Effects of Escitalopram on Plasma Concentrations of Aripiprazole and its Active Metabolite, Dehydroaripiprazole, in Japanese Patients

Abstract

Introduction: The effects of escitalopram (10?mg/d) coadministration on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in 13 Japanese psychiatric patients and compared with those of paroxetine (10?mg/d) coadministration. Methods: The patients had received 6?24?mg/d of aripiprazole for at least 2 weeks. Patients were randomly allocated to one of 2 treatment sequ?ences: paroxetine-escitalopram (n=6) or escitalopram-paroxetine (n=7). Each sequence consisted of two 2-week phases. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection. Results: Plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during paroxetine coadministration were 1.7-fold (95% confidence intervals [CI], 1.3?2.1, p<0.001) and 1.5-fold (95% CI 1.2?1.9, p<0.01) higher than those values before the coadministration. These values were not influenced by escitalopram coadministration (1.3-fold, 95% CI 1.1?1.5 and 1.3-fold, 95% CI 1.0?1.5). Plasma dehydroaripiprazole concentrations remained constant during the study. Conclusion: The present study suggests that low doses of escitalopram can be safely coadministered with aripiprazole, at least from a pharmacokinetic point of view.

Application of a Pharmacogenetics-Based Precision Medicine Model (5SPM) to Psychotic Patients That Presented Poor Response to Neuroleptic Therapy

“…The pharmacogenetic profile of the population (CYP1A2 HI: 0.86; CYP2D6 EM: 0.85; CYP3A4 EM: 0.91) could explain the need to apply a higher dose with its consequent adverse effects in patients treated with olanzapine [41], clozapine [42], or asenapine [43], all related to CYP1A2, while favoring the use of aripiprazole or risperidone in those who have a wt-like haplotype in CYP2D6 [44][45][46][47][48][49] and CYP3A4 [44,50] cytochromes, a situation frequently found in our population.…”

Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

“…The mood stabilizers carbamazepine and valproate were found to decrease ARI (AM) BLs by 65% and 23%, respectively (Nakamura et al 2009;Eryilmaz et al 2014). No influence of escitalopram (Nemoto et al 2014), haloperidol (Nakamura et al 2014) or clozapine (Zuo et al 2006) coadministration was found. Concurrent treatment with CYP3A4 inducers, CYP2D6 inhibitors, alimemazine, or lithium changed BLs by 40%-60%, which has to be considered clinically relevant (Waade et al 2009).…”

“…This finding was confirmed in another study (Nemoto et al 2012). The same group was not able to replicate this result (Nemoto et al 2014). A Japanese study found that dose-corrected ARI and AM concentrations increased with a general increase in the number of the mutated CYP2D6 alleles *5, *10, and *14 (Nagai et al 2012).…”

“…Most studies that were interested in the effect of comedication measured drug concentrations before and after the add-on of a pharmacokinetically relevant drug. Two studies showed an increase of ARI BLs after the administration of paroxetine (Nemoto et al 2012(Nemoto et al , 2014 (Table 4). The mood stabilizers carbamazepine and valproate were found to decrease ARI (AM) BLs by 65% and 23%, respectively (Nakamura et al 2009;Eryilmaz et al 2014).…”

Review: Influence of the CYP450 Genetic Variation on the Treatment of Psychotic Disorders

“…The presence of duplication in the absence of inactive or reduced-activity alleles results in an ultrarapid metabolizer (UM) [46]. PM individuals were found to have higher aripiprazole/risperidone active moieties exposure [21,28,[47][48][49][50][51], with this exposure even being proportional to the number of affected alleles in some studies [47,48]. Furthermore, it has been found that PM individuals tend to have lower aripiprazole/risperidone doses administered, as it has been recommended in some studies [28,52], and, alongside UM individuals, have a higher risk of risperidone treatment failure [51].…”