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  1. Department of Psychiatry, Allina Health Abbott Northwestern Hospital, Minneapolis, Minnesota
  2. Corresponding Author: Jessica L. W. Mayer, MD, Department of Psychiatry, Abbott Northwestern Hospital Mental Health Clinic, Allina Health, 800 E 28th St, Minneapolis, MN 55407 ([email protected]).
  3. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
  4. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  5. Asher Center for the Study and Treatment of Depressive Disorders, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  6. Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  7. Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  8. Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  9. Children’s National Hospital and George Washington University School of Medicine, Washington, District of Columbia
  10. Department of Psychiatry, University of Toronto, Women’s College Hospital, Toronto, Canada
  11. Asher Center for the Study and Treatment of Depressive Disorders, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  1. Bloom DE, Cafiero ET, Jané-Llopis E, et al. The Global Economic Burden of Noncommunicable Diseases. World Economic Forum; 2011. Accessed June 26, 2023. https://www3.weforum.org/docs/WEF_Harvard_HE_GlobalEconomicBurdenNonCommunicableDiseases_2011.pdf
  2. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905–1917. PubMed CrossRef
  3. Brown LC, Stanton JD, Bharthi K, et al. Pharmacogenomic testing and depressive symptom remission: a systematic review and meta-analysis of prospective, controlled clinical trials. Clin Pharmacol Ther. 2022;112(6):1303–1317. PubMed CrossRef
  4. Fabbri C, Tansey KE, Perlis RH, et al. Effect of cytochrome CYP2C19 metabolizing activity on antidepressant response and side effects: meta-analysis of data from genome-wide association studies. Eur Neuropsychopharmacol. 2018;28(8):945–954. PubMed CrossRef
  5. Relling MV, Klein TE. CPIC: clinical pharmacogenetics implementation consortium of the pharmacogenomics research network. Clin Pharmacol Ther. 2011;89(3):464–467. PubMed CrossRef
  6. Genetic testing and psychiatric disorders: a statement from the International Society of Psychiatric Genetics. International Society of Psychiatric Genetics. Accessed October 4, 2023. https://ispg.net/genetictesting-statement/
  7. Table of pharmacogenetic associations. U.S. Food and Drug Administration. October 26, 2022. Accessed June 27, 2023. https://www.fda.gov/medicaldevices/precision-medicine/table-pharmacogenetic-associations
  8. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127–134. PubMed CrossRef
  9. Greden JF, Rosthschild AJ, Thase M, et al. 49 combinatorial pharmacogenomics to guide treatment selection for major depressive disorder: a large, blinded, randomized controlled trial. CNS Spectrums. 2019;24(1):202–203.
  10. Winner JG, Carhart JM, Altar CA, et al. A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov Med. 2013;16(89):219–227. PubMed
  11. Hodgson K, Tansey KE, Uher R, et al. Exploring the role of drug-metabolising enzymes in antidepressant side effects. Psychopharmacology (Berl). 2015;232(14):2609–2617. PubMed CrossRef
  12. Hodgson K, Tansey K, Dernovsek MZ, et al. Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. J Psychopharmacol (Oxf). 2014;28(2):133–141. PubMed CrossRef
  13. Veldic M, Ahmed AT, Blacker CJ, et al. Cytochrome P450 2C19 poor metabolizer phenotype in treatment resistant depression: treatment and diagnostic implications. Front Pharmacol. 2019;10:83. PubMed
  14. Pérez V, Salavert A, Espadaler J, et al. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial. BMC Psychiatry. 2017;17:250. PubMed
  15. Hippman C, Slomp C, Morris E, et al. A cross-sectional study of the relationship between CYP2D6 and CYP2C19 variations and depression symptoms, for women taking SSRIs during pregnancy. Arch Womens Ment Health. 2022;25(2):355–365. PubMed
  16. Gaynes BN, Gavin N, Meltzer-Brody S, et al. Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess (Summ). 2005;(119):1–8. PubMed CrossRef
  17. Wisner KL, Sit DKY, McShea MC, et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. JAMA Psychiatry. 2013;70(5):490–498. PubMed CrossRef
  18. Mitchell AA, Gilboa SM, Werler MM, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976–2008. Am J Obstet Gynecol. 2011;205(1):51.e1–51.e8. PubMed CrossRef
  19. Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006;295(5):499–507. PubMed CrossRef
  20. Yonkers KA, Gotman N, Smith MV, et al. Does antidepressant use attenuate the risk of a major depressive episode in pregnancy? Epidemiology. 2011;22(6):848–854. PubMed CrossRef
  21. Feghali M, Venkataramanan R, Caritis S. Pharmacokinetics of drugs in pregnancy. Semin Perinatol. 2015;39(7):512–519. PubMed CrossRef
  22. Tracy TS, Venkataramanan R, Glover DD, et al. National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units. Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A activity) during pregnancy. Am J Obstet Gynecol. 2005;192(2):633–639. PubMed CrossRef
  23. Sit DK, Perel JM, Helsel JC, et al. Changes in antidepressant metabolism and dosing across pregnancy and early postpartum. J Clin Psychiatry. 2008;69(4):652–658. PubMed CrossRef
  24. Anderson GD. Pregnancy-induced changes in pharmacokinetics: a mechanistic based approach: a mechanistic-based approach. Clin Pharmacokinet. 2005;44(10):989–1008. PubMed CrossRef
  25. Fay EE, Czuba LC, Sager JE, et al. Pregnancy has no clinically significant effect on the pharmacokinetics of bupropion or its metabolites. Ther Drug Monit. 2021;43(6):780–788. PubMed CrossRef
  26. Kreitchmann R, Schalkwijk S, Best B, et al. Efavirenz pharmacokinetics during pregnancy and infant washout. Antivir Ther. 2019;24(2):95–103. PubMed CrossRef
  27. Duloxetine Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. https://www.pharmgkb.org/pathway/PA166255221
  28. Sirot EJ, Harenberg S, Vandel P, et al. Multicenter study on the clinical effectiveness, pharmacokinetics, and pharmacogenetics of mirtazapine in depression. J Clin Psychopharmacol. 2012;32(5):622–629. PubMed
  29. Okubo M, Murayama N, Miura J, et al. Effects of cytochrome P450 2D6 and 3A5 genotypes and possible coadministered medicines on the metabolic clearance of antidepressant mirtazapine in Japanese patients. Biochem Pharmacol. 2015;93(1):104–109. PubMed CrossRef
  30. Ververs FFT, Voorbij HAM, Zwarts P, et al. Effect of cytochrome P450 2D6 genotype on maternal paroxetine plasma concentrations during pregnancy. Clin Pharmacokinet. 2009;48(10):677–683. PubMed CrossRef
  31. Paroxetine Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. http://pharmgkb.org/pathway/PA166121347
  32. Bupropion Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. https://www.pharmgkb.org/pathway/PA166170276
  33. Sertraline Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. https://www.pharmgkb.org/pathway/PA166181117
  34. Johansson M, Strahm E, Rane A, et al. CYP2C8 and CYP2C9 mRNA expression profile in the human fetus. Front Genet. 2014;5:58. PubMed CrossRef
  35. Citalopram and Escitalopram Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. https://www.pharmgkb.org/pathway/PA164713429
  36. Fluoxetine Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. https://www.pharmgkb.org/pathway/PA161749012
  37. Venlafaxine Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. https://www.pharmgkb.org/pathway/PA166014758
  38. Trazodone Pathway, Pharmacokinetics. PharmGKB. Accessed May 29, 2023. https://www.pharmgkb.org/pathway/PA166280701
  39. Mlugu EM, Minzi OM, Kamuhabwa AAR, et al. Pregnancy increases CYP3A enzymes activity as measured by the 4β-hydroxycholesterol/cholesterol ratio. Int J Mol Sci. 2022;23(23):15168. PubMed CrossRef
  40. Boinpally R, Gad N, Gupta S, et al. Influence of CYP3A4 induction/inhibition on the pharmacokinetics of vilazodone in healthy subjects. Clin Ther. 2014;36(11):1638–1649. PubMed CrossRef
  41. Gene-specific information tables for CYP3A5. PharmGKB. Accessed May 3, 2023. https://www.pharmgkb.org/page/cyp3a5RefMaterials
  42. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(suppl 20):22–33; quiz 34–57. PubMed
  43. Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001;62(suppl 16):10–17. PubMed
  44. Rush AJ, Gullion CM, Basco MR, et al. The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med. 1996;26(3):477–486. PubMed CrossRef
  45. Spitzer RL, Kroenke K, Williams JBW, et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–1097. PubMed CrossRef
  46. Guidelines. Cpicpgx.org. Accessed May 3, 2023. https://cpicpgx.org/guidelines/
  47. PGx gene-specific information tables. PharmGKB. Accessed May 3, 2023. https://www.pharmgkb.org/page/pgxGeneRef
  48. Gene-specific information tables for CYP2B6. PharmGKB. Accessed May 3, 2023. https://www.pharmgkb.org/page/cyp2b6RefMaterials
  49. Gene-specific information tables for CYP2C19. PharmGKB. Accessed May 3, 2023. https://www.pharmgkb.org/page/cyp2c19RefMaterials
  50. Gene-specific information tables for CYP2C9. PharmGKB. Accessed May 3, 2023. https://www.pharmgkb.org/page/cyp2c9RefMaterials
  51. Gene-specific information tables for CYP2D6. PharmGKB. Accessed May 3, 2023. https://www.pharmgkb.org/page/cyp2d6RefMaterials
  52. CYP2C9 CDS table. Cpicpgx.org. Accessed May 3, 2023. https://files.cpicpgx.org/data/report/current/gene_cds/CYP2C9_CDS.xlsx
  53. CYP2D6 CDS table. Cpicpgx.org. Accessed May 3, 2023. https://files.cpicpgx.org/data/report/current/gene_cds/CYP2D6_CDS.xlsx
  54. Stika CS, Wisner KL, George AL Jr, et al. Changes in sertraline plasma concentrations across pregnancy and postpartum. Clin Pharmacol Ther. 2022;112(6):1280–1290. PubMed CrossRef
  55. Fukasawa T, Suzuki A, Otani K. Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. J Clin Pharm Ther. 2007;32(4):333–341. PubMed CrossRef
  56. Antipsychotics Pathway. PharmGKB. Accessed October 28, 2023. https://www.pharmgkb.org/pathway/PA166170742