title: Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring.
abstract: OBJECTIVE
  Pharmacotherapy for mood disorders during pregnancy is often complicated by pregnancy-related pharmacokinetic changes and the need for dose adjustments. The objectives of this review are to summarize the evidence for change in perinatal pharmacokinetics of commonly used pharmacotherapies for mood disorders, discuss the implications for clinical and therapeutic drug monitoring (TDM), and make clinical recommendations.
  
  
  METHODS
  The English-language literature indexed on MEDLINE/PubMed was searched for original observational studies (controlled and uncontrolled, prospective and retrospective), case reports, and case series that evaluated or described pharmacokinetic changes or TDM during pregnancy or the postpartum period.
  
  
  RESULTS
  Pregnancy-associated changes in absorption, distribution, metabolism, and elimination may result in lowered psychotropic drug levels and possible treatment effects, particularly in late pregnancy. Mechanisms include changes in both phase 1 hepatic cytochrome P450 and phase 2 uridine diphosphate glucuronosyltransferase enzyme activities, changes in hepatic and renal blood flow, and glomerular filtration rate. Therapeutic drug monitoring, in combination with clinical monitoring, is indicated for tricyclic antidepressants and mood stabilizers during the perinatal period.
  
  
  CONCLUSIONS
  Substantial pharmacokinetic changes can occur during pregnancy in a number of commonly used antidepressants and mood stabilizers. Dose increases may be indicated for antidepressants including citalopram, clomipramine, imipramine, fluoxetine, fluvoxamine, nortriptyline, paroxetine, and sertraline, especially late in pregnancy. Antenatal dose increases may also be needed for lithium, lamotrigine, and valproic acid because of perinatal changes in metabolism. Close clinical monitoring of perinatal mood disorders and TDM of tricyclic antidepressants and mood stabilizers are recommended.
authors: From the *Department of Psychiatry and Obstetrics and Gynecology, †Depression Specialty Clinic, ‡Women's Mental Health Specialty Clinic, Center for Psychopharmacologic Research and Treatment, and §Psychosomatic Medicine, Women's Mental Health Specialty Clinic, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester; and ∥Department of Psychiatry, Perinatal and Reproductive Psychiatry Program, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors: Kristina M
authors: KM
authors: Deligiannidis
authors: Nancy
authors: N
authors: Byatt
authors: Marlene P
authors: MP
authors: Freeman
mesh_terms: D000928:Antidepressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000627:therapeutic use; D016903:Drug Monitoring / Q000592:standards*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D019964:Mood Disorders / Q000188:drug therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D014227:Triazines / Q000493:pharmacokinetics / Q000627:therapeutic use; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D000077213:Lamotrigine