Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum

Bipolar Disorder Clinical Trial

— Quetiapine  

Official title:

Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02978534
• Other study ID #: 00201540
• Status: Completed
• Start date: March 2016
• Est. completion date: December 2020

Study information

• Verified date: September 2022
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: December 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in plasma concentration/elimination	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.	2 timepoints during pregnancy (second and third trimesters), and at four and twelve weeks postpartum
Secondary	Arterial and Venous Umbilical Cord Concentration of Quetiapine and 7-N-desalylquetiapine	Arterial and venous cord blood samples will be obtained immediately post-delivery and banked for later analysis	30 minutes
Secondary	Cerebrospinal Fluid (CSF) Quetiapine and 7-N-desalkyquetiapine Concentrations		CSF to be obtained within 10 minutes of the epidural placement during labor
Secondary	Scores on Depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR)	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.	Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum
Secondary	Scores on anxiety scale, Generalized Anxiety Disorder (GAD-7)	To determine if there is a pattern of increasing scores on GAD-7 and declining plasma levels	Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum
Secondary	Scores on mania assessment, Young Mania Reporting Scale (YMRS)	To determine if there is a pattern of increasing scores on clinician administered mania assessment (YMRS) and declining plasma levels	Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Secondary	Scores on Brief Psychosis Rating Scale (BPRS)	assessment to evaluate psychotic symptoms	Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Secondary	Positive responses on SAFTEE	surveys general and specific side effects including somatic, behavioral, and affective symptoms	Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Secondary	Delivery outcomes as determined by the Peripartum Events Scale (PES)	assessment to quantify stressful events related to delivery.	4 and 12 weeks postpartum
Secondary	Scores on the separate domains of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health	Assesses patient perceptions in 5 domains:physical function, pain, emotional distress, social function, and fatigue.	Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.