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British Journal of Clinical Pharmacology Oct 2023Aripiprazole is one of the most commonly prescribed antipsychotic drugs to children and adolescents worldwide, but it is associated with serious side-effects, including... (Observational Study)
Observational Study
AIMS
Aripiprazole is one of the most commonly prescribed antipsychotic drugs to children and adolescents worldwide, but it is associated with serious side-effects, including weight gain. This study assessed the population pharmacokinetics of aripiprazole and its active metabolite and investigated the relationship between pharmacokinetic parameters and body mass index (BMI) in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side-effects and drug effectiveness.
METHODS
Twenty-four children and adolescents (15 males, 9 females) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side-effects and drug effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were determined. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 92 aripiprazole and 91 dehydro-aripiprazole concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-h area under the curves (AUCs) were analysed to predict outcomes using generalized and linear mixed-effects models.
RESULTS
For both aripiprazole and dehydro-aripiprazole, one-compartment models best described the measured concentrations, with albumin and BMI as significant covariates. Of all the pharmacokinetic parameters, higher sum (aripiprazole plus dehydro-aripiprazole) trough concentrations best predicted higher BMI z-scores (P < .001) and higher Hb1Ac levels (P = .03) during follow-up. No significant association was found between sum concentrations and effectiveness.
CONCLUSIONS
Our results indicate a threshold with regard to safety, which suggests that therapeutic drug monitoring of aripiprazole could potentially increase safety in children and adolescents with ASD and behavioural problems.
Topics: Male; Female; Adolescent; Child; Humans; Aripiprazole; Autism Spectrum Disorder; Antipsychotic Agents; Weight Gain; Body Mass Index; Drug-Related Side Effects and Adverse Reactions
PubMed: 37222228
DOI: 10.1111/bcp.15800 -
Journal of the European Academy of... May 2024Data remain scarce for the first-line antipsychotic choice in treating delusional infestation (DI).
BACKGROUND
Data remain scarce for the first-line antipsychotic choice in treating delusional infestation (DI).
OBJECTIVES
We evaluated the treatment responses associated with different antipsychotics in DI patients.
METHODS
We undertook a multicentre, retrospective observational study using anonymised electronic patient records from two hospitals in the United Kingdom from 1 January 2011 to 1 January 2023. Eligible participants were adults (≥18 years) diagnosed with DI treated with an antipsychotic, and had both an assigned baseline and follow-up Clinical Global Impression Scale (CGI-S) score. The CGI-S is a validated psychiatric research tool. Participants were excluded if they had known limited or non-adherence to an antipsychotic, or if no CGI-S scores were present at follow-up. First clinic visits before the initiation of an antipsychotic were assigned as the baseline CGI-S score. The last available CGI-S score before the patient either changed antipsychotic or left the clinic for any reason was used to assign follow-up CGI-S scores. The primary outcome was the response to each individual antipsychotic treatment, measured by the difference in the baseline and last available follow-up CGI-S scores. Differences in CGI-S changes between antipsychotic episodes were tested by analysis of variance (ANOVA).
RESULTS
In total, 414 patient records were analysed, and data were extracted. The mean age was 61.8 years (SD 14.1). One hundred seventy (41%) of 414 patients were men and 244 (59%) were women. In total, 156 (38%) of 414 patients were eligible, yielding a total of 315 antipsychotic prescribing episodes. The ANOVA, ranking in order of treatment response, showed that the highest mean score (expressing highest treatment response) was observed in amisulpride (31 [67%] of 46) and risperidone (95 [57%] of 167), followed by some distance by quetiapine (9 [36%] of 25), aripiprazole (13 [28%] of 46) and olanzapine (7 [25%] of 28).
CONCLUSIONS
Amisulpride and risperidone were associated with a higher treatment response than quetiapine, aripiprazole and olanzapine. Amisulpride and risperidone should therefore be considered the first-line treatment options in DI patients.
PubMed: 38727630
DOI: 10.1111/jdv.20081 -
Healthcare (Basel, Switzerland) Jan 2024This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)-aripiprazole, cariprazine, brexpiprazole, and lurasidone-for the... (Review)
Review
This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)-aripiprazole, cariprazine, brexpiprazole, and lurasidone-for the management of substance-induced psychosis (SIP). SIP is a psychiatric condition triggered by substance misuse or withdrawal, characterized by unique features distinct from those of primary psychotic disorders. These distinctive features include a heightened prevalence of positive symptoms, such as hallucinations and delusions, in addition to a spectrum of mood and cognitive disturbances. This review comprehensively investigates various substances, such as cannabinoids, cocaine, amphetamines, and LSD, which exhibit a greater propensity for inducing psychosis. TGAs exhibit substantial promise in addressing both psychotic symptoms and issues related to substance misuse. This review elucidates the distinctive pharmacological properties of each TGA, their intricate interactions with neurotransmitters, and their potential utility in the treatment of SIP. We advocate for further research to delineate the long-term effects of TGAs in this context and underscore the necessity for adopting an integrated approach that combines pharmacological and psychological interventions. Our findings underscore the intricate and multifaceted nature of treating SIP, highlighting the potential role of TGAs within therapeutic strategies.
PubMed: 38338224
DOI: 10.3390/healthcare12030339 -
Turk Psikiyatri Dergisi = Turkish... 2023Aripiprazole, a second-generation antipsychotic (SGA) medication, is an efficacious treatment for schizophrenia and bipolar disorder. However, its effects on pregnancy...
Aripiprazole, a second-generation antipsychotic (SGA) medication, is an efficacious treatment for schizophrenia and bipolar disorder. However, its effects on pregnancy and lactation are not yet fully documented. Despite aripiprazole being available since 2002, there is only limited information on the risks and benefits of this treatment during pregnancy. Most of the information is limited to populationbased studies examining malformation risk or case studies or small case series. The knowledge in this topic is still insufficient and there is a need to expand the literature. In this report, we present 2 cases exposed to aripiprazole during pregnancy and lactational period. In both our cases of aripiprazole exposure, no teratogenic effects were reported, and it was reassuring that the mothers did not develop gestational diabetes. However, both patients reported lactation failure. Keyword: Mental illness, antipsychotics, aripiprazole, pregnancy.
Topics: Pregnancy; Female; Humans; Aripiprazole; Antipsychotic Agents; Schizophrenia; Bipolar Disorder; Lactation
PubMed: 37357900
DOI: 10.5080/u26681 -
British Journal of Clinical Pharmacology Dec 2023Bruxism is a movement disorder of uncertain aetiology. Beside local peripheral and central psychological factors, drugs were suspected. Using the World Health...
Bruxism is a movement disorder of uncertain aetiology. Beside local peripheral and central psychological factors, drugs were suspected. Using the World Health Organization (WHO) global pharmacovigilance database, Vigibase®, we investigated through disproportionality analyses potential associations between exposure to drugs and bruxism reports. All reports of bruxism in adults between 01/01/2000 and 31/12/2022 were included. Results are expressed as reporting odds ratio (ROR). Among the 564 reports of bruxism, an association was found with eight antidepressants (first sertraline followed by escitalopram, venlafaxine, vortioxetine, citalopram, paroxetine, fluoxetine, duloxetine) and four antipsychotics (first ziprasidone followed by aripiprazole, olanzapine, risperidone). A signal was also described for oxybate sodium and metoclopramide. For antidepressants, a negative association was found between ROR values and NET (norepinephrine transporter) but not SERT (serotonin transporter) pKi values, suggesting this ADR is more closely linked to norepinephrine than serotonin reuptake inhibition.
Topics: Adult; Humans; Selective Serotonin Reuptake Inhibitors; Pharmacovigilance; Bruxism; Antidepressive Agents; World Health Organization
PubMed: 37574820
DOI: 10.1111/bcp.15884 -
Molecular Psychiatry Sep 2023This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia...
This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia initiating LAIs January 2015-December 2016 were enrolled from the French National Health Data System (SNDS). Standardized mean differences (SMD > 0.1 deemed clinically significant) were calculated for psychiatric healthcare resource utilization measures assessed one year before (during oral AP treatment) and one year after LAI initiation. LAI effectiveness was analyzed overall and by age group, gender and compliance to oral AP, defined as exposure to an AP for at least 80% of the year before LAI initiation. 12,373 patients were included. LAIs were more frequently initiated in men (58.1%), young (18-34 years, 42.0%) and non-compliant (63.7%) patients. LAI initiation was effective in reducing the number and duration of psychiatric hospitalizations and psychiatric emergency department (ED) admissions in non-compliant patients (SMD = -0.19, -0.26 and -0.12, respectively), but not in compliant patients. First-generation LAIs, paliperidone and aripiprazole LAIs reduced psychiatric hospitalizations (SMD = -0.20, -0.24, -0.21, respectively) and ED admissions (SMD = -0.15, -0.13, -0.15, respectively). No differences in effectiveness were found for age or gender. In compliant patients, only aripiprazole LAI reduced the number of psychiatric hospitalizations (SMD = -0.13). Risperidone and paliperidone LAIs increased hospitalization duration (SMD = 0.15 and 0.18, respectively). The prescription of LAIs (except risperidone) should be recommended in all non-compliant patients, even in women and patients aged 35 or older. The lower frequency of administration of LAIs than of oral APs may improve compliance and hence reduce the risk of relapse. Aripiprazole LAI may represent a treatment of choice for compliant patients that should be further investigated.
Topics: Male; Humans; Female; Antipsychotic Agents; Schizophrenia; Risperidone; Paliperidone Palmitate; Aripiprazole; Injections; Administration, Oral
PubMed: 37479781
DOI: 10.1038/s41380-023-02175-z -
European Archives of Psychiatry and... Dec 2023Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with altered bioenergetic pathways and mitochondrial dysfunction. Antipsychotic medications, both...
Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with altered bioenergetic pathways and mitochondrial dysfunction. Antipsychotic medications, both first and second-generation, are commonly prescribed to manage SCZ symptoms, but their direct impact on mitochondrial function remains poorly understood. In this study, we investigated the effects of commonly prescribed antipsychotics on bioenergetic pathways in cultured neurons. We examined the impact of risperidone, aripiprazole, amisulpride, and clozapine on gene expression, mitochondrial bioenergetic profile, and targeted metabolomics after 24-h treatment, using RNA-seq, Seahorse XF24 Flux Analyser, and gas chromatography-mass spectrometry (GC-MS), respectively. Risperidone treatment reduced the expression of genes involved in oxidative phosphorylation, the tricarboxylic acid cycle, and glycolysis pathways, and it showed a tendency to decrease basal mitochondrial respiration. Aripiprazole led to dose-dependent reductions in various mitochondrial function parameters without significantly affecting gene expression. Aripiprazole, amisulpride and clozapine treatment showed an effect on the tricarboxylic acid cycle metabolism, leading to more abundant metabolite levels. Antipsychotic drug effects on mitochondrial function in SCZ are multifaceted. While some drugs have greater effects on gene expression, others appear to exert their effects through enzymatic post-translational or allosteric modification of enzymatic activity. Understanding these effects is crucial for optimising treatment strategies for SCZ. Novel therapeutic interventions targeting energy metabolism by post-transcriptional pathways might be more effective as these can more directly and efficiently regulate energy production.
PubMed: 38072867
DOI: 10.1007/s00406-023-01727-2 -
International Immunopharmacology May 2024The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Inflammatory cytokines and the kynurenine...
BACKGROUND
The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Inflammatory cytokines and the kynurenine pathway (KP) play important roles in IBD and associated depression. Aripiprazole (ARP), an atypical antipsychotic, shows various anti-inflammatory properties and may be useful in treating major depressive disorder. This study aimed to evaluate the protective effects of ARP on TNBS-induced colitis and subsequent depression in rats, highlighting the role of the KP.
MATERIAL AND METHODS
Fifty-six male Wistar rats were used, and all groups except for the normal and sham groups received a single dose of intra-rectal TNBS. Three different doses of ARP and dexamethasone were injected intraperitoneally for two weeks in treatment groups. On the 15th day, behavioral tests were performed to evaluate depressive-like behaviors. Colon ulcer index and histological changes were assessed. The tissue levels of inflammatory cytokines, KP markers, lipopolysaccharide (LPS), nuclear factor-kappa-B (NF-κB), and zonula occludens (ZO-1) were evaluated in the colon and hippocampus.
RESULTS
TNBS effectively induced intestinal damages and subsequent depressive-like symptoms in rats. TNBS treatment significantly elevated the intestinal content of inflammatory cytokines and NF-κB expression, dysregulated the KP markers balance in both colon and hippocampus tissues, and increased the serum levels of LPS. However, treatment with ARP for 14 days successfully reversed these alterations, particularly at higher doses.
CONCLUSION
ARP could alleviate IBD-induced colon damage and associated depressive-like behaviors mainly via suppressing inflammatory cytokines activity, serum LPS concentration, and affecting the NF-κB/kynurenine pathway.
Topics: Animals; Male; Trinitrobenzenesulfonic Acid; Kynurenine; Rats, Wistar; Anti-Inflammatory Agents; Aripiprazole; Colitis; Depression; Rats; NF-kappa B; Cytokines; Signal Transduction; Colon; Hippocampus; Disease Models, Animal; Humans
PubMed: 38691917
DOI: 10.1016/j.intimp.2024.112158 -
Pharmacy (Basel, Switzerland) Nov 2023This systematic review compared the efficacy and tolerance of oral antipsychotics (APDs) used in the treatment of schizophrenia following the PRISMA-P© statement ( =... (Review)
Review
This systematic review compared the efficacy and tolerance of oral antipsychotics (APDs) used in the treatment of schizophrenia following the PRISMA-P© statement ( = 21). The primary outcomes of interest were clinical response measured with symptoms' improvement, tolerance to side effects and discontinuation reasons. There was better individual patients' response to aripiprazole vs. ziprasidone and quetiapine ((CDSS = 0.04), BPRS = 0.02, YMRS = 0.001) and ziprasidone vs. quetiapine (CGI = 0.02, CDSS = 0.02). Aripiprazole was more tolerated than risperidone, ziprasidone and quetiapine ( < 0.05). Quetiapine was more tolerated than aripiprazole, ziprasidone and risperidone ( < 0.05). Ziprasidone was more tolerated than quetiapine haloperidol and olanzapine ( < 0.05). Risperidone was more tolerated than olanzapine ( = 0.03) and haloperidol was more tolerated than olanzapine and quetiapine ( < 0.05). Olanzapine caused less discontinuation than quetiapine; quetiapine caused less discontinuation than ziprasidone, aripiprazole and haloperidol; ziprasidone caused less discontinuation than quetiapine, aripiprazole and haloperidol; aripiprazole caused less discontinuation than quetiapine, ziprasidone and olanzapine and olanzapine caused less discontinuation than ziprasidone and haloperidol ( < 0.05). It was concluded that individual patient clinical response, tolerance to side effects and life-threatening side effects remain the most reliable basis for selecting and continuing the use of APD.
PubMed: 37987385
DOI: 10.3390/pharmacy11060175 -
Health Science Reports Aug 2023Obsessive-compulsive disorder (OCD) is a mental illness with a chronic coarse and waxing and waning of symptoms. Treatment of OCD in patients with bipolar disorder (BD)...
Comparison of Aripiprazole and Risperidone effectiveness in treating obsessive-compulsive disorder in patients with bipolar disorder: Double-blind, randomized clinical trial.
BACKGROUND
Obsessive-compulsive disorder (OCD) is a mental illness with a chronic coarse and waxing and waning of symptoms. Treatment of OCD in patients with bipolar disorder (BD) remains challenging.
OBJECTIVES
The present study aims to compare the safety and effectiveness of Risperidone and Aripiprazole as adjunctive therapy with valproate sodium, in treating mania, depression, and OCD in patients with comorbidity of OCD-BD.
METHODS
This research is 3 phase, double-blind, randomized clinical trial, with a total number of 64 patients. The diagnostic psychiatrist clinical interview was based on diagnostic and statistical manual of mental disorders, 5th edition (DSM-5) criteria. For assessing severity of OCD, mania, and depression, Yale-Brown obsessive-compulsive scale (Y-BOCS), young mania rating scale (YMRS), and Hamilton depression rating scale (HAM-D) scores were used. Patients were randomly assigned to the two parallel groups. All patients in both group were received valproate sodium, one group was treated with Aripiprazole and the other group was treated with Risperidon as adjective therapy with valproate sodium.The SPSS software (version 22), test, -test, and analysis of variance with repeated measures were used to analyze the data.
RESULTS
The dosage and time of both drugs were statistically significant in reducing the mean score of all three mentioned scales, but the effect of group was not statistically significant in HAM-D and YMRS scores, only in terms of OCD, the mean of the Y-BOCS score was significantly lower in the Aripiprazole group ( < 0.001). In relation to side effects, Risperidone induced statistically significant weight gain ( < 0.001) and Aripiprazole induced statistically significant sleep disturbance ( < 0.05).
CONCLUSIONS
Both Aripiprazole and Risperidone can be used effectively as adjunctive therapy with valproate sodium in treating OCD in patients with BD without any serious and life threatening adverse effect. Aripiprazole is more effective than Risperidone in treating OCD in BD.
PubMed: 37645033
DOI: 10.1002/hsr2.1531