Serum N-Desmethylcitalopram Concentrations are Associated with the Clinical Response to Citalopram of Patients with Major Depression.

OBJECTIVE: Citalopram (CITA) is a widely used and well-tolerated selective serotonin reuptake inhibitor. The aim of the study was to evaluate the possible influences of serum concentrations of CITA and its major metabolite n-desmethylcitalopram (NDCITA) on the efficacy and tolerability of CITA in patients with major depressive disorder. METHODS: The study included 46 outpatients with major depressive disorder who received CITA. The efficacy and tolerability were assessed for 6 weeks. Serum CITA and NDCITA levels were measured at the 4th week. RESULTS: The HDRS17 total scores of the patients with high NDCITA and CITA & NDCITA concentrations showed a more significant reduction compared to the patients with expected and low serum NDCITA and CITA & NDCITA concentrations. However, we did not observe a correlation between the serum concentrations and the side effects of CITA, NDCITA, and CITA & NDCITA. CONCLUSION: Our results suggested the potential contribution of NDCITA to the antidepressant effect of CITA. Further studies involving larger clinical samples are required to confirm the impact of serum NDCITA concentrations on the efficacy of CITA.

Influence of ABCB1 polymorphisms and serum concentrations on venlafaxine response in patients with major depressive disorder.

BACKGROUND: The pharmacokinetics and the pharmacodynamics of antidepressants show large inter-individual variations which result in unpredictable clinical responses. AIM: The aim of the study was to examine the effect of ABCB1 polymorphisms and the serum concentrations on the efficacy and tolerability of venlafaxine in patients with major depressive disorder (MDD). METHODS: Fifty-two outpatients who met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for MDD were recruited for the study. The severity of depression was assessed using the 17-item Hamilton Rating Scale for Depression scale (HDRS17) and tolerability was assessed based on a query regarding side-effects for 6 weeks. The ABCB1 C3435T/A and G2677T/A polymorphisms were genotyped by PCR/RFLP and steady-state serum venlafaxine concentrations were measured by high-performance liquid chromatography. RESULTS: Patients with the TT genotype for the C3435T and the TT/TA genotype for the G2677T/A polymorphism showed significantly higher frequencies in venlafaxine-induced akathisia. This relationship was not observed for efficacy. As regards serum venlafaxine concentrations, patient groups showed no significant differences in efficacy and tolerability. CONCLUSION: The results suggest that individuals with the TT-TT/TA genotypes for the C3435T-G2677T/A polymorphisms of ABCB1 may be pre-disposed to a risk of akathisia.

ABCB1 C3435T polymorphism is associated with susceptibility to major depression, but not with a clinical response to citalopram in a Turkish population.

BACKGROUND: The ATP-binding cassette sub-family B member 1 (ABCB1) gene, which encodes the p-glycoprotein at the blood-brain barrier, is investigated for patients' susceptibility to major depressive disorder (MDD) and their therapeutic response to antidepressants. However, there is an inconsistency between the studies of different ethnic groups. The current study aimed to determine the potential correlations of the ABCB1 gene C3435T polymorphism with the susceptibility to MDD and the therapeutic response to citalopram in a Turkish population. METHODS: Fifty-four patients with MDD who received citalopram and 70 controls from the Turkish population were genotyped for ABCB1 C3435T polymorphism. To assess the therapeutic response to citalopram, all patients were rated baseline, first, second, fourth and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAMD-17). RESULTS: There was a significant correlation between the patient and control groups for ABCB1 C3435T polymorphism. Distribution of CC genotype and C allele frequency were higher in the patients than in the control group (p = 0.006, p = 0.020, respectively). However, no correlation between ABCB1 C3435T polymorphism and a therapeutic response to citalopram was observed. CONCLUSION: Our results suggested that C3435T polymorphism in the ABCB1 gene may be an indicator of the susceptibility to major depression, without a likely treatment response to citalopram in a Turkish population. These findings should be replicated in studies on larger patient groups with different ethnicities.

Lack of a time-dependent effect of melatonin on radiation-induced apoptosis in cultured rat lymphocytes.

Ionizing radiation is widely used for the treatment of solid tumors and it is thought to act by directly targeting tumor clonogens, also known as stem cells. Apoptosis is a genetically programmed mechanism of cell death often characterized by internucleosomal DNA cleavage. Although it has been previously shown that lymphocytes readily undergo apoptosis in patients receiving anticancer drugs or treatment with ionizing radiation, this is the first study to investigate the influence of radiotherapy and melatonin on apoptosis in rat lymphocytes at two different times of the day. Melatonin, a free radical scavenger, is an endogenous neurohormone predominantly synthesized in and secreted by the pineal gland. It has been shown that melatonin inhibits apoptosis in normal cells but it increases the rate of apoptosis in various cancer cells. Therefore, in the present study, the effect of melatonin on apoptosis in cultured lymphocytes was studied after total body irradiation (TBI) was given to rats in the morning (1 HALO) or evening (13 HALO) with morphological and DNA fragmentation analysis. Two-way analysis of variance (ANOVA) revealed that radiation increased the rate of apoptosis in rat lymphocytes after TBI, and melatonin treatment did not reduce the rate of apoptosis after TBI at either time point. We conclude that the lack of an effect of melatonin on the apoptosis rate in rat lymphocytes might be due to the dose-dependent effect of melatonin, the time course of apoptosis investigated, or the cell type in which apoptosis was examined.