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Purpose: Some reports have described arterial hypertension (AH) in patients treated by serotonin reuptake inhibitor (SRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants. The mechanism remains discussed, some authors suggesting a role of SERT (SERotonin Transporter) inhibition whereas others discussing NET (NorEpinephrine Transporter) involvement. The present study used the pharmacoepidemiological-pharmacodynamic (PE-PD) method to investigate the role of these transporters in SRI- and SNRI-induced AH. Methods: The study involved two successive approaches: first, a PE study (disproportionality analysis) investigating in VigiBase®, the World Health Organization Individual Case safety Report (ICSR) database, the relationships between exposure to SRI AND SNRI, and reports of AH. The primary analysis compared patients receiving one SRI (or one SNRI) with non-users. Secondary analyses were performed according to the pharmacological classes. Results are expressed as reporting odds ratios (ROR) with 95% CI and information component (IC), an indicator for disproportionate Bayesian reporting. Second, we performed a PD study using linear regression analyses to explore the association between the AH signal and binding affinities for NET and SERT (expressed as their pKi ratio) of SRIs and SNRIs. Results: A significant ROR value was found for each individual SRI (except fluvoxamine) and each individual SNRI. ROR values were also significant for SRIs and SNRIs in general with higher values for SNRIs than for SRIs. Similar trends were found using IC. A significant correlation was found between the signal of AH and the NET/SERT pKi ratio (y = 6.57x – 2.55, R2 = 0.68, Pearson coefficient correlation = 0.82). Conclusion: The present study found a positive association between the NET/SERT pKi ratio and the occurrence of arterial hypertension with SRI and SNRI antidepressants. These results are important for the selection of antidepressants in hypertensive and/or at risk depressive patients as well as for future development of antidepressants devoid of hypertensive effect. [ABSTRACT FROM AUTHOR]

Background: Use of antidepressants is seen to be a risk factor for type 2 diabetes, even though the underlying mechanisms remain unclear. We examined whether antidepressant use was associated with change in fasting plasma glucose, glycated haemoglobin (HbA1c), β-cell function (HOMA2-%B) and insulin sensitivity (HOMA2-%S) over time.Methods: Participants in the French D.E.S.I.R. cohort study included over 4700 men (48.1%) and women, free of diabetes, aged 30-65 years at baseline in 1994-96 (D.E.S.I.R. 0), who were followed for 9 years at 3-yearly intervals (D.E.S.I.R. 3, 1997-99; 6, 2000-02; 9, 2003-05). Antidepressant use, fasting plasma glucose, HbA1c, HOMA2-%B and HOMA2-%S were assessed concurrently at four medical examinations. Linear mixed models were used to examine the cross-sectional and longitudinal associations of time-dependent antidepressant use with changes in these four biological parameters.Results: Mean fasting plasma glucose and HbA1c increased whereas HOMA2-%B and HOMA2-%S decreased over the follow-up. In a fully adjusted model, there were no differences in: mean fasting plasma glucose (β = 0.01 mmol/l, P = 0.702); HbA1c (β = 0.01 %, P = 0.738); HOMA2-%B (β = 0.00, P = 0.812); or HOMA2-%S (β =-0.01, P = 0.791) at baseline (1994-96) between antidepressant users and non-users. The interaction term with time also suggested no differences in the annual change in: fasting plasma glucose (β = 0.00 mmol/l, P = 0.322); HbA1c (β = 0.00 %, P = 0.496); HOMA2-%B (β = 0.00, P = 0.609); or HOMA2-%S (β = 0.00, P = 0.332) between antidepressant users and non-users. Similar associations were observed in analyses of type and cumulative use of antidepressants over follow-up.Conclusion: Our longitudinal data show that use of antidepressants is not associated with altered glucose metabolism, suggesting that the association between antidepressant use and diabetes reported by previous studies may not be causal. Detection bias or clinical ascertainment bias may account for much of this apparent association. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this prospective observational study was to evaluate changes in self-reported disability in patients with anxiety or mood disorders 3 months after initiating antidepressant treatment. Methods: This study included 8396 patients consulting 2433 general practitioners in France for a major mood episode, generalized anxiety disorder, social anxiety disorder, panic disorder, or obsessive-compulsive disorder. Treatment was initiated with the antidepressant that the physician considered appropriate. Patients were evaluated with the Sheehan Disability Scale (SDS), Hospital Anxiety and Depression Scale, and Clinical Global Impression-Severity (CGI-S) at baseline and after 6 and 12 weeks. Results: At 12 weeks, 6617 patients (78.8%) were evaluable. At inclusion, the mean SDS subscores were 6.5 ± 2.2 on the work/school activities dimension, 6.8 ± 1.9 on the social activities dimension, and 6.5 ± 2.0 on the family life dimension. At the 12-week follow-up visit, the mean change in score on these three dimensions was -3.9 ± 2.6, -4.2 ± 2.5, and -4.0 ± 2.5, respectively. At the 12-week follow-up visit, 90.0% of patients were responders (defined as patients whose SDS dimension scores decreased by at least one point) on the work/school SDS subscores; 92.8% were responders on the social life SDS subscores, and 91.1% were responders on family life/home responsibilities SDS subscores. Functional remission (defined as an SDS subscore of 0 at study end) rates were 18.0% for the work/school dimension, 16.8% for the social activities dimension, and 19.5% for the family life dimension. Using a cutoff of ≤2, remission rates were 56.8%, 55.0%, and 58.0%, respectively. Improvements in self-rated disability were correlated with improvements in symptoms measured with clinician-rated CGI-S. Conclusion: Patients consulting for anxiety or mood disorders report significant disability, which can be effectively reduced by antidepressant treatment. [ABSTRACT FROM AUTHOR]