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- Wikman, Anna, et al.
(författare)
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Factors associated with re-initiation of antidepressant treatment following discontinuation during pregnancy : a register-based cohort study.
- 2020
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Ingår i: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 23:5, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Antidepressant treatment when facing a pregnancy is an important issue for many women and their physicians. We hypothesized that women with a greater burden of pre-pregnancy psychiatric illness would be more likely to re-initiate antidepressants following discontinuation of treatment during pregnancy. A register-based cohort study was carried out including 38,595 women who gave birth between the 1st of January 2007 and the 31st of December 2014, who had filled a prescription for an antidepressant medication in the year prior to conception. Logistic regressions were used to explore associations between maternal characteristics and antidepressant treatment discontinuation or re-initiation during pregnancy. Most women discontinued antidepressant treatment during pregnancy (n = 29,095, 75.4%), of whom nearly 12% (n = 3434, 11.8%) re-initiated treatment during pregnancy. In adjusted analyses, parous women (aOR 1.22, 95% CI 1.12-1.33), with high educational level (aOR 1.21, 95% CI 1.08-1.36); born within the EU (excluding Nordic countries, aOR 1.41, 95% CI 1.03-1.92) or a Nordic country (aOR 1.42, 95% CI 1.22-1.65); who more often reported prior hospitalizations due to psychiatric disorders (aOR 1.50, 95% CI 1.10-2.03, for three or more episodes); and had longer duration of pre-pregnancy antidepressant use (aOR 6.10, 95% CI 5.48-6.77, for >2 years antidepressant use), were more likely to re-initiate antidepressants than were women who remained off treatment. Women with a greater burden of pre-pregnancy psychiatric illness were more likely to re-initiate antidepressants. Thus, pre-pregnancy psychiatric history may be particularly important for weighing the risks and benefits of discontinuing antidepressants during pregnancy.
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| 2. |
- Abu-Bakar, A'edah, et al.
(författare)
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Metabolism of bilirubin by human cytochrome P450 2A6
- 2012
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 261:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- The mouse cytochrome P450 (CYP) 2A5 has recently been shown to function as hepatic "Bilirubin Oxidase" (Abu-Bakar, A., et al., 2011. Toxicol. Appl. Pharmacol. 257, 14-22). To date, no information is available on human CYP isoforms involvement in bilirubin metabolism. In this paper we provide novel evidence for human CYP2A6 metabolising the tetrapyrrole bilirubin. Incubation of bilirubin with recombinant yeast microsomes expressing the CYP2A6 showed that bilirubin inhibited CYP2A6-dependent coumarin 7-hydroxylase activity to almost 100% with an estimated K-i of 2.231 mu M. Metabolite screening by a high-performance liquid chromatography/electrospray ionisation mass spectrometry indicated that CYP2A6 oxidised bilirubin to biliverdin and to three other smaller products with m/z values of 301,315 and 333. Molecular docking analyses indicated that bilirubin and its positively charged intermediate interacted with key amino acid residues at the enzyme's active site. They were stabilised at the site in a conformation favouring biliverdin formation. By contrast, the end product, biliverdin was less fitting to the active site with the critical central methylene bridge distanced from the CYP2A6 haem iron facilitating its release. Furthermore, bilirubin treatment of HepG2 cells increased the CYP2A6 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A6 compared to cells treated only with CHX. Collectively, the observations indicate that the CYP2A6 may function as human "Bilirubin Oxidase" where bilirubin is potentially a substrate and a regulator of the enzyme.
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