Lithium Therapy: Understanding Mothers, Metabolism and Mood
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Observational

Summary: 
      Lithium, the gold standard for treatment of Bipolar Disorder (BD) and a common augmentation
      to medication therapy for Major Depression, is commonly continued in pregnancy due to its
      therapeutic benefit and more recent data that suggests the teratogenic effects of lithium are
      less than historically believed. Due to the increased elimination of lithium during
      pregnancy, lithium concentration decreases in the blood and women with BD are vulnerable to
      BD episode recurrence in pregnancy. Uncontrolled symptoms of BD in pregnancy increase the
      risk for postpartum exacerbation of BD and psychosis. Our study will investigate the
      pharmacokinetics (PK) of lithium prior to pregnancy, during pregnancy, and postpartum. Twenty
      women taking lithium in pregnancy or planning to become pregnant and continue lithium will be
      invited to participate in a study to measure repeated blood levels of lithium at six time
      points between preconception and 3 months postpartum. The data collected will inform the
      dose, timing of dose, and frequency of dosing of lithium that will lead to fewer untoward
      effects for the mother and baby. Change in elimination clearance of lithium will be
      correlated with symptom worsening to develop a dosing algorithm that will help maintain
      wellness for pregnant women with mood disorders.
    

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).
      Similar guidelines to that of women with epilepsy would benefit pregnant women with BD who
      are taking mood stabilizing medications in pregnancy. Current evidence suggests that lithium
      has a more favorable reproductive profile than many mood stabilizing antiepileptic agents.
      However, the pharmacokinetics as well as the utility of therapeutic dose monitoring of
      lithium in pregnant patients with Bipolar Disorder has not been well studied.

      This study is an observational protocol to explore the longitudinal pharmacokinetics (PK) of
      lithium during pregnancy and postpartum in 20 women with Bipolar Disorder. The correlation
      between changes in bioavailability and concentrations 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 describe the changes in lithium elimination and
      serum concentration across pregnancy and postpartum to establish its efficacious use and
      dosing requirements during childbearing 2.) To evaluate the associations between maternal and
      umbilical cord lithium serum levels. 3.) To explore the relationship between declining
      lithium serum concentrations during pregnancy and the increase in psychiatric symptoms and
      recurrence of syndromal BD.

      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.
    

Intervention name(s): Lithium
Intervention type(s): Drug
Intervention description(s): Patients taking lithium as a mood stabilizer during pregnancy are eligible to participate in the study. Their dose and serum concentration levels of lithium will be monitored throughout pregnancy and up to three months postpartum.
Other intervention name(s): lithium carbonate
Intervention MeSH terms: Lithium Carbonate
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pre-conception planning and pregnant women taking lithium for the purpose of mood
        stabilizing 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 will be enrolled into the study.
      
Biospecimen description: 
      Blood serum specimen will be obtained to measure lithium levels. Urine will be collected to
      measure lithium levels and creatinine clearance. Standard of care labs will be obtained on
      every participant that is eligible and signs informed consent. Participants will also have
      the option to have blood drawn for DNA banking.

      Participants in the study that elect to receive analgesia for pain related to labor and have
      a spinal-epidural at Northwestern University will have CSF stored and banked for future
      analysis.
    
Keywords: pregnant; female; women; lithium; bipolar