Serotonergic antidepressant use and the risk of fracture: a population-based nested case-control study.

UNLABELLED: This is the first study to investigate the association between the use of selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) and the risk of fractures using a nationwide representative cohort of ethnic Chinese. Current use of SSRI/SNRI and the co-morbidity, especially osteoporosis and history of falling, play an important role in the increased risk of fractures. INTRODUCTION: This nested case-control study examines the association between the timing, intensity, and individual components of serotonergic antidepressant (including SSRIs and SNRIs) use and the risk of all-cause fracture. METHODS: Using the 2002-2011 Taiwan National Health Insurance Research Database, we identified patients who received at least three prescriptions of antidepressants between January 1st 2002 and December 31st 2010 as our study cohort. In the study cohort, we identify 8250 patients who had first admission for fracture and 33,000 matched controls (1:4, matched by age, sex, and cohort entry date). Multivariate conditional logistic regression was used to estimate the association between the use of serotonergic antidepressants and the risk of fracture. RESULTS: Current users of serotonergic antidepressants were associated with an increased risk of fracture (adjusted odds ratio (aOR) 1.16 [95 % confidence interval 1.07-1.25]). Furthermore, a higher risk of fractures was found in patients with osteoporosis (aOR 3.05 [2.73-3.42]) or a history of falling (aOR 6.13 [3.41-11.0]). The risks of fracture between SSRI and SNRI users were comparable. CONCLUSION: Current use of SSRI/SNRI is associated with an increased risk of all caused fractures. Additionally, the co-morbidity, especially osteoporosis and a history of falling, plays an important role in the risk of fractures.

Adherence and medication utilisation patterns of fixed-dose and free combination of angiotensin receptor blocker/thiazide diuretics among newly diagnosed hypertensive patients: a population-based cohort study.

OBJECTIVE: The study aimed to compare the adherence and persistence among newly diagnosed hypertensive patients using fixed-dose (FDC) and free combinations (FC) of angiotensin receptor blocker (ARB)/thiazide diuretic using Taiwan's National Health Insurance Research Database. METHODS: General linear regression and Kaplan-Meier analyses were used to estimate the impact of FDC on adherence [measured by medication possession ratio (MPR)] and persistence (time from day of initiation to treatment discontinuation) of ARB/thiazide diuretic. RESULTS: The adjusted MPRs were all significantly higher among FDC group compared with FC group (6 months: 66.55% vs. 63.86%; 1 year: 52.58% vs. 46.73%, 1.5 year: 46.30% vs. 38.07%; 2 year: 42.06% vs. 32.45%, all p < 0.001). Patients received FDC therapy were less likely to discontinue their therapy [adjusted hazard ratio (HR) 0.79, 95% CI = 0.74-0.85]. CONCLUSIONS: Our findings suggest that use of FDC is associated with higher adherence and persistence rates than use of FC in newly diagnosed hypertensive patients.

Influence of everolimus on cyclosporine Neoral pharmacokinetics in Chinese de novo cardiac transplant recipients.

OBJECTIVE: This study sought to determine the influence of everolimus on cyclosporine Neoral (CsA) pharmacokinetics over the first 6 months after heart transplantation in Chinese recipients. METHODS: Six de novo cardiac recipients receiving a CsA-everolimus-based immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction were compared with six age-matched recipients receiving a CsA-azathioprine-based regimen. We compared CsA 12-hour area-under-curve (AUC) of the first dose (PK-1) and steady state dose (PK-S) at 1 month after transplantation. The CsA trough concentrations (Cmin) were compared over the first 6 months after transplantation. RESULTS: There was no significant difference between the two groups in age, gender, and body weight. With respect to dose-normalized CsA AUC(0-infinity) of PK-1 and dose-normalized CsA AUC(0-12) of PK-S, the difference between the everolimus- and the azathioprine-based regimens was not significant. The dose-normalized CsA trough concentrations (Cmin/dose) were significantly lower in the everolimus-based group than in the azathioprine-based group during the first 5 months after heart transplantation, but the difference was not significant at posttransplantation month 6. CONCLUSIONS: When CsA pharmacokinetic profiles were considered, the CsA dose requirement was not lower in Chinese patients receiving everolimus than that in patients receiving azathioprine. The results differed from reports from Western countries.

Therapeutic drug monitoring of cyclosporine Neoral in de novo Chinese cardiac transplant recipients treated with an everolimus-cyclosporine immunosuppressive regimen.

UNLABELLED: This study determined cyclosporine Neoral (CsA) pharmacokinetics and the accuracy of a limited sampling strategy to predict the 12-hour CsA area-under-the-curve (AUC) to provide a practical method for more accurate therapeutic drug monitor of CsA among de novo Chinese heart transplant recipients treated with an everolimus-CsA immunosuppressive regimen. METHODS: Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after oral administration of CsA in six de novo heart recipients receiving a CsA, everolimus, and methylprenisolone immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction. We analyzed the pharmacokinetics of the first dose (PK-1) and steady state dose (PK-2) at 1 month after transplantation. The accuracy of a single-point sampling method to predict the AUC was generated by linear regression analyses. RESULTS: The t(max) and dose-normalized C(max) of PK-1 and PK-2 were similar. The correlations in single-point blood levels of PK-1 to predict the AUC(0-infinity) were much lower than the corresponding sampling times in PK-2. In PK-2 study, C4 had the best correlation (r(2) = 0.913, P = .003) to predict AUC(0-12). In addition, the trough concentrations, C(0) (r(2) = 0.875, P = .006) and C(12) (r(2) = 0.783, P = .02) also showed good correlations. C2 had insufficient correlation to predict AUC(0-infinity) in PK-1 or AUC(0-12) in the PK-2 study. In conclusion, the absorption of CsA was similar during PK-1 and PK-2. At steady dose, C4 had the best single-point correlation to predict AUC(0-12). Trough blood levels may be more practical in clinical use to monitor CsA.