A Pilot Study of Prophylactic Management of Lamotrigine for Bipolar Disorder in Pregnant Women
Conditions: Bipolar Disorder, Major Depressive Disorder, Schizo Affective Disorder
Sponsor: Johns Hopkins University

 
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A Pilot Study of Prophylactic Management of Lamotrigine for Bipolar Disorder in Pregnant 
Women 
 
09-10-2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Date: __September 10, 2018 
 
    
Principal Investigator: _Jennifer Payne________________ 
Application Number: __IRB000162134 
 
 
JHM IRB - eForm A – Protocol 
 
1. 
Abstract 
The management of Bipolar Disorder during pregnancy is not simple. Studies have 
demonstrated that at least 80% of women who stop mood stabilizing medications for pregnancy 
relapse psychiatrically 1,2. 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 1,2. Depression during pregnancy is associated with functional impairment 
and unhealthy behaviors in the mother, including higher body mass index, less prenatal care, 
higher rates of substance use, less healthy nutrition, and decreased rates of breastfeeding 3-8. 
Untreated psychiatric illness in pregnancy is also directly correlated with worse neonatal and child 
outcomes, including significantly increased risks of preterm birth and low birth weight,3-8 increased 
cortisol levels in infants, and increased rates of child behavioral and emotional problems 9-12.  
Untreated antepartum depression is also one of the strongest risk factors for postpartum depression, 
13 which is associated with increased colic, impaired maternal-infant bonding 14 and parenting 
behavior 15 16, worse child outcomes (including lower IQ, slower language development and 
behavioral disturbance 17, and potentially devastating consequences including suicide and 
infanticide. Thus, many women with Bipolar Disorder choose to continue medication during 
pregnancy- but it remains unclear if there are specific approaches that will minimize their risk of 
relapse. 
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. 
During pregnancy, the increased volume of distribution, alterations in hepatic clearance of drugs 
(including metabolism through cytochrome P450 enzymes), increased hepatic blood flow, 
increased glomerular filtration rate, and direct interactions with sex steroids 18 can all lead to 
substantial differences in the drug dose-serum level relationship across pregnancy, with dramatic 
and rapid changes in the postpartum.  
Therapeutic drug monitoring (TDM) is considered standard of care for a number of psychiatric 
medications – including those with a narrow therapeutic window, established therapeutic ranges, or 
significant variability in their pharmacokinetic properties.  TDM 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. We 
propose to collect pilot data on the psychiatric outcomes, adverse events, and obstetrical and infant 
outcomes of pregnant women with Bipolar Disorder who undergo prophylactic TDM for a 
commonly used mood stabilizing medication during pregnancy- lamotrigine. Our primary 
hypothesis is that prophylactic TDM for lamotrigine will result in a lower than expected rate of 
psychiatric relapse which, based on the literature, is approximately 30%. Along with testing this 
hypothesis we will collect adverse event data and obstetrical and infant outcomes to assess the 
safety of our protocol. 
 
2. 
Objectives:  

 
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a) Specific Aim 1:  Collect preliminary data on the psychiatric outcomes of pregnant women 
with Bipolar Disorder who undergo a TDM protocol for lamotrigine. Hypothesis: Women 
undergoing a TDM protocol for lamotrigine will have a low rate (defined as <30%) of 
psychiatric relapse. Psychiatric outcomes will be defined by clinician interview, the Edinburgh 
Postnatal Rating Scale (EPDS) and the Young Mania Rating Scale (YMRS). 
 
b) Specific Aim 2: Collect adverse event data from pregnant women with Bipolar Disorder 
undergoing a TDM protocol for lamotrigine.  Adverse event data will be collected using the 
UKU side effect semi-structured interview and the Frequency, Intensity, and Burden of Side 
Effects Rating (FIBSER) scale. 
 
c) Specific Aim 3: Collect preliminary data on the obstetrical outcomes of pregnant women 
with Bipolar Disorder who undergo a TDM protocol for lamotrigine. Obstetrical outcomes 
will be defined by review of the delivery admission chart by an obstetrician using the 
Peripartum Events Scale (PES). 
 
d) Specific Aim 4: Collect preliminary data on infant outcomes whose mothers underwent a 
TDM protocol for lamotrigine. Pediatric outcomes will be defined by review of the infant 
delivery chart by a pediatrician and by a neurobehavioral assessment using the Neonatal 
Intensive Care Unit (NICU) Network Behavioral Scale (NNNS). 
 
3. 
Background: 
Evidence indicates that serum levels of lamotrigine decrease by 200-250% across pregnancy 19, and 
that the clearance of lamotrigine can be increased 10-fold across pregnancy in many but not all women 20.  
In the epilepsy literature, levels between 2.5 and 15 have been reported for therapeutic efficacy with 
higher levels correlated with increasing signs of toxicity 21.  In the epilepsy literature, there is a published 
protocol for lamotrigine management before, during, and after pregnancy 22 for seizure control as follows:   
 Prior to pregnancy, adjust lamotrigine dose to minimum effective dose to attain clinical 
stability.  Obtain a reference concentration (RC), preferably when the patient is not taking 
oral contraceptives. 
 During pregnancy, monitor lamotrigine concentration every 4 weeks.  If serum 
concentration falls below RC, increase lamotrigine dose by 20-25% and re-measure serum 
level after 4 additional weeks.  If serum level does not fall below RC, maintain same dose 
but check level again in four weeks. 
 After pregnancy, obtain serum level within 1-2 weeks.  IF level is above the RC, decrease 
dose by 20-25% and re-measure serum level in 1-2 weeks.  Continue until RC is reached, 
and level is stable on two repeated checks.  If patient had dose increased more than 3 times 
during pregnancy, do no wait until after delivery to obtain serum level; rather, implement 
first dose decrease (by 20-25%) in the first days following delivery, then monitor every 1-2 
weeks as described above. 
In Bipolar Disorder, there has been one study examining lamotrigine blood levels in pregnant 
patients. Clark et al followed 8 women taking lamotrigine during pregnancy and obtained blood 
samples at 20, 30 and 36 weeks of pregnancy 23. They found that lamotrigine level to dose ratios 
were lower in pregnancy and increased in the postpartum time period with up to a 600% increase 
in the level-dose relationship after childbirth. The authors recommended that, based on their 
findings, psychiatrists should monitor lamotrigine levels on a monthly basis in pregnant women 
with Bipolar Disorder and prophylactically increase lamotrigine based on a pre-pregnancy or early 
pregnancy RC. They also recommended tapering lamotrigine (if increased during pregnancy) in the 
immediate postpartum time period. This recommendation has not been further tested for safety and 
it remains unclear if prophylactic TDM will prevent destabilization of Bipolar Disorder. 
a)  

 
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4. 
Study Procedures 
a. Study design, including the sequence and timing of study procedures    
 
Our primary hypothesis is that prophylactic TDM for lamotrigine will result in a lower than 
expected rate of psychiatric relapse. The study will be an unblinded pilot study testing a TDM 
protocol for lamotrigine and will examine psychiatric, adverse event, obstetrical and infant 
outcomes. Because this is a pilot study we have chosen not to recruit a comparison group of 
women and instead focus on collecting outcomes for a larger sample of women who will 
undergo TDM for lamotrigine. Based on the literature we would expect the relapse rate in 
women who are maintained on their pre-pregnancy lamotrigine dosage to be at least 30%1,2. 
Although our study design will not demonstrate superiority, it will provide preliminary evidence 
of efficacy and safety data for both the participant and her infant and will be the largest study 
examining a specific approach to managing lamotrigine during pregnancy in patients with 
Bipolar Disorder. We hope these data will then serve as a basis for a multisite randomized trial 
of prophylactic TDM for lamotrigine compared to treatment as usual in the future. 
 
Pregnant women with Bipolar Disorder 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 TDM protocol described below their lamotrigine dosing will 
be adjusted as needed based on their blood levels compared to the RC that was obtained prior to 
pregnancy or early in pregnancy while clinically stable. After delivery women and their infants 
will be assessed at 1, 2, 4, and 6 weeks postpartum. 
Sample Size. We will recruit and follow up to 20 women with Bipolar Disorder who have 
chosen to take lamotrigine during pregnancy with a goal of maintaining a sample size of 16 
allowing 4 drop-outs.  
Recruitment. Participants will primarily be recruited through the Johns Hopkins Women’s 
Mood Disorders Center (WMDC) and through referrals from the Obstetrics department. We 
will advertise on the WMDC Facebook site, the WMDC research site, EPIC and in local 
publications. 
Lamotrigine Dosing Adjustments. At the time of study enrollment each participant will 
have a RC defined based on either 1) a pre-pregnancy serum level (for the current lamotrigine 
dosage) or 2) a serum level drawn at the time of enrollment.  While we will preferentially use a 
pre-pregnancy RC since pregnancy hormone levels can affect lamotrigine levels, many 
psychiatrists do not routinely check lamotrigine levels and from a practical perspective we will 
obtain a lamotrigine at study entry to promote study participation and recruitment. Participants 
will be clinically well at the time of enrollment so that the serum level will be correlated with 
clinical stability. Lamotrigine levels will then be drawn monthly and the dose adjusted to 
maintain the RC. Specifically, if the monthly serum level is more than 0.5µg/mL lower than the 
RC, the dose will be adjusted by 20-25% and checked again at the next monthly visit. Higher 
levels than the RC are unlikely, since levels generally decrease across the course of pregnancy, 
but the dose will not be adjusted down unless there is a clinical indication (i.e. toxicity). 
Postpartum, all participants will be instructed to taper to the lamotrigine dose that was being 
taken at the time of the RC over the course of two weeks. While this does not follow the exact 
neurology, protocol described above (Background), we believe this approach makes sense 
since it will be more consistent and avoid the potential problem of toxicity. It also follows the 
recommendations of Clark et al 23. 
Data Collection 
a) Maternal Psychiatric Outcomes: We will monitor maternal psychiatric outcomes 
based on the EPDS, YMRS and clinical interview. The primary endpoint is the proportion of 
women who experience psychiatric relapse from the time of enrollment to 6 weeks postpartum. 
Relapse will be defined as one of the following: meeting SCID criteria for a Major Depressive 
Episode, meeting SCID criteria for a hypomanic or manic episode, development of high risk 
suicidal plan or attempt, or psychiatric hospitalization.  

 
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b) Maternal Adverse Event Outcomes: Adverse events will be monitored by using a 
semi-structured interview, (the UKU side effects rating scale) at every visit as well as the self-
rated Frequency, Intensity and Burden of Side Effects Rating scale (FIBSER). Adverse events 
will be considered as related to the TDM protocol if they were not present at baseline or 
worsened in severity and were noted after a change in dosing. A preliminary analysis will be 
conducted comparing adverse events in participants who underwent dose increases during 
pregnancy to those that did not (assuming there are participants who did not undergo dosage 
increase).  
c) Maternal Obstetrical Outcomes: Maternal obstetrical outcomes will be extracted 
from the delivery admission chart which will be reviewed by the study obstetrician, Dr. 
Hueppchen. The Perinatal Events Scale (PES) will be used to collect a majority of these 
outcomes including Past Obstetrics History, Medical Risk Factors, Obstetric Risk Factors, 
Progress in Labor, Method of Delivery and Complications. A preliminary analysis will be 
conducted comparing obstetrical outcomes in participants who underwent dose increases in 
pregnancy to those that did not (assuming there are participants who did not undergo dosage 
increase).  
d) Newborn Outcomes:  Newborn outcomes will be extracted from the delivery 
admission chart which will be reviewed by the study pediatrician, Dr. Katznelson.  We will use 
the infant outcomes portion of the Peripartum Events Scale (which includes Apgar scores and 
Infant Complications) and, in addition, collect infant weight, measurements, gestational age and 
need for medical interventions or NICU admission. A preliminary analysis will be conducted 
comparing infant outcomes for participants who underwent dose increases during pregnancy to 
those that did not (assuming there are participants who did not undergo dosage increase). All 
infants will also undergo a neurobehavioral assessment at weeks 2, 4 and 6 postpartum using the 
Neonatal Intensive Care Unit (NICU) Network Behavioral Scale (NNNS). Our research assistant 
will receive training at the Brown Center for the Study of Children at Risk which has a 
standardized training on the use of NNNS. The NNNS will be used to identify any infant 
neurobehavioral effects of the TDM protocol. A preliminary analysis will be conducted 
comparing infant neurobehavioral outcomes for participants who underwent dose increases 
during pregnancy to those that did not (assuming there are participants who did not undergo 
dosage increase).  
 
b. Study duration and number of study visits required of research participants. Each subject 
will be seen approximately 12 times across the course of the study.  We will attempt to recruit 
subjects who are less than 20 weeks pregnant and will plan for monthly study visits during 
pregnancy. Women and their infants will also be assessed after delivery at 1, 2, 4, and 6 weeks 
postpartum. We expect that most study visits will take place in the Women’s Mood Disorders 
Center, however home visits by research assistants will be used if a participant cannot come to 
the Center (for example if a participant is on bedrest) to maintain participation and continuity. 
 
c. Blinding, including justification for blinding or not blinding the trial, if applicable.  Not 
applicable. Subjects will be receiving the drug that is part of their usual care and we will be 
collecting pilot data. 
 
d. Justification of why participants will not receive routine care or will have current therapy 
stopped. Participants will undergo more clinical care than is currently routine in that they will 
be monitored on a monthly basis and their lamotrigine dosing adjusted as part of a TDM 
protocol. 
 
e. Justification for inclusion of a placebo or non-treatment group.  There will be no placebo or 
non-treatment group. 

 
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f. Definition of treatment failure or participant removal criteria.  Participants will be removed 
from the study if they meet criteria for Relapse as described above. Participants will also be 
removed if they are lost to follow-up or are noncompliant with the study protocol.   
 
g. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely.  Participants will return for 
clinical care to their outpatient provider at the end of the study or if their participation ends 
prematurely. 
 
5. 
Inclusion/Exclusion Criteria   
Inclusion Criteria. Pregnant women with a history of Bipolar Disorder (Bipolar Disorder I, 
Bipolar Disorder II or Bipolar Disorder not otherwise specified) who are taking lamotrigine 
and who intend to continue lamotrigine through pregnancy will be enrolled. All participants 
must be in the first 20 weeks of pregnancy at the time of enrollment. All participants must also 
be on stable doses of lamotrigine (for the past 4 weeks), have an EPDS <13, a YMRS <12 and 
be judged by the study clinician to be clinically stable. Participants may be taking other 
psychiatric and nonpsychiatric medications. 
Exclusion Criteria. Participants who have active suicidal ideation or who are clinically 
unstable will be excluded. Participants who are dependent on alcohol, marijuana or other 
substances in the 90 days prior to study entry will be excluded.  
 
6. 
Drugs/ Substances/ Devices 
a. The rationale for choosing the drug and dose or for choosing the device to be used.  
Lamotrigine is an evidence-based treatment for Bipolar Disorder in pregnancy.  The rationale 
for our TDM/dosing regimen is based on recommendations in the epilepsy literature. There is 
currently no established protocol for the dosing of these drugs in pregnant patients with Bipolar 
Disorder. 
 
b. Justification and safety information if FDA approved drugs will be administered for non-
FDA approved indications or if doses or routes of administration or participant 
populations are changed.  There are no drugs with FDA approval for the management of mood 
disorders in pregnancy.  Therefore, we must use FDA approved drugs for non-FDA approved 
indications, a common clinical practice. 
 
c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered. Not applicable. 
 
7. 
Study Statistics.   
We will perform descriptive statistics that include percent tabulations for categorical 
variables, means with standard deviations for continuous variables, and medians with ranges where 
more appropriate. The primary endpoint is the proportion of women who experience psychiatric 
relapse from the time of enrollment to 6 weeks postpartum. Relapse will be defined as one of the 
following: meeting SCID criteria for a Major Depressive Episode, meeting SCID criteria for a 
hypomanic or manic episode, development of high risk suicidal plan or attempt, or psychiatric 
hospitalization. We do not have a comparison group but would normally expect a relapse rate of 
approximately 30% based on the literature We will also collect and describe adverse events, 
obstetrical and infant outcomes.  
 
8. 
Risks. 

 
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a) Medical Risks. The risks and discomforts are expected to be minimal and rare. During 
interviews, the participants may experience some discomfort or anxiety because of the personal 
nature of the questions. There may be some risk that the research participant may find the 
diagnostic interview uncomfortable or feel it is an invasion of privacy. Venipuncture may be 
associated with the momentary discomfort of the needle stick, fainting, bruising and rarely 
infection. There is also a risk for loss of confidentiality. Other risks include maternal side 
effects or toxicity from lamotrigine, infant side effects or toxicity from lamotrigine, and 
maternal psychiatric relapse.  
 
b) Steps Taken to Minimize Risks: 
 
Interviews, Questionnaires: A trained research assistant will be available at all times while 
the participant is filling out questionnaires.  The Principal Investigator will also be available by 
telephone, and WMDC clinicians (including a psychiatrist) will be onsite during the 
administration as well.  Should the participant become distressed, the study staff member can 
provide reassurance and evaluate her psychiatric state. Participants will be informed during 
screening and consenting procedures that they do not have to answer or complete tasks that 
cause them distress.  Each participant will be directed to inform the study team member if she 
wishes to skip a certain part. If the study staff member determines that the participant is 
experiencing a psychiatric emergency, the steps listed below under that heading will be taken. 
 
Blood draw:  In order to decrease the risks associated with venipuncture, we will employ 
staff that is experienced in blood drawing procedures.   
 
Psychiatric Urgency/Emergency: Management of Psychiatric Urgency/Emergency:  In 
order to minimize the risk of suicide, we will follow the following procedures for protection 
against this risk: 
 
 Each participant will be asked directly at every visit whether or not they are having thoughts 
about harming themselves or anyone else, including their child/children. All study personnel 
have (or will have) experience in interviewing participants with psychiatric disorders and 
will have been trained how to handle reports of suicidal ideation or threats of harm to others 
– including when to call 911 or campus security.  
 
 The study psychiatrists will be available by pager to the participants and the research 
assistants during the study.  
 
 An emergency contact information sheet will be maintained at each clinical site on each 
participant including telephone contacts, an emergency contact person, the participant’s 
psychiatric outpatient treatment provider’s name and contact information and the 
participant’s home address as well as contact information for the participant’s obstetrician 
and the infant’s pediatrician. This will provide important information in case of psychiatric 
or medical urgency/emergency. All participants will sign a release of information form in 
order to allow study personnel to contact their emergency contact and/or providers if 
necessary during the study.  
 
 If a participant who reports suicidal or otherwise harmful thoughts (to themselves or others) 
is judged to be at risk by the study psychiatrist, they will be taken to the Emergency 
Room/Emergency Mental Health. The Emergency Room is on the same campus as the study 
sites.  If the participant is interviewed by phone and is judged to be at risk, the participant 
will be instructed to go to the emergency room and if there is a question regarding 

 
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compliance with this request the study psychiatrist will call 911 as well as the emergency 
contact information maintained for each participant.  If the participant is interviewed by 
phone and is judged to be at imminent risk of suicide, the study psychiatrist will call 911 and 
have the police complete a welfare check. 
 
 If the participant is not at risk of harming herself or others but is psychiatrically ill, the study 
psychiatrist will provide clinical care as necessary until the participant can be seen by her 
treating outpatient clinical psychiatrist. The participant will remain in the study and undergo 
all study visits and procedures as long as consent continues.   
 
Obstetrical Urgency/Emergency: Should one of the participants develop an urgent 
obstetrical problem, the participant will either be taken to the local Obstetrics and Gynecology 
Clinic or Emergency Room, whichever seems more appropriate. Both the Clinic and the 
Emergency Room are on the same campus as the study site. The subject’s private obstetrician 
will also be contacted.  
 
Lamotrigine toxicity: Every participant will be monitored closely for side effects/signs of 
toxicity during the trial. Because the RC will be established prior to pregnancy or early in 
pregnancy we anticipate that the likelihood of significant side effects or toxicity in the 
participants is very low. If a participant does develop side effects or signs of toxicity the dose of 
lamotrigine will be lowered by the study psychiatrist. At every visit the participant will fill out a 
Frequency, Intensity and Burden of Side Effect Scale (FIBSER) to monitor for significant side 
effects from the protocol. Obstetrical outcomes will be assessed by Dr. Hueppchen from the 
Gynecology and Obstetrics Department. 
 
Neonatal toxicity: It is possible that increased dosing of lamotrigine during pregnancy will 
lead to increased side effects or toxicity in the newborn. We do not anticipate this outcome 
since the protocol is used in the management of seizure disorders and there have not been 
reports of adverse effects in infants whose mothers participate in these protocols. We will 
monitor for this potential risk by collecting neonatal outcomes via a review of the medical 
record by a pediatrician (Dr. Katznelson) and by undergoing a neurobehavioral exam using the 
Neonatal Intensive Care Unit (NICU) Network Behavioral Scale (NNNS) at 2, 4, and 6 weeks 
postpartum. Our research assistant will undergo specialized training at Brown University in 
order to conduct the exam appropriately. 
 
Neonatal Intensive Care Unit (NICU) Network Behavioral Scale (NNNS) Examination: 
The NNNS is a standardized neurobehavioral exam that is used in infants. It primarily consists 
of observation of the infant, reflex testing and holding the infant. The primary risk is that the 
infant will become upset and cry. Our research assistant will have undergone an intensive 5 day 
training at Brown and will learn as part of the training how to minimize this risk.  
 
c) Plan for reporting unanticipated problems or study deviations.  
Reports will be made to the IRB and necessary healthcare providers in the event of an 
unanticipated problems or study deviations. The study team will follow IRB protocol to 
determine if a deviation or problem needs to be reported immediately or if it can be reported at 
the yearly continuing review. All serious adverse events will be reported to the IRB 
immediately by the PI. 
 
d) Legal Risks: 
Confidentiality: Careful procedures will be employed to protect the confidentiality of all 
participants.  Participants will be assigned unique ID identifiers not associated with personally 

 
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identifying information.  These will be used on all interview protocols and lab results.  No 
identifying information other than the unique ID will appear on interview protocols. All data 
files and analyses will be performed on research computers using only code numbers to 
identify participants. Only summaries of group data will be reported in any publications or 
presentations, with no identification of individuals. All study personnel will maintain their 
certification in the Protection of Human Subjects training program prior to participating in the 
research. Only authorized persons will be granted access to enter and view study data. Subject 
IDs with subject names will be kept in CRMS and only designated personnel on the research 
team will have access. Charts containing subject data for active subjects will be kept in a 
locked filing cabinet or room and will be identified only by subject ID. All precautions will be 
taken to protect the confidentiality of the study participants. As with participation in any 
research study there is a slight risk of a breach in the security procedures that would affect the 
confidentiality of the research participant. Every effort will be employed to minimize this risk. 
If such a breach occurs, the research participant will be informed as well as the IRB. 
Additional Protections for Pregnant Women, Human Fetuses and Neonates. This study 
meets all requirements for research in this vulnerable population as described by DHHS 
regulations and OHRP guidance. This study is essentially an observational study with blood 
and clinical data collection only and no active study intervention that increases the risk beyond 
what the woman and her child would face outside of participation in the study.  
 
9. 
Benefits 
Participants will be paid for their time and will undergo more regular psychiatric evaluation 
than is standard for most psychiatric patients. Participants may avoid psychiatric relapse by 
participating in the study due to the increased monitoring of lamotrigine blood levels and 
adjustment of lamotrigine dosing.  
Developing more effective management strategies for bipolar disorder during pregnancy 
will allow us to decrease the associated maternal and infant morbidity and mortality by working 
towards decreasing the relapse rate during the perinatal time-period.  
 
10. 
Payment and Remuneration. Detail compensation for participants including possible total 
compensation, proposed bonus, and any proposed reductions or penalties for not completing 
the protocol.  Participants will be compensated for parking or taxi service for their visits.  In 
addition, they will receive compensation up to the amount of $450 if they complete the entire 
study.  If the participant fails to complete all visits, they will be paid based on the visits spent in the 
study: Participants will be paid $25 for each pregnancy visit completed and $75 for each 
postpartum visit. If participants opt for a home visit postpartum, they will receive $50 instead. 
Participants will also be paid a bonus of $100 for achieving a minimum of 5 pregnancy visits and 2 
postpartum visits in order to encourage continuity of participation.  Lab costs for lamotrigine levels 
will be covered by the study as well.  If acute medical care or medical or psychiatric hospitalization 
is required during the course of the study, the individual participant and/or their health insurance 
will be expected to cover those costs. 
 
11. 
Costs 
The participant and her insurance company will cover the cost of lamotrigine and any other 
prescribed medications. The study will cover the cost of the lamotrigine blood draws and laboratory 
processing. If acute medical care or medical or psychiatric hospitalization is required during the 
course of the study, the individual participant and/or their health insurance will be expected to cover 
those costs. 
 
 
 

 
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