A Pilot Study of Prophylactic Management of Lamotrigine in Pregnant Women

NCT03774641 | Completed FDA Drug

• 2 other identifiers: IRB001621341R01AG058671
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bipolar Disorder; Major Depressive Disorder; Schizo Affective Disorder

Keywords

Lamotrigine; Bipolar Disorder; Major Depressive Disorder; Schizo Affective Disorder

Outcome Measures

Primary Outcomes (17)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Gestational Age at Birth in Weeks assessed by Review of the Infant Delivery Chart

  At 2 weeks postpartum visit, up to 15 minutes

• Birth Length in Inches assessed by Review of the Infant Delivery Chart

  At 2 weeks postpartum visit, up to 15 minutes

• Birth Weight in pounds assessed by Review of the Infant Delivery Chart

  At 2 weeks postpartum visit, up to 15 minutes

• APGAR Score at 1 Minute assessed by Review of the Infant Delivery Chart

  At 2 weeks postpartum visit, up to 15 minutes

• APGAR Score at 5 Minutes assessed by Review of the Infant Delivery Chart

  At 2 weeks postpartum visit, up to 15 minutes

• 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

Study Arms (1)

Taking Lamotrigine

Lamotrigine (Lamictal), dosage will be based on a reference concentration of blood-serum levels

Drug: Lamictal

Interventions

Lamictal DRUG

Blood-serum levels will be checked monthly during pregnancy and reference concentration will be maintained

Also known as: Lamotrigine

Taking Lamotrigine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women who are currently taking Lamotrigine for Bipolar Disorder, Major Depressive Disorder, Schizoaffective Disorder, or another psychiatric illness, and plan to continue throughout pregnancy.

You may qualify if:

• 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

You may not qualify if:

• suicidal/clinically unstable
• alcohol, marijuana, or other drug dependence in last 90 days

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

550 N Broadway

Baltimore, Maryland, 21205, United States

Location

Related Publications (23)

• 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.

  PMID: 18056236 BACKGROUND

• 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.

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• 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.

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• Barker ED, Kirkham N, Ng J, Jensen SK. Prenatal maternal depression symptoms and nutrition, and child cognitive function. Br J Psychiatry. 2013 Dec;203(6):417-21. doi: 10.1192/bjp.bp.113.129486. Epub 2013 Oct 10.

  PMID: 24115347 BACKGROUND

• 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.

  PMID: 25086989 BACKGROUND

• 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.

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• Grigoriadis S, VonderPorten EH, Mamisashvili L, Tomlinson G, Dennis CL, Koren G, Steiner M, Mousmanis P, Cheung A, Radford K, Martinovic J, Ross LE. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013 Apr;74(4):e321-41. doi: 10.4088/JCP.12r07968.

  PMID: 23656857 BACKGROUND

• Dennis CL, McQueen K. The relationship between infant-feeding outcomes and postpartum depression: a qualitative systematic review. Pediatrics. 2009 Apr;123(4):e736-51. doi: 10.1542/peds.2008-1629.

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• Diego MA, Field T, Hernandez-Reif M, Cullen C, Schanberg S, Kuhn C. Prepartum, postpartum, and chronic depression effects on newborns. Psychiatry. 2004 Spring;67(1):63-80. doi: 10.1521/psyc.67.1.63.31251.

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• Ashman SB, Dawson G, Panagiotides H, Yamada E, Wilkinson CW. Stress hormone levels of children of depressed mothers. Dev Psychopathol. 2002 Spring;14(2):333-49. doi: 10.1017/s0954579402002080.

  PMID: 12030695 BACKGROUND

• Essex MJ, Klein MH, Cho E, Kalin NH. Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior. Biol Psychiatry. 2002 Oct 15;52(8):776-84. doi: 10.1016/s0006-3223(02)01553-6.

  PMID: 12372649 BACKGROUND

• 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.

  PMID: 14960290 BACKGROUND

• 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.

  PMID: 15234824 BACKGROUND

• Akman I, Kuscu K, Ozdemir N, Yurdakul Z, Solakoglu M, Orhan L, Karabekiroglu A, Ozek E. Mothers' postpartum psychological adjustment and infantile colic. Arch Dis Child. 2006 May;91(5):417-9. doi: 10.1136/adc.2005.083790. Epub 2006 Feb 1.

  PMID: 16452109 BACKGROUND

• Flynn HA, Davis M, Marcus SM, Cunningham R, Blow FC. Rates of maternal depression in pediatric emergency department and relationship to child service utilization. Gen Hosp Psychiatry. 2004 Jul-Aug;26(4):316-22. doi: 10.1016/j.genhosppsych.2004.03.009.

  PMID: 15234828 BACKGROUND

• 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.

  PMID: 16818531 BACKGROUND

• 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.

  PMID: 14628179 BACKGROUND

• Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014 Apr;34(2):244-55. doi: 10.1097/JCP.0000000000000087.

  PMID: 24525634 BACKGROUND

• 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.

  PMID: 19272754 BACKGROUND

• 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.

  PMID: 24883336 BACKGROUND

• 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.

  PMID: 15452293 BACKGROUND

• 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.

  PMID: 22150770 BACKGROUND

• 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.

  PMID: 24185239 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum

MeSH Terms

Conditions

Bipolar Disorder; Depressive Disorder, Major; Psychotic Disorders

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Depressive Disorder; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lindsay Standeven, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 13, 2018
• Study Start: December 3, 2018
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: March 5, 2025

Record last verified: 2025-03

Locations

US (1)