Acceptability and efficacy of a smartphone application intervention for mental health care based on interpersonal psychotherapy for improving depression symptoms in prenatal women: Protocol for a randomized controlled trial

Abstract

Background

Perinatal depression is a predominant and serious condition that adversely affects prenatal and postpartum women and their children. Prenatal depression is a notable predictor of postpartum depression, highlighting the need for mental health care during pregnancy. Therefore, we developed an innovative smartphone application based on interpersonal psychotherapy (IPT) to improve depressive symptoms in women in the perinatal period (i.e., from pregnancy through the first year postpartum). Here, we present a randomized controlled trial (RCT) protocol to investigate the potential of this intervention for prenatal women.

Methods

This study is an 8-week, open-label, parallel-group, stratified block RCT. In total, 350 primiparous women were randomly assigned to the intervention group—combining the smartphone application for mental health care based on IPT and care as usual—and the control group, with only care as usual. The women assigned to the intervention were encouraged to use the application for approximately 5–10 min daily. The primary outcomes included the proportion of participants with moderate-to-high satisfaction (scoring ≥17 on the 8-item Client Satisfaction Questionnaire) and changes in depressive symptoms measured by the Patient Health Questionnaire-9 from baseline to the end of the 8-week intervention.

Discussion

To our knowledge, this RCT is the first to investigate the acceptability and efficacy of an IPT-based smartphone application for reducing depressive symptoms in prenatal women. If successful, the findings will contribute to the growing evidence supporting digital mental health interventions during pregnancy, offering a scalable and accessible solution for prenatal mental health care.

Highlights

• •This protocol describes a novel study tackling perinatal mental health care with digital health solutions.
• •This study investigates the acceptability and efficacy of a smartphone application grounded in interpersonal psychotherapy.
• •The findings potentially contribute valuable evidence for developing digital mental health tools.

1. Introduction

According to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, Text Revision (DSM-5-TR), perinatal depression is defined as depression that develops during pregnancy and within the first 4 weeks postpartum, but considerably includes depression occurring during pregnancy and up to 12 months postpartum. A meta-analysis estimated that the period prevalence of depression is 18.4 % during pregnancy and 19.2 % ≤3 months postpartum in high-income countries (Howard et al., 2014), with even higher rates reported in low- and middle-income countries (Fisher et al., 2012). Prenatal depression is a strong predictor of postpartum depression (Robertson et al., 2004), which increases the risk of preterm delivery and low birth weight (Howard and Khalifeh, 2020) (Jarde et al., 2016). Postpartum depression affects mothers' psychological health and quality of life, impairs child development (Slomian et al., 2019), and is associated with child maltreatment (Chaffin et al., 1996). Additionally, depression during the antenatal and postpartum periods can contribute to paternal depression (Underwood et al., 2017). Moreover, perinatal suicide has become a critical concern, with depression and depressive symptoms being strongly associated with such incidents during pregnancy and postpartum (Zivin et al., 2024). Given the high prevalence and risks of perinatal depression, mental health care during this period is crucial.

The US Preventive Services Task Force (US Preventive Services Task Force et al., 2019) (O'Connor et al., 2019) and several European clinical practice guidelines (Motrico et al., 2022) recommend psychological preventive interventions for perinatal women who are at high risk for depression, with interpersonal psychotherapy (IPT) (Sockol, 2018) and cognitive behavior therapy (CBT) (Sockol, 2015) effectively preventing perinatal depression. However, perinatal women often face barriers while accessing face-to-face mental health, such as time constraints, stigma, and logistical challenges related to childcare (O'Mahen and Flynn, 2008) (Goodman, 2009) (Kim et al., 2010). Mobile health (mHealth) application presents a promising solution, offering accessible, anonymous, and cost-effective mental health support (Fairburn and Patel, 2017).

However, evidence on the efficacy of mHealth applications in reducing depressive symptoms in pregnant and postpartum women remains inconclusive. Some systematic reviews and meta-analyses suggest that mHealth applications improve Edinburgh Postnatal Depression Scale (EPDS) (Cox et al., 1987) scores in the intervention group compared with the control group (Miura et al., 2023). However, other studies have reported no considerable reduction in maternal depression symptoms (Tsai et al., 2022). Perinatal women experience unique psychosocial changes, including adapting to the parental role and managing conflicts with partners or close relationships. IPT is particularly suited for addressing these challenges, as it incorporates strategies that help perinatal women adapt to psychosocial changes and navigate interpersonal conflicts (Weissman et al., 2017; Spinelli, 2017). Indeed, the efficacy of IPT-based preventive intervention for pregnant women at high risk for postpartum depression and brief IPT intervention for depression in pregnancy have been demonstrated (Zlotnick et al., 2016; Hankin et al., 2023). However, while the limited number of internet-delivered IPT interventions for depression have been evaluated, even fewer have been specifically examined among perinatal women with depressive symptoms. A previous study demonstrated the feasibility and acceptability of web-based applications delivering Internet-based IPT modules with guided support for prenatal mental health (Bright et al., 2022). However, participants overwhelmingly preferred receiving the IPT modules through a smartphone application rather than the Internet. This preference underscores the need to develop a smartphone-based mental health care application for perinatal women (Bright et al., 2022). In addition, a smartphone application incorporating CBT and IPT-based psychotherapies was acceptable among postpartum women (Suharwardy et al., 2023). However, there is limited research on smartphone-based IPT interventions pertaining to pregnant women. Given the accessibility and convenience of mHealth applications, we identified a critical need for an IPT-based smartphone application to provide mental health care during pregnancy.

To acknowledge this gap, we developed an IPT-based application designed for women in the perinatal period (i.e., from pregnancy through the first year postpartum). Subsequently, we designed a randomized controlled trial (RCT) to examine the acceptability and efficacy of this application in supporting mental health during pregnancy.

2. Methods

2.1. Trial design and study setting

This study is a two-arm, parallel-group, open-label, randomized trial to confirm the acceptability and efficacy of a smartphone application. Participants were randomly assigned to an intervention group combining 8 weeks of using the application and routine health checkups that participants undergo voluntarily as their usual care, or a control group with routine health checkups alone at a ratio of 1:1. The protocol is Version 2.0, last revised on October 18, 2024. The study targets first-time pregnant women (primiparous) aged 18–39 years in Japan. Evidently, primiparous women in Japan have a higher prevalence of postpartum depression than multiparous women (Tokumitsu et al., 2020). Therefore, this study specifically focuses on primiparous women who are at high risk of postpartum depression. The trial follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline (Chan et al., 2013) and has been approved by the Asai Dermatology Institutional Review Board. The study was registered in the Japanese clinical trials registry (UMIN000056014). The SPIRIT checklist is provided in Appendix B. As of May 2025, recruitment and intervention have been completed, and statistical analyses will be conducted in the next phase of the study.

2.2. Eligibility criteria

Participants were recruited per the following inclusion criteria: primiparous women, age 18–39 years, pregnant women between 16 weeks 0 days and 28 weeks 6 days of gestation, have a partner or spouse, possess basic reading and writing skills in Japanese, and provide informed consent to participate. The inclusion procedure was conducted by e-mail.

The exclusion criteria are as follows: currently receiving treatment at a psychiatric or psychosomatic clinic (regardless of medical history); a score of ≥2 on item 9 (suicidal ideation) of the Patient Health Questionnaire-9 (PHQ-9) (Kroenke et al., 2001) (Muramatsu et al., 2018), indicating suicidal ideation; lack of a partner or spouse, or pregnancy with someone other than the partner or spouse; and deemed inappropriate for participation because of concomitant medications or medical findings.

2.3. Interventions

2.3.1. Smartphone application

The mental health care application features a character that is always visible on the home screen, providing explanations and recommendations for different features as well as navigation support (Fig. 1). Participants were encouraged to use the application for approximately 5–10 min every day during the 8-week intervention period, as recommended in the informed consent document. In practice, if participants had not logged into the application for more than one week since their last login, the research secretariat sent reminder emails and followed up with phone calls. The character served specific functions and motivated participants to incorporate the gained insights into their daily lives. Moreover, the participants were encouraged to complete all eight lessons in the self-care program described below within the 8-week period. The first author (YT), a certified trainer and supervisor authorised by the International Society of Interpersonal Psychotherapy, supervised the design and functions of the application which was developed in collaboration with Shionogi & Co., Ltd. (Shionogi). The smartphone-based mental health care application comprises the six components, which are detailed in Appendix A.

Fig. 1.

The home screen of the mental health care application where the character says, “We have a variety of features and a program to help you care for your mental health! We hope this application is useful for you∼(*^^*)”.

2.3.2. Care as usual: Routine prenatal and postpartum health checkups

Participants in both groups received care as usual on a voluntary basis, comprising routine prenatal and postpartum health checkups conducted by an obstetrician or midwife. The care was provided at the health care provider of the participant's choice. In Japan, approximately 14 periodic antenatal checkups are recommended. These checkups are scheduled as follows: (i) early pregnancy to 23 weeks: once every 4 weeks; (ii) 24–35 weeks: once every 2 weeks; and (iii) 36 weeks to childbirth: once a week. During these checkups, various measurements are conducted to assess material and fatal health, and fetal development. At prenatal checkups, pregnant women also receive advice on nutritional intake and lifestyle adjustments during pregnancy.

Postpartum care includes infant health checkups conducted at 1 month after childbirth and postpartum health checkups for the mothers at 2 weeks and 1 month after childbirth. There are no restrictions on concomitant interventions other than the application during the study period. If participants receive drugs, psychotherapy, or other interventions from their physicians, we ask the participants to respond using a survey form.

2.4. Criteria for discontinuing interventions

The interventions were discontinued for all participants or individual participants if any of the following criteria are met:

1. The participant is to withdraw consent.

2. The clinical trial has been completely discontinued.

3. The participant is considered ineligible after registration.

4. A serious violation or noncompliance with the study protocol is identified. Such cases are assessed on an individual basis by the study team, including those retrospectively identified as violating the eligibility criteria.

5. Member(s) of the research team (psychiatrists, obstetricians, or psychologists) decide that the participant should discontinue the study, including the intervention or related measurements.

The date and reason for discontinuation were carefully documented. Participants who discontinued the intervention were encouraged to the furthest extent possible to complete assessments related to the primary and follow-up endpoints to evaluate the safety and efficacy of the intervention.

If participants withdraw consent, they are considered to have dropped out of the study. The availability of data collected up to the point of withdrawal depends on the participant's choice. During an adverse event (AE), details such as the nature, duration, severity, outcome, and relevance to study participation are assessed and documented. As this study is non-invasive, reporting of AEs to the Asai Dermatology Institutional Review Board is not required. However, a summary of all serious adverse events will be reported to the Ethics Committee annually.

2.5. Outcomes

The primary outcomes of this study are the acceptability and efficacy of the application.

2.5.1. Acceptability

A primary measure for evaluating acceptability is the proportion of participants in the intervention group reporting moderate-to-high satisfaction based on the 8-item Client Satisfaction Questionnaire Japanese version (CSQ-8 J) (Larsen et al., 1979; Nguyen et al., 1983; Tachimori and Ito, 1999) Each item on the CSQ-8 J is evaluated on a four-point scale, with total scores of 8–32. Higher scores indicate greater overall satisfaction with the service. Herein, a CSQ-8 J score of ≥17 indicates moderate-to-high satisfaction.

2.5.2. Efficacy

The other primary efficacy outcome is the change in the PHQ-9 score from baseline to the end of the 8-week intervention.

2.5.3. Secondary outcome

The secondary outcome is the change in the EPDS scores from baseline to 4 weeks after the expected date of childbirth.

2.6. Recruitment timeline

Participants were recruited across Japan using online advertisements and research postcards that included a link to the online webpage. This webpage described the study in detail and had a prescreening Google Forms, inclusive of the study eligibility and exclusion criteria. Respondents meeting the inclusion criteria and not meeting any exclusion criterion received an email invitation to proceed with the electronic consent process. Participants who provided electronic consent underwent baseline assessments and were randomly assigned to either the intervention or control group. The trial period is illustrated in the CONSORT diagram (Fig. 2) (Moher et al., 2010) and the assessment schedule (Table 1). The recruitment and registration of participants began on November 18, 2024 and ended on December 6, 2024.

Fig. 2.

CONSORT diagram of the study design.

Table 1.

Assessment schedule.

STUDY PERIOD
	Enrollment	Baseline	Allocation	Intervention					Postpartum follow-up
Time point			0	Week 0	Week 2	Week 4	Week 6	Week 8	4 weeks after the expected date of childbirth
ENROLLMENT
Eligibility screen	X
Identification		X
Informed consent		X
Allocation			X
INTERVENTION
Intervention group				X	X	X	X	X
Control group
ASSESMENTS
Demographics	X	X		X				X	X
CSQ-8 J								X	X
PHQ-9	X				X	X	X	X	X
EPDS		X						X	X
Adverse events				X	X	X	X	X	X

CSQ-8 J, the 8-item Client Satisfaction Questionnaire Japanese version; PHQ-9, Patient Health Questionnaire-9; EPDS, the Edinburgh Postnatal Depression Scale.

The CSQ-8 J was administered only to participants in the intervention group.

2.7. Sample size estimation

The sample size was estimated based on analyses of the CSQ-8 J scores (acceptability) and PHQ-9 scores (efficacy).

2.7.1. Sample size for acceptability assessment

The required sample size for the intervention group was calculated using a one-sided hypothesis test for population proportion. Key parameters included the following: null hypothesis: 0.5; alternative hypothesis: 0.65; alpha level: 0.025; power: 80 %; and attrition rate: 21.1 %. Considerably, the required sample size for the intervention group was 108 and 216 participants for the both groups.

2.7.2. Sample size for efficacy

The sample size required for the intervention and control groups, as measured by the PHQ-9, was calculated using a t-test. This estimation assumes a mean change difference of −1.19 and a standard deviation of 3.40 immediately following the 8-week application intervention, with an allocation ratio of 1:1 for the intervention and control groups. These values were derived from a previous RCT investigating a mental health application intervention among postpartum women using the PHQ-9 (Suharwardy et al., 2023). Considering these assumptions, a two-sided, an alpha level of 0.05, a power of 80 %, and an attrition rate of 21.1 % were used to determine the target sample size. This calculation yielded 165 participants per group, resulting in 330 participants required for the trial. The attrition rate was estimated based on data from a 2-week pilot test conducted in March 2023, which involved pregnant and postpartum women using a prototype of the application. This pilot reported an attrition rate of 5.275 %. As a result, it was assumed that 5.275 % of enrolled participants would drop out every two weeks, resulting in a cumulative dropout rate of 21.1 % by week 8 of the intervention. Accordingly, the final sample size calculation accounted for potential dropout, ensuring sufficient statistical power to evaluate the efficacy of the intervention.

2.8. Allocation and blinding

All eligible participants were randomized in a 1:1 ratio into the intervention and control groups after completing baseline assessments. Allocation was stratified by the baseline PHQ-9 score (≤4 vs. ≥5), with stratified block randomization employed to maintain balance between the groups. Random numbers generated using Excel software determined the allocation sequence. Owing to the explicit nature of the intervention, neither participants nor study personnel were blinded to group assignments. Participants in the intervention group received access to the application, while primary and follow-up outcome assessments were self-reported by all participants, precluding blinding of assessments. Additionally, the statisticians at Emeraid Inc. were not blinded to the allocation, as they are responsible for analyzing the data.

2.9. Data collection

Data collection is conducted using Google Forms and the application.

2.9.1. Baseline characteristics

Baseline data were collected per the schedule provided in Table 1. This study was conducted to gather demographic and clinical information, including age, education, occupation; expected date of childbirth; method of pregnancy (e.g., natural conception or assisted reproductive techniques); presence or absence of multiple pregnancies; history of miscarriages or stillbirths; history of psychiatric visits; current medications; and psychological care being administered.

2.9.2. Primary outcome measures

2.9.2.1. 8-item client satisfaction questionnaire Japanese version

The CSQ is widely used to assess patient satisfaction in psychiatric settings (Miglietta et al., 2018; Woodward et al., 2017). Among the several versions available (ranging from 3 to 18 items), the 8-item CSQ-8 is a predominantly used self-reporting tool. Each question is rated on a four-point scale, with total scores ranging between 8 and 32—higher the scores, greater the satisfaction with the service (Larsen et al., 1979; Nguyen et al., 1983). The CSQ-8 J has been previously confirmed as reliable and valid (Tachimori and Ito, 1999). The CSQ-8 J was administered only to participants in the intervention group. Before completing the CSQ-8 J, participants were presented with the following explanatory statement: “We ask you about your satisfaction with the use of the application.”

2.9.2.2. Patient health Questionnaire-9

The PHQ-9 is a frequently used nine-item self-report instrument designed to assess and evaluate the severity of depression in clinical and research contexts (Kroenke et al., 2001). Each item is rated on a scale of 0–3, giving a total score of 0–27. A score of ≥10 typically indicates moderate-to-severe depression (Kroenke et al., 2001). The reliability and validity of the Japanese version of PHQ-9 have been previously established (Muramatsu et al., 2018).

2.9.3. Secondary outcome measure

2.9.3.1. Edinburgh postnatal depression scale

The EPDS is the most frequently used 10-item self-report instrument for screening perinatal depression. It is specifically designed to exclude physical symptoms that may otherwise lead to false-positive results during pregnancy or postpartum and instead focuses on the cognitive symptoms of depression (Cox et al., 1987). Each item is rated on a four-point scale, with a total score of 0–30. Higher scores indicate more severe depressive symptoms. The Japanese version of the EPDS has previously been confirmed as valid and reliable (Okano, 1996). Herein, a score of ≥9 considerably indicates postpartum depression.

2.9.4. Adverse events

Safety is evaluated based on the number and proportion of participants who experience any AE during the trial period. Adverse events include death and illnesses that are life-threatening illnesses, require prolonged hospitalization, result in permanent disability, and lead to birth defects in offspring, regardless of their causal relationship with the intervention. All AEs are recorded. Events determined by psychiatrists or obstetricians in the research team to be causally related to the application are classified as side effects.

2.10. Plan to promote participant retention and complete follow-up

Outcome measures are collected even if the participants do not complete the assigned intervention, unless they wish to withdraw from the study. If participants cannot respond, research personnel—blinded to the allocation—attempt to contact them via email or phone to elicit responses. Participants receive compensation for the time, psychological effort, and the financial burden of communication costs required to use the application and complete assessments. Compensation is provided as follows: ¥1000 for assessment at weeks 0, 2, 4, and 6; ¥3000 for the 8-week assessment; and ¥5000 for the postnatal assessment (conducted 4 weeks after the expected date of childbirth). Participants who complete all assessments receive a total compensation of ¥12,000.

2.11. Data management, confidentiality, and access to data

All recruitment and assessment data collected via Google Forms, randomization data, and intervention delivery data are stored on a secure server with restricted access, managed by the contracted research organization, Integrity Healthcare Inc. (Integrity Healthcare). Access is also granted to DCT Japan Inc. (DCT Japan), a subsidiary of Integrity Healthcare. Integrity Healthcare and DCT Japan are certified by the Information Security Management System, an international standard for information security. Data is managed under the supervision of information security managers following certified internal regulations. Data that exclude information identifying specific individuals is provided to statisticians at Emeraid by the research secretariat at Integrity Healthcare and DCT Japan using the server. The data is transferred to Shionogi via Integrity Healthcare using a secure file-sharing platform called “box.” This platform enables file sharing and transfer with access right settings. Once transferred, all analysis data is managed and stored in the “box” system under Shionogi's administration. Data collected via the application are stored on a restricted-access server managed by SELF Co. Ltd. (SELF). Deidentified data from SELF is also transferred to Shionogi through the “box” platform for further management and storage. All other data, including signed consent forms, is securely stored on a dedicated restricted-access server managed by the research secretariat at Integrity Healthcare and DCT Japan. Data is retained for 5 years after the trial has concluded. To project confidentially, the research secretariat assigns each participant a unique identification number using a pseudonym. Access to the complete dataset before publication is restricted to the research secretariat.

2.12. Statistical methods

2.12.1. Primary analyses

Using the intention-to-treat principle, all assigned participants' data will be included in the analysis. However, participants who are identified as violating the eligibility criteria after randomization or who provide no questionnaire responses after randomization will be excluded. This population constitutes the Full Analysis Set (FAS). Notably, the questionnaires delivered at each designated week are part of a single, continuous set, and participants either respond to all of them or to none at all. By default, only observed data will be used in the analyses, and missing values will not be imputed. As an exception, missing values will be imputed only for the sensitivity analysis of the primary endpoint (acceptability). Additionally, participants will be excluded from the analysis of any endpoint for which they lack the minimum required data.

2.12.1.1. Acceptability

For the acceptability analysis, only participants in the FAS who were assigned to the intervention group and provided a CSQ-8 J response at the end of the 8-week intervention will be included. The number and proportion of participants in the intervention group reporting moderate-to-high satisfaction on the CSQ-8 J (score ≥ 17) at the end of the 8-week intervention will be calculated. A statistical hypothesis test will be conducted at a 2.5 % significance level (right one-sided test) to evaluate the null hypothesis that the proportion equals 0.5. The p-value and 95 % confidence interval will be calculated using a normal approximation. In addition, summary statistics for the CSQ-8 J score at the end of the 8-week intervention will be calculated. As part of a sensitivity analysis to consider the impact of missing data on the primary analysis, missing values will be uniformly imputed using the following assumptions, and the same analysis will be conducted, excluding the summary statistics calculation:

1. Participants with missing CSQ-8 J data will have a score of ≥17.

2. Participants with missing CSQ-8 J data will have a score of <17.

No.1 assumes a more unconservative situation (the percentage of people with medium to high satisfaction is higher than in the primary analysis), while No.2 assumes a more conservative situation (the percentage of people with medium to high satisfaction is lower than in the primary analysis). In particular, if the analysis in No.2, which is a conservative situation, is statistically significant like the primary analysis, satisfaction can be considered to have been high regardless of the true value of the missing data.

2.12.1.2. Efficacy

For the efficacy analysis, only participants in the FAS who provided PHQ-9 response data at any of the following time points — the 2nd, 4th, or 6th week of the intervention, or at the end of the 8-week intervention — are included. A mixed-effects repeated-measures (MMRM) analysis will be applied (Mallinckrodt et al., 2001), with the change in PHQ-9 scores from baseline as the response variable. The fixed effects will include the following: group (intervention/control), time point (2nd, 4th, and 6th weeks of intervention and the end of the 8-week intervention), and interaction between group and time point. The PHQ-9 score at baseline will be included as a continuous covariate. When the result of CSQ-8 is significant, a hypothesis test will be conducted at the 0.05 significance level (two-sided test) using the t-statistic calculated by MMRM for the primary endpoint to control the alpha level at 0.05. Additionally, the p-value and 95 % confidence interval will be calculated.

2.12.2. Secondary analysis

The secondary analysis will use the same models used in the primary efficacy analysis. The MMRM analysis will be applied, with the change in EPDS score from baseline as the response variable. The fixed effects will include group (intervention/control), data point (end of the 8-week intervention, 4 weeks after the expected date of childbirth), and the interaction between group and data point. The EPDS score at baseline will be included as a continuous covariate.

2.12.3. Subgroup analysis

Subgroup analyses will be conducted to examine whether the intervention's efficacy in reducing depressive symptoms differs by baseline severity. Participants will be classified into two groups based on their baseline PHQ-9 scores—those with scores ≤4 and those with scores ≥5—according to the factors used for stratified randomization. The outcomes for these subgroup analyses will be changes in PHQ-9 scores from baseline to the end of the 8-week intervention and to 4 weeks after the expected date of childbirth.

2.12.4. Interim analysis

No interim analyses are planned.

2.12.5. Safety analysis

The proportion of participants who experienced any AE during the trial will be calculated for the SAS group. The Clopper–Pearson method will be used to calculate the 95 % confidence interval for this proportion.

2.13. Data monitoring and auditing

The study relies on data collected directly from participants via smartphones without involving healthcare institutions, therefore no data monitoring is conducted to verify the accuracy of the data. The psychological intervention provided by the application is not expected to result in harmful effects or serious outcomes during the trial period. Participants scoring ≥2 points on the suicidal ideation item (item 9) of the PHQ-9 are identified as having a high possibility of depressive symptoms. The application does not include content for grief care in cases of fetal or neonatal deaths. Participants reporting such cases are advised to discontinue and uninstall the application, and are referred to external resources better suited to address these complex clinical situations. Therefore, monitoring of the scores on the suicidal ideation item (item 9) of the PHQ-9 and situations related to fetal or neonatal deaths is conducted to detect early risks.

2.14. Ancillary and posttrial care

After the 8-week intervention, participants continue to have access to the application till the trial concludes. While no unanticipated health hazards are expected during or after the trial, participants are advised that any health issues are covered by the Public Health Insurance system.

2.14.1. Ethics and dissemination

This trial has been approved by the Asai Dermatology Institutional Review Board (approval number: NBP-24-01) and adheres to the principles outlined in The Code of Ethics of the World Medical Association's Declaration of Helsinki. If significant protocol revisions become necessary, the investigators discuss and submit the same to the Asai Dermatology Institutional Review Board for approval. Once approved, these revisions are communicated to all investigators and, if required, to the participants. Potential participants receive detailed information about the risks and benefits of participation. Electronic informed consent is obtained from participants who agree to participate before the intervention.

3. Discussion

This study outlines the study protocol for a RCT designed to investigate the acceptability and efficacy of a smartphone-based, IPT-driven application for mental health care among general primiparous women during pregnancy. This study is primarily designed to evaluate the acceptability and efficacy of the application at the end of the 8-week intervention. The follow-up outcome is intended to evaluate the efficacy of the application 4 weeks after the expected date of childbirth (approximately 1 month postpartum).

3.1. Strengths

First, to our knowledge, this is the first study to evaluate a smartphone-based, completely automated IPT application tailored for mental health care in primiparous women during pregnancy. Second, beyond face-to-face IPT-based intervention, the 8-week IPT application may synergize with other components, such as daily events and emotional expression exercises, IPT-based psychoeducation, and interpersonal circles. Third, the application enables consistent, accessible interventions for perinatal women, irrespective of location or time, provided they have a smartphone. This accessibility makes the application especially beneficial for pregnant women dealing with morning sickness, childbirth preparation, work, and household responsibilities, and for postpartum women managing childcare who may struggle to prioritize mental health care.

3.2. Limitations

The primary and follow-up outcomes relied on self-reported measures, potentially influenced by the participants' perceptions. In addition, the follow-up period is limited to 4 weeks after the expected date of childbirth (approximately 1 month postpartum); this is insufficient because many perinatal women continually experience depressive symptoms beyond 2 months postpartum (Tokumitsu et al., 2020).

4. Conclusion

The findings of this study will provide valuable insights into the acceptability and efficacy of new interventions for pregnant women during the prenatal and postpartum periods. These results potentially have important implications for the design and widespread adoption of interventions that address depression in perinatal women.

Author contributions

All authors contributed to the concept and implementation of this study. YT (Yuko Toshishige), NC, SK, SG, MS, TO, and HM contributed to developing the smartphone application. The study design involved contributions from YT (Yuko Toshishige), NC, SK, SG, YY, YT (Yusaku Takahashi), TO, GS, TAF, and TA. The manuscript was drafted by YT (Yuko Toshishige), NC, SK, and TA, with all authors participating in its review and approval.

Funding sources

This study is supported by Shionogi.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Misaki Shimasaki reports financial support was provided by Shionogi & Co., Ltd. Toshiaki A Furukawa is in the Editorial Board of Internet Interventions. He was excluded from editorial decision-making related to the acceptance and publication of this article. The other authors declare no conflict of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A.

(1) Mental health questionnaire

Participants will complete the EPDS, evaluating their current stress levels based on their EPDS scores. Participants will receive feedback on their stress levels, with tailored advices. This activity allows for an objective assessment of the degree of stress currently felt by the participant and, if a reasonable degree of stress is present, may motivate the participant to address the interpersonal events associated with that stress. If a participant's EPDS score is ≥9, or if they score ≥ 1 on item 10 of the EPDS (which assesses thoughts of self-harm), the application will recommend consulting an external public service for further support. As a rule, recommendations for participants in the intervention group to discontinue the application are not implemented. Therefore, participants whose EPDS scores are ≥9, or who score ≥ 1 on item 10 of the EPDS (which assesses thoughts of self-harm), are not excluded from the study. However, if an adverse event is reported by a study subject, the appropriateness of continuing the study is determined by the psychiatrists on the study team.

(2) Tracking feelings.

This component encourages participants to practice relating daily events with emotions. IPT focuses on the link between interpersonal events and symptoms/emotions. The practice of linking interpersonal daily events with emotions helps participants link life events to stress onset, which is conducted in content (4). In addition, being able to link interpersonal events with stress/emotions is valuable for helping participants cope with interpersonal challenges once the problem area is identified in content (4). It can also facilitate emotional processing simply by helping participants recognize their perceptions and feelings about daily events.

(3) Log.

Linked to components (1) and (2), this feature displays the results of the activities in calendar format. This method allows participants to track their stress levels and emotions over the medium to long term, helping them to observe patterns and trends.

(4) Self-care program.

Delivered through a Chatbot, the IPT-based program focuses on enhancing mental health by improving interpersonal functioning. The first three lessons include psychoeducation on mental health during pregnancy and childbirth, an overview of IPT, and conducting an interpersonal inventory, while the fourth lesson includes linking the life event of pregnancy and childbirth to stress onset. From the fifth lesson, The program offers two courses automatically assigned based on the participants' needs: The first course focuses on adjusting to the psychosocial changes associated with the role of a parent. The second course addresses the adaptation to psychosocial changes associated with the role of a parent and management of conflicts in intimate relationships. These courses are tailored to participants' interpersonal concerns, specifically addressing role transitions, or a combination of role transitions and interpersonal role disputes, as interpersonal problem area(s) in IPT. Each course is delivered once a week, comprising a total of eight lessons. Each lesson lasts approximately 5–10 min (20 min maximum) and is designed to be completed in a single session. The program cannot be backtracked while it is being implemented until all 8 lessons in the self-care program are completed. However, it is possible to review the program since the program content can be left in the “Conversation History”. Lessons 5–8 can be repeated at the participant's option.

(5) Columns.

The column section provides psychoeducation on IPT and relevant obstetrics, including a case study featuring a pregnant woman navigating partner conflict and discussing strategies with a counselor to address and resolve these conflicts; a case study focusing on a pregnant woman experiencing distress about her pregnancy, highlighting her conversations with a counselor to adapt to the changes of becoming a mother; and additional articles addressing common concerns, such as painless childbirth, difference between breast milk and formula, morning sickness management, and the availability of parenting support services before and after childbirth. This activity provides participants with useful knowledge about pregnancy and childbirth, as well as psychoeducation about the stresses they are likely to experience during this time, to help them become aware of their current situation and find ways to cope with it. This can also motivate them to implement component (4).

(6) Graphical representation of interpersonal circle.

This feature uses a simple diagram with three concentric circles to represent the participant's interpersonal network. The participants placed themselves in the center, while others were arranged in circles based on their proximity. This activity helps participants identify differences in interpersonal expectations and issues and can support the implementation program in component (4).

Appendix B.

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents^⁎.

Section/item	Item No	Description	Addressed on page number
Administrative information
Title	1	Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym	P1
Trial registration	2a	Trial identifier and registry name. If not yet registered, name of intended registry	P4
	2b	All items from the World Health Organization Trial Registration Data Set	P4
Protocol version	3	Date and version identifier	P4
Funding	4	Sources and types of financial, material, and other support	P13
Roles and responsibilities	5a	Names, affiliations, and roles of protocol contributors	P1, 13, 14
	5b	Name and contact information for the trial sponsor	P13
	5c	Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities	P13
	5d	Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee)	N/A
Introduction
Background and rationale	6a	Description of research question and justification for undertaking the trial, including summary of relevant studies (published and unpublished) examining benefits and harms for each intervention	P3, 4
	6b	Explanation for choice of comparators	P4
Objectives	7	Specific objectives or hypotheses	P4
Trial design	8	Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)	P4
Methods: Participants, interventions, and outcomes
Study setting	9	Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained	P4
Eligibility criteria	10	Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)	P4, 5
Interventions	11a	Interventions for each group with sufficient detail to allow replication, including how and when they will be administered	P5
	11b	Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)	P5, 6
	11c	Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)	P5
	11d	Relevant concomitant care and interventions that are permitted or prohibited during the trial	P5
Outcomes	12	Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended	P6
Participant timeline	13	Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure)	P17, 18
Sample size	14	Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations	P7
Recruitment	15	Strategies for achieving adequate participant enrolment to reach target sample size	P7
Methods: Assignment of interventions (for controlled trials)
Allocation:
Sequence generation	16a	Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions	P8
Allocation concealment mechanism	16b	Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned	P8
Implementation	16c	Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions	P8
Blinding (masking)	17a	Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how	P8
	17b	If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant's allocated intervention during the trial	P8
Methods: Data collection, management, and analysis
Data collection methods	18a	Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol	P8
	18b	Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols	P9
Data management	19	Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol	P9, 10
Statistical methods	20a	Statistical methods for analyzing primary and secondary outcomes. Reference to where other details of the statistical analysis plan can be found, if not in the protocol	P10, 11
	20b	Methods for any additional analyses (eg, subgroup and adjusted analyses)	P11
	20c	Definition of analysis population relating to protocol non-adherence (eg, as randomized analysis), and any statistical methods to handle missing data (eg, multiple imputation)	P10
Methods: Monitoring
Data monitoring	21a	Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed	P12
	21b	Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial	P11
Harms	22	Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct	P9
Auditing	23	Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor	N/A
Ethics and dissemination
Research ethics approval	24	Plans for seeking research ethics committee/institutional review board (REC/IRB) approval	P12
Protocol amendments	25	Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes, analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals, regulators)	P12
Consent or assent	26a	Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how (see Item 32)	P12
	26b	Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable	N/A
Confidentiality	27	How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial	P9, 10
Declaration of interests	28	Financial and other competing interests for principal investigators for the overall trial and each study site	Declared Separately
Access to data	29	Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators	P9, 10
Ancillary and post-trial care	30	Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation	P12
Dissemination policy	31a	Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals, the public, and other relevant groups (eg, via publication, reporting in results databases, or other data sharing arrangements), including any publication restrictions	N/A
	31b	Authorship eligibility guidelines and any intended use of professional writers	P13, 14
	31c	Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code	N/A
Appendices
Informed consent materials	32	Model consent form and other related documentation given to participants and authorised surrogates	N/A
Biological specimens	33	Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable	N/A

^⁎It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons “Attribution-NonCommercial-NoDerivs 3.0 Unported” license.