Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum

Sponsor

Northwestern University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02978534

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Quetiapine

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.

Study Design

Study Type:

Observational

Actual Enrollment :

4 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum

Study Start Date :

Mar 1, 2016

Anticipated Primary Completion Date :

Aug 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Quetiapine Patients taking quetiapine during pregnancy are eligible to participate in the study. Their dose and plasma concentration levels of quetiapine will be monitored throughout pregnancy and up to three months postpartum.	Drug: Quetiapine 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 Names: Seroquel

Arm

Intervention/Treatment

Quetiapine

Patients taking quetiapine during pregnancy are eligible to participate in the study. Their dose and plasma concentration levels of quetiapine will be monitored throughout pregnancy and up to three months postpartum.

Drug: Quetiapine

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 Names:

Seroquel

Outcome Measures

Primary Outcome Measures

Change in plasma concentration/elimination [2 timepoints during pregnancy (second and third trimesters), and at four and twelve weeks postpartum]
For patients taking the immediate release formulation, plasma levels will be obtained beginning at time 0 and at hours, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16. For patients on the extended release formulation, plasma levels will be obtained at time 0 and at hours 0.5, 1, 1.5, 2, 2,5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, and 24.

Secondary Outcome Measures

Arterial and Venous Umbilical Cord Concentration of Quetiapine and 7-N-desalylquetiapine [30 minutes]
Arterial and venous cord blood samples will be obtained immediately post-delivery and banked for later analysis
Cerebrospinal Fluid (CSF) Quetiapine and 7-N-desalkyquetiapine Concentrations [CSF to be obtained within 10 minutes of the epidural placement during labor]
Scores on Depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR) [Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum]
To determine if there is a pattern of increasing scores on self-report depression assessment (IDS-SR) and declining plasma levels. Increasing scores indicate worsening symptoms or depression episode recurrence.
Scores on anxiety scale, Generalized Anxiety Disorder (GAD-7) [Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum]
To determine if there is a pattern of increasing scores on GAD-7 and declining plasma levels
Scores on mania assessment, Young Mania Reporting Scale (YMRS) [Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.]
To determine if there is a pattern of increasing scores on clinician administered mania assessment (YMRS) and declining plasma levels
Scores on Brief Psychosis Rating Scale (BPRS) [Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.]
assessment to evaluate psychotic symptoms
Positive responses on SAFTEE [Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.]
surveys general and specific side effects including somatic, behavioral, and affective symptoms
Delivery outcomes as determined by the Peripartum Events Scale (PES) [4 and 12 weeks postpartum]
assessment to quantify stressful events related to delivery.
Scores on the separate domains of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health [Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.]
Assesses patient perceptions in 5 domains:physical function, pain, emotional distress, social function, and fatigue.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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