A Pilot Study of Prophylactic Management of Lamotrigine in Pregnant Women

Major Depressive Disorder Clinical Trial

Official title:

A Pilot Study of Prophylactic Management of Lamotrigine for Bipolar Disorder in Pregnant Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03774641
• Other study ID #: IRB00162134
• Secondary ID: 1R01AG058671
• Status: Recruiting
• Start date: December 3, 2018
• Est. completion date: March 30, 2025

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Kelsey Hannan
• Phone: (443)583-4329
• Email: khannan1[@]jhmi.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pregnant women who are taking lamotrigine will be evaluated monthly during pregnancy including a clinical evaluation and a blood draw for lamotrigine levels at each visit. Based on the Therapeutic Drug Monitoring protocol, participant's lamotrigine dosing will be adjusted as needed based on participant's blood levels compared to the reference concentration that was obtained prior to pregnancy or early in pregnancy while clinically stable. After delivery participant and participant's infants will be assessed for mood and functioning at 1, 2, 4, and 6 weeks postpartum.

Description:

Studies have demonstrated that at least 80% of women who stop mood stabilizing medications for pregnancy relapse psychiatrically. However, relapse is also quite common in women who continue taking mood stabilizing medication with studies demonstrating approximately a 30-37% relapse rate-most with depressive episodes. One likely explanation for the high relapse rate of Bipolar Disorder during pregnancy despite continued mood stabilizing medication is decreasing blood levels of mood stabilizing medications during the course of pregnancy. Pregnancy induces both pharmacokinetic and pharmacodynamic changes, which can result in decreased serum blood levels and decreased treatment efficacy. Therapeutic drug monitoring is considered standard of care for a number of psychiatric medications. Therapeutic drug monitoring can be an especially crucial guide to clinical treatment during pregnancy, but remarkably, there are no established protocols for the monitoring of levels and dosing of psychiatric medications in pregnancy. Most pregnant psychiatric patients are therefore managed based on symptom recurrence. In contrast, there are established protocols for monitoring blood levels and prophylactic management of antiepileptic medications for epilepsy, including lamotrigine which is also a mood stabilizing medication. The investigators will collect pilot data on the psychiatric outcomes, adverse events, and obstetrical and infant outcomes of pregnant women with Bipolar Disorder who undergo prophylactic therapeutic drug monitoring for a commonly used mood stabilizing medication during pregnancy- lamotrigine. In the epilepsy literature, there is a published protocol for lamotrigine management before, during, and after pregnancy for seizure control; the investigators will use this protocol as a guide.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 30, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• pregnant, prior or 20 weeks

• currently taking Lamotrigine and plan to continue throughout pregnancy

• history of Bipolar Disorder, Major Depressive Disorder, Schizoaffective Disorder or other psychiatric illness, currently stable

• may be taking other psychiatric medications

Exclusion Criteria:

• suicidal/clinically unstable

• alcohol, marijuana, or other drug dependence in last 90 days

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Mood Disorders
• Psychotic Disorders
• Schizo Affective Disorder

Intervention

Drug:
• Lamictal
Blood-serum levels will be checked monthly during pregnancy and reference concentration will be maintained

Locations

Country	Name	City	State
United States	550 N Broadway	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (23)

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Fotopoulou C, Kretz R, Bauer S, Schefold JC, Schmitz B, Dudenhausen JW, Henrich W. Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period. Epilepsy Res. 2009 Jul;85(1):60-4. doi: 10.1016/j.eplepsyres.2009.02.011. Epub 2009 Mar 9. — View Citation

Grace SL, Evindar A, Stewart DE. The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health. 2003 Nov;6(4):263-74. doi: 10.1007/s00737-003-0024-6. — View Citation

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Halligan SL, Herbert J, Goodyer IM, Murray L. Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biol Psychiatry. 2004 Feb 15;55(4):376-81. doi: 10.1016/j.biopsych.2003.09.013. — View Citation

Hirsch LJ, Weintraub D, Du Y, Buchsbaum R, Spencer HT, Hager M, Straka T, Bazil CW, Adams DJ, Resor SR Jr, Morrell MJ. Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy. Neurology. 2004 Sep 28;63(6):1022-6. doi: 10.1212/01.wnl.0000138424.33979.0c. — View Citation

Kim HG, Mandell M, Crandall C, Kuskowski MA, Dieperink B, Buchberger RL. Antenatal psychiatric illness and adequacy of prenatal care in an ethnically diverse inner-city obstetric population. Arch Womens Ment Health. 2006 Mar;9(2):103-7. doi: 10.1007/s00737-005-0117-5. Epub 2005 Dec 29. — View Citation

Le Strat Y, Dubertret C, Le Foll B. Prevalence and correlates of major depressive episode in pregnant and postpartum women in the United States. J Affect Disord. 2011 Dec;135(1-3):128-38. doi: 10.1016/j.jad.2011.07.004. Epub 2011 Jul 29. — View Citation

McLearn KT, Minkovitz CS, Strobino DM, Marks E, Hou W. The timing of maternal depressive symptoms and mothers' parenting practices with young children: implications for pediatric practice. Pediatrics. 2006 Jul;118(1):e174-82. doi: 10.1542/peds.2005-1551. — View Citation

McPhie S, Skouteris H, Fuller-Tyszkiewicz M, Hill B, Jacka F, O'Neil A. Relationships between mental health symptoms and body mass index in women with and without excessive weight gain during pregnancy. Midwifery. 2015 Jan;31(1):138-46. doi: 10.1016/j.midw.2014.07.004. Epub 2014 Jul 19. — View Citation

Newport DJ, Stowe ZN, Viguera AC, Calamaras MR, Juric S, Knight B, Pennell PB, Baldessarini RJ. Lamotrigine in bipolar disorder: efficacy during pregnancy. Bipolar Disord. 2008 May;10(3):432-6. doi: 10.1111/j.1399-5618.2007.00565.x. — View Citation

Polepally AR, Pennell PB, Brundage RC, Stowe ZN, Newport DJ, Viguera AC, Ritchie JC, Birnbaum AK. MODEL-BASED LAMOTRIGINE CLEARANCE CHANGES DURING PREGNANCY: CLINICAL IMPLICATION. Ann Clin Transl Neurol. 2014 Feb;1(2):99-106. doi: 10.1002/acn3.29. — View Citation

Robertson E, Grace S, Wallington T, Stewart DE. Antenatal risk factors for postpartum depression: a synthesis of recent literature. Gen Hosp Psychiatry. 2004 Jul-Aug;26(4):289-95. doi: 10.1016/j.genhosppsych.2004.02.006. — View Citation

Sabers A. Algorithm for lamotrigine dose adjustment before, during, and after pregnancy. Acta Neurol Scand. 2012 Jul;126(1):e1-4. doi: 10.1111/j.1600-0404.2011.01627.x. Epub 2011 Dec 9. — View Citation

Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, Zurick A, Cohen LS. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007 Dec;164(12):1817-24; quiz 1923. doi: 10.1176/appi.ajp.2007.06101639. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mood as assessed by The Edinburgh Postnatal Rating Scale	Self-reported experience of depressive symptoms over the past 7 days, each item is scored 0-3 (0=not experiencing the symptom, 3=experiencing the symptom most of the time) yielding a total between 0 and 30. A score of 0-9 indicates little to no depressive symptoms and a score from 10-30 indicates significant depressive symptoms.	Monthly, after enrollment, up to 10 months
Primary	Change in Mood as assessed by The Young Mania Rating Scale	Clinical interview that measures manic symptoms in the past 2 weeks, each item is scored 0-4 (0=absent, 4=fully present) yielding a total between 0 and 44. Any score above 0 indicates a possible manic episode.	Monthly, after enrollment, up to 10 months
Primary	Side Effect as assessed by the Udvalg for Kliniske Undersøgelser Side Effects Rating Scale	Clinical interview that measures current, or in the past 72 hours, side effects of medication, each item is scored 0-3 (0=not or doubtfully present, 3=severe), yielding a total between 0 and 168. Any score above 0 indicates a possible causal relationship between medication and side effects.	Monthly, after enrollment, up to 10 months
Primary	Side Effect as assessed by the Frequency, Intensity, and Burden of Side Effects Rating Scale	Self-reported frequency, intensity, and burden of side effects in the past week, each item is scored 0-6 (0=no side effects/impairment, 6=present all the time/intolerable/unable to function) yielding a total between 0 and 18. For each item, a score of 0-2 indicates treatment should continue, a score of 3-4 indicates the side effect should be addressed, and a score of 5-6 indicates a change in treatment is needed.	Monthly, after enrollment, up to 10 months
Primary	Change in Infant Habituation as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale	Neurobehavioral assessment measuring infant's ability to shut down response to a stimulus, the item is scored 1-9, a low score indicates no decrement in response over 10 stimuli and a high score indicates a shut down of response after 1-2 stimuli	At 1, 2, 4, and 6 weeks postpartum
Primary	Change in Infant Attention as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale	Neurobehavioral assessment measuring infant's response to a stimulus, the item is scored 1-9, a low score indicates no response and a high score indicates alerting to stimulus	At 1, 2, 4, and 6 weeks postpartum
Primary	Change in Infant Self-Regulation as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale	Neurobehavioral assessment measuring infant's ability to self-regulate, the item is scored 1-9, a low score indicates the infant makes no attempt to quiet self and a high score indicates the infant consistently quiets self for sustained periods	At 1, 2, 4, and 6 weeks postpartum
Primary	Change in Infant Arousal as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale	Neurobehavioral assessment measuring infant's arousal, the item is scored 1-9, a low score indicates a low level of arousal to all stimuli and a high score indicates the infant achieves insulated crying	At 1, 2, 4, and 6 weeks postpartum
Primary	Change in Infant Tonicity as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale	Neurobehavioral assessment measuring infant's body tone, the item is scored 1-9, a low score indicates the infant is flaccid and a high score indicates the infant is hypertonic	At 1, 2, 4, and 6 weeks postpartum
Primary	Change in Infant Reflexes as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale	Neurobehavioral assessment measuring infant's reflexes, the item is scored 1-5, a low score indicates no response and a high score indicates a strong response	At 1, 2, 4, and 6 weeks postpartum
Primary	Change in Infant Quality of Movement as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale	Neurobehavioral assessment measuring infant's power and flexibility, the item is scored 1-5, a low score indicates no resistance/movement and a high score indicates strong resistance/movement	At 1, 2, 4, and 6 weeks postpartum
Primary	Gestational Age at Birth in Weeks assessed by Review of the Infant Delivery Chart		At 2 weeks postpartum visit, up to 15 minutes
Primary	Birth Length in Inches assessed by Review of the Infant Delivery Chart		At 2 weeks postpartum visit, up to 15 minutes
Primary	Birth Weight in pounds assessed by Review of the Infant Delivery Chart		At 2 weeks postpartum visit, up to 15 minutes
Primary	APGAR Score at 1 Minute assessed by Review of the Infant Delivery Chart		At 2 weeks postpartum visit, up to 15 minutes
Primary	APGAR Score at 5 Minutes assessed by Review of the Infant Delivery Chart		At 2 weeks postpartum visit, up to 15 minutes
Primary	Assessment of Neonatal Intensive Care Unit Admission by Review of the Infant Delivery Chart	By reviewing the infant delivery chart, the outcome will be "yes" if the infant was admitted to the Neonatal Intensive Care Unit and "no" if the infant was not admitted	At 2 weeks postpartum visit, up to 15 minutes