Aripiprazole for the management of schizophrenia in the Japanese population: a systematic review and meta-analysis of randomized controlled trials

Kishi, Taro; Matsuda, Yuki; Matsunaga, Satoru; Iwata, Nakao

doi:10.2147/ndt.s78977

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…Furthermore, aripiprazole significantly reduced both PANSS and CGI-S scores [ 78 ]. However, the evidence that aripiprazole is more efficacious than other antipsychotics is lacking [ 79 ]. In a comparative study looking at treatment continuation of various atypical antipsychotics, aripiprazole seemed to have lower rates of relapse; however, the study design was a large observational study, which carries a lower level of evidence and provides less convincing support [ 80 ].…”

Section: Role Of Antipsychotics In Prevention Of Dspmentioning

confidence: 99%

Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review

Yin¹,

Barr²,

Ramos-Miguel³

et al. 2017

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Chronic prescription of antipsychotics seems to lose its therapeutic benefits in the prevention of recurring psychotic symptoms. In many instances, the occurrence of relapse from initial remission is followed by an increase in dose of the prescribed antipsychotic. The current understanding of why this occurs is still in its infancy, but a controversial idea that has regained attention recently is the notion of iatrogenic dopamine supersensitivity. Studies on cell cultures and animal models have shown that long-term antipsychotic use is linked to both an upregulation of dopamine D2-receptors in the striatum and the emergence of enhanced receptor affinity to endogenous dopamine. These findings have been hypothesized to contribute to the phenomenon known as dopamine supersensitivity psychosis (DSP), which has been clinically typified as the foundation of rebound psychosis, drug tolerance, and tardive dyskinesia. The focus of this review is the update of evidence behind the classification of antipsychotic induced DSP and an investigation of its relationship to treatment resistance. Since antipsychotics are the foundation of illness management, a greater understanding of DSP and its prevention may greatly affect patient outcomes.

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Section: Role Of Antipsychotics In Prevention Of Dspmentioning

confidence: 99%

Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review

Yin¹,

Barr²,

Ramos-Miguel³

et al. 2017

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“…Since medication choice is based on evidence and past treatment experiences and since FES patients lack past treatment experiences, evidence becomes even more important. Although expected to be better tolerated, aripiprazole had mixed efficacy results in chronic patients regarding total psychopathology compared to olanzapine and risperidone, being either inferior to olanzapine (Fleischhacker et al, 2009; Kane et al, 2009) or risperidone (Kishi et al, 2015; Leucht et al, 2013) or of comparable efficacy (Potkin et al, 2003). Additionally, two randomised controlled trials (RCTs) in FES suggested that aripiprazole might be superior to risperidone regarding negative symptoms (Liemburg et al, 2011; Robinson et al, 2015a).…”

Section: Introductionmentioning

confidence: 99%

An open-label randomised comparison of aripiprazole, olanzapine and risperidone for the acute treatment of first-episode schizophrenia: Eight-week outcomes

et al. 2019

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Purpose: This study aimed to investigate the efficacy and tolerability of aripiprazole, olanzapine and risperidone in first-episode schizophrenia (FES). Methods: The eight-week, open, randomised study was conducted in six Chinese medical centres. Altogether, 498 FES subjects were randomised to aripiprazole ( n = 165), olanzapine ( n = 168) or risperidone ( n = 165). Efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), tolerability with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and functioning with the Personal and Social Performance Scale (PSP). Results: All three antipsychotics significantly improved the baseline to end-point PANSS total and each of the sub-scale scores ( p < 0.001). Risperidone was superior to olanzapine and aripiprazole regarding PANSS total end-point scores ( p < 0.05). Cumulative response (PANSS total score reduction ⩾30%) was similar between risperidone, olanzapine and aripiprazole (74.8%, 73.5% and 70.1%; p = 0.707), but risperidone was superior to aripiprazole regarding PANSS total score reduction ⩾50% (37.8% vs. 26.6%; p < 0.05). Olanzapine was associated with the largest weight gain at week 4 and 8 ( p < 0.01), weight gain ⩾7% (olanzapine = 49.0% vs. risperidone = 32.5% vs. aripiprazole = 17.0%; p < 0.01), more psychic side effects at week 8 ( p < 0.01 each) and more ‘other’ side effects at week 4 ( p < 0.001) and week 8 ( p < 0.05) but fewer neurological side effects at week 4 ( p < 0.05) and week 8 ( p < 0.01). PSP improved more with risperidone than with aripiprazole at week 4 and 8 ( p < 0.05). Conclusions: For FES, risperidone might be a better choice than aripiprazole due to improved efficacy and functional improvement, without inferior tolerability. Aripiprazole is a better choice to avoid relevant short-term weight gain. Olanzapine could be chosen to avoid neurological adverse effects.

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“…Aripiprazole has unique receptor-binding properties acting as a partial agonist at dopaminergic D 2 and serotonergic 5-HT 1A receptors, and as an antagonist at 5-HT 2A receptors [8,9,12]. It has advantages, such as lower risk of extrapyramidal symptoms, hyperprolactinemia, bodyweight gain, diabetes mellitus and sedation; however, the treatment discontinuation rate associated with aripiprazole inefficacy seems to be higher than that of olanzapine or haloperidol [10,[13][14][15]. Almost complete dopamine receptor occupancy (>85%) has been observed at the plasma concentration of 100-150 ng/ml, and the optimal serum concentrations that result in the best improvement and no or mild side effects in patients, have been suggested to range between 150 and 300 ng/ml, whereas the risk of moderate to severe adverse effects increases at higher concentrations [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure

Kiss

Menus

Tóth

et al. 2019

Eur Arch Psychiatry Clin Neurosci

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The efficacy of aripiprazole therapy and the risk of adverse reactions are influenced by substantial interindividual variability in aripiprazole metabolizing capacity. In vitro studies assigned the potential role in aripiprazole metabolism to CYP2D6 and CYP3A enzymes; therefore, the association between the steady-state aripiprazole plasma concentrations and patients' CYP2D6-and CYP3A-status (CYP2D6, CYP3A4, CYP3A5 genotypes and CYP3A4 expression) and/or co-medication with CYP-function modifying medications has been investigated in 93 psychiatric patients on stable aripiprazole therapy. The patients' CYP2D6 genotype had a major effect on aripiprazole plasma concentrations, whereas the contribution of CYP3A genotypes and CYP3A4 expression to aripiprazole clearance was considered to be minor or negligible. The role of CYP3A4 expression in aripiprazole metabolism did not predominate even in the patients with non-functional CYP2D6 alleles. Furthermore, dehydroaripiprazole exposure was also CYP2D6 genotype dependent. Dehydroaripiprazole concentrations were comparable with aripiprazole levels in patients with functional CYP2D6 alleles, and 35% or 22% of aripiprazole concentrations in patients with one or two non-functional CYP2D6 alleles, respectively. The concomitant intake of CYP2D6 inhibitors, risperidone, metoprolol or propranolol was found to increase aripiprazole concentrations in patients with at least one wild-type CYP2D6*1 allele. Risperidone and 9-hydroxyrisperidone inhibited both dehydrogenation and hydroxylation of aripiprazole, whereas metoprolol and propranolol blocked merely the formation of the active dehydroaripiprazole metabolite, switching towards the inactivation pathways. Patients' CYP2D6 genotype and co-medication with CYP2D6 inhibitors can be considered to be the major determinants of aripiprazole pharmacokinetics. Taking into account CYP2D6 genotype and co-medication with CYP2D6 inhibitors may improve outcomes of aripiprazole therapy.

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Aripiprazole for the management of schizophrenia in the Japanese population: a systematic review and meta-analysis of randomized controlled trials

Cited by 8 publications

References 36 publications

Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review

Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review

An open-label randomised comparison of aripiprazole, olanzapine and risperidone for the acute treatment of first-episode schizophrenia: Eight-week outcomes

Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure

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