Lithium Therapy: Understanding Mothers, Metabolism and Mood

NCT ID: NCT02490241

Last Updated: 2022-10-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 9 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-06-30

Brief 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.

Conditions

Bipolar Disorder

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Lithium

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.

Intervention Type: DRUG

Other Intervention Names

lithium carbonate

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, Major Depressive Disorder, or Mood Disorder Not Otherwise Specified
• Able to provide informed consent
• Daily dosing of lithium

Exclusion Criteria

• Active substance abuse within last 6 months and/or positive urine drug screen
• Active suicidality
• No obstetrical care
• Use of other drugs that affect metabolism of lithium
• Medications in FDA categories F or X that are not antimanic drugs
• Chronic Kidney Disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Crystal Clark

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Crystal T Clark, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern Memorial Hospital

Chicago, Illinois, United States

Countries

United States

Related Links

http://accp1.onlinelibrary.wiley.com/doi/10.1002/jcph.2089

Completed manuscript of pharmacokinetic analysis

Other Identifiers

00200026

Identifier Type: -

Identifier Source: org_study_id