Effects of personality on the association between paroxetine plasma concentration and response

Abstract

BackgroundWe studied the differences between groups that were divided according to personality characteristics with respect to the relationship between drug concentration and symptom improvement.MethodsA total of 120 patients with major depressive disorder were treated with paroxetine for 6 weeks, and 89 patients completed the protocol. The Montgomery–Åsberg Depression Rating Scale (MADRS) was used to evaluate the patients. Patients’ paroxetine plasma concentrations at week 6 were measured. Their personalities were evaluated by the Temperament and Character Inventory (TCI) at the first visit. We divided the patients into two groups according to the median of each TCI dimension. We compared the responder rate between “high” and “low” groups in each TCI dimension and analyzed Pearson’s correlation coefficients of paroxetine plasma concentration and MADRS-improvement rate.ResultsA total of 62 patients completed the TCI. Low-novelty-seeking, high-harm-avoidance, low-reward-dependence, and low-self-directedness groups exhibited significant negative correlations between paroxetine plasma concentration and MADRS improvement. Among the groups with combined personality traits, the high-harm-avoidance and low-self-directedness groups showed a markedly significant negative correlation.ConclusionPatients with depression exhibiting specific personality traits, especially those with high harm-avoidance and low self-directedness scores, exhibited a significant negative association between paroxetine plasma concentration and MADRS-improvement rate. Therefore, a lower dose might be suitable for patients with specific personality traits.

Automated Interlaboratory Comparison of Therapeutic Drug Monitoring Data and Its Use for Evaluation of Published Therapeutic Reference Ranges

“…Our data on paroxetine, which are supported by the findings of Reis et al, showed a higher upper therapeutic analytical range than the reference provided in the AGNP [ 3 , 8 ]. This is interesting as a negative effect on the treatment at higher dosage has been shown for this drug [ 57 ]. The higher upper limit of the calculated therapeutic analytical range may suggest that a relatively large number of the patients receiving paroxetine may be above the limit where there is negative response to the treatment [ 57 , 58 ].…”

“…This is interesting as a negative effect on the treatment at higher dosage has been shown for this drug [ 57 ]. The higher upper limit of the calculated therapeutic analytical range may suggest that a relatively large number of the patients receiving paroxetine may be above the limit where there is negative response to the treatment [ 57 , 58 ]. It is therefore important that this difference is resolved.…”

Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

“…The pregnancy PBPK modelling approach was used to provide a clinically relevant dose titration strategies [71] when considering the CYP2D6 phenotype status patients by targeting a paroxetine plasma window of 20-60 ng/mL [72,73]. The PBPK model workflow validated the pregnancy model through: (i) 3 single dose and 2 multiple dosing studies in non-pregnancy subjects; (ii) non-genotyped pregnant subjects throughout gestation and (iii) genotyped (EM, PM and UM) pregnant subjects at the mid-point of each trimester.…”