes, while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.
RESULTS
PLTc significantly increased in patients treated with aripiprazole (F=6.00, p=0.003), ziprasidone (F=7.10, p<0.001) and haloperidol (F=3.59, p=0.029). It exhibited a positive association with white blood cell count and metabolic indicators. Higher baseline PLTc was observed in non-responders, particularly in those defined by the PANSS-negative subscale. In the structural equation model, PLTc, white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale scores. Moreover, higher baseline PLTc was observed in individuals with less metabolic change, although this association was no longer significant after accounting for baseline metabolic values.
CONCLUSIONS
Platelet parameters, specifically PLTc, are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with schizophrenia. Elevated PLTc levels and associated factors may impede symptom improvement by promoting inflammation. Given PLTc's easy measurement and clinical relevance, it warrants increased attention from psychiatrists.
TRIAL REGISTRATION NUMBER
ChiCTR-TRC-10000934.
PubMed: 38616969
DOI: 10.1136/gpsych-2023-101347 -
Soa--ch'ongsonyon Chongsin Uihak =... Apr 2024The purpose of this study was to examine the patterns of use of oral aripiprazole treatment in children and adolescents diagnosed with autism spectrum disorder (ASD) at...
OBJECTIVES
The purpose of this study was to examine the patterns of use of oral aripiprazole treatment in children and adolescents diagnosed with autism spectrum disorder (ASD) at a university medical center in Korea.
METHODS
We retrospectively reviewed the medical records of 164 outpatient children and adolescents diagnosed with ASD by child and adolescent psychiatrists. Patient demographic characteristics, clinical features, age and dose of aripiprazole treatment, associated adverse events, and concomitant medications, etc. were evaluated.
RESULTS
Aripiprazole treatment was initiated at a mean age of 7.64 years, at a mean initial dose of 1.15 mg. Methylphenidate was often co-administered with aripiprazole. The most commonly reported adverse effects were increased appetite and weight gain, which in some cases led to discontinuation of medication.
CONCLUSION
A follow-up study is warranted to evaluate the efficacy and safety of aripiprazole treatment in Korean children and adolescents diagnosed with ASD, and it is crucial to consider their clinical characteristics and response to treatment in the evaluation.
PubMed: 38601108
DOI: 10.5765/jkacap.230057 -
ACS Omega Apr 2024[This retracts the article DOI: 10.1021/acsomega.3c02550.].
[This retracts the article DOI: 10.1021/acsomega.3c02550.].
PubMed: 38585105
DOI: 10.1021/acsomega.4c02182 -
Therapie Mar 2024The past twenty years have seen a rise in cocaine-related statistics in France, including cocaine use in the general population, emergency ward presentations of acute...
AIM OF THE STUDY
The past twenty years have seen a rise in cocaine-related statistics in France, including cocaine use in the general population, emergency ward presentations of acute cocaine intoxication, cocaine use disorders related outpatient appointments and cocaine-related deaths. This study's objectives were to describe trends in patients' admission for specific cocaine detoxification as well as changes in patients' characteristics in the Assistance publique-Hôpitaux de Paris (AP-HP) hospitals group located in Paris region, France.
METHODS
We reviewed the international classification of diseases 10 edition (ICD-10) discharge codes of the AP-HP hospitals group between 2011 and 2021. In addition, medical reports of the largest addiction medicine ward were also analysed for changes across the years 2009, 2014, 2019 and 2022.
RESULTS
The regional database showed an almost 3-fold increase in cocaine-related disorders discharge codes between 2011 and 2019. This occurred due to a rise in hospital stays for cocaine dependence or cocaine acute intoxication prior to the fall in levels of inpatient stays associated with the coronavirus disease 2019 (COVID-19) pandemic. The in-depth analysis of inpatients' stays in the specialized addiction medicine ward also showed an increase in admissions for cocaine detoxification programs, with a prevalence of 1.19% in 2009 to 15.73% in 2022 (P=1.44×10). Inpatient characteristics showed significant changes, especially in 2022, namely: more daily users, less intravenous administration and less comorbid illicit substances use disorders, with heightened levels of cured hepatitis C patients (P<0.05). Inpatient prescriptions were primarily dopaminergic antagonists with sedatives properties (cyamemazine, loxapine and chlorpromazine), dopamine-receptors partial agonist (aripiprazole) and serotonin reuptake inhibitors.
CONCLUSION
The referral to hospital care for cocaine detoxification has increased in Paris region since 2011, coupled with changes in inpatients' characteristics. This trend has significant implications for the management of inpatient hospital services.
PubMed: 38582619
DOI: 10.1016/j.therap.2024.03.001