Perinatal Depression: Dyadic-IPT to Improve Health of Mother and Baby
Phase: NA
Conditions: Depressive Disorder, Major, Postpartum Depression
Sponsor: Washington University School of Medicine

 
 
Mommy-Baby Treatment for Perinatal Depression 
Principal Investigator: Shannon N. Lenze, PhD 
 
 
Protocol Version 10.1 
12/03/2014 
NCT# 01744041 
 
 
 
 

A Randomized Controlled Trial of IPT-Dyad treatment for Perinatal Depression 
Principal Investigator: Shannon N. Lenze, PhD 
 
Study Team Members: 
Shannon Lenze, PhD 
Jennifer Rodgers, MA, PLPC 
Joan Luby, MD 
George Macones, MD 
Kenneth Freedland, PhD 
 
Overview 
Perinatal depression is a major public health problem, affecting 15 % of women during 
pregnancy through the postpartum period, with adverse consequences for the mother, 
the fetus, the infant, and the family. Despite increasing evidence of the importance of 
this critical risk interval, there is a paucity of research investigating the effects of 
depression treatment initiated during pregnancy on infant outcomes. Recent findings 
suggest the need for robust, integrated peripartum depression treatments that target 
maternal depressive symptoms, parenting skills, and the mother-infant relationship.  
 
A treatment manual for a new intervention, Interpersonal psychotherapy for the 
mother-infant dyad (IPT-Dyad), was developed based upon an established 
psychotherapeutic treatment for depression (Interpersonal Psychotherapy). This 
intervention begins during pregnancy and continues with the mother and infant until one 
year post-partum. The purpose of this study is to test the feasibility, acceptability, and 
effectiveness of this new intervention in a small randomized controlled trial. We will 
enroll approximately 40 patients aged 18 and older, pregnant, with depressive 
disorders. We will treat them with 20-22 sessions of psychotherapy for a period of 14-18 
months (depending on gestational weeks at enrollment).   
We will assess acceptability and feasibility of the intervention. Maternal 
depressive symptoms, psychosocial functioning, parenting self-efficacy will be assessed 
as well as mother-infant relationship quality and infant emotional development. A small 
subsample (n=10) of infants will participate in a MRI brain scan to generate pilot data 
regarding mechanisms of psychotherapy effectiveness on infant outcomes.   
 
Background: 
Perinatal depression is a major public health concern: Perinatal depression refers 
to depressive disorders that occur during pregnancy through the first postpartum year. 
As many as 18% of pregnant women experience depressive symptoms and 13-15% 
develop a major depressive episode during pregnancy through the first three months 
postpartum. Incidence of perinatal depression is higher in low income, minority 
populations, with rates ranging from 24% to 47%. Depression during pregnancy is 
associated with increased risk of miscarriage, pre-term birth, low birth weight, small for 
gestational age babies, gestational hypertension, and preeclampsia. It may also lead to 
poor adherence to prenatal care, poor self care, and other unhealthy lifestyle choices, 
including nicotine, alcohol, and drug use.  At least 50% of women who are depressed 
antenatally remain depressed postpartum: detection and treatment that integrates pre 

and postnatal periods is imperative to decrease the burden of illness on mothers and 
their children. 
Consequences of Perinatal Depression on Infant Development: The effects of 
maternal depression are evident in early infancy across a range of domains.  Infants of 
depressed mothers display more negative affect, show less secure attachment 
relationships, and experience difficulties in emotion regulation. Such infants show 
abnormalities in frontal EEG patterns and neurotransmitter levels, patterns which 
remain stable from one week to at least three years of age.  An important potential 
mechanism for intergenerational risk transmission of depression is the infant’s inability 
to regulate emotions. This involves a combination of innate and environmental 
elements, with parenting behaviors a key factor. Infants may be particularly vulnerable 
to the effects of maternal depression because of their immature neuroregulatory abilities 
and reliance on mother for external emotional regulation. The mother’s inability to model 
self-regulatory strategies and to provide external regulation for the infant may increase 
the stress of the maternal-infant interaction while also not providing the infant with the 
needed comfort and support.  Therefore, treatment for maternal depression should 
address these impairments in the mother-infant dyad to enhance infant emotion 
development and decrease risk for later psychopathology.  
Early intervention is critical: There is substantial evidence that the developmental 
trajectory towards health or disease is encoded during the fetal stage. Prenatal stress 
via maternal depression is one such stressor thought to alter the intrauterine 
environment. Processes underlying emotion regulation and attention seem to be 
particularly sensitive to prenatal stressors. Given these recent developments in both 
animal and human models, there is increasing evidence of the need for the earliest 
possible intervention or prevention efforts.  
The overall level of “exposure” to depressive symptoms over the course of 
pregnancy is the most robust predictor of neonatal behavior. Maternal depressive 
symptoms in the first few months of an infant’s life have greater developmental 
consequences than maternal depressive symptoms experienced during toddler or later 
stages. Therefore, an integrated treatment of depression during the perinatal continuum 
has the potential to influence prenatal psychosocial risk factors (health behaviors, social 
support), prenatal physiological risk factors (HPA-axis regulation), and postnatal risk 
(parenting, health behaviors, social support). Despite increasing evidence of the 
importance of this critical risk interval, there is a paucity of research investigating the 
effects of depression treatment initiated during pregnancy on infant outcomes.  
Effective interventions for perinatal depression: Few randomized trials have 
investigated the efficacy of antenatal treatment of maternal depression. Use of 
antidepressant medications during pregnancy involves risks and many women prefer 
psychotherapy. Cognitive Behavioral Therapy (CBT) has been used successfully to 
treat or prevent postpartum depression. Few studies have investigated CBT for 
treatment of depression during pregnancy.  
Another evidence-based treatment, Interpersonal Psychotherapy (IPT), is 
recognized as an ideal psychosocial treatment for depression during the perinatal 
period. IPT focuses on four problem areas that are related to disruptions in social 
support networks and communications with others: grief, role disputes, role transitions, 
and interpersonal deficits. As perinatal depression is often associated with lack of social 

support from partner or families, as well as life changes resulting from pregnancy and 
parenthood, IPT is well suited to address perinatal depression and has been shown to 
be an efficacious treatment of peri and postpartum depression. It can be difficult to 
engage pregnant women, especially low-income or minority women, into treatment for 
depression. In an effort to address some of the barriers associated with psychotherapy, 
Swartz and colleagues developed a brief eight-session form of IPT (IPT-B). Building 
upon this model, Grote and colleagues developed a multicomponent model of 
depression care, “Enhanced IPT-B”, which includes a pre-treatment engagement 
interview (designed to address psychological and cultural barriers to care), 8 prenatal 
sessions of IPT, and pragmatic case management (i.e., bus passes, child care, and free 
baby supplies). In a recent RCT with low-income, depressed, pregnant women, those 
who received Enhanced IPT-B were more likely to show improvements in depressive 
symptoms and social functioning than women in usual care. These results suggest that 
this is an effective treatment for perinatal depression in a difficult to engage, non-
treatment seeking population.  
Parent-Infant Psychotherapies: One of the best-known mother-infant 
psychotherapies, Infant-Parent Psychotherapy (IPP) focuses on identifying negative 
experiences of being parented that may be influencing a mother’s ability to be 
emotionally available to her child and to parent effectively – often referred to as the 
“ghosts in the nursery”. Examples of other interventions designed to improve parent-
child relationships are Watch, Wait, and Wonder, Keys to Caregiving, and Circle of 
Security. Although these interventions are effective in improving the quality of the 
mother-infant relationship, they were not designed to address maternal depression. For 
example, IPP alone had no effect on maternal depression scores in a study of toddlers 
of depressed mothers. Recently, interventions have been developed to improve 
maternal depressive symptoms as well as the mother-infant relationship. For example, 
M-ITG, a multicomponent group intervention for postpartum depression focused on 
mother-infant and family relationships, was effective in treating maternal depressive 
symptoms and increasing positive affective involvement with infants. Van Doesum and 
colleagues developed a home-visiting intervention that included cognitive restructuring, 
education, and infant massage; however, there were no significant reductions in 
depressive symptoms in comparison to the telephone support control group. Currently, 
Toth and colleagues are investigating the efficacy of IPT plus Infant-Parent 
Psychotherapy (beginning at one year of age) in preventing emergent psychopathology 
in the offspring of low-income depressed mothers. Altogether, these results suggest that 
dyadic interventions hold promise in reducing maternal depressive symptoms and 
enhancing mother-infant relationships. Much work remains as these treatments have 
not been initiated in the potentially critical interval of pregnancy or the immediate 
postpartum period, and applicability to newborns or young infants is unknown. The 
intervention proposed in the current project would begin during pregnancy thereby 
improving the new mother’s ability to engage in effective mother-infant interactions and 
enhance the infant’s emotion development. 
Providing for the Needs of Mother and Infant with IPT: While some studies suggest 
postpartum depression treatment benefits mother-infant interactions, others have failed 
to find such benefits or beneficial effects on attachment security, cognitive development, 
or emotionality. These findings support the need for a more robust, integrated 

peripartum depression treatment that targets parenting skills and the parent-infant dyad 
in addition to maternal depressive symptoms. Therefore, integrating principles of infant-
parent psychotherapy into IPT, during a key window of risk, represents a novel and 
efficient approach to perinatal depression care. This type of dyadic therapy can be 
readily incorporated into IPT. Primary goals of IPT treatment are to help restore self-
esteem by developing a sense of mastery over a new role and improving 
communication strategies and skills, thus making it an ideal treatment for reducing 
maternal insecurity and isolation. Interpersonal communication skills are the foundation 
of mother-infant relationship development and infant emotional regulation. By enriching 
IPT in the postpartum phase of the perinatal period with interactive mother-infant 
exercises, the IPT therapist is able to explore and directly target this new mother-infant 
dyad in vivo. Enhancements specific to the maternal-infant relationship and maternal 
attunement to the infant will advance our abilities to treat perinatal depression and 
prevent intergenerational transmission. 
 
 
Research Objectives: 
The purpose of this study is to examine feasibility, acceptability, and effectiveness of 
Interpersonal Psychotherapy for the Mother-Infant Dyad (IPT-Dyad) for women who 
experience depression during the perinatal period. We will assess maternal depressive 
symptoms, psychosocial functioning, and mother-infant relationships before, during, and 
after a course of IPT-Dyad. Data will be utilized to further refine and subsequently 
perform a large scale trial of this adapted psychotherapeutic intervention for perinatal 
depression.   
 
Primary Aims: 
1) Conduct a preliminary RCT comparing IPT-Dyad versus enhanced treatment as 
usual (TAU) in 40 women with antenatal depression to establish feasibility. 
Hypothesis: IPT-Dyad will be better than TAU in: 
a) Reducing antenatal depressive symptoms 
b) Preventing postpartum depression relapse 
c) Improving psychosocial functioning 
d) Reducing parenting stress and improving parenting self-efficacy 
e) Increasing maternal sensitivity and responsiveness, enhancing 
mother-infant relationship quality, and improving infant social 
and emotional regulation 
 
A secondary aim of this study is to investigate potential mechanisms of psychotherapy 
treatment response on infant brain development. 
 
Potential Contribution:  
Perinatal depression is a major public health concern for both the mother and her infant. 
Even mild depression in new mothers has been shown to negatively impact mother-
child bonding. Effective treatment for depression can significantly improve outcomes for 
both the mother and child. The perinatal period is a window of opportunity in which to 

address depression in women because they are more likely to come in contact with the 
health care system.  
 
 
Methods 
Timeline: 
 
April 2012-October 
2012 
October 2012-December 2014 
December 2014-October 
2015 
Set-up, train 
clinicians 
Accrue and randomize 40 
patients   
Complete follow-up data 
collection  
Obtain HRPO 
approval 
Take participants through study 
protocol  
Data analysis and 
dissemination of findings 
Establish recruiting, 
consenting, and 
scheduling 
procedures 
Gather treatment outcome data, 
including depressive symptoms 
and functioning 
 
Establish data 
management 
system 
Gather treatment process data, 
including model fidelity, patient 
acceptability, feedback from 
ObGyn physicians and clinical 
staff 
Estimated end date is 
December 2015 
 
 
General Inclusion Criteria (women): 
1) Pregnant women ages 18 and older 
2) Between 12 and 30 weeks gestation 
3) Score greater than or equal to 10 on the Edinburgh Depression Scale 
4) Meet diagnostic criteria for a depressive disorder (MDD, dysthymia, Depressive 
Disorder NOS, or Bipolar -depressed) based on the SCID-IV 
5) English speaking.  
 
General Exclusion Criteria (women): 
1) Substance abuse or dependence in the previous 3 months 
2) Active suicidal or homicidal ideation such as to preclude safety in an outpatient 
settings 
3)Current mania (Young Mania Rating Scale >12), psychotic disorder, or organic mental 
disorder 
4) Unstable medical condition (i.e. untreated hypertension) or other medical/obstetrical 
complications (multiple gestation, history of prior pre-term birth) 
5) Evidence of severe intimate partner violence 
6) Ongoing psychosocial therapy or pharmacotherapy for depression. Patients taking 
psychopharmacologic medications for depression will be included on a case by case 
basis decided after consultation with the PI, Dr. Luby, and the prescribing provider.    
 
General Inclusion Criteria for babies: 
1) Those born to participants in the study during their enrollment in the study. 

General Exclusion Criteria for babies: 
1) None 
 
For the Neuroimaging subset: 
Inclusion (women): 
1) Must be enrolled in the general study 
Exclusion (women): 
1) absence of major maternal medical illness  
2)chronic maternal medication treatment (e.g., insulin, steroids, thyroid replacement, 
antidepressants, and anticonvulsants) 
3) history of maternal substance abuse (including alcohol or tobacco) at any time during 
the pregnancy 
 
Inclusion (infants): 
1) Must be enrolled in the general study 
2) 5-minute APGAR score >8 
3) Weight and head circumference at birth appropriate for gestational age (between 
10th and 90th percentile) 
 
Exclusion (infants): 
1)pre-term delivery (prior to 37 weeks gestation) 
2) admission to neonatal or special care nursery 
3) congenital or chromosomal abnormality, congenital or acquired infection (e.g., HIV, 
sepsis, toxoplasmosis, rubella, cytomegalovirus, and herpes simplex) 
4) known prenatal brain lesions (e.g., cysts or malformations) or neonatal seizures 
5) absence of prenatal care 
 
Recruitment and Informed Consent: 
Participants will be recruited from the Barnes-Jewish Hospital outpatient ObGyn Clinics 
and community providers. Recruitment strategies will include the use of IRB approved 
flyers and pamphlets, referrals by community providers and word of mouth, and 
referrals by ObGyn providers. Interested patients will be interviewed individually by 
research clinicians trained in the protection of human subjects. Recruitment procedures 
will protect participant confidentiality and no cold calling will occur. No individually 
identifiable health information will be shared with the research investigators until a 
potential participant signs a HIPAA authorization for sharing health information consent 
form, if applicable. If the referring entity is Washington University, then the referring 
entity will document verbal permission of the participant to share protect health 
information with the researchers.  To ensure that the risk to the privacy of the involved 
participant remains minimal: 1) the potential participant’s recorded contact information 
will be stored by the researchers in a secure manner accessible only to the relevant 
members of the research team, and 2) the potential participant’s recorded contact 
information will be destroyed immediately after the researchers have contacted the 
participant to discuss the research study for which this information was provided; 
unless, upon such contact, the potential participant indicates further interest in study 
participation. 

For potential participants who indicate further interest in study participation, the 
participant will be engaged in an informed consent process to further determine 
research study eligibility and/or study interest. The recorded participant contact 
information will not be reused or re-disclosed to any other person or entity (other than 
the members of the research team) except as required by law or for authorized 
oversight of the study.  
Potential participants will complete an informed consent procedure and provide 
written consent to participate. The informed consent procedure will include a discussion 
of study risks, measures to protect against risks, and possible benefits. Participants will 
be informed of their right to refuse to answer questions. They will also be informed of 
their right to refuse participation at any time without penalty. All participants will sign 
separate HIPAA consent documents, medical release forms, and videotaping release 
forms as required. Per Federal regulations: 1) no inducements will be offered to 
terminate the pregnancy 2) no member of the research team will have any part in 
decisions as to timing, method, or procedures used to terminate pregnancy, and 3) no 
member of the research team will have any part in determining the viability of the 
neonate.  As assent for participation in research cannot be obtained from infants, upon 
the birth of the baby informed consent procedures will be re-initiated with the mother for 
continued participation in the study. Participants will be asked to provide written consent 
to continue with the intervention and to include the infant in the study. Per Missouri state 
law, any suspected case of child abuse or neglect must be reported to the Missouri 
Department of Social Services Children’s Division. All participants will be informed of 
this risk during the informed consent procedures. 
The PI or trained study staff will be responsible for discussing the components of 
the study and the risks and benefits of participation. Written informed consent will be 
obtained from all participants prior to their involvement in the study.  
 
Procedures: 
 
Approximately 40 pregnant (between 12-30 weeks gestation) women with scores >10 
on the Edinburgh Depression Scale will be asked to participate. Women meeting all 
inclusion and exclusion criteria who provide written informed consent will be randomized 
to receive IPT-Dyad or enhanced treatment as usual (TAU).  
 
A small subsample (n=10) of women and infants may be eligible to participate in a MRI 
scan of the newborn’s brain. Participation in the study is not contingent upon consenting 
to the MRI. If the participant and her baby meet eligibility criteria and consent to 
participation in the scan, the scan will take place during their postpartum hospitalization 
post delivery of the baby. The infant will be fed within an hour of the scan. Infants will be 
wrapped with blankets and be accompanied by a research nurse or physician at all 
times. The infant will be gently restrained in the standard manner, and will receive 
continuous monitoring by a research nurse present throughout the entire scan. The 
neuroimaging takes about one-hour to complete. No narcotic or sedative agents will be 
administered to the infant for study purposes. After completion of the scan, the infant 
will  be returned to the postpartum nursery or the infant's mother.   
 

Enhanced TAU: Participants randomized to receive treatment as usual will be 
informed of any psychiatric diagnosis revealed during the clinical and diagnostic 
assessments and will be given psychoeducation about depression. The clinician will 
give the woman a referral to appropriate treatment, ensure that an appointment is 
scheduled within 2 weeks, and help to problem solve any practical barriers to care. 
Material supports (i.e., free diapers, bus passes) will be provided at regular intervals. 
Assessments will be completed (in home or via telephone) every two weeks or on the 
same assessment schedule as the IPT-Dyad group to monitor depressive symptoms 
and suicidality. This extra contact by trained clinicians is greater than is usually incurred 
during routine care and may help to retain these women in the study. Results from the 
assessments will be available to the woman’s treatment provider if she provides a 
written authorization for release of research information. 
 
IPT-Dyad: Figure 1 illustrates the study timeline for participants randomized to 
the IPT-Dyad intervention.  All sessions will be video or audiotaped for supervision and 
treatment fidelity monitoring. In the current project, adequate indicators of acceptability 
will include attendance to at least 80% of treatment sessions, less than 20% attrition in 
the IPT-dyad group, and scores and feedback obtained from the Client Satisfaction 
Questionnaire. Indicators of feasibility will include therapist adherence ratings. A 
treatment fidelity checklist will be modified that will be used to monitor adherence to the 
model.  
 
 
 
The IPT-Dyad intervention consists of the engagement session plus eight 60-
minute sessions of weekly treatment during the antenatal period followed by 4 weekly, 4 
bi-weekly and 3 monthly 60-minute sessions conducted with the infant during the 
postnatal period for the first six post-birth months plus one 60-minute booster session at 
month 9.  A brief description of the intervention is provided in the following sections. 
 
 
 
 
 
 
 
 
 
 
 
Gestation wks. 12-30 
9 mos. 
6 mos. 
3 mos. 
Weekly Enhanced IPT-B  
Bi-weekly 
sessions 
Monthly 
sessions 
9 mos. 
Booster 
session 
Birth 
Screening 
Enrollment + 
Baseline 
assessment 
Post-Antenatal 
Tx assessments 
3 mos. 
postpartum 
assessments 
6 mos. 
postpartum 
assessments 
9 mos. 
postpartum 
assessments 
Final 
Outcome 
Assessment
12 mos. 
Figure 1. IPT-Dyad participant flow through the study. 
Weekly 
sessions 
1 mo. 
12 mos. 
Termination 
session 
Antenatal Period 
(Mother Only) 
9 sessions 
10-12 sessions 
Postpartum Period 
(Mother and Infant) 

 
Antepartum Sessions: 
Engagement Session (session 1): The engagement session, based on Grote and 
colleagues, is designed to elucidate the woman’s view on several factors related to 
treatment engagement, including: the woman’s experience of depression, acute and 
chronic stressors, practical or psychological barriers to receiving care, goals/hopes for 
treatment or therapist, and health related beliefs or practices (i.e. importance of 
spirituality). The overall effect of the engagement session personalizes the treatment to 
the woman’s views about depression and depression treatment and barriers to receiving 
care. The engagement session will be conducted by the same therapist who will 
conduct the remaining phases of treatment. 
 
Initial Sessions (sessions 2-3): As in IPT-B, the next two sessions of treatment are 
dedicated to completing the interpersonal inventory (a careful review of all interpersonal 
relationships) and agreeing upon the IPT focus or problem area (role transitions, role 
disputes, or grief).  
 
Middle Sessions (sessions 4-9): The middle sessions of treatment are based on IPT-B 
and maintain the essential features and strategies of standard IPT treatment. Specific 
techniques used include communication analysis, decision analysis, and role playing. 
Behavioral activation strategies, including using a graded approach to challenging the 
patient to re-engage in pleasurable activities and promoting self-mastery are also used.  
 
Protocol Guidelines for Antepartum Sessions: The goal is to complete 9 sessions prior 
to delivery of the baby (1 engagement session and 8 IPT sessions). We need to 
balance the therapeutic ideal of weekly sessions with the reality that patients have 
conflicts that arise and other barriers that may prevent regular attendance. Therefore, 
patients have 16 weeks to complete the antepartum sessions or they will be withdrawn 
from the study and provided referrals. More than 9 sessions will be provided if the 
patient has completed all 9 sessions and has not given birth yet.  
 
Sessions will be provided once weekly. Session 7 to the postpartum phase can be 
provided bi-weekly if PHQ-9 scores <10 and there is sufficient time to complete all 9 
sessions prior to delivery. 
 
Emergency sessions may be added to a max of 2 sessions/week. Referral for additional 
treatment or withdrawal from the study will be considered for any patient needing >2 
consecutive emergency sessions.  
 
Patients not achieving at least partial response as evidenced by at least 2 point 
decrease from baseline in PHQ-9 score by session #4 or response as evidenced by a 5 
point decrease from baseline in PHQ-9 score by session #8 will discuss with the 
therapist the possible need for psychiatric consultation or referral for alternative 
treatment.  Patients necessitating in-patient psychiatric hospitalization may be 
withdrawn from the study at the PI’s discretion. This will be reviewed on a case by case 
basis. 

 
Postpartum Sessions:  
Postpartum Sessions (approximate sessions 12-22): The postpartum focus of IPT-Dyad 
is based on traditional IPT strategies that were developed to prevent depression relapse 
and enhance interpersonal functioning. The goal is to help the patient to develop more 
effective strategies to cope with interpersonal problems that might arise following 
remission of depression. For example, patients are encouraged to develop stronger 
social networks, refine social skills, enhance existing relationships with others, or modify 
maladaptive communication skills. Drawing from the model of infant mental health risk 
transmission and infant emotional development theories discussed in the background 
and significance sections, the postpartum sessions of IPT-Dyad will also include several 
techniques designed to specifically target the mother-infant relationship. Table 2 
highlights essential elements of infant emotional development and how IPT-Dyad will 
address these elements. Techniques used will include: modeling, coaching, floor play, 
gaze and contact exercises, and education.   
 
 
 
Protocol 
Guidelines for 
Postpartum 
Sessions: 
  
The goal is to 
complete 10 
sessions in the 
first year 
postpartum (8 
sessions by 3 
months, 11 
sessions by 6 months, and 12 sessions by 12 months). Patients may complete more or 
less depending on individual therapeutic needs. All sessions will be terminated at 12 
months postpartum. Patients needing additional treatment will be provided with an 
appropriate referral.  
 
Up to 3 months postpartum  
Weekly sessions are indicated for all patients in the first month postpartum. After the 
first month, weekly sessions are indicated for patients with PHQ-9 scores > 15. 
Alternative treatment should be considered for any patient whose scores do not 
decrease below 15 or increase 3 consecutive weeks. Weekly sessions are also 
indicated for patients who did not complete all 9 sessions of antepartum therapy (i.e. 
due to premature delivery). Weekly sessions can continue until 9 sessions have been 
completed and/or PHQ-9 scores < 14.  
 
Bi-weekly sessions are indicated for patients with PHQ-9 scores < 14.  
 

Emergency sessions may be added to a max of 2 sessions/week. Referral for additional 
treatment or withdrawal from the study will be considered for any patient needing >2 
consecutive emergency sessions.  
 
3 to 6 months postpartum 
Weekly sessions are indicated for patients with PHQ-9 scores > 15. Alternative 
treatment should be considered for any patient whose scores do not decrease below 15 
or increase 3 consecutive weeks. Emergency sessions may be added to a max of 2 
sessions/week. Referral for additional treatment or withdrawal from the study will be 
considered for any patient needing >2 consecutive emergency sessions.  
 
Bi-weekly sessions are indicated for patients with PHQ-9 scores < 14 but the clinician 
determines more intensive mother-infant relationship work is needed (the Parent Infant 
Relationship-Global Assessment Scale should be used to help make this determination 
in suspected cases).   
 
Monthly sessions are indicated for patients with PHQ-9 scores < 10 or there has been at 
least a 50% reduction from baseline scores for 4 consecutive weeks and the mother-
infant relationship is functioning in the optimal range.  
 
6 to 12 months postpartum 
Weekly sessions are indicated for patients with PHQ-9 scores > 15. However, 
alternative treatment should be discussed with the patient and withdrawal from the 
study considered. Emergency sessions may be added to a max of 2 sessions/week. 
Referral for additional treatment or withdrawal from the study will be considered for any 
patient needing >2 consecutive emergency sessions. 
 
Bi-weekly sessions are indicated for patients with PHQ-9 scores < 14 but the clinician 
determines more intensive mother-infant relationship work is needed (the Parent Infant 
Relationship-Global Assessment Scale should be used to help make this determination 
in suspected cases).   
 
Monthly sessions are indicated for patients with PHQ-9 scores < 10 or there has been at 
least a 50% reduction from baseline scores for 4 consecutive weeks and the mother-
infant relationship is functioning in the optimal range. Patients with 8 consecutive weeks 
of PHQ-9 scores < 10 and solid mother-infant relationship functioning may extend time 
between sessions up to 12 weeks. 
 
Remuneration:  Participants will receive $15 at the screening visit, $30 at baseline 
assessments, $20 at 37-39wks gestation assessments, $20 at 3 month postpartum 
assessment, $30 at 6 month postpartum assessment, $20 at 9 month postpartum 
assessment, and $45 at the 12 month postpartum assessment.  Participants whose 
newborns receive a brain MRI scan will be paid $25. Additionally, women will be 
provided with material supports such as free diapers, developmentally appropriate toys 
and books on a regular basis. Parking reimbursement or bus passes will be available for 
assistance with transportation to and from appointments if needed. 

 
Measures:  
Regular assessments will be conducted throughout the course of treatment. The 
frequency of assessments was chosen to minimize participant burden while still 
maximizing the ability to capture treatment-related changes. The measure and rationale 
for the measures are described below. Table 3 describes the measures and the timeline 
for administration.  *It should be noted that the Patient Health Questionnaire, 
Depression, Anxiety and Stress Scale and the Brief State Trait Anxiety Inventory will be 
administered at each psychotherapy session in addition to the assessment schedule 
below. The Hypomania Symptom Checklist will be administered as needed if the 
clinician suspects onset of hypomanic symptoms.  
 
Table 3. Measures Administered and Assessment Timeline 
 
Antenatal 
Postnatal 
 
Enrollment 
37-39wks 
gestation 
3 mos. 
6 mos. 
9 mos. 
12 mos. 
Obstetrical Chart Review  
–prenatal complications 
X 
X 
 
 
 
 
Structured Clinical Interview for 
the Diagnosis for DSM-IV (SCID) 
 -evaluates for psychopathology and 
provides broad coverage for psychiatric 
diagnosis  
X 
 
 
 
 
 
Inventory of Interpersonal 
Problems -25 item (IIP-25) 
-self report measure of interpersonal 
functioning 
X 
 
 
 
 
X 
Edinburgh Depression Scale 
(EDS) 
-self report scale for measuring pre and 
postnatal depressive symptoms 
X 
X 
X 
X 
X 
X 
Young Mania Rating Scale 
(YMRS) 
-brief interview to assess manic symptoms 
x 
x 
x 
x 
x 
x 
Hypomania Symptom Checklist-
32 (HCL32)*  
-self-report checklist to measure manic 
symptoms 
x 
 
 
 
 
 
State Trait Anxiety Inventory -
Brief 
-Self report scale measuring transient 
anxiety symptoms 
X 
X 
X 
X 
X 
X 
Depression Anxiety and Stress 
Scale (DASS21) 
-Self report scale measuring negative 
emotionality 
X 
X 
X 
X 
X 
X 
Patient Health Questionnaire -9 
item (PHQ-9)* 
 -Self report measures of depressive 
symptoms 
X 
 
 
 
 
 
Social Support Questionnaire 
(SSQ) 
-self report measure of social network size 
and satisfaction 
X 
X 
 
X 
 
X 
Abuse Assessment Screen 
X 
 
 
 
 
 

-self report assessment of risk for current 
physical, emotional, or sexual abuse while 
pregnant 
Experiences in Close 
Relationships –Revised (ECR-R) 
-self report measure of attitudes towards 
close relationships with intimate partners 
X 
 
 
 
 
X 
Difficult Life Circumstances 
(DLC) 
-self-report measure of stressful life events 
X 
X 
X 
X 
X 
X 
Postpartum Adjustment 
Questionnaire (PPAQ) 
-self report assessment of social role 
adjustment postpartum 
 
 
X 
X 
X 
X 
Parenting Stress Index (PSI) 
-questionnaire evaluating seven domains of 
parenting including attachment, competence, 
support, isolation, and health status 
 
 
 
X 
 
X 
Infant Behavior Questionnaire 
(IBQ) 
-assesses six domains of infant 
temperament 
 
 
 
X 
 
X 
Mullen Scales of Early Learning 
(MSEL) 
-brief assessment of infant motor, 
perceptual, and language abilities 
 
 
X 
 
 
 
Still-Face Paradigm 
-structured paradigm used to characterize 
parent-infant interactions 
 
 
 
X 
 
X 
Emotional Availability Scales 
-structured paradigm used to characterize 
maternal sensitivity and responsiveness 
 
 
X 
X 
X 
X 
Infant-Toddler Social and 
Emotional Assessment (ITSEA) 
-parent questionnaire used to assess 
competencies and difficulties across a range 
of social and emotional developmental 
domains 
 
 
 
 
X 
X 
Community Life Skills Scale 
(CLS) 
-measures ability to negotiate for self and 
family in the community 
X 
 
 
 
 
X 
Client Satisfaction Questionnaire 
(CSQ) 
-measures satisfaction with psychological 
treatment 
 
X 
X 
X 
X 
X 
Emotion Regulation 
Questionnaire (ERQ) 
-measures emotion regulation 
X 
X 
X 
X 
X 
X 
 
 
Protocol Guidelines for Assessments: 
Assessments must be completed no more than 10 days prior to the assessment due 
date and within 4 weeks after the assessment due date. If infants are not able to 
participate in the observational assessments (due to fussiness, sleeping, or other 
reasons), they should be rescheduled within 2 weeks.   
 
Participants may drop out of therapy by still participate in assessments. 

 
Procedures for Maintaining Confidentiality 
There is a potential risk of breach of confidentiality that is inherent in all research 
protocols. Procedures have been established, and will be followed to minimize the risk 
of breach of confidentiality. Data will be entered into password-secured databases by 
staff authorized by the PI to do this, and they will abide by the confidentiality regulations 
of the IRB. Participant anonymity will be preserved by the use of a code number (not 
related to name, social security number, or date of birth) on all questionnaires and 
reports. A list of participant names will be kept in a separate locked cabinet will access 
only to study personnel authorized by the PI. No participant names will be identified by 
name in any published reports.  
 
Assessment of Risks and Benefits 
Risk to Participants: The anticipated risks to participants are few, as IPT-Dyad is an 
adaptation of an empirically supported treatment for depression. Some participants may 
experience emotional discomfort when discussing interpersonal problems or emotionally 
laden material. Some emotional discomfort may be associated with the clinical 
assessments conducted in the study. All clinical assessors will make every effort to 
conduct interviews and administer questionnaires in a sensitive and supportive manner. 
Participants may be stressed or uncomfortable about being separated from their infants 
during the MRI scan. There is slight risk for breach of confidentiality. There are no 
known adverse effects of psychotherapy to the fetus. Risks to infants may include 
frustration, boredom, or fatigue. Infants might experience transient discomfort or 
distress during the infant observational paradigm, but nothing more than is experienced 
routinely on a daily basis. The MRI scan may cause the infant to experience discomfort 
from the pillow restraint device if he/she awakes during the MRI. There may be 
abnormalities detected on the MRI. If this is the case, the participant and pediatrician 
will be notified. The overall benefit to the infant is thought to clearly outweigh the risk. 
 
Possible Benefits: Participants who receive IPT-Dyad may benefit in terms of reduced 
depression. Participants will be informed that there are no guarantees that they will 
benefit from IPT-Dyad. Participants will receive a comprehensive mental health 
assessment at no charge, which they otherwise may not receive at all. Receiving a 
psychosocial intervention administered by a highly trained and supervised Master’s 
level or higher clinician at no cost may be beneficial. Participants may benefit by 
learning new communication skills, improve social support, and effectively manage 
interpersonal problems, which may result in a decrease in depressive symptoms and 
increase day to day functioning. Results from this study may inform long-term treatment 
strategies for perinatal depression. These benefits, both to the participants and to 
others, outweigh the minor risks to study participants.  
 
Alternative Procedures/Therapies: Participants may choose to receive treatment from 
their ObGyn, primary care doctor, or other mental health care provider.  
 
Revised Data Monitoring Plan (11/2014) 
I. Study Overview 
 

A. Brief Description of the Purpose of the Study: In this clinical trial we test the 
feasibility and acceptability of Interpersonal Psychotherapy for the Mother-Infant Dyad 
(IPT-Dyad), a new intervention for perinatal depression. This intervention proposes a 
novel integration of ante- and postnatal depression treatment based on an evidence-
based treatment for depression (IPT) and infant emotional developmental theory to 
address both maternal depressive symptoms and infant emotion development. 
B. Adherence Statement: The Data Safety Monitoring Plan (DSMP) outlined below will 
adhere to the protocol approved by the NIMH and the Washington University IRB. 
C. General description of monitoring plan: This is a single-site study.  Dr. Lenze will be 
the primary monitoring entity.  She will have primary responsibility for the monitoring of 
participants during the entire time they participate in the study, both with respect to their 
safety (including confidentiality) and the integrity of their research data. 
 
The study PI will maximize the safety and privacy of all study participants and ensure 
the integrity, validity, and confidentiality of data collection procedures through regular 
monitoring of clinical and research activities during weekly (and additional as needed) 
project meetings with the study staff.  Areas of particular concern will be 1) the number 
of subjects in each phase of the protocol and the number who have completed the 
protocol; 2) the amount of data lost, including subject withdrawal, reason for loss, and 
steps taken to avoid loss in the future; 3) presence of any adverse consequences 
(whether minor or severe) to any subject, together with the short- and long-term 
remedies to the problem; and 4) the presence of any new information, especially from 
this study or from other sources, regarding the expected efficacy and safety of any 
therapy or procedure used in this study. The agenda for protocol meetings will include 
tracking of subject recruitment, enrollment, and retention, including assessment of 
diversity; data collection and entry; accuracy and/or issues with the implementation of 
the intervention; documentation and review of any subject symptoms, concerns, or 
adverse effects. The PI and her mentor will use this information to monitor whether the 
research progress is satisfactory, whether the participant’s risk/benefit ratio has 
changed (in which the IRB will be informed), and whether any changes need to be 
made to any protocol procedures. The PI will also ensure that data archives and quality 
control procedures are in place and working well. The PI will report any serious and 
unexpected adverse events, unexpected problems that involve risks to the participants 
or others, and any breeches of confidentiality to the IRB. An adverse event (AE) will be 
defined as any undesirable experience of a nature likely to require medical attention that 
occurs after informed consent for the study has been obtained, without regard to 
treatment group assignment. A serious adverse event (SAE) will be defined as any 
event that precipitates or prolongs hospitalization, is potentially life threatening, or 
results in chronic disability or significant chronic discomfort. If an AE or SAE occurs, the 
treating clinician will immediately take appropriate clinical action and contact the PI, who 
will immediately consult with her mentors. Adverse events will be reported to the local 
IRB as soon as possible per IRB policy. SAE’s will be reported to mentors, local IRB, 
and NIMH project officer within 24 hours. More detailed information regarding this 
process is outlined below. 
 
II. Confidentiality  
 
A.  Protection of Participant Confidentiality  

The PI and her staff will provide adequate safeguards for the protection of confidentiality of all 
research records. Procedures designed to maintain confidentially include: (1) training for all 
research staff emphasizing the importance of confidentiality; (2) specific procedures developed 
to protect participants’ confidentiality, and (3) formal mechanisms limiting access to information 
that can link data to individual participants. Data forms that include identifying information will be 
kept in locked cabinets. Only the unique ID number, assigned by the research coordinator at the 
time of initial contact will represent participants during data entry, data transfer, data analysis, or 
other file management procedures. To facilitate tracking, a password-protected computer file will 
be maintained containing the identity of participants, their ID numbers, and information about how 
they can be reached. This file, however, will contain no clinical data. Only members of the 
investigative group will have access to secured files or to master lists for participant code numbers 
and will be well informed regarding the protection of patients’ rights to confidentiality. Identities of 
participants will not be revealed in the publication or presentation of any results from this project. 
 
Videotaping permission and confidentiality: participants will be videotaped for the purposes of 
observing the therapists and providing training material.  Participants will sign a consent which 
indicates the use of the videotaping, who may have access to the videotaping, and the length of 
time that the videotape will be kept by investigators.  Videotapes will be kept with the same 
confidentiality procedures as other research data. 
 
B. Database Protection  
All participant research data is stored separate from participant contact information, which is 
stored on our secure servers with network and database level passwords, only accessible to 
research staff who need contact with the participants.  
 
C. Confidentiality During Adverse Event (AE) Reporting  
AE reports and annual summaries will not include participant- or group-identifiable material. 
Each report will only include the identification code. 
 
III. Adverse Event Information 
 
A.  Definition 
 
An adverse event (AE) is any untoward medical occurrence in a participant temporally 
associated with participation in the clinical study or with use of the experimental agent being 
studied. An adverse finding can include a sign, symptom, abnormal assessment (laboratory 
test value, vital signs, electrocardiogram finding, etc.), or any combination of these. 
 
A Serious Adverse Event (SAE) is any adverse event that results in one or more of the 
following outcomes: 
 
• Death 
• A life-threatening event 
• Inpatient hospitalization or prolongation of existing hospitalization  
• A persistent or significant disability/incapacity 
• A congenital anomaly or birth defect 
• Important medical event based upon appropriate medical judgment 
 
 
B. Classification of AE Severity  

 
AEs will be labeled according to severity, which is based on their impact on the patient. An 
AE will be termed “mild” if it does not have a major impact on the patient, “moderate” if it 
causes the patient some minor inconvenience, and “severe” if it causes a substantial 
disruption to the patient’s well being.  
 
C. AE Attribution Scale  
 
AEs will be categorized according to the likelihood that they are related to the study 
intervention or other study procedures. Specifically, they will be labeled definitely unrelated, 
definitely related, probably related, or possibly related to the study intervention or 
procedures.   
 
D. Expected Risks  
Study assessments: The assessments to be conducted as part of this study are non-
invasive and carry with them no more than minimal risk. The most significant risks to the 
participants related to assessments are those that would follow a breach of confidentiality 
and the disclosure of clinical information or video recordings.  
IPT-Dyad Psychotherapy: Participants assigned to IPT-Dyad may feel uncomfortable 
disclosing private and/or emotional experiences. This risk is minimized by using well-trained 
and supervised staff.  
Enhanced Treatment as Usual (ETAU): Participants assigned to ETAU may also feel 
uncomfortable disclosing private and/or emotional experiences. This risk is minimized by 
using well-trained and supervised staff.   
 
Because this study involves participants with depression, there is a risk of suicidal behavior. 
However, these are risks associated with the illness not the study.   
Risks in relation to benefits: No participants will be denied interventions; participants receive 
either standard of care in the community or the IPT-Dyad intervention.  No risks other than 
possible emotional distress exist from the study assessments.  Thus, the risks involved in 
participating in this study are deemed low, which justifies the data and safety monitoring 
plan described here. 
Protections for mother (both pre- and postnatal) 
Potential risks: 
Potential risks to the mother during her participation in the study include worsening of 
depressive symptoms, decrease in self or prenatal care due to worsening of symptoms, suicidal 
ideation or behaviors, homicidal ideation or behaviors, and the development of manic or 
psychotic symptoms.  
 
Protections in place to manage risks: 
1) Research clinicians will be clinically experienced and will receive additional training in 
delivering IPT-Dyad and the research assessments. Clinicians will be closely supervised 
by Drs. Lenze and Luby. Participants in the study will be provided with 24-hour access to 
Dr. Lenze or a back-up on-call clinician. 
2) Depressive symptoms are monitored at every contact via the Edinburgh Depression 
Scale and/or the Patient Health Questionnaire -9 item scales. Per protocol, emergency 
sessions may be added to a max of 2 sessions/week. Referral for additional treatment or 
withdrawal from the study will be considered for any patient needing >2 consecutive 
emergency sessions. Patients not achieving at least partial response as evidenced by at 
least 2 point decrease from baseline in PHQ-9 score by session #4 or response as 

evidenced by a 5 point decrease from baseline in PHQ-9 score by session #8 will 
discuss with the therapist the possible need for psychiatric consultation or referral for 
alternative treatment.  Alternative treatment should be considered for any patient whose 
PHQ-9 scores do not decrease below 15  or increase 3 consecutive weeks. Patients 
necessitating in-patient psychiatric hospitalization may be withdrawn from the study at 
the PI’s discretion. This will be reviewed on a case by case basis by Drs. Lenze and 
Luby. If Drs. Lenze or Luby have any concerns about the appropriateness of 
continuation, Dr. Lenze will arrange for the patient to have an independent consultation 
from a psychiatrist not associated with the study.  
3) All research clinicians will be trained to assess suicidality and homicidality, including 
thoughts about harming the fetus or baby, and to take appropriate steps. Suicide risk will 
be probed at each assessment via several mechanisms, including the Edinburgh 
Depression Scale or the Patient Health Questionnaire (9-item), and clinical interview. For 
those who endorse suicidal ideation, severity of suicidal ideation will be assessed using 
the Scale for Suicidal Ideation, which assesses the extent of suicide risk (i.e. wish to live 
vs. die, plans, intent). If a patient endorses suicidal ideation, intent, or plan, the clinician 
will follow an operationalized protocol developed to manage high-risk depressed 
participants in clinical research (Pearson et al., 2001). This plan, and its implications with 
respect to the need to balance safety with confidentiality and autonomy, will be 
explained to the participant at the time of consent. Suicidal or homicidal attempts or 
hospitalizations are considered serious adverse events and are reported to the IRB and 
to NIMH program staff as per their guidelines.  
4) Other mental health crises (e.g., onset of psychosis, mania or other behavioral 
disturbance, infanticidal ideation) will be managed similarly. The decision to withdraw any 
patient from the trial will be made on a case by case basis with regard to safety for 
outpatient management and appropriateness of IPT-Dyad as an intervention (i.e. IPT-
Dyad is not appropriate for patients with mania or psychosis).  
 
Protections for Fetus 
Potential Risks: 
There are no known risks to the fetus from maternal participation in psychotherapy. 
 
Protections for Infant 
Potential Risks: 
Infants engaged in mother-infant psychotherapy may become bored, fussy, or overstimulated. 
 
 
Protection against risks: 
 
1) Research staff and clinicians will be trained and closely supervised by Drs. Lenze and 
Luby to monitor the infant’s response to study interventions. The infant’s mother will 
always be allowed to comfort her baby or otherwise attend to the baby’s needs. In cases 
where the infant clearly is too distressed to continue, study sessions will be rescheduled. 
 
Participants will be reviewed at baseline with Dr. Lenze; exclusion criteria (e.g., psychosis, 
unstable medical conditions, suicidal ideation that precludes outpatient treatment) will reduce the 

risk to participants. Dr. Macones, a Maternal-Fetal Medicine specialist, will provide advice 
regarding medical stability for this study. Depressive symptoms are monitored throughout the 
study using the Patient Health Questionnaire-9 item.  
  
 
E. AE Reporting and Follow-Up  
Study staff will systematically collect AEs and summarize them in a running table throughout 
the study, including date of onset/offset, type of AE, severity, and interventions if any. Per 
Washington University IRB policy, reportable AEs are those that are possibly, probably, or 
definitely related to the study intervention or procedures. 
 
F. SAE Reporting 
SAEs that are unanticipated, serious, and possibly related to the study intervention will be 
reported to the IRB, and NIMH in accordance with requirements.   
 
• 
Unexpected fatal or life-threatening SAEs related to the intervention will be reported to 
the NIMH Program Officer within 24 hours. Other serious and unexpected AEs related to 
the intervention will be reported to the NIMH Program Official within 15 days. 
 
 
V. Data Quality and Safety Review Plan and Monitoring 
 
 
 
A. Data Quality and Management 
 
 
Research staff and participants will provide data through paper forms.  Tracking forms will 
document that procedures were followed and completed at each visit.  A closed and password-
protected data-entry system will track data in real time as they are entered.  This will allow 
continuous checks on data completion and integrity (e.g., errors).  Range checks, review 
screens, and error trapping routines will be built into the system as quality control procedures to 
minimize the chance of data entry errors.  Hard copy data summaries of all active and recent 
participants will be provided to the PI who will review them for any apparent errors, missing 
data, or discrepancies.  The frequency of this formal review of the integrity of the accumulating 
study data will be approximately weekly. This information will be reviewed with Dr. Luby 
monthly, or more frequently if errors are detected.      
 
 
B. Participant Accrual and Compliance 
 
1) Measurement and Reporting of Participant Accrual, Compliance with Inclusion/Exclusion 
Criteria: Review of the rate of participant accrual and compliance with inclusion/exclusion 
criteria will occur weekly at PI/study staff meetings during the recruitment phases of the 
project, to ensure that a sufficient number of participants are being enrolled and that they 
meet eligibility criteria and the targeted ethnic diversity goals outlined in the grant proposal 
(Targeted/Planned Enrollment Table). Dr. Lenze and all research study staff will be present 
at these meetings. This information will be reviewed with Dr. Luby on a bi-weekly basis 
during the progress and safety meeting.  
 
2) Measurement and Reporting of Participant Adherence to Treatment Protocol  
 

Data on participant adherence to the protocol (i.e., therapy participation, completion of 
research measures) will be collected in real time by study staff, and reviewed (weekly if 
nonadherence is detected, so that study staff can intervene) by the PI.  
 
 
 
C. Safety Review Plan  
 
Study progress and safety will be reviewed at weekly meetings with Drs. Lenze and 
Luby and all study staff (and more frequently if needed). Progress reports will be 
provided to the NIMH on a yearly basis. The IRB will review progress of this study on an 
annual basis.  
 
 
VI. Informed Consent 
 
Written informed consent will be obtained from each participant at entry into the study. 
Informed consent is obtained by the following process: 
 
1. The participant will be asked to review the study consent form. 
2. Study staff will confirm the participant’s understanding of the study using a formal scale 
to assess understanding of consent, and to answer any questions the participant might 
have. 
3. Once the participant demonstrates understanding of the study and agrees to participate 
in the study, the consent will be signed in the presence of study staff. 
 
 
VII. Reporting Changes in Study Status 
 
During the funding of this study, any action by an IRB or one of the study investigators that 
results in a temporary or permanent suspension of the study will be reported to the NIMH 
Program Official within 1 business day of notification.