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

• Serum L/D ratio change [ 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 ]
  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.
• Area Under the Concentration Curve (AUC 0-24h) [ 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 ]
  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.

• 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.
• 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.
• 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.
• 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. ]

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.

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