The Incidence of Akathisia in the Treatment of Schizophrenia with Aripiprazole, Asenapine and Lurasidone: A Meta-Analysis

Thomas, Jennifer E.; Caballero, Joshua; Harrington, Catherine

doi:10.2174/1570159x13666150115220221

Cited by 44 publications

(32 citation statements)

References 43 publications

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“…Since N-dealkyl-aripiprazole and hydroxy-aripiprazole are inactive metabolites, the inactivation pathways may become the principal route of aripiprazole metabolism upon co-medication with metoprolol or propranolol, resulting in potential modification of aripiprazole efficacy. Aripirazole has been reported to have a significantly higher risk of akathisia compared to other second generation antipsychotics [58], and beta-adrenerg receptor blockers, such as propranolol or metoprolol, are frequently used in the clinical management of antipsychotics induced akathisia [59]. The fact that co-administration of aripiprazole and beta-blockers is common, underlines the clinical significance of our findings.…”

Section: Discussionsupporting

confidence: 60%

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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Section: Discussionsupporting

confidence: 60%

Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure

Kiss

Menus

Tóth

et al. 2019

Eur Arch Psychiatry Clin Neurosci

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“…Similarly, it was important to examine the potential influence of psychotic severity, owing to a previously reported relationship by which the severity of psychotic episode predicted more anxiety [26] and concerns about symptom differentiation that prompted a call to account for psychotic severity in anxiety studies in this population [27]. Our and other studies, furthermore, confirmed the presence of anxiety symptoms during the acute phase among some patients, toppling the outdated notion that anxiety symptoms in schizophrenia would be limited to the post-psychotic period [18,31,45].…”

Section: Discussionsupporting

confidence: 68%

“…Undifferentiated anxiety was found discernible without evidence of a confounding influence by akathisia, the severity of psychotic symptoms, or medication. It was important to examine akathisia as potential confounder as it may be confused with anxiety and vice versa [3,28,45,46]. Similarly, it was important to examine the potential influence of psychotic severity, owing to a previously reported relationship by which the severity of psychotic episode predicted more anxiety [26] and concerns about symptom differentiation that prompted a call to account for psychotic severity in anxiety studies in this population [27].…”

Section: Discussionmentioning

confidence: 99%

Discerning undifferentiated anxiety from syndromal anxiety in acute-phase schizophrenia

2020

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Background: Literature on anxiety in schizophrenia is confined to well-established diagnostic syndromes and the diagnostic category of unspecified anxiety disorder has not been quantitatively verified in this population. This study examined whether anxiety that is not differentiated into the well-established syndromes is empirically discernible from syndromal anxiety and no anxiety in acute-phase schizophrenia. Methods:After sampling 111 acute-phase schizophrenia patients, they were stratified into three groups: syndromal anxiety; undifferentiated anxiety; and without anxiety disorder. The groups were compared statistically in two data sets on measures for anxiety, psychotic severity, depressive features, akathisia and medication use.Results: On two measures of anxiety and for both data sets, the groups were significantly different without evidence of a confounding influence by akathisia, medication, or psychotic severity. The undifferentiated group was different from the syndromal group on the Staden Schizophrenia Anxiety Rating Scale (S-SARS) for both data sets (mean difference = 7.46, p < 0.001; mean difference = 7.69, p < 0.002) and on the Hamilton Anxiety Rating Scale for the one data set (mean difference = 14.68, p < 0.001) but not for the replicative data set (mean difference = 1.49, p = 0.494). The undifferentiated anxiety group was different from the no anxiety group for the respective data sets on both anxiety scales (S-SARS: mean difference = 8.67, p < 0.001; mean difference = 8.64, p < 0.001)(HAM-A: mean difference = 6.05, p < 0.001; mean difference = 8.67, p = 0.002). When depressive features had a confounding effect, it was small relative to the group differences. Conclusions:The results suggest some patients in acute-phase schizophrenia present with undifferentiated anxiety that is discernible from both syndromal anxiety and those without an anxiety disorder. This finding may serve as empirical grounds for clinicians to recognise undifferentiated anxiety in acute-phase schizophrenia, and for further research into the clinical importance of undifferentiated anxiety in this population.

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“…A study conducted in 2015 revealed that risk of akathisia was higher for Aripiprazole, Asenapine and Lurasidone. 23 Chronic insomnia is a problem in Schizophrenics and two cases of insomnia was reported at a dose of 5mg/day. The addition of benzodiazepine resolved this problem.…”

Section: Resultsmentioning

confidence: 99%

Adverse Drug Reactions Affiliated with Atypical Antipsychotics in Patients with Schizophrenia

Oommen¹,

P²,

Mc³

et al. 2019

JYP

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An Adverse drug reaction cannot be avoided especially with drugs like antipsychotics which are the mainstay for the treatment of schizophrenia, a chronic disease, as well for the treatment of psychosis. Hence monitoring of adverse drug reactions is the key factor in ensuring patient compliance and safety. This study was a prospective, descriptive, follow up study. The reported ADRs were assessed for causality using both WHO causality assessment scale and Naranjo's algorithm. The severity of the reported reactions was assessed using Modified Hartwig and Siegel scale. The predictability and preventability of the reported ADRs was assessed using developed criteria for determining predictability of an ADR and Modified Schumock and Thornton scale respectively. A total of one hundred and forty three adverse drug reactions were observed from One hundred and two patients that were recruited. ADR's were noted and the majority of these adverse reactions was seen with Olanzapine and Risperidone. These include weight gain, sedation, tremors, drug induced parkinsonism and disturbances in menstrual cycle. Mild ADR's using Hartwig scale were fatigue, dry mouth, insomnia, weight gain and GI disturbances. Moderate ADR's were tardive dyskinesia, pill rolling movements, drug induced parkinsonism and hyper salivation. Severe reactions included disturbances in lipid profile, delirium, menstrual disturbances and hypertension Of the ADR's, 92% were predictable and 7.4% unpredictable. 67.8% ADR's were not preventable, 29.6% ADR's were definitely preventable and 3.70% probably preventable. WHO causality assessment revealed 55.5% ADR's to be certain, 29.6% to be probable and 14.8% to be possible. Need of the hour is active surveillance of adverse drug reaction with an efficient pharmacovigilance centre in every established hospital.

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The Incidence of Akathisia in the Treatment of Schizophrenia with Aripiprazole, Asenapine and Lurasidone: A Meta-Analysis

Cited by 44 publications

References 43 publications

Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure

Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure

Discerning undifferentiated anxiety from syndromal anxiety in acute-phase schizophrenia

Adverse Drug Reactions Affiliated with Atypical Antipsychotics in Patients with Schizophrenia

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