Pregnant Women Taking Lamictal for Bipolar Disorder (PK-LAPB)

September 26, 2022 updated by: Crystal Clark, Northwestern University

Pharmacokinetics of Lamotrigine in Pregnant and Postpartum Women With Bipolar Disorder

This study seeks to examine how the dose of lamotrigine (Lamictal) should be adjusted during pregnancy for women with Bipolar Disorder. The investigators predict that the concentration of Lamictal in women's blood will decrease during pregnancy, and increase after postpartum. Because the concentration of the medication is likely to decrease during pregnancy, it is important for doctors to know how much they should increase a patient's dose in order to prevent worsening of Bipolar symptoms. In this study, the investigators will ask that participants complete up to five overnight visits to our clinical research unit where their blood will be drawn every couple of hours, through an IV catheter, to measure how the concentration of lamotrigine (Lamictal) changes over time. Participants will be compensated for their time.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

There is an increased risk of recurrence of Bipolar Disorder (BD) episodes or worsening symptoms in pregnancy after the discontinuation of mood stabilizers. Similarly, changes in medication concentration due to the physiological changes in pregnancy may effectively reduce the medication dose and thus its efficacy in pregnancy. Therapeutic dose monitoring has proven to have great utility in preventing seizure recurrence in women with epilepsy (WWE), specifically, dose monitoring of lamotrigine (LTG). Similar guidelines to that of women with epilepsy would benefit pregnant women with BD who are taking lamotrigine (LTG) in pregnancy. However, the pharmacokinetics as well as the utility of therapeutic dose monitoring of LTG in pregnant patients with Bipolar Disorder has not been well studied.

This study is an observational protocol to explore the longitudinal pharmacokinetics (PK) of LTG during pregnancy and postpartum in 10 women with Bipolar Disorder. The correlation between changes in bioavailability and level-to-dose (L/D) ratios and increases in symptoms of depression, mania and anxiety and recurrence of syndromal BD episodes that fulfill Diagnostic and Statistics Manual of Mental Disorders (IV) (DSM4) criteria will be investigated.

The primary aims of this study are 1.) To assess the impact of the dynamic physiology of pregnancy on the L/D ratio and bioavailability of LTG in women with BD. 2.) To evaluate the correlations between maternal and umbilical cord LTG serum levels. 3.) To explore the relationship between declining LTG L/D ratios during pregnancy, bioavailability and the increase in psychiatric symptoms and recurrence of syndromal BD. 4.) To explore the relationship between declining LTG L/D ratios during pregnancy, bioavailability and the recurrence of anxiety symptoms.

Additionally this study will evaluate correlations between estradiol levels and change in LTG L/D ratios during pregnancy. To optimize the research yield from this investigation, participants will have the option to allow banking of cerebrospinal (CSF) fluid and DNA for future analyses.

Study Type

Observational

Enrollment (Actual)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Participants 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 for Bipolar Disorder, any subtype, will be enrolled into the study.

Description

Inclusion Criteria:

  • Age 18 or older
  • If Pregnant, equal to or less than 26 weeks
  • English-speaking
  • DSM-IV Bipolar Disorder, any subtype
  • Able to provide informed consent
  • Daily dosing of Lamictal

Exclusion Criteria:

  • Active substance abuse within last 6 months and/or positive urine drug screen
  • Active suicidality
  • No obstetrical care
  • Antiepileptic drugs that affect metabolism of LTG
  • Medications in FDA categories F or X that are not antimanic drugs
  • Liver or kidney disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Lamotrigine for Bipolar
antepartum and peripartum women taking lamotrigine for Bipolar Disorder
Drug: lamotrigine
Lamotrigine will be observed in women who have already under the guidance of a physician decide to continue lamotrigine for the treatment of Bipolar Disorder
Other Names:
  • Lamictal, Lamiktal, Labileno, Triazines

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum concentration/elimination
Time Frame: An average of every 10 weeks; Hours 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, or 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16
For patients on 1x day dosing, serum levels will be obtained beginning at time 0 and at hours, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24 and L/D ratio will be determined at each time point. This series of serum levels will be completed an average of every 10 weeks across pregnancy, and postpartum. For patients on 2x dosing, serum levels will be obtained at hours 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16 hours.
An average of every 10 weeks; Hours 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, or 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infant (umbilical cord)/Maternal ratio of LTG
Time Frame: 30 min
Ratio of umbilical cord (infant) LTG serum level to maternal LTG serum level will be determined at delivery.
30 min
Scores on depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR)
Time Frame: 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 L/D ratios. 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.
Scores on mania assessment, Young Mania Reporting Scale (YMRS)
Time Frame: 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 L/D ratios.
Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Scores on anxiety scale, Generalized Anxiety Disorder (GAD-7)
Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.

Other Outcome Measures

Outcome Measure
Time Frame
Percent increase in estradiol levels and their correlation to percent decrease in LTG L/D ratio
Time Frame: Estradiol levels will be examined an average of every 10 weeks from the time the participant enters the study, up to 12 weeks postpartum.
Estradiol levels will be examined an average of every 10 weeks from the time the participant enters the study, up to 12 weeks postpartum.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Investigators

  • Principal Investigator: Crystal T Clark, MD, MSc, Associate professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

August 1, 2020

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

November 15, 2013

First Submitted That Met QC Criteria

November 21, 2013

First Posted (Estimate)

November 27, 2013

Study Record Updates

Last Update Posted (Actual)

September 28, 2022

Last Update Submitted That Met QC Criteria

September 26, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00079810

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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