Clinical trial NCT01996293: Pregnant Women Taking Lamictal for Bipolar Disorder
Official title: Pharmacokinetics of Lamotrigine in Pregnant and Postpartum Women With Bipolar Disorder
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bipolar Disorder
Keywords: pregnant
bipolar
lamotrigine
lamictal
women
female
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2013-11-27
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Serum concentration/elimination
timeFrame: 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 outcomes:
measure: Infant (umbilical cord)/Maternal ratio of LTG
timeFrame: 30 min
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 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 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.
Other outcomes:
measure: Percent increase in estradiol levels and their correlation to percent decrease in LTG L/D ratio
timeFrame: Estradiol levels will be examined an average of every 10 weeks from the time the participant enters the study, up to 12 weeks postpartum.
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Associate Professor
name: Crystal T Clark, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry. 2013 Nov;170(11):1240-7. doi: 10.1176/appi.ajp.2013.13010006.