Abstract
IntroductionThe efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD) can differ depending on the patient's serotonin transporter-linked polymorphic region (5-HTTLPR) genotype, and the effects of varying plasma concentrations of drugs can also vary. We investigated the association between the paroxetine plasma concentration and clinical response in patients with different 5-HTTLPR genotypes.MethodsFifty-one patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate patients at 0, 1, 2, 4, and 6 weeks. The patients' paroxetine plasma concentrations at week 6 were measured using high-performance liquid chromatography. Additionally, their 5-HTTLPR polymorphisms (alleles S and L) were analyzed using a polymerase chain reaction with specific primers. We divided the participants into two groups based on their L haplotype: the SS group and the SL and LL group. We performed single and multiple regression analyses to investigate the associations between MADRS improvement and paroxetine plasma concentrations or other covariates for each group.ResultsThere were no significant differences between the two groups with regard to demographic or clinical data. In the SS group, the paroxetine plasma concentration was significantly negatively correlated with improvement in MADRS at week 6. In the SL and LL group, the paroxetine plasma concentration was significantly positively correlated with improvement in MADRS at week 6 according to the results of the single regression analysis; however, it was not significantly correlated with improvement in MADRS at week 6 according to the results of the multiple regression analysis.ConclusionAmong patients with MDD who do not respond to paroxetine, a lower plasma concentration or a lower oral dose of paroxetine might be more effective in those with the SS genotype, and a higher plasma concentration might be more effective in those with the SL or LL genotype.
Highlights
The efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD) can differ depending on the patient’s serotonin transporter-linked polymorphic region (5-HTTLPR) genotype, and the effects of varying plasma concentrations of drugs can vary
We investigated the association between the paroxetine plasma concentration and clinical response in patients grouped according to their 5-HTTLPR polymorphisms
There were no significant differences between the groups regarding any of the patient characteristics, including sex, age, height, body weight, baseline Montgomery-Asberg Depression Rating Scale (MADRS) score, MADRS improvement at each week, numbers of responders and remitters, or paroxetine plasma concentrations
Summary
The efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD) can differ depending on the patient’s serotonin transporter-linked polymorphic region (5-HTTLPR) genotype, and the effects of varying plasma concentrations of drugs can vary. We investigated the association between the paroxetine plasma concentration and clinical response in patients with different 5-HTTLPR genotypes. Therapeutic ranges have been established for several major psychotropic drug classes, including mood stabilizers (e.g., lithium) [7,9], tricyclic antidepressants (TCAs) [10,12,15], and ‘atypical’ antipsychotics (e.g., clozapine) [17]. The American Psychiatric Association Task Force on the Use of Laboratory Tests in Psychiatry (1985) concluded that, when treating patients with MDD, there was robust evidence for the utility of plasma concentration measurements of imipramine, desmethylimipramine (desipramine), and nortriptyline, but not of other TCAs [11]. On the basis of these findings, therapeutic drug monitoring has been shown to be clinically useful for a number of tricyclic
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