Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Observational

Summary: 
      The widespread and common use of quetiapine in childbearing and pregnant women demands more
      data to inform dosing and toxicity in pregnancy. The new FDA Pregnancy and Lactation Labeling
      Final Rule (PLLR) will go into effect on June 30th, 2015 and will replace the prior A, B, C,
      D, and X categories. Additionally, the PLLR will require information to aid prescribing
      decisions in three categories 1) Pregnancy (including labor and delivery), 2) Lactation, and
      3) Females and Males of Reproductive Potential. The pregnancy category will include a
      subsection that will describe pharmacokinetic and pharmacodynamic characteristics of the
      medication in pregnancy, fetal risk, and data quality. The data collected in this study will
      update the FDA pregnancy pharmacokinetic section for quetiapine and inform physicians that
      prescribe to childbearing women.
    

Detailed description: 
      Bipolar Disorder (BD) and Schizophrenia (SCHZ) in pregnancy are associated with pregnancy
      complications and increased maternal mortality due to physiological and psychosocial changes
      independent of second-generation antipsychotic (SGA) use. Untreated BD and SCHZ have been
      associated with an increased risk of placental abnormalities, antepartum hemorrhage, preterm
      birth, pre-eclampsia, low birth-weight, intrauterine growth retardation, small for
      gestational age, fetal distress, neonatal hypoglycemia, stillbirth and congenital defects,
      and the potential for adverse neurodevelopmental outcomes. Severe maternal stress in
      pregnancy increases the risk for offspring mental disorders, and eye, ear, respiratory,
      digestive, skin, musculoskeletal, and genitourinary diseases and congenital malformations
      (i.e., cleft palate, cleft lip). Also, BD and SCHZ illness symptoms are linked to
      psychosocial consequences that result in poor perinatal outcomes including impulsivity that
      leads to reckless behavior such as increased indiscriminate sex and exposure to sexually
      transmitted infections, smoking, increased alcohol and drug use, less prenatal care, and poor
      nutrition. Furthermore, women with recurrence of mental illness in the perinatal period have
      increased risk for suicide, a leading cause of maternal death.

      The only published case of quetiapine plasma concentrations in a pregnant woman included
      cross-sectional levels of a woman on 300 mg of quetiapine across pregnancy and postpartum.
      Compared to six months postpartum, the area under the curve decreased by 27%, 42%, and 18% in
      the first, second, and third trimester, respectively. Given the complexity of the metabolism
      of quetiapine to a very active metabolite, it is important to understand the altered
      metabolism of quetiapine and its active metabolite in pregnancy and the implication for
      dosing adjustments.

      This study will investigate the longitudinal pharmacokinetics of quetiapine in pregnancy,
      delivery, and postpartum. The long-term goal of this line of research is to establish
      psychotropic medication dosing algorithms informed by longitudinal pharmacokinetic data to
      improve mental health and pregnancy outcomes for mothers with serious mental illness.

      The primary aims are: 1) Determine the elimination clearance of quetiapine and its major
      active metabolite, 7-N-desalkyquetiapine, across pregnancy and postpartum; 2) Determine the
      effect of pharmacokinetic changes on symptoms and toxicity during pregnancy and postpartum,
      and; 3) Examine the maternal-to-cord plasma concentrations ratios of quetiapine and its major
      active metabolite, 7-N-desalkylquetiapine.
    

Intervention name(s): Quetiapine
Intervention type(s): Drug
Intervention description(s): Quetiapine concentrations will be observed in women who have already (under the guidance of a physician) decided to continue taking Quetiapine for the treatment of Bipolar Disorder (any subtype) or Schizophrenia during pregnancy.
Other intervention name(s): Seroquel
Intervention MeSH terms: Quetiapine Fumarate
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant women taking quetiapine for the purpose of mood stabilizing will be recruited
        broadly from Northwestern clinical services, including Internal Medicine, OB/GYN, Family
        Medicine, and Psychiatry, registries, and from the local Chicagoland community. Patients
        that sign consent, complete the evaluation and meet criteria will be enrolled into the
        study.
      
Biospecimen description: 
      Blood serum specimen will be obtained to measure quetiapine and estradiol levels. Standard of
      care labs will be obtained on every participant that is eligible and signs informed consent.
      Participants will not have more than 50 ml of blood drawn every 8 weeks. Participants will
      also have the option to have blood drawn for DNA banking.

      Participants in the study that elect to receive analgesia for pain related to labor and have
      a spinal-epidural at Northwestern University will have CSF stored and banked for future
      analysis.
    
Keywords: pregnant; quetiapine; bipolar; women; female; postpartum; seroquel; perinatal; manic-depressive