Effectiveness of a guided mobile app intervention for depression and anxiety in university students (PROMES-U study): protocol of a multicenter randomized controlled trial

Abstract

Background

Symptoms of depression and anxiety are common among Spanish university students. Minimally guided online interventions have shown promise in reducing symptomatology and preventing increased mental distress. Here we describe the protocol of a controlled study which aims to evaluate the effectiveness of a guided preventive mental health intervention for depression and anxiety in Spanish university students.

Methods

Ongoing two-arm multicenter randomized controlled trial (RCT) targeting undergraduate students from 6 public universities with symptoms of depression and/or anxiety. Students are evaluated (between February and November 2024) through a web-based survey assessing mental health problems, use of mental health services, self-perceived health, childhood and adolescent adversities, recent stressful events, social networks, university experiences, as well as sociodemographic variables. A total of 428 students, fulfilling the inclusion criteria, are randomly assigned to: intervention group (minimally guided mhealth prevention intervention) or control group (treatment as usual plus self-monitoring including periodic evaluations on mood and stress). The intervention is based on cognitive behavioral therapy principles, such as relaxation and cognitive restructuring, and includes weekly asynchronous feedback from a psychologist based on content and participation, along with self-monitoring. Participants are assessed at baseline, and 3, 6 and 12 months after randomization. The primary outcome consists of the reduction of depressive and/or anxiety symptoms post-intervention, assessed with the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Patient Health Questionnaire-Anxiety and Depression Scale. Secondary outcomes of the RCT will be symptoms of other mental health conditions, psychological wellbeing, academic stress, acceptability and adherence. Primary analyses will be conducted on an intention-to-treat basis.

Discussion

The results of the PROMES-U RCT will provide valuable information on the effectiveness of a minimally guided preventive mental health intervention to reduce symptoms of depression and anxiety among university students that could be delivered in the campus context. Results will also provide information on the potential impact of the intervention on other relevant factors involved in mental health among university students and on the acceptability and adherence of this intervention. Trial registration number: NCT06078007.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12889-025-24752-3.

Introduction

Mental health has become a primary global concern due to the high prevalence of mental disorders in the general population, with one in eight people suffering from a condition such as depression (4.4%) or anxiety (3.6%) in 2019 [1]. The majority of mental disorders tend to first appear between mid-adolescence and early adulthood [2]. This stage of life often coincides with tertiary education, a period when students must learn to manage psychosocial distress and academic pressure in a new environment [3]. Prevalence of mental disorders in university students have been found to be high, ranging between 20% and 60% [4–7]. The World Mental Health-International College Student (WMH-ICS) Initiative reported that the most common mental disorders among first year college students were major depressive disorder (18.5%), generalized anxiety disorder (16.7%), and alcohol use disorder (6.3%) [8].

Bruffaerts et al. (2019) found that only 36.3% of first-year students with possible mental disorders sought mental health treatment in the past year [9]. Similarly, another study found that 34% of university students with mood disorder received any form of specialized treatment (mental health professional attention or psychopharmacological treatment) [10]. Some of the main reasons why students do not seek professional help are attitudinal barriers, such as preferring to cope on their own, talking with friends or family, or the associated stigma. Structural barriers, although rated as less important, include cost, displacement and scheduling issues [11]. Internet-based programs for screening and treatment can bring down some of these barriers by providing anonymity and reducing time to treatment [12]. These barriers highlight the need for alternative forms of intervention.

Internet-based intervention programs have been shown to be an effective alternative to face-to-face treatments for many mental health problems in the general population [13, 14]. Regarding university population, findings suggest small to moderate effects on depression and anxiety [15]. Evidence shows that guided interventions achieve higher adherence [16]. Emerging “mobile health” (mHealth), i.e. the delivery of health services through mobile technology [17, 18], is of interest because of its availability, immediate support, anonymity and acceptability in young people [19, 20]. Despite this, insufficient research has been done on the effectiveness of mHealth apps using randomized controlled designs [18, 21, 22].

The Promoting Mental Health among University Students (PROMES-U) project is part of the WMH-ICS. The project takes place in 6 public universities in Spain and combines two sub-studies. The first is a prospective observational cohort study to estimate the frequency of mental disorders and assess possible proximal and distal associated factors [23]. PROMES-U also aims to evaluate the effectiveness of a preventive mental health intervention among university students, which the current protocol confers, following the Recommendations for Interventional Trials (SPIRIT) [24] and the Consolidated Standards of Reporting Trials in EHealth (CONSORT-EHEALTH) [25].

The objective of this study is to test the effectiveness of a minimally guided mHealth prevention intervention based on cognitive behavioral therapy (guided mHealth CBT) aimed at reducing symptoms of depression and anxiety among university students in Spain. Secondary objectives of this study are: (a) to evaluate the effect of the mHealth intervention on other outcomes: symptoms of other mental health conditions, psychological wellbeing, academic stress; (b) to analyze moderators and mediators of the minimally guided mHealth prevention intervention; and, (c) to evaluate adherence and acceptability of the intervention.

Methods

This study is a multicenter pragmatic Randomized Controlled Trial (RCT) of a minimally guided mHealth intervention based on cognitive behavioral therapy (guided mHealth CBT), that consists of a two-arm superiority RCT with an allocation ratio of 1:1 for comparing the guided mHealth prevention intervention to treatment as usual plus self-monitoring.

Study setting and recruitment

This study is conducted in 6 Spanish public universities across 5 autonomous regions: Andalusia, Aragon, Balearic Islands, Catalonia, and the Valencian Community. The Hospital del Mar Research Institute coordinates the study management.

All undergraduate students from the participating universities, as well as university students that participated to the PROMES-U observational study who provided personal email for further contacts, are invited to participate between February and November 2024 through various recruitment strategies, such as email invitations from academic authorities, classroom visits, university activities, advertisements (posters, websites, social media), and recommendations from student counselling services. In four of the six universities, invitation emails are sent by academic authorities. A link is provided to students to access a Qualtrics^® platform to visualize the information sheet and informed consent form. Adult undergraduate students who have provided informed consent are requested to complete the baseline survey, for the assessment of eligibility criteria and pre-intervention information.

Eligibility criteria

Eligible participants are all undergraduate students at the 6 participating universities and students followed in the PROMES-U observational study, who are 18 years old or older, have literacy in Spanish, access to a smartphone (Android or Apple), and a positive screen for mild or moderate depression and/or anxiety (i.e., depression (5 ≤ PHQ-9 ≤ 14) and/or anxiety (5 ≤ GAD-7 ≤ 14) [26, 27] assessed through the baseline survey. We will exclude participants: with moderately severe or severe depression and/or anxiety (i.e., PHQ-9 ≥ 15 and/or GAD-7 ≥ 15), high suicide risk, a history of severe mental disorder (e.g., bipolar disorder, psychosis) and those who are receiving mental health treatment (i.e., psychiatric medication, psychotherapy or other mental health interventions). Students at high risk of suicide, defined with items assessing suicide attempts in the past 12 months and the likelihood to act on their suicidal ideation in the next 30 days, will receive a clinical alert recommending them to visit a healthcare professional and a list of available mental health resources and services. The PROMES-U RCT study flow chart is shown in Fig. 1.

Fig. 1.

Flow chart of the PROMES-U RCT study

Allocation

After completing the web-based baseline survey, a concealed automatic randomization will be performed for those who fulfill eligibility criteria, using randomization procedure implemented in the Qualtrics^® platform, with an allocation ratio of 1:1, to intervention (guided mHealth CBT) or control (treatment as usual plus self-monitoring) groups. The randomization is stratified using information from the baseline survey: gender and severity of symptoms of depression and anxiety according to the cut-off points on the instruments: mild or moderate depression or anxiety (PHQ-9 or GAD-7 between 5 and 9 and PHQ-9 or GAD-7 between 10 and 14, respectively) [26, 28].

One researcher will be designated as the RCT coordinator of the study. The RCT coordinator will invite participants to download the app used in this study through the Apple or Android stores and will coordinate the intervention period. Students will be informed of the assignment to the intervention or control group via a message on the last screen of the Qualtrics^® platform. Participants, coaches and the researcher are not blinded to study conditions.

Guided mHealth CBT intervention group: My Mood Coach app

Among the existing online CBT interventions for the treatment of depression and anxiety [29–32], we are using the MyMoodCoach, a smartphone app powered by the company Monsenso^®. The MyMoodCoach app is an evidence-based online resource that adopts CBT principles such as behavioral activation, problem solving and challenging negative thoughts. MyMoodCoach was developed in a self-help version and targeted to the university population by researchers of the Ecoweb Project [33, 34]. The Ecoweb project was composed by two trials and three arms, aiming to enhance mental wellbeing and reducing mental distress. The MyMoodCoach app is available in Spanish and has been adapted for the PROMES-U study, including the design of the guided version of the intervention using a clinical portal for coaches. The main objectives of the intervention guidance are to increase adherence and detect adverse effects of the intervention. The app is structured with a library, tools and challenges sections, and includes periodic evaluations on mood, stress and achievement of the weekly goals and visualization of results, a system of alerts and notifications, and a chat for contact with the coach. The content of the app is shown in Table 1.

Table 1.

Content of the My Mood Coach smartphone app [33] powered by Monsenso^®

Section	Content
Library	Thoughts and actions change behaviors
	Building up positive activities
	Changing avoidance to coping
	Building positive thoughts
	Cognitive biases
	Scheduling better plans
Challenges	Beliefs and rules
	My personal MyMoodCoach
	Identifying avoidance
	Identify goals and activities to be achieved
	Identifying and challenging anxious thoughts
	Identifying and challenging sad thoughts
	Identifying and challenging angry thoughts
	Enjoyable activities from the past
	Key steps of problem-solving
Tools	First aid problem-solving
	Relaxation exercise
	Challenging anxious thoughts
	Challenging sad thoughts
	Challenging angry thoughts
	Instant Mood Boost

The intervention period will last 8 weeks. During this time, students in the intervention arm will receive minimal guidance from a coach via the app’s chat feature and will have the option to contact their assigned coach directly. This guidance consists of giving asynchronous written feedback once a week regarding the modules, tools and challenges that the participants have completed and recommending content for the following week. Students will be encouraged to complete one module, one tool and one challenge per week during the 8-week intervention, which is the period that the coach will be in contact with them. In addition, coaches will encourage participants to continue with the intervention plan.

Coaches will be psychology graduates and students of the Master’s degree in General Health Psychology. They will receive training on how to provide feedback and about the clinical portal of the Monsenso^® platform. A total of six psychologists will be trained and supervised by the RCT coordinator. After the eight weeks of the guided intervention, participants will retain access to the app, without coach support, until the end of 2024 (when the license expires), allowing for optional continued self-help use.

Control group: treatment as usual plus self-monitoring

Participants in the control arm will receive treatment as usual (TAU), meaning that they could be able to seek and use mental health services and resources available at the university and in the community in Spain. In addition, they will be offered access to a basic version of the app (also developed by Monsenso^®), in which they will be able to monitor their mood with periodic questions about mood and stress and visualization of the results. This app contains psychoeducational information on depression, anxiety and suicidal thoughts, and a list of available mental health resources. Access to the app will be open until the end of 2024.

Data collection methods

Participant timeline

Data collection started in February 2024 (academic year 2023-24) and is carried out inviting all undergraduate students from the participating 6 universities to complete the baseline survey. Those students fulfilling eligibility criteria are randomized automatically in the intervention or control group. Participants in the intervention group and control group will receive follow-up assessment 3 months, 6 months and 12 months after randomization. The assessments will be carried out through online surveys programmed in Qualtrics^® and RedCAP^®.

The schedule of enrollment, assessments and interventions can be found in Fig. 2.

Fig. 2.

SPIRIT Schedule of enrolment, intervention, and assessments in the PROMES-U RCT study

Participation and retention strategies

Students will receive up to 5 reminder emails to answer and complete each of the online surveys and receive a 10€ Amazon voucher for each follow-up they complete. To increase participation in the intervention, coaches will send weekly messages to participants in the intervention group encouraging them to continue with the intervention. In addition, the RCT coordinator will send weekly reminder emails to participants who have not started the intervention to encourage them to download the app.

Measures

The baseline and follow-up assessments will be self-reported scales based on the WMH-ICS Questionnaire.

The baseline survey will include seventeen sections covering the main variables to be considered in the study. They can be regrouped in eight areas: sociodemographic, general physical health, depression and anxiety, other mental health disorders, treatment, relationships and stressful events.

1. Sociodemographic are set out in Sect. 1: Your background. These will include age, gender, student status, work status, living arrangement and distance of permanent residence from school.

2. General health can be found in Sect. 2: Your health. Perception of physical health, weight and height, physical health related interference and frequency of physical activity are measured. This section also includes: traumatic brain injury, general mental health, lifetime mental disorders, sleep disorders and role impairment.

3. Depression and Anxiety will be evaluated in Sect. 5: depression and Sect. 6: worry and anxiety through the PHQ-9, GAD-7 and PHQ-ADS. The PHQ-9 [27, 35] is a widely used questionnaire for screening the severity of depressive symptoms in the prior 2 weeks. It is composed of 9 items with a Likert scale from 0 to 3. The total score ranges from 0 to 27 and its interpretation is according to the following cutoff points: 5 (mild), 10 (moderate), 15 (moderately severe) and, 20 (severe). Internal consistency of 0.9 and sensitivity and specificity of 80–90% have been found [28, 36, 37]. The GAD-7 [26, 38] is the instrument used to assess anxiety symptoms. The GAD-7 is composed of 7 items with a Likert scale from 0 to 3. The total score is from 0 to 20 and is interpreted according to the following cut-off points: 5 (mild), 10 (moderate) and 15 (severe). This measure showed an internal consistency of 0.9 and sensitivity and specificity of 80% [26, 39]. The PHQ-ADS is a composite measure for screening depression and anxiety symptoms [40]. It includes the sum of the PHQ-9 and GAD-7 items, ranging from 0 to 48 and indicating severity of symptoms of 10 (mild), 20 (moderate) and 30 (severe). The PHQ-ADS showed an internal consistency of 0.8–0.9.

4. Other mental health disorders includes Sect. 3: ADHD evaluated with 6-month Adult ADHD Self-Report Scale (ASRS-V1.1) [41]; Sect. 4: substance Use with PhenX ToolKit [42]; Sect. 7: Panic Attacks measured with an adapted version of the Composite International Diagnostic Interview Screening Scales (CIDI-SC) [43, 44]; Sect. 8: Social Anxiety considering the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria [45]; Sect. 9: High Mood with an adapted version of the Composite International Diagnostic Interview Screening Scales (CIDI-SC) [43, 44]; Sect. 11: Other behavioral problems with items adapted from the Patient Health Questionnaire (PRIME-MD) will be used to assess eating disorders [27] and Sect. 12: Self-harm that will evaluate Suicidal thoughts and behaviors with adapted items from the Self-Injurious Thoughts and Behaviors Interview (SITBI) and the Columbia Suicidal Severity Rating Scale (C-SSRS) instruments [46, 47].

5. Treatment will be evaluated with Sect. 13: treatment. It will be assessed the current treatment and the barriers to seeking treatment with the Post-Katrina Survey and the Healthy Minds Survey [48, 49], treatment history evaluated with the CIDI [50].

6. Relationships cover Sect. 14: Personal relationships and Sect. 15: social networks. Sexual orientation, sexual attraction and sexual behavior will be evaluated through the American College Health Association – National College Health Assessment (ACHA-NCHA III) [51] and the Williams Institute Best Practices for Asking Questions about Sexual Orientation on Surveys [52].

7. Stressful events, Sect. 10: Stressful experiences, Sect. 16: Childhood experiences and Sect. 17: University experiences. They will measure symptoms with the 6-question Short-Form PCL-5 Scale [53], age onset with the CIDI-SC [43], severity with the MIDUS Self-Report Scale of Perceived Stress [54], resilience with the 5-Item Resilience Scale [55], bullying based on various bullying measures developed by Dr. Kessler [56], trauma experiences based on questions from the Army STARRS [57], childhood stressful experiences with the Adverse Childhood Experiences (ACE) Study Survey [58], childhood trauma with the Childhood Trauma Questionnaire – Short Form (CTQ-SF) [59], academic stress with the Perception of Academic Stress Scale [60] and psychological wellbeing with the Flourishing Scale [61].

To allow assessment of inclusion/exclusion criteria and subsequent randomization, participants must complete the baseline survey through Sect. 13 (Treatment).

Sociodemographic characteristics, high mood, personal relationships, social networks and childhood experiences will be evaluated at baseline. Follow-up surveys at 3, 6 and 12 months will evaluate: general physical and mental health, substance use, depression, worry and anxiety, panic attacks, social anxiety, behavioral problems, self-harm, treatment and university experiences. And at 3-month follow-up, the survey will also evaluate acceptability.

Outcomes

The primary outcome will be the reduction of depressive and anxiety symptoms separately and overall at post-intervention (3 months, and again, at 6 and 12 months), considering the minimal clinically relevant change in the scores of the PHQ-9, GAD-7 and PHQ-ADS measures. A reduction of 5 points or more in PHQ-9 will be considered a meaningful change, as found in the study by Löwe et al. (2004) for longitudinal assessment results and corresponding to two standard errors of measurement [62]. For GAD-7, 4 points were estimated as the minimal clinically important difference in longitudinal assessments and corresponding to two standard error of measurement [63]. And for PHQ-ADS, a reduction of 3 points or more will be considered [64]. The primary outcome will also be considered as a binary outcome defining improvement as a reduction of at least 50% of the scores on the baseline survey [29, 65].

Secondary outcomes will be the change in symptoms of other mental health conditions, psychological wellbeing, and academic stress. Symptoms of other mental health disorders will be assessed with adapted versions of the following instruments: panic attacks (adapted version of the Composite International Diagnostic Interview Screening Scales; CIDI-SC) [43, 44]; social anxiety symptoms (5th Edition of the Diagnostic and Statistical Manual of Mental Disorders criteria; DSM-5) [45]; post-traumatic stress disorder symptoms (adapted PTSD Checklist from the DSM-5; PCL-5) [53]; eating disorders (items from the Patient Health Questionnaire (PRIME-MD) [27]; suicidal thoughts and behaviors (adapted items from the Self-Injurious Thoughts and Behaviors Interview; SITBI and the Columbia Suicidal Severity Rating Scale; C-SSRS) [46, 47]; assessing statistically significant differences between baseline and follow-up assessments. Substance use frequency (i.e., alcohol and drugs consumption) will be evaluated with measures from the PhenX ToolKit [42]. Psychological wellbeing will be measured with 4 items from the Flourishing Scale [61] and academic stress will be assessed through 4 items from the Perception of Academic Stress Scale (PAS) [60].

Secondary outcomes will also include adherence and acceptability of treatment. Adherence will be evaluated considering “technical” data and acceptability of the intervention. “Technical” data are data automatically collected in the Monsenso^® app and they include: information about the number of logins, the time spent in the app, the number of challenges and tools visualized, the number of questionnaires sent and answered and the responses in the questionnaires. Acceptability will be evaluated with items adapted from the Client Satisfaction Questionnaire (CSQ) [66–69], where a high score indicates higher satisfaction.

Primary and secondary outcomes will be assessed at four time points: baseline, 3-, 6- and 12-months through Qualtrics^® and RedCAP^®. During the baseline survey, the inclusion and exclusion criteria and the primary and secondary outcomes will be assessed.

Sample size and power calculation

The sample size calculation is based on the t-test of two independent means. Based on an existing meta-analysis, we anticipate a conservative effect size of 0.35 [70]. With a statistical power of 0.8 and two-sided alpha level of 0.05, a sample size of 129 participants per group is needed to detect an effect size of 0.35 (total n = 258). Considering a drop-out rate of 40%, the minimum required sample for the RCT is n = 428 participants (n = 214 participants per group).

Statistical methods

Descriptive analyses of sociodemographic variables and primary outcomes of the PROMES-U RCT study (i.e., symptoms of depression and anxiety) will be performed. Continuous variables will be summarized using the mean and categorical variables by absolute and relative frequencies.

Differences in outcomes of the study will be analyzed on an Intention-To-Treat (ITT) basis including all randomized participants [24, 71, 72]. Analyses of primary outcomes will be performed at post-intervention (i.e., at 3 months) as well as considering 6 and 12 months of follow-up.

Primary analyses will be conducted with generalized linear models (GLM) with different link functions and error structure according to the nature of the outcomes. In the case of continuous outcomes, the PHQ-9, GAD-7 and PHQ-ADS scores at post-intervention will be the dependent variable, the treatment variable as the independent variable in the model and adjusting for baseline outcome scores [73–75]. The magnitude of the effect for continuous outcomes will be calculated with Cohen’s d and 95% confidence intervals (95%CI), allowing interpreting the effect as no effect (< 0.2), small effect (0.2–0.5), medium effect (0.5–0.8) and large effect (> 0.8) [76]. For binary outcomes, effects will be reported as adjusted relative risk (aRR) with 95%CI.

For analyses involving longitudinal data (i.e., follow-up assessments at 3, 6 and 12 months), generalized linear mixed models (GLMM) will be used, considering individuals as a random effect and treatment and time being fixed effects, and adjusting for baseline outcome scores. Different link functions and error structure will be considered depending on the nature of the outcomes.

As a pre-planned secondary analysis, the treatment effect on compliers will be estimated. Complier Average Causal Effect (CACE) analyses [77] will be conducted using the instrumental variable method and including specific models for continuous and categorical outcomes. Compliance to the minimally guided mhealth CBT will be defined as completing at least 5 Challenges and 3 Tools and accessing the app for at least four weeks once a week, which corresponds to almost half of the content and duration of the intervention.

Additionally, adjusted analyses will be performed including the covariates assessed in the baseline survey in the model. For secondary outcomes at post-intervention, bivariate and multiple GLM with different link functions and error structure depending on the outcomes will be conducted. Interaction effects and mediation effects, using structural equation modeling, will be evaluated including variables assessed at baseline and follow-ups [78, 79].

Item-level missing data and dropout will be summarized, providing patterns of missingness, and considered in the interpretation of the results [80]. To deal with missing data at the item level, Multiple Imputation with Chained Equations (MICE) or Full Information Maximum Likelihood (FIML) will be applied [81, 82]. Alternatively, the assumption that these data are missing not at random will be tested in a sensitivity analysis, applying a reference-based imputation approach [83]. To correct for follow-up losses, inverse probability weighting will be calculated based on covariates evaluated in previous assessments [84, 85]. All statistical analysis will be carried out in RStudio [86].

Ethics, data management and dissemination

The project complies with national and international regulations, including the Declaration of Helsinki and the Code of Ethics, and ethical approval was provided by the Parc de Salut Mar-Clinical Research Ethics Committee (2020/9198/I) and the corresponding Ethics Committees of all participating universities. If there are major modifications to the protocol, they will be agreed with the research team and communicated to the Ethics Committee, as well as participants and university authorities.

Participants will be able to access the baseline assessment only after they have provided explicit online informed consent. Students with possible high suicide risk will receive a clinical alert with indications to consult a healthcare professional and a list of available mental health resources and services.

Reported adverse events and other unintended effects of the trial intervention will be collected with self-reported data at each follow-up. Information can also be obtained if participants in the intervention group report information to their coach. In addition, questions about mental health symptoms and suicidal thoughts and behaviors will be collected at each follow-up assessment (3-, 6- and 12-months). A Data Monitoring Committee will be established to review the adverse events and will decide whether the trial should be discontinued.

Information from the online surveys will be collected using the Qualtrics^® and RedCAP^® platform. The only personal information that will be requested to participants is a personal email address to invite them to download the app and answer follow-up online surveys. Data will be pseudo-anonymized by assigning an identification number to each student. Information on participation to the intervention will be collected on the Monsenso^® platform and this data will be linked to the survey responses with the identification number. The anonymized data set will be used to perform all data analyses. Data analyst will be blinded to study conditions.

The dissemination of results will be adapted to the different target audiences of the PROMES-U RCT. Dissemination strategies will include the publication of peer-reviewed scientific articles and participation in conferences. Information sessions and reports will also be elaborated to provide information to university authorities. For the general population and specifically university students, results will be presented through reports, sessions, social media or news.

Discussion

A large number of university students with emotional problems do not receive a diagnosis or treatment [5, 6, 9]. Reasons to not seek professional care include stigma, cost, lack of access or misinformation about mental health care. There is an urgent need in the management of depressive and anxiety symptoms in university students to reduce their impact in academic or social functioning or to prevent later mental disorders.

Based on results of a previous study (UNIVERSAL project [87]), we evaluate a mHealth intervention that can be easily delivered to a targeted population, such as university students. Attitudes towards using e-health interventions for mental disorders are generally positive, useful and well accepted. In terms of cost, scalability, and anonymity, app-interventions have important advantages in university students. They offer the possibility to reach a group of persons who could experience barriers to participate in a face-to-face assessment or treatment as young population.

In this study we will analyze the effectiveness of a minimally guided CBT intervention for treating depressive and anxious symptoms among students of six different Spanish universities delivered by a minimally guided mobile app. This multicenter pragmatic RCT will evaluate the effectiveness of MyMoodCoach app [33] in students with depressive or anxiety symptoms vs. treatment as usual with self-monitoring. We will evaluate potential moderators and mediators of the guided intervention, as well as adherence and acceptability.

This trial has several anticipated limitations. First, the control group will receive access to a basic version of the Monsenso^® app, which includes mood and stress monitoring, psychoeducational information, and mental health resources. This minimal intervention may reduce the contrast with the guided intervention and potentially underestimate effect sizes. Second, app uptake and intensity of use are expected to be modest, which could limit intervention exposure. Third, follow-up response rates, particularly at 6 and 12 months, may be reduced, which could affect power and introduce bias. Finally, although the guided intervention is standardized at 8 weeks, the length of subsequent unguided access to the MyMoodCoach app until the end of 2024 varies depending on the date of randomization, potentially leading to heterogeneity in long-term outcomes.

To mitigate these limitations, we will conduct analyses estimating treatment effects among compliers, apply Complier Average Causal Effect (CACE) methods, use inverse probability weighting to account for attrition, and perform sensitivity analyses to explore the impact of the variable duration of unguided app access.

This study will provide relevant information for policy makers and will have implications for public health and research on the integration of digital interventions on university campuses.

Abbreviations

DSM-5

5th Edition of the Diagnostic and Statistical Manual of Mental Disorders

ASRS-V1.1

Adult ADHD Self-Report Scale

ACHA-NCHA III

American College Health Association – National College Health Assessment

ADHD

Attention-Deficit/Hyperactivity Disorder

CSQ

Client Satisfaction Questionnaire

CONSORT-EHEALTH

Consolidated Standards of Reporting Trials in Ehealth

CBT

Cognitive Behavioral Therapy

C-SSRS

Columbia Suicidal Severity Rating Scale

CACE

Complier Average Causal Effect

CIDI-SC

Composite International Diagnostic Interview Screening Scales

FIML

Full Information Maximum Likelihood

GAD-7

Generalized Anxiety Disorder 7-item

GLMM

Generalized Linear Mixed Models

ITT

Intention-To-Treat

mHealth

Mobile Health

MICE

Multiple Imputation with Chained Equations

PRIME-MD

Patient Health Questionnaire

PHQ-9

Patient Health Questionnaire-9

PHQ-ADS

Patient Health Questionnaire Anxiety and Depression Scale

PAS

Perception of Academic Stress Scale

PROMES-U

Promoting Mental Health among University students project

PCL-5

PTSD Checklist from the DSM-5

RCT

Randomized Controlled Trial

SITBI

Self-Injurious Thoughts and Behaviors Interview

SPIRIT

Standard Protocol Items: Recommendations for Interventional Trials

WHO

World Health Organization

WMH-ICS

World Mental Health-International College Student initiative

Authors’ contributions

Co-first authors: LB, MG, and MR contributed equally to this work. JA, PM, GV, LB, MG, MR were responsible of study conceptualization and design. LB, IF-R, MG, MR wrote the first draft of the article. VS-S, GV, FAA, BM, PM, JAP, AP-VD, MR, TR, and JA provided critical revisions. All authors read and approved the submitted manuscript.

Funding

This work is supported by Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union, grant number PI20/00006; by the Departament de Recerca i Universitats of the Generalitat de Catalunya (AGAUR 2021 SGR 00624); and CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB06/02/0046), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea.Subdirecció General d'Addiccions, VIH, ITS i Hepatitis Víriques, Secretaria de Salut Pública, Departament de Salut, Generalitat de Catalunya.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Ethical approval was provided by the Parc de Salut Mar-Clinical Research Ethics Committee (Reference: 2020/9198/I) and the Ethics Committees at each participating university. Written informed consent will be obtained from all subjects.

Consent for publication

Not applicable.

Competing interests

MR received research funding from the European Union, Spanish Ministry of Economy, Commerce and Business and Janssen, Lundbeck and Rovi. MG received research funding from the European Union, and Spanish Ministry of Economy, Commerce and Business.