Clinical trial NCT02978534: Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum
Official title: Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bipolar Disorder
Keywords: pregnant
quetiapine
bipolar
women
female
postpartum
seroquel
perinatal
manic-depressive
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2016-12-01
Enrollment: 4
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
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.

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Age 18-45 years
* Pregnant, second trimester
* English-speaking
* DSM-V diagnosis of Bipolar Disorder or Schizophrenia, any subtype
* Medically healthy
* Singleton gestation

Exclusion Criteria:

* Chronic use of drugs for medical disorders, except thyroid replacement for stable hypothyroidism
* No psychiatrist or obstetrician
* QIDS-SR 16 positive answer 3 on item 12, "I have made specific plans for suicide or have actually tried to take my life" within the past week
* DSM-V diagnosis of substance abuse or dependence in last 6 months, with the exception of cannabis; positive urine drug screen

Primary outcomes:
measure: Change in plasma concentration/elimination
timeFrame: 2 timepoints during pregnancy (second and third trimesters), and at four and twelve weeks postpartum
Secondary outcomes:
measure: Arterial and Venous Umbilical Cord Concentration of Quetiapine and 7-N-desalylquetiapine
timeFrame: 30 minutes
measure: Cerebrospinal Fluid (CSF) Quetiapine and 7-N-desalkyquetiapine Concentrations
timeFrame: CSF to be obtained within 10 minutes of the epidural placement during labor
measure: Scores on Depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR)
timeFrame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum
measure: Scores on anxiety scale, Generalized Anxiety Disorder (GAD-7)
timeFrame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum
measure: Scores on mania assessment, Young Mania Reporting Scale (YMRS)
timeFrame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
measure: Scores on Brief Psychosis Rating Scale (BPRS)
timeFrame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
measure: Positive responses on SAFTEE
timeFrame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
measure: Delivery outcomes as determined by the Peripartum Events Scale (PES)
timeFrame: 4 and 12 weeks postpartum
measure: Scores on the separate domains of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health
timeFrame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Northwestern University
name: Crystal T Clak, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: