ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment.

OBJECTIVE: ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) is a drug transporter protein expressed on the epithelial cells of the intestine and the endothelial cells of the blood-brain barrier. Intestinal ABCB1 actively transports drugs from the cell membrane and prevents them from entering the blood stream whereas the blood-brain barrier ABCB1 prevents drugs from entering the central nervous system. In this study, we tested whether genetic polymorphisms within the ABCB1 gene are associated with the severity of depression and the effectiveness of the antidepressant, escitalopram (S-CIT), in treating major depressive disorder (MDD). METHODS: Twenty single nucleotide polymorphisms in the ABCB1 gene were selected and genotyped in 100 MDD patients who had undergone S-CIT treatment continuously for 8 weeks. The serum concentrations of S-CIT and its metabolites (S-desmethylcitalopram and S-didesmethylcitalopram) were then measured at weeks 2, 4, and 8. RESULTS: The ABCB1 genotypes of rs1922242 (P=0.0028) and rs1202184 (P=0.0021) showed significant association with the severity of depressive symptoms as assessed by the Hamilton Rating Scale for Depression adjusted with Hamilton Rating Scale for Anxiety. The haplotype block, rs1882478-rs2235048-rs2235047-rs1045642-rs6949448 (from intron 27 to intron 26), of ABCB1 was found strongly associated with the remission rate (global P=0.003, d.f.=69) in which haplotype T-T-T-C-C was associated with a slower remission rate on S-CIT treatment (P=0.001). The haplotypes may not be indicators of the severity of depression or anxiety. CONCLUSION: Our findings suggest that single nucleotide polymorphisms in the ABCB1 gene may be indicators of the severity of depression and of the likely S-CIT treatment remission response in MDD.

CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions.

AIM: The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT) to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This study tested whether genetic polymorphisms in the CYP1A2 gene are associated with the treatment responses to S-CIT. MATERIALS & METHODS: Ten SNPs in CYP1A2 were selected and genotyped in 158 patients under S-CIT treatment. The serum levels of S-CIT and its metabolites were measured by HPLC. RESULTS: CYP1A2 SNPs rs2069521, rs2069526, rs4646425 and rs4646427 are significantly associated with the metabolic ratios of S-DDCIT/S-DCIT (p = 0.002, 0.018, 0.008 and 0.004, respectively) at week 2 of treatment. Carriers of the allele types associated with higher S-DDCIT/S-DCIT ratios had more severe side effects. CONCLUSION: These results suggest that genetic variants in CYP1A2 may be indicators for S-CIT metabolism and that the fast metabolizers may experience more severe adverse reactions in the early stages of S-CIT treatment. Original submitted 27 December 2012; Revision submitted 15 May 2013.

Comparison of escitalopram and paroxetine in the treatment of major depressive disorder.

This is a single-blind, parallel, flexible-dose study to compare the efficacy and tolerability of escitalopram and paroxetine in the treatment of patients with major depressive disorder. We recruited 399 patients from the outpatient clinics of five hospitals in northern Taiwan. Patients were administered either escitalopram (10-30 mg) or paroxetine (20-40 mg) according to the judgment of clinicians. These patients were assessed using the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety at weeks 0, 1, 2, 4, 6, and 8. A total of 302 patients fulfilled the evaluation criteria and were included in a statistical analysis. We found that escitalopram induced more significant symptom reduction and response rate in terms of the mean HAM-D scores at week 6 (P<0.05) and week 8 (P<0.05) than paroxetine, but that there were no significant differences between the two groups in the remission rate. Escitalopram induced significantly less frequency of adverse effects of weakness (P<0.01), nausea and vomiting (P<0.001), drowsiness (P<0.01) as well as somnolence (P<0.01) than paroxetine, although all these side effects were mild and tolerable. However for a more definitive result, future prospective trials with the inclusion of a placebo group and a double-blind design are needed. In patients who did not have severe depression (HAM-D score at baseline<21), but not in severely depressed patients, escitalopram was statistically superior to paroxetine, as shown by the mean change in the HAM-D score.