Background:Plasma concentrations of the S-enantiomer of citalopram were different between extensive and poor CYP2C19 metabolizers in healthy subjects and depressed patients. However, most studies applied dose-corrected concentrations. Thus, we studied the effects of polymorphisms of the CYP2C19 gene on raw plasma drug concentrations in Japanese patients with depression.Methods:Subjects in this study consisted of 412 depressed patients receiving 5, 10, 15, or 20 mg of escitalopram once a day. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using HPLC. CYP2C19 genotypes were identified using polymerase chain reaction methods.Results:There were no differences in the steady-state plasma concentrations of escitalopram or desmethylescitalopram in each dose group (5, 10, 15, or 20 mg of escitalopram) among CYP2C19 genotype groups. However, 1-way analysis of variance showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram but not in the dose-adjusted plasma concentration of desmethylescitalopram. Analysis of covariance including age, sex, and body weight showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram and the ratio of desmethylescitalopram to escitalopram.Conclusions:These findings suggest that the CYP2C19 variants are associated with steady-state plasma concentrations of escitalopram to some extent but are not associated with desmethylescitalopram.

Care should be taken when administering donepezil to patients with atrioventricular block, or patients taking other drugs that can prolong the PR interval. Copyright © 2014 John Wiley & Sons, Ltd.

Background Insulin-like growth factor I (IGF-I) is a neurotrophic factor produced by the hypothalamic-pituitary-somatotropic axis and is considered a potential contributor to the pathology of major depressive disorder (MDD). Although it is known that the hypothalamic-pituitary-adrenal axis and cortisol are involved in the pathology of MDD, the association with dehydroepiandrosterone sulfate (DHEAS) remains unclear. The current study sought to clarify the relationship between these hormones and the pathology of MDD. Methods Subjects were 91 Japanese patients with a diagnosis of MDD. Serum IGF-I, cortisol, and DHEAS were measured. Samples were taken before breakfast after overnight fasting. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D). Results Subjects included 59 men and 32 women with an average age of 44.1 ± 13.1 years (mean ± SD). The blood IGF-I level was 152.0 ± 50.0 ng/mL, the cortisol level was 10.1 ± 4.6, and the DHEAS level was 201.3 ± 112.7 μg/dL. The mean HAM-D score was 13.9 ± 9.0. Serum IGF-I levels were not correlated with cortisol. Higher IGF-I, cortisol, and cortisol/DHEAS ratios were associated with higher HAM-D scores (adjusted R 2 = 0.240, P < 0.001), and higher IGF-I and cortisol were associated with higher melancholic or suicide subscores (adjusted R 2 = 0.200, P < 0.001; adjusted R 2 = 0.273, P < 0.001). Conclusions Our findings suggest that hormonal dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-somatotropic axes may be related to the symptom severity of MDD, melancholia, and suicide-related factors.

It has long been known that antipsychotic drugs (ATP) causes tachycardia, however details such as the differences between ATP are not well known. In recent years, the relationship between the rise in resting heart rate (RHR) and the increased risk of death in the general population has been garnering attention. In this study, we examined the difference in action on RHR between olanzapine (OLZ) and aripiprazole (ARP). The changes in the RHR on switching from OLZ to ARP and on increasing from the starting OLZ dose to the final one were evaluated in 19 outpatients (Study 1) and in 29 outpatients with schizophrenia (Study 2), respectively. To analyze the RHR, electrocardiographic measurements were obtained. At the same day, the Brief Psychiatric Rating Scale (BPRS) was evaluated, and fasting blood samples were drawn after an overnight fast of at least 8 h to examine electrolytes. Both Study 1 and 2 were conducted with the approval of the Gene Ethics Committee of Niigata University Graduate School of Medical and Dental Sciences, and the patients were treated at the outpatient psychiatric clinic at Niigata University Medical and Dental Hospital. All patients had been diagnosed with schizophrenia based on the DSM-IV-TR. In the Study 1, OLZ of 14.6 ± 9.2mg (mean ± standard deviation) was switched to ARP of 20.8 ± 8.1mg. Significant decreases were observed in the mean RHR after the switch to ARP (73.7 ± 9.7 vs 65.8 ± 10.9 beats/min, p = 0.008). In the Study 2, the starting OLZ dose was 7.2 ± 3.2mg and the increasing OLZ dose was 18.3 ± 7.4mg. Significant increases were observed in the mean RHR after increasing OLZ (69.7 ± 14.0 vs 75.6 ± 14.3 beats/min, p = 0.004). In this study, it was shown that OLZ has a stronger RHR enhancing effect compared to ARP and its effects are dose-dependent. If the increase in RHR increases the mortality rate of patients with schizophrenia, it may be necessary to further investigate the differences between ATP in terms of the effect on RHR of second-generation antipsychotics with a strong anticholinergic action or phenothiazine antipsychotics.

Background Hormones of the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–adrenal (HPA), and hypothalamic–pituitary–somatotropic (HPS) axes are potentially involved in major depressive disorder (MDD), but these hormones have not been simultaneously investigated in male patients with MDD. We investigated the association between male MDD symptoms and estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF1). Methods Serum estradiol, testosterone, cortisol, DHEAS, and IGF1 levels were measured in 54 male patients with MDD and 37 male controls and were compared with clinical factors. We investigated the associations between hormone levels and Hamilton Depression Rating Scale (HAM-D) scores. The correlations among hormones were also investigated. Results Patients had significantly lower estradiol levels than controls (22.4 ± 8.4 pg/mL vs. 26.1 ± 8.5 pg/mL, P = 0.040). Serum estradiol levels were negatively correlated with HAM-D scores (P = 0.000094) and positively correlated with Global Assessment of Functioning scores (P = 0.000299). IGF1 levels and the cortisol:DHEAS ratio were higher in patients than in controls (IGF1: 171.5 ± 61.8 ng/mL vs. 144.1 ± 39.2 ng/mL, P = 0.011; cortisol:DHEAS ratio: 0.07 ± 0.05 vs. 0.04 ± 0.02, P = 0.001). DHEAS levels were lower in patients than in controls (227.9 ± 108.4 μg/dL vs. 307.4 ± 131.2 μg/dL, P = 0.002). IGF1, cortisol:DHEAS ratio, and DHEAS were not significantly correlated with HAM-D scores. Cortisol and testosterone levels were not significantly different between patients and controls. Serum estradiol levels were positively correlated with DHEAS levels (P = 0.00062) in patients, but were not significantly correlated with DHEAS levels in controls. Conclusion Estradiol may affect the pathogenesis and severity of patients with MDD in men, and other hormones, such as those in the HPA and HPS axes, may also be involved in male MDD. Additionally, a correlation between estradiol and DHEAS may affect the pathology of MDD in men.