JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Original Paper Effectiveness of a Transdiagnostic Guided Internet-Delivered Protocol for Emotional Disorders Versus Treatment as Usual in Specialized Care: Randomized Controlled Trial Alberto González-Robles1, PhD; Amanda Díaz-García1, PhD; Azucena García-Palacios1,2, PhD; Pablo Roca3, MSc; Josep Antoni Ramos-Quiroga4,5,6,7, PhD; Cristina Botella1,2, PhD 1 Department of Basic and Clinical Psychology, and Psychobiology, Universitat Jaume I, Castellón de la Plana, Spain 2 CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Carlos III, Madrid, Spain 3 Department of Personality, Assessment, and Clinical Psychology, Universidad Complutense de Madrid, Madrid, Spain 4 Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain 5 Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain 6 Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain 7 Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain Corresponding Author: Alberto González-Robles, PhD Department of Basic and Clinical Psychology, and Psychobiology Universitat Jaume I Sos Baynat Avenue, Campus del Riu Sec Research II Building, Labpsitec Castellón de la Plana, 12071 Spain Phone: 34 964387646 ext 7646 Email: vrobles@uji.es Abstract Background: Anxiety disorders and depression (emotional disorders) are highly prevalent mental disorders. Extensive empirical evidence supports the efficacy of cognitive behavioral therapy (CBT) for the treatment of these disorders. However, there are still some barriers related to their dissemination and implementation, which make it difficult for patients to receive these treatments, especially in public health care settings where resources are limited. Recent advances in improving CBT dissemination encompass different perspectives. One is the transdiagnostic approach, which offers treatment protocols that can be used for a range of emotional disorders. Another approach is the use of the internet to reach a larger number of people who could benefit from CBT. Objective: This study aimed to analyze the effectiveness and acceptability of a transdiagnostic internet-delivered protocol (EmotionRegulation) with human and automated guidance in patients from public specialized mental health care settings. Methods: A 2-armed randomized controlled trial (RCT) was conducted to compare the effectiveness of EmotionRegulation with treatment as usual (TAU) in specialized mental health care. In all, 214 participants were randomly assigned to receive either EmotionRegulation (n=106) or TAU (n=108). Measurement assessments were conducted at pre- and postintervention and at a 3-month follow-up. Results: The results revealed the superiority of EmotionRegulation over TAU on measures of depression (d=0.41), anxiety (d=0.35), and health-related quality of life (d=−0.45) at posttreatment, and these gains were maintained at the 3-month follow-up. Furthermore, the results for expectations and opinions showed that EmotionRegulation was well accepted by participants. Conclusions: EmotionRegulation was more effective than TAU for the treatment of emotional disorders in the Spanish public mental health system. The implications of this RCT, limitations, and suggestions for future research are discussed. Trial Registration: ClinicalTrials.gov NCT02345668; https://clinicaltrials.gov/ct2/show/NCT02345668 (J Med Internet Res 2020;22(7):e18220) doi: 10.2196/18220 https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 1 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al KEYWORDS transdiagnostic; internet; cognitive behavioral therapy; emotional disorders; depression; anxiety; specialized care treatment as usual (TAU) [28-31], with pooled effect sizes Introduction (Hedges g) in the medium to large range for overall measures Disorder-Specific Cognitive Behavioral Therapy for of anxiety (0.65-0.82) and depression (0.79-0.84). Moreover, an additional meta-analysis reported equivalent effects of Emotional Disorders transdiagnostic treatments (g=1.06) and disorder-specific Anxiety and depressive disorders, also known as emotional treatments (d=0.95) on anxiety outcomes [32]. However, these disorders (EDs) [1], have the highest prevalence rates among meta-analyses include a number of mixed studies of different psychological disorders [2,3], and are associated with substantial orientations, such as theory-based transdiagnostic treatments costs [4,5] and disability [6,7]. In the past three decades, and tailored CBT. Therefore, these studies make it difficult to research efforts to decrease the burden of these disorders have determine the effectiveness of each orientation (eg, the led to the development and evaluation of cognitive behavioral effectiveness of theory-based transdiagnostic treatments). The treatments in randomized controlled trials (RCTs) for each ED effectiveness of transdiagnostic treatments has also been shown (ie, disorder-specific protocols), such as depression [8,9] and in a meta-analysis by García-Escalera et al [33], with pooled several anxiety disorders, including generalized anxiety disorder effect sizes of g=0.80 for anxiety and g=0.72 for depression. (GAD) [10,11], panic disorder (PD) and agoraphobia (AG) [12], Unlike the abovementioned meta-analyses, this study has the social anxiety disorder (SAD) [13], and obsessive compulsive particularity that it only included theory-based transdiagnostic disorder (OCD) [14]. treatments. The main characteristic of theory-based Although there is a large body of evidence showing the efficacy transdiagnostic treatments, also known as mechanistically and effectiveness of disorder-specific cognitive behavioral transdiagnostic treatments or transdiagnostic treatments based therapy (CBT), in the past 15 years, an increasing number of on shared mechanisms [34], is that they are designed to address researchers have agreed that there are some problems that hinder the common psychopathological processes underlying anxiety the optimal deployment of these treatments. The main drawback and depression. Among the mechanistically transdiagnostic of disorder-specific treatments stems from the high comorbidity treatments for EDs, the Unified Protocol (UP) [35,36] stands rates observed among anxiety disorders and between anxiety out as one of the most empirically supported transdiagnostic disorders and depressive disorders, with comorbidity estimates protocols for anxiety and depression [23,37,38]. The UP is a for these disorders ranging between 40% and 80% [15,16]. CBT transdiagnostic protocol developed to address the Thus, because disorder-specific treatment protocols focus on underlying psychopathological processes that are common to treating a specific diagnosis, the accompanying comorbid anxiety and depressive disorders, with a particular focus on disorders do not receive therapeutic attention [17,18]. This neuroticism, (low) extraversion, and emotion dysregulation, problem becomes clearer when we take into account research which have been shown to play a key role in the onset and linking comorbidity to aspects such as greater severity [3], maintenance of these disorders [39,40]. Thus, the main goal of increased chronicity rates [19], and a worse clinical course [20]. the UP is to teach patients strategies to regulate their emotions Another problem with disorder-specific treatments is that in a more adaptive way through the following core treatment subthreshold symptoms that do not meet diagnostic thresholds modules: (1) present-focused emotional awareness, (2) cognitive for a particular disorder, but might be important to treat, flexibility, (3) identification and prevention of emotional normally go untreated [17]. Similarly, these protocols do not avoidance patterns, (4) increasing awareness and tolerance to address diagnoses that do not fit any specific category, despite emotion-elicited physical sensations, and (5) graded their clinical relevance, that is, not otherwise specified (NOS) (interoceptive and situational) exposure procedures. The overall anxiety and depressive disorders [15]. Finally, each efficacy of the UP was first shown in an RCT where it was disorder-specific treatment requires the use of different compared with a waitlist control group [23] and, more recently, handbooks and protocols, which increases the economic costs in a larger RCT where it was compared with well-established and the amount of training needed to gain the knowledge and disorder-specific CBT protocols for anxiety disorders [37]. In skills necessary to cover the array of anxiety and depressive addition, some research shows the long-term effects of the UP disorders [17]. [41] and its ability to produce changes in the temperament dimensions of behavioral inhibition (BI) and behavioral Transdiagnostic Treatments for Anxiety and activation (BA) [42]. BI and BA have been conceptualized as Depression 2 neurological systems representing motivational tendencies Transdiagnostic treatments have emerged as an alternative to that are sensitive to threat and reward environmental cues, the traditional disorder-specific approach that has dominated respectively [43]. These aspects have been intimately linked to CBT research for the past 30 years. Transdiagnostic treatments neuroticism and negative affect and extraversion and positive have been developed and tested in several RCTs for anxiety affect [42]. Another treatment approach that includes principles disorders [21-24] and anxiety and depressive disorders [25-27], or components that could be useful to target EDs is dialectical and their number continues to grow. Moreover, the efficacy and behavioral therapy (DBT) [44,45]. DBT initially emerged as a effectiveness of transdiagnostic treatments have been shown in theoretical model and a treatment approach for the treatment of different meta-analytic reviews, comparing them with different suicidal behaviors and borderline personality disorder, with the control groups, such as waiting list, attention control, and general aim of teaching strategies to change patterns of emotion https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 2 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al dysregulation [46]. Of the range of strategies, DBT places a patients is one of the lowest in Europe [59], and patients have special emphasis on increasing experiential awareness and to endure long waitlists to receive treatment [60]. Fourth, acceptance (mindfulness what and how techniques), but it also transdiagnostic treatments can be provided at a lower cost (eg, includes behavioral strategies such as the opposite action, in terms of training) [61]. Finally, the use of the internet can designed to diminish distress by engaging in behaviors or actions help improve mental health services, for instance, by reducing opposite to those associated with negative emotions [44]. More the waiting period to receive face-to-face treatment [62] or by recently, DBT skills have been adapted and successfully applied implementing these treatments as part of a stepped-care model to several anxiety and depressive disorders [47,48], which that takes patients’ profiles and needs into account. Thus, each suggests that they could be used in a transdiagnostic manner to patient can be assigned the most appropriate treatment [63], improve the symptomatology of these disorders. For example, leaving face-to-face therapy for those patients who are less DBT principles may be combined with other evidence-based likely to benefit from internet-delivered interventions. components (eg, components of the UP) to strengthen their effectiveness. The strategy of integrating CBT principles and This Study components from different evidence-based therapies and Taking all of this into consideration, in this study, an RCT was orientations is consistent with the notion of process-based CBT, conducted to test the effectiveness of a transdiagnostic defined by Hofmann and Hayes [49]. As the authors state, internet-delivered protocol for ED (EmotionRegulation), “modern CBT places much less focus on protocols for compared with TAU provided in Spanish public specialized syndromes and more focus on evidence-based processes linked mental health care. EmotionRegulation includes components to evidence-based procedures” [49]. of the UP and the skills from DBT (eg, mindfulness what and how techniques), and it was designed to target a wide range of Internet-Delivered Interventions EDs, including major depressive disorder (MDD), dysthymic In the past two decades, one of the most evident efforts made disorder (DD), PD, AG, SAD, GAD, OCD, anxiety NOS, and by researchers has been to take advantage of the possibilities depression NOS. It was hypothesized that (1) the offered by information and communication technologies to EmotionRegulation group would outperform the TAU group improve the assessment and treatment of psychological on measures of overall anxiety and depression, temperament disorders. A clear example would be the use of the internet to (ie, BI and BA), and health-related quality of life (QoL) at increase the dissemination of empirically supported posttreatment; (2) these posttreatment changes would be psychological treatments to anyone in need [50]. Research has maintained at follow-up; (3) a significantly greater clinical shown promising and compelling evidence that change would be observed in EmotionRegulation compared internet-delivered psychological interventions are effective for with TAU; and (4) participants in the EmotionRegulation group a variety of psychosocial problems, including anxiety and would rate the treatment as acceptable (scores on expectations depressive disorders [51,52]. The main advantages of and opinion ≥7/10). internet-delivered treatments over traditional delivery methods (eg, face-to-face therapy) include widespread access and Methods dissemination [53], a nonstigmatizing way of receiving psychological treatment [54], and increased cost-effectiveness Study Design [55]. A 2-armed RCT was conducted. Participants were randomly Research has shown that transdiagnostic internet-delivered assigned in a 1:1 ratio to one of the following 2 conditions: (1) treatments are more effective than control groups [29] and that EmotionRegulation and (2) TAU. Participants were stratified these treatments are at least as effective as individual and group by principal diagnosis, performing block randomization in face-to-face transdiagnostic treatments [33]. However, most of blocks of 4 to ensure that all the principal diagnoses were the existing literature on transdiagnostic treatments is limited equally represented across conditions. Computer-generated to studies conducted in community settings, with few studies random number sequences were obtained using statistical carried out in public contexts such as primary or specialized software (Epidat 4.1, SourceForge). This task was performed care [21]. Indeed, to our knowledge, no transdiagnostic by an independent researcher who was unaware of the internet-delivered treatments for anxiety and depression have characteristics of the study. been conducted in specialized public mental health care. This The study was conducted in compliance with the study protocol, is somewhat surprising because transdiagnostic the Consolidated Standards of Reporting Trials (CONSORT) internet-delivered treatments in this particular setting could statement [64,65], the CONSORT of Electronic and Mobile have several advantages for both clinicians and the patients HEalth Applications and onLine TeleHealth guidelines [66], attending these centers. First, anxiety and depressive disorders and the Declaration of Helsinki and good clinical practice. A are disorders with the highest prevalence rates [2,3]. Second, full description of the study protocol has been reported resources in these settings are usually scarce, which affects both elsewhere [67]. The RCT obtained ethical approval from the the quantity and the quality of the mental health care provided Ethics Committee of Universitat Jaume I (Castellón, Spain) and [56]. Third, a large percentage of patients with anxiety and the Clinical Research Ethics Committees of 3 hospitals depressive disorders do not receive treatment in mental health (Consorcio Hospitalario Provincial de Castellón, Hospital care centers [57]. In the specific case of Spain, most patients Universitario de la Ribera, and Hospital Universitario Vall attending public mental health units suffer from anxiety and d’Hebron). The study protocol was registered at depressive disorders [58], the ratio of clinical psychologists to ClinicalTrials.gov (NCT02345668) on July 27, 2015. The https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 3 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al duration of the intervention period was 18 weeks for participants Participants were selected based on the following inclusion in both conditions, and participants’ assessments were conducted criteria: (1) aged 18 years or older; (2) ability to understand and at pre- and posttreatment and at 3- and 12-month follow-ups. read Spanish; (3) having access to the internet at home and an Both the intervention (EmotionRegulation) and the assessment email address; (4) meeting Diagnostic and Statistical Manual instruments, except the diagnostic interview, were delivered of Mental Disorders, Fourth Edition (DSM-IV) diagnostic through a web platform designed by our research group [68]. criteria [74] for ED (ie, MDD, DD, depression NOS, PD, AG, All transferred data were secured via Advanced Encryption SAD, GAD, anxiety NOS, and OCD); (5) providing written Standard-256 encryption. Study researchers conducting informed consent; (6) not suffering from a severe mental posttreatment and follow-up assessments (ie, diagnostic disorder (schizophrenia, bipolar disorder, and alcohol and/or interviews) were blinded to the participants’ treatment substance dependence disorder); (7) not presenting a high risk conditions. To ensure blinding of the evaluators, participants of suicide; (8) not suffering from a disabling medical disease were informed that an independent researcher would contact that prevented the participant from carrying out the them to conduct follow-up assessments, and they were asked psychological treatment; and (9) not receiving another not to disclose the treatment condition to which they had been psychological treatment during the study (in the experimental allocated. This study reports pre- to posttreatment data and data group). Pharmacological treatment was allowed, but participants at 3-month follow-up. had to be taking the same dose during the 2 months before enrolling in the study. In addition, participants in the Sample Size experimental group whose medication was increased or changed Several studies were considered for the calculation of the during the study period were excluded from the trial (decreases expected sample size [23,69,70]. On the basis of a minimum in pharmacological treatment were accepted). There was no power of 0.80 in a 1-tailed test (ie, t test for differences between monetary compensation for participation in the study under any 2 independent means), an α of .05, and an estimated dropout of the treatment conditions. rate of approximately 30%, a sample size of 78 participants per condition was determined to detect a posttreatment effect size Instruments of 0.40 (Cohen d) between the 2 conditions. In addition, based Clinical Outcomes on the literature [71,72], an estimated dropout rate of approximately 30% was expected. Thus, the final sample size Diagnosis Interview was set at 100 participants per condition (total of 200 Clinical diagnoses were obtained using the mini-international participants). The G*Power software (version 3.1.9.4, neuropsychiatric interview (MINI) version 5.00 [75,76], a brief Heinrich-Heine-Universität) was used to calculate the sample structured diagnostic psychiatric interview for the assessment size [73]. of key DSM-IV and International Classification of Diseases, 10th Revision, diagnoses. Participants Participants were recruited from adult outpatients attending Principal Outcomes Spanish public specialized mental health care services (mental Beck Depression Inventory, Second Edition health units) to seek psychological and/or psychiatric treatment Beck depression inventory, second edition (BDI-II) [77,78], is between July 2015 and June 2019. Initial recruitment was a self-report questionnaire with 21 items about the different performed by clinical psychologists and psychiatrists working symptoms characterizing MDD, added together to obtain the in these centers, and it took place in 3 different hospitals: total score, which can be a maximum of 63 points. The Consorcio Hospitalario Provincial de Castellón (Castellón de instrument has shown good internal consistency (α=.76-.95). la Plana), Hospital Universitario de la Ribera (Valencia), and The Spanish version also showed high internal consistency Hospital Universitario Vall d’Hebrón (Barcelona). Recruitment (α=.87) for both the general and clinical populations (α=.89). was performed as follows: (1) once psychiatrists and clinical Cronbach α for the BDI-II in this study was .90. psychologists had identified a potential candidate, they offered the patient the possibility of participating in the study and Beck Anxiety Inventory described the study characteristics to him or her; (2) patients The Beck anxiety inventory (BAI) [79,80] is a 21-item who were interested in participating gave their informed written self-report scale that assesses anxiety, with a maximum score consent, and the clinician filled out a document with the of 63 points. Each item has a 4-point severity scale (from not participants’ sociodemographic and clinical characteristics at all to severely) that addresses symptoms experienced during (moreover, in this stage, participants were provided with a the previous week. Previous validation studies have shown an document containing information about the study); (3) one of internal consistency ranging from 0.85 to 0.94 as well as the researchers involved in the study contacted the participants convergent and divergent validity. The Spanish version of the by phone to schedule a face-to-face appointment to evaluate BAI has demonstrated high internal consistency (α=.93). eligibility criteria using a structured diagnostic interview; and Cronbach α for the BAI in this study was .92. (4) whenever a participant met the eligibility criteria, an independent researcher (unaware of the study characteristics) Secondary Outcomes was contacted to implement randomization, and participants Behavioral Inhibition Scale and Behavioral Activation Scale completed the remaining assessment instruments (self-reported The behavioral inhibition scale (BIS) and behavioral activation questionnaires) through web-based surveys. scale (BAS) [81,82] contains 20 items rated from 1 to 4, with https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 4 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al 7 BIS subscale items that evaluate emotional responses of problems?), and its usefulness for the patient’s problem (To individuals to impending negative events and 13 BAS items what extent do you think this treatment will be/was helpful to that evaluate the behavioral and emotional responses of you?). The expectation scale was applied after the treatment individuals to potentially positive events. The BIS and BAS rationale was explained. Its objective is to measure subjective have shown good reliability in individuals with EDs (α=.73-.92) patient expectations regarding this treatment. The opinion scale and good convergent and discriminant validity as indicators of was administered when the patient had completed the treatment, temperament. The internal consistency of the Spanish version and it was designed to assess satisfaction with this treatment. ranges between 0.65 and 0.82. Cronbach α for the BIS and BAS subscales in this study were .61 and .80, respectively. Treatments Quality of Life EuroQoL-5D-3L Questionnaire EmotionRegulation Quality of life EuroQoL-5D-3L (EQ-5D-3L) questionnaire Following randomization, participants in the treatment condition [83,84] is a generic instrument that measures health-related QoL were contacted via telephone by a researcher who provided free and consists of 2 parts. Part 1 assesses self-reported problems access to EmotionRegulation, a 12-module transdiagnostic in each of the following 5 domains: mobility, self-care, daily internet-delivered protocol for the treatment of ED, namely, activities, pain/discomfort, and anxiety/depression. Each domain MDD, DD, depression NOS, PD, AG, GAD, SAD, anxiety is divided into 3 levels of severity corresponding to no problems, NOS, and OCD. The protocol is delivered through a web some problems, and extreme problems, yielding a platform [68] designed by our research group. Access to the population-based preference score or societal index (SI). A total web platform is through a unique username-password of 243 theoretically possible health states can be obtained, and combination and is available 24 hours a day. The treatment was the SI is calculated on the basis of these health states. Values first developed as a manualized transdiagnostic treatment range from 1 (best health state) to 0 (death). However, this index protocol with handbooks for both patient and therapist and then may also provide negative values that correspond to health states adapted to be delivered through a web-based platform. The web perceived as worse than death. Utility scores for these health platform has successfully been used in previous RCTs exploring states were assigned using the available Spanish population the efficacy of internet-delivered treatments for several tariffs. Part 2 records the subjects’ self-assessed health on a disorders, such as depression [94] and flying phobia [95]. visual analog scale (VAS), a 10-cm vertical line on which the The main core components are based on the UP [35,36], but best and worst imaginable health states score 100 and 0, the protocol also contains treatment strategies derived from respectively. In this study, health-related QoL was assessed DBT [46]. The principal aim of the treatment components in using the VAS. EmotionRegulation is to learn and practice adaptive ways to Disorder-Specific Measures regulate emotions from a transdiagnostic perspective, with the following treatment components: present-focused emotional Disorder-specific symptoms were evaluated using 4 different awareness, cognitive flexibility, emotional avoidance and self-report questionnaires. Symptoms of GAD were assessed emotion-driven behaviors, and exposure procedures using the Penn State Worry Questionnaire [85,86]. PD and AG (interoceptive and situational). The protocol also contains a symptoms were evaluated using the Panic Disorder Severity module to facilitate the patient’s engagement with the therapy Scale, Self-Reported [87,88]. SAD symptoms were evaluated (motivation for change), a module with psychoeducation about using the Social Interaction Anxiety Scale [89,90], and OCD emotions, and a relapse prevention module. Regarding the DBT symptoms were assessed using the Obsessive Compulsive components, greater emphasis was placed on the present-focused Inventory-Revised [91,92]. All 4 instruments have shown emotional awareness component by adapting and including adequate psychometric properties in both the original and strategies such as the what and how techniques and the concept Spanish validations. Cronbach αs for these scales in this study of radical acceptance. Moreover, the opposite action was were .78, .89, .80, and .91, respectively. More details about integrated into the treatment as a way to address emotion-driven these assessment instruments have been described elsewhere behaviors. EmotionRegulation includes a Welcome module that [67]. contains general information about the protocol and its goals Treatment Acceptability as well as recommendations for benefiting from it and 12 treatment modules (described in Table 1). Expectations and Opinions of Treatment Scales These questionnaires were adapted from the study by Borkovec The modules are sequential to enable step-by-step movement and Nau [93]. Each scale is made up of 5 items, rated from 0 through the program. The program duration can vary among (nothing at all) to 10 (completely), which ask how logical the the users, and participants had access to the protocol for a treatment seems to be (How logical do youthink this treatment maximum period of 18 weeks. Moreover, participants were is?), to what extent it satisfies the patient (How satisfied are allowed to use the program any time they wanted during the you with the treatment?), whether the patient would recommend trial period (ie, during the follow-up periods). it to a person with the same problem (To what extent do you Regarding guidance, all participants in this condition received feel confident recommending this treatment to a friend who has therapist and automated support. Therapist support consisted the same problems?), whether it could be used to treat other of (1) an initial face-to-face session to explain the characteristics psychological problems (To what extent do you think this of the study and administer the diagnostic interview to confirm treatment could be useful in treating other psychological the eligibility criteria, (2) an initial phone call encouraging https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 5 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al participants to start the intervention after the baseline predefined contents, and they did not include personal assessments had been completed, (3) 1 weekly brief phone call information that could have identified the participants. (maximum of 10 min) during the treatment period, and (4) a Additional details about the treatment and support protocols, final phone call (once the treatment had ended) to remind as well as other functionalities of the web-based platform, have participants that they would be allowed to use the program at been published elsewhere [67]. Finally, it is important to note any time during the trial period and that they would be contacted that all participants in this condition were allowed to continue for follow-up assessments. Automated support consisted of 2 to receive TAU, but only for monitoring of pharmacological weekly text messages reminding participants about the treatment. Participants who received other forms of treatment importance of completing the homework tasks and encouraging during the study period (eg, psychological treatment) or who them to review the treatment modules. Text messages were sent experienced increases or changes in pharmacological treatment through a secure web platform [96]. This web platform was were excluded from the analyses. only used to send text messages (unidirectionally) with Table 1. Treatment modules and their objectives. Module Objective 1. Introduction to treatment Provides a framework about the role of emotion regulation in EDa. 2. Motivation for change and goal setting To analyze pros and cons of changing, emphasize the importance of being motivated, and help to establish significant life goals. 3. Understanding the role of emotions Provides psychoeducation about the roles and functions of emotions and trains the patient to track the 3 components of emotional experiences. 4. Nonjudgmental emotional awareness and Aims to train the patient in nonjudgmental emotional awareness (ie, mindfulness what and how skills) acceptance of emotional experiences and the acceptance of emotional experiences. 5. Practicing present-focused awareness To continue to practice the acceptance of emotional experiences and increase awareness of physical sensations, thoughts, emotions, and daily activities. 6. Learning to be flexible Focuses on the identification of maladaptive ways of thinking (ie, thinking traps). 7. Practicing cognitive flexibility Aims to teach the patients strategies to modify thinking traps (ie, cognitive reappraisal). It also provides information about intrusive thoughts and how to deal with them. 8. Emotional avoidance Aims to teach the patients to identify the emotion avoidance strategies that contribute to the maintenance of ED. 9. Emotion-driven behaviors To learn the concept of EDBsb and replace their maladaptive EDB with other more adaptive behaviors. 10. Accepting and facing physical sensa- To teach the role of physical sensations in the emotional response and provide training in interoceptive tions exposure. 11. Facing emotions in the contexts in To build exposure hierarchies to help the patients begin to face situation-elicited avoided emotions. which they occur 12. Relapse prevention To review what patients have learned throughout the program, schedule the future practice of the learned strategies, and teach the patient how to identify and cope with future high-risk situations. a ED: emotional disorder. b EDBs: emotion-driven behaviors. provided to the participant. Patients in the TAU condition who Treatment as Usual were already receiving any of the aforementioned treatments at TAU was treatment as delivered in current daily practice by the time of enrollment were informed that they would continue psychiatrists and clinical psychologists in the mental health to receive these services during the treatment period. centers in Spain. TAU in this study was provided by 3 hospitals: Furthermore, participants receiving a treatment other than those Consorcio Hospitalario Provincial de Castellón (Castellón de provided in the mental health unit were excluded from the trial. la Plana), Hospital Universitario de la Ribera (Valencia), and All participants allocated to TAU were offered free access to Hospital Universitario Vall d’Hebron (Barcelona). To maximize the treatment platform after the study ended. the external validity of this RCT, participants in this condition were allowed to receive either psychiatric treatment (ie, Therapists and Treatment Fidelity prescription and monitoring of antidepressant and/or anxiolytic The treatment and support protocols were administered by medication), psychological treatment (including case doctoral students with at least two years of experience in the management, group psychotherapy, empathic listening, and/or diagnosis, psychological assessment, and application of CBT supportive counseling), or a combination of both. The frequency for different ED. Several steps were taken to ensure treatment of visits during the 18-week treatment period varied depending fidelity. First, therapists had previously been trained in the on the type of treatment (ie, psychiatric or psychological) application of the treatment modules. Second, a support protocol https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 6 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al (ie, weekly phone calls and automated text messages) was corrected using Greenhouse-Geisser whenever the sphericity developed to be applied to all the participants in the assumption was violated. Moreover, pairwise EmotionRegulation condition. This support protocol has been Bonferroni-corrected tests were used for posthoc comparisons. briefly described earlier, but more details can be found in the To compute the magnitude of both within-group and study by González-Robles et al [67]. Third, to increase diagnosis between-group changes, effect sizes (Cohen d) were calculated reliability, all therapists involved in the participants’ assessment by dividing the differences between means by the pooled SD. were trained in the application of the diagnostic interview Effect sizes were interpreted according to Cohen convention: (MINI). effect sizes of 0.20 are considered low, effect sizes of 0.50 are Data Analysis Plan considered medium, and effect sizes of 0.80 and above are All analyses were performed using the Statistical Package for considered large [102]. Social Sciences version 25. To test the third hypothesis, we explored the clinical significance First, chi-square tests for categorical data and independent of the changes achieved by the participants as well as potential samples t tests for continuous data were performed to confirm deterioration rates using Jacobson and Truax’s reliable change that there were no significant differences between the groups index (RCI) [103] for the main outcome measures (BDI-II and at baseline on any of the sociodemographic and clinical BAI) in the completer sample for posttreatment and follow-up variables. measurements. First, the cutoff points for the posttreatment and follow-up scores were determined to be within the range of a Intention-to-treat (ITT) analyses were performed following functional distribution. The RCI was then calculated to test the Newman’s guidelines [97], using maximum likelihood (ML) clinically significant change, with an RCI of |1.96| or greater estimation through the expectation maximization imputation (P<.05). Finally, both criteria were taken into account to classify method. To handle missing data, we followed the procedure participants into the following 4 categories: (1) recovered: when suggested by Hair et al [98]. First, we explored the types of the change is significantly reliable (RCI≥|1.96|; P<.05) and the missing data and determined that data were missing at the posttreatment score is located within the range of the functional construct level. On the basis of this, we concluded that the data distribution (mean [SD 2]), (2) improved: when the change is were susceptible to imputation. Second, the quantity of missing significantly reliable but the posttreatment score is below the data was analyzed to ensure that none of the measures exceeded functional level, (3) not changed: when the change is not the recommended limits to implement this method [99]. Third, significantly reliable and the posttreatment score does not reach Little’s missing completely at random (MCAR) tests were the functional level, and (4) deteriorated: when the change is carried out to analyze the pattern of missing data, concluding significantly reliable but the posttreatment score is worse than that all missing data were MCAR (X225=28.7; P=.28). Finally, the pretreatment score. a sensitivity analysis was performed on the main outcomes to Finally, to test the fourth hypothesis, the scores on expectations compare the results of the per-protocol sample (ie, completers) and opinions were analyzed by calculating means and SDs for with the imputed values. This analysis revealed that the ML each of the items on the expectation and opinion of treatment estimation was not likely to produce biased estimations in the scales. In addition, 1-way ANOVAs were performed to analyze main analyses, reaching the same conclusions in both the the significance of the differences between expectations and completers and the imputed dataset (per-protocol: FBAI opinions. (1,127)=6.1; P=.02; and FBDI (1,127)=15.54; P<.001; ITT: FBAI (1,197)=4.79; P=.03; and FBDI (1,197)=12.97; P<.001). Results To test the first hypothesis and control for baseline differences, Participant Flow and Attrition analyses of covariance (ANCOVAs) were performed to compare A flowchart of the study participants is displayed in Figure 1. the effects of the groups on measures of anxiety, depression, A total of 326 patients expressed interest in the study, 281 of temperament, and health-related QoL, taking condition as the whom were assessed for eligibility. Of these 281, 67 participants between-subject variable and the pretreatment scores as were excluded from the study. A total of 214 participants were covariates. The use of ANCOVAs for the analysis has been randomized to either EmotionRegulation (n=106) or TAU recommended by several authors as a more powerful tool to (n=108). In addition, 7 patients in each condition withdrew from analyze data in studies with randomized designs [100,101]. the study before the pretreatment assessment. Consequently, To test the second hypothesis, a 2 (condition: these participants were not included in any of the analyses. EmotionRegulation vs TAU) × 3 (time: pretreatment vs Regarding attrition, 35 participants in the EmotionRegulation posttreatment vs 3-month follow-up) mixed analysis of variance condition (35/106, 33.0%) and 34 in the TAU condition (34/108, (ANOVA) was performed to test whether the differences 31.5%) dropped out of the study (reasons for dropout are shown between EmotionRegulation and TAU (ie, between-subjects in Figure 1). In addition, 3 participants in the EmotionRegulation factors) were maintained at follow-up (ie, within-subject factor). condition had to be excluded from the trial because of a change The following assumptions for the mixed ANOVA were in their pharmacological treatment during the treatment period. analyzed: normality (Shapiro-Wilk test), homoscedasticity Posttreatment data were obtained from 63 participants (63/99, (Levene test), independence (nonparametric Runs test), and 64%) in the EmotionRegulation condition and from 67 sphericity (Mauchly test). The degrees of freedom were participants (67/101, 66.3%) in the TAU condition. Follow-up https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 7 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al data were collected from 51 participants (51/99, 52%) in the EmotionRegulation group and 101 participants in the TAU EmotionRegulation condition and 56 participants (56/101, condition were included in the ITT analysis. 55.4%) in the TAU condition. Finally, 99 participants in the Figure 1. Flowchart of participants. ED: emotional disorder; DSM-IV-TR; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; ITT: intention-to-treat. significant differences between the EmotionRegulation and Baseline Characteristics TAU groups at baseline on any of the sociodemographic and Participants (N=200) had a mean age of 38.44 years (SD 10.80; clinical characteristics. Moreover, no significant differences range 18-68), and they were mostly females (138/200, 69.0%). were found for medication, principal diagnosis, number of Table 2 provides the sociodemographic and clinical comorbid diagnoses, or clinical severity on any of the measures. characteristics for both conditions at baseline. There were no https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 8 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Table 2. Demographic and clinical characteristics of the sample at baseline (N=200). Variable EmotionRegulation regulation Treatment as usual X2 (df) t test (df) P value (n=99) (n=101) Age (years), mean (SD) 38.64 (10.61) 38.25 (11.03) N/Aa 0.25 (198) .80 Sex, n (%) 1.3 (1) N/A .26 Female 72 (72) 66 (65.3) Male 27 (27) 35 (34.7) Marital status, n (%) 1.1 (3) N/A .78 Single 22 (22) 26 (25.7) Married or partnered 63 (63) 65 (64.4) Divorced or widowed 14 (14) 10 (9.9) Education, n (%) 2.1 (2) N/A .35 Basic studies 26 (26) 36 (35.6) Secondary studies 41 (41) 35 (34.7) University studies 32 (32) 30 (29.7) Occupation, n (%) 3.3 (6) N/A .77 Student 9 (9) 11 (10.9) Housekeeper 6 (6) 9 (8.9) Employed 45 (45) 36 (35.6) Unemployed 23 (23) 22 (21.8) Off work 13 (13) 17 (16.8) Retired 3 (3) 6 (5.9) Monthly income (€), n (%) 1.0 (4) N/A .91 None 27 (27) 28 (27.7) <641.40 (US $699.45) 20 (20) 16 (15.8) 641.40-1282.80 (US $699.46- 32 (32) 38 (37.6) 1398.89) 1282.81-2565.60 (US $1398.90- 18 (18) 17 (16.8) 2797.78) >2565.60 (US $2798.78) 2 (2) 2 (2.0) Principal diagnosis, n (%) 2.7 (8) N/A .95 GADb 23 (23) 26 (27.7) c AG 16 (16) 13 (12.9) PDd 9 (9) 5 (5.0) SADe 4 (4) 4 (4.0) OCDf 8 (8) 12 (12.0) g MDD 20 (20) 22 (21.8) DDh 7 (7) 6 (5.9) Anxiety NOSi 10 (10) 9 (8.9) Depression NOS 2 (2) 3 (3.0) Comorbid diagnoses, n N/A N/A N/A GAD 10 18 PD 6 5 https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 9 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Variable EmotionRegulation regulation Treatment as usual X2 (df) t test (df) P value (n=99) (n=101) AG 18 22 SAD 7 10 OCD 2 4 MDD 15 18 DD 15 5 Anxiety NOS 3 1 Depression NOS 1 0 Alcohol abuse 1 2 Substance abuse 0 2 Number of comorbid disorders, n (%) 2.3 (3) N/A .50 0 49 (49) 41 (40.6) 1 29 (29) 38 (37.6) 2 15 (15) 13 (12.9) ≥3 6 (6) 8 (7.9) Medication, n (%) 5.2 (3) N/A .16 None 29 (29) 18 (17.8) Antidepressant 22 (22) 20 (19.8) Anxiolytic 10 (10) 17 (16.8) Both 38 (38) 46 (45.5) a N/A: not applicable. b GAD: generalized anxiety disorder. c AG: agoraphobia. d PD: panic disorder. e SAD: social anxiety disorder. f OCD: obsessive compulsive disorder. g MDD: major depressive disorder. h DD: dysthymic disorder. i NOS: not otherwise specified. weekly text messages, participants in the EmotionRegulation Amount of Support Provided group were sent a mean of 24.61 text messages (SD 8.80). Participants in the EmotionRegulation condition were provided a mean of 49.97 min (SD 41.20 min) of clinician support Effectiveness of EmotionRegulation on Primary and delivered through phone calls. In addition, an initial face-to-face Secondary Outcome Measures session was scheduled with all the patients in both conditions Table 3 provides the means and SDs for the 2 conditions at pre- (EmotionRegulation and TAU) to explain the study and perform and posttreatment and at 3-month follow-up on both primary the screening assessment, with an approximate duration of 60 and secondary outcome measures. Additional data on change min for each participant. Regarding automated support, that is, scores and within-group effect sizes for diagnosis-specific measures are reported in Multimedia Appendix 1. https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 10 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Table 3. Descriptive statistics for EmotionRegulation and treatment as usual at pretreatment, posttreatment, and 3-month follow-up. Instrument EmotionRegulation (n=99), mean (SD) Treatment as usual (n=101), mean (SD) Pre-Ta Post-Tb F/Uc Pre-T Post-T F/U Beck depression inventory-II 23.49 (11.01) 15.54 (10.9) 15.70 (11.97) 24.08 (11.69) 19.85 (12.85) 17.90 (13.23) Beck anxiety inventory 20.00 (11.88) 15.08 (10.12) 15.41 (10.50) 22.27 (12.93) 18.88 (11.31) 18.11 (11.21) Behavioral inhibition and behav- 23.32 (2.76) 22.30 (2.67) 21.81 (2.67) 23.40 (2.87) 22.87 (2.44) 22.44 (2.42) ioral activation scale—behav- ioral inhibition system Behavioral inhibition scale and 35.26 (5.93) 36.26 (5.31) 34.94 (5.27) 35.84 (5.58) 35.01 (5.98) 34.07 (6.04) behavioral activation scale—behavioral activation system EuroQoL-5D-3L questionnaire 55.86 (16.72) 65.38 (14.63) 63.12 (15.18) 53.56 (18.25) 58.02 (17.46) 57.81 (17.28) a Pre-T: pretreatment. b Post-T: posttreatment. c F/U: follow-up. significant (P>.99), revealing that the reductions in depression Pretreatment to Posttreatment Effects scores were maintained at the 3-month follow-up. Principal Outcome Measures The analyses showed no condition×time interaction effect on The ANCOVAs of the baseline-corrected postintervention scores anxiety (F1.62,319.88=0.75; P=.45; η2 partial=0.004). However, revealed a significant condition effect on anxiety (BAI: there was a significant time effect (F1.62,319.88=29.35; P<.001; F1,197=4.79; P=.03; η2 partial=0.02) and depression (BDI-II: η2 partial=0.13) and a significant condition effect on anxiety F1,197=12.97; P<.001; η2 partial=0.06), reflecting that the scores (F1,198=4.20; P=.04; η2 partial=0.02). Although there EmotionRegulation group showed significantly lower was no interaction effect, we decided to perform posthoc tests posttreatment anxiety and depression scores than the TAU to preliminarily explore the direction of the changes. In the group. EmotionRegulation group, posthoc comparison tests revealed Secondary Outcome Measures significant differences between pre- and posttreatment (P<.001), Regarding the measures of BI and BA (BISBAS), the but no significant differences between posttreatment and ANCOVAs yielded a significant condition effect for the BA follow-up in the EmotionRegulation group (P>.99). dimension (BAS: F1,197=9.66; P=.002; η2 partial=0.05), Secondary Outcome Measures indicating that patients in the EmotionRegulation group had Regarding temperament measures, no significant condition×time significantly higher BA scores than those in the TAU group. interaction effect was found for the BIS subscale Although patients in the EmotionRegulation group showed (F1.49,295.29=0.93; P=.34; η2 partial=0.005). A significant time greater improvements in the BI dimension, no significant differences between groups were observed for this dimension effect was found (F1.49,295.29=15.33; P<.001; η2 partial=0.07), (BIS: F1,197=2.44; P=.12; η2 partial=0.01). On the other hand, but the effect of condition was not significant (F1,198=2.51; the ANCOVA revealed a significant condition effect on P=.12; η2 partial=0.01). health-related QoL (EQ-5D-3L: F1,197=10.38; P=.001; η2 For the BAS subscale, a significant condition×effect interaction partial=0.05), indicating that health-related QoL scores were effect was found (F1.84,363.40=5.62; P=.02; η2 partial=0.03). In significantly higher in the EmotionRegulation group the EmotionRegulation group, posthoc tests showed that BAS posttreatment than in the TAU group. scores were significantly higher at posttreatment than at baseline Follow-Up Effects (P=.05). However, these differences vanished at follow-up, as shown by the comparison between pretreatment and follow-up Principal Outcome Measures scores (P>.99). For depression, a significant condition×time interaction effect Regarding health-related QoL, the analyses did not reveal a was found (F2,396=6.18; P=.01; η2 partial=0.03). There was a condition×time interaction effect (F1.7,336.93=2.73; P=.08; significant time effect (F2,396=102.07; P<.001; η2 partial=0.34) η2partial=0.01). However, there was a significant time effect and a nonsignificant condition effect on anxiety scores (F2,396=23.34; P=.001; η2 partial=0.11) and a significant (F1,198=2.25; P=.14; η2 partial=0.01). In the EmotionRegulation condition effect (F1,198=6.3; P=.01; η2 partial=0.03), which condition, Bonferroni tests indicated that the differences between indicated a significant improvement in health-related QoL at pre- and posttreatment were significant (P<.001), but the posttreatment in both EmotionRegulation and TAU and differences between posttreatment and follow-up were not https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 11 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al generally higher health-related QoL in the EmotionRegulation between-group comparisons. group. Table 4 provides the effect sizes for the within- and Table 4. Within- and between-group effect sizes and 95% CIs. Instrument EmotionRegulation (n=99), d (95% CI) TAUa (n=101), d (95% CI) EmotionRegulation versus TAU, d (95% CI) Pre-post Pre-F/Ub Pre-post Pre-F/U Posttreatment F/U Beck depression inven- 0.72c (0.54 to 0.90) 0.70 (0.54 to 0.36 (0.23 to 0.52 (0.39 to 0.41 (0.13 to 0.69) 0.24 (−0.04 to tory-II 0.87) 0.49) 0.66) 0.52) Beck anxiety inventory 0.41 (0.25 to 0.57) 0.38 (0.20 to 0.26 (0.09 to 0.32 (0.13 to 0.35 (0.07 to 0.63) 0.25 (−0.03 to 0.56) 0.43) 0.51) 0.53) Behavioral inhibition 0.37 (0.10 to 0.63) 0.54 (0.26 to 0.18 (−0.07 to 0.33 (0.06 to 0.22 (−0.06 to 0.50) 0.25 (−0.03 to scale and behavioral 0.82) 0.44) 0.61) 0.52) activation scale—behav- ioral inhibition system Behavioral inhibition −0.17c (−0.31 to 0.05 (−0.09 to 0.15 (0.01 to 0.31 (0.15 to −0.22 (−0.50 to 0.06) −0.15 (−0.43 to scale and behavioral −0.03) 0.20) 0.29) 0.48) 0.12) activation scale—behav- ioral activation system EuroQoL-5D-3L ques- −0.57 (−0.76 to −0.43 (−0.64 to −0.24 (−0.44 to −0.23 (−0.44 to −0.45 (−0.74 to −0.17) −0.33 (−0.60 to tionnaire −0.37) −0.22) −0.04) −0.02) −0.05) a TAU: treatment as usual. b F/U: 3-month follow-up. c Positive effect sizes denote a decrease in scores, whereas negative effect sizes denote an increase. only 58.4% (59/101) did so in the TAU group, and these Significance of Clinical Improvements differences were significant (X21=10.5; P=.001). In the The results for the significance of the clinical changes on EmotionRegulation group, 59% (58/99) of participants measures of overall depression and anxiety (BDI-II and BAI, recovered, 25% (25/99) improved, 10% (10/99) did not change, respectively) are summarized below. and 6% (6/99) deteriorated; whereas in the TAU group, 38.6% Changes in Depression (39/101) of participants recovered, 18.8% (19/101) improved, 32.7% (33/101) did not change, and 8.9% (9/101) deteriorated Baseline to Posttreatment Changes (Figure 2). Differences betweeen groups were significant In the EmotionRegulation group, 84% (85/99) of the patients (X23=11.7; P=.009). achieved a functional change in their depression scores, whereas https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 12 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Figure 2. Percentages of participants recovered, improved, did not change, and deteriorated on depression scores (Beck depression inventory-II) in EmotionRegulation (outer circle) and treatment as usual (inner circle). F/U: follow-up. Baseline to Follow-Up Changes Changes in Anxiety In the EmotionRegulation group, 80% (79/99) of the patients Baseline to Posttreatment Changes achieved a functional change in their depression scores, whereas There were no significant differences in the proportion of only 70.3% (71/101) of the patients did so in the TAU group, patients who achieved a functional change in their anxiety scores and these differences were not significant (X21=1.6; P=.20). In between the 2 conditions (X21=1.2; P=.28). However, 73% the EmotionRegulation group, 65% (64/99) of participants (72/99) of participants in the EmotionRegulation group achieved recovered, 16% (16/99) improved, 16% (16/99) did not change, a functional change in anxiety and 64.4% (65/101) did so in the and 4% (4/99) deteriorated; whereas in the TAU group, 50.5% TAU group. . In the EmotionRegulation group, 56% (55/99) of (51/101) of participants recovered, 19.8% (20/101) improved, participants recovered, 18% (18/99) improved, 21% (21/99) did 17.8% (18/101) did not change, and 12.9% (13/101) had not change, and 6% (6/99) deteriorated. In contrast, in the TAU deteriorated (Figure 2). No significant differences betweeen group, 36.6% (37/101) of participants were recovered, 26.7% groups were found (X23=3.7; P=.30). (27/101) were improved, 17.8% (18/101) did not change, and 17.8% (18/101) had deteriorated (Figure 3). Differences betweeen groups were marginally significant (X23=7.3; P=.06). https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 13 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Figure 3. Percentages of participants recovered, improved, did not change, and deteriorated on anxiety scores (Beck anxiety inventory) in EmotionRegulation (outer circle) and treatment as usual (inner circle). F/U: follow-up. and 7.81): logic of the treatment, satisfaction with the treatment, Baseline to Follow-Up Changes recommending the treatment to other people with similar There were no significant differences in the proportion of problems, usefulness of the treatment for other psychological patients who achieved a functional change in their anxiety scores problems, and usefulness of the treatment for one’s specific between the 2 conditions (X21=0.9; P=.34). In the problem. After receiving the intervention, scores for treatment EmotionRegulation group, 49% (49/99) of participants opinions were generally higher than scores for treatment recovered, 14% (14/99) improved, 28% (28/99) did not change, expectations (scores between 7.67 and 8.24). and 10% (10/99) deteriorated. In contrast, in the TAU group, A 1-way repeated measures ANOVA showed that, compared 47.5% (48/101) of participants were recovered, 22.8% (23/101) with treatment expectations, the opinion of treatment was were improved, 8.9% (9/101) did not change, and 19.8% significantly better for item 1 (logic of the treatment; F1,62=7.81; (20/101) had deteriorated (Figure 3). Differences betweeen P=.007; η2 partial=0.11), item 3 (recommending the treatment groups were significant (X23=8.2; P=.04). to other people with similar problems; F1,62=4.80; P=.03; η2 Treatment Acceptability partial=0.07), and item 4 (usefulness of the treatment for other Table 5 provides the means and SDs for expectations and psychological problems; F1,62=4.92; P=.30; η2 partial=0.07). opinions about treatment in the completer sample of the No significant differences were found for item 2 (satisfaction EmotionRegulation condition (n=63). As hypothesized, the with the treatment; F1,62=3.05; P=.09; η2 partial=0.05) or item results indicate that participants reported high scores on all the 5 (usefulness of the treatment for one’s specific problem; items measuring treatment expectations (scores between 7.56 F1,62=.21; P=.65; η2partial=0.003). Table 5. Means and SDs for expectations and opinions of treatment (n=63). Item Expectations, mean (SD) Opinion, mean (SD) Treatment is logical 7.65 (1.88) 8.19 (1.62) Satisfaction with the treatment 7.56 (1.81) 7.90 (1.71) Recommend to others 7.81 (1.91) 8.24 (1.85) Usefulness for other psychological problems 7.64 (1.86) 8.05 (1.65) Usefulness for one’s specific problems 7.76 (1.83) 7.67 (2.13) https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 14 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Furthermore, to evaluate the significance of the clinical gains, Discussion Jacobson and Truax’s RCI was obtained for the principal Principal Findings outcome measures, that is, BDI-II and BAI. The objective of this RCT was to explore whether a Consistent with the aforementioned results, significant transdiagnostic internet-delivered protocol (EmotionRegulation) differences were observed in the proportion of patients who could be effective in treating a wide range of anxiety and achieved a functional change in depression scores, with a depressive disorders, compared with TAU as provided in significantly higher number of patients within the functional Spanish public specialized mental health care services. The range in the EmotionRegulation condition (85/99, 84%) than effectiveness of EmotionRegulation was evaluated on measures in the TAU group (59/101, 58.4%). Regarding anxiety scores, of overall anxiety and depression, temperament (ie, BI and BA), although no significant differences were observed between the and health-related QoL. Finally, expectations and opinions were 2 groups in the proportion of patients reaching a functional evaluated to examine the acceptability of EmotionRegulation change, a higher proportion of patients in the EmotionRegulation for the patients. To our knowledge, this is the first RCT to report group (72/99, 73%) than those in the TAU group (65/101, data on a transdiagnostic internet-delivered protocol for ED in 64.4%) reached a functional change. Furthermore, significant public specialized mental health care. differences were found in the proportion of patients recovered, improved, did not change, and deteriorated, with better general Regarding our first hypothesis, the ANCOVAs revealed that results for the intervention group than for the TAU group. At participants in the intervention group (EmotionRegulation) follow-up, there were no differences in the proportion of patients improved their depression and anxiety symptoms at reaching a functional change in either depression or anxiety. posttreatment to a greater degree than participants in the TAU Therefore, it can be concluded that these differences tended to group. Regarding the magnitude of the changes at posttreatment, diminish between groups at follow-up. the analyses showed small but significant between-group effect sizes for both depression and anxiety. With regard to measures Regarding the acceptability of EmotionRegulation, expectations of temperament, the findings were mixed. Overall, although about the treatment were high (scores ≥7). After receiving the patients in the EmotionRegulation group showed better scores treatment, compared with expectations, the participants rated on the 2 subscales of the BIS and BAS than the TAU group, the program as significantly more logical, more recommendable only the differences on the BAS subscale were significant, for other people with similar problems and more useful for the favoring the EmotionRegulation group. These results suggest treatment of other psychological problems. The study of that the intervention tested in this study was able to modify acceptability is important because expectations about treatment temperament, in line with a mechanistically transdiagnostic have been shown to affect treatment outcomes [107]. approach that assumes the existence of underlying mechanisms Furthermore, because most transdiagnostic internet-delivered that account for the occurrence of specific symptoms. To our protocols have been conducted in community samples [108], it knowledge, only 1 study has previously investigated the effect is necessary to continue to explore the acceptability of these of a mechanistically transdiagnostic treatment on the dimensions interventions in specialized care. of BI and BA [42]. Similar to the results obtained in our study, Overall, the findings showed that the transdiagnostic in the study by Carl et al [42], both BI and BA improved internet-delivered protocol tested in this RCT was more effective following treatment with the UP compared with a waitlist control than TAU for the treatment of anxiety and depressive disorders group, with small between-group effect sizes found for both the in public specialized mental health care. On the one hand, the BIS and BAS temperament dimensions. Moreover, these authors results show that EmotionRegulation led to greater showed associations between the gains in temperament improvements at posttreatment, and these gains were maintained dimensions and symptoms of anxiety and depression, at follow-up. Regarding TAU, the results reveal that patients particularly for BI, because lower BI scores were associated undergoing TAU also experienced improvement over time, but with greater improvements in anxiety and depressive symptoms. it was slower and less pronounced than in patients receiving However, a limitation of this study was that the sample size was EmotionRegulation. The generally lower intensity of TAU (ie, small, and so the findings were preliminary. Thus, future RCTs lower frequency of therapy sessions) and the fact that for most of mechanistically transdiagnostic treatments should analyze patients TAU was limited to pharmacotherapy (with no access the extent to which these interventions are able to modify BI to psychological treatment) might partly account for these and BA and other related temperament dimensions such as results. On the other hand, as anticipated, and in line with negative and positive affect to shed more light on this question previous studies conducted by our research group using the [104,105]. Finally, as hypothesized, EmotionRegulation was same treatment platform [94,109], scores on expectations and superior to TAU in improving health-related QoL, with a small opinions demonstrated EmotionRegulation’s acceptability for but significant between-group effect size observed for the participants. EQ-5D-3L scale. In this regard, it is known that pharmacological treatment could be linked to some variables associated with The results obtained in this RCT have implications for both health-related QoL, such as fatigue and sexual functioning [106]. research and clinical practice, especially in the context of public Therefore, decreases in medication may have indirectly specialized mental health care. First, the findings obtained in influenced the QoL in some patients. However, these decreases this study support the effectiveness of a mechanistically were not measured, and hence, no analyses could be performed transdiagnostic internet-delivered protocol for the treatment of to analyze this aspect. EDs, and they contribute to the literature in this particular field https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 15 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al [23,27,36,110-112]. Specifically, a combination of the researchers), these data were not monitored during the trial. components of the UP and DBT regulation skills was found to Finally, the results for acceptability (ie, expectations and be more effective than TAU in treating ED. Second, as far as opinions) might not be entirely representative because data from we know, this is the first study to explore a transdiagnostic patients who dropped out of the intervention were not included internet-delivered treatment in public specialized mental health in these analyses. care. As mentioned earlier, most research on transdiagnostic web-based treatments has been conducted in community Conclusions and Future Directions settings, with a few of these studies carried out in primary care The effectiveness of a mechanistically transdiagnostic [108]. The results showed that the intervention was found to be internet-delivered protocol for ED was compared with TAU in more effective than TAU on the measures of generic depression, public specialized mental health care. Although the results are anxiety, and QoL. These results are consistent with the literature promising, more research in specialized care should be showing the superiority of CBT over TAU. For instance, a conducted to extend the findings obtained in this study. First, meta-analysis showed that CBT outweighed TAU, with effect research on predictors and moderators of treatment outcomes sizes in the medium range on measures of generic anxiety and dropout in this specific setting can help to delineate the (Hedges g=0.70) and depression (Hedges g=0.69) [70]. As profiles of participants who are more likely to benefit from these surprising as these data might seem, the truth is that current treatments and help to answer the classic question, “what public mental health services still have to deal with a number treatment, by whom, is most effective for this individual with of barriers that hinder appropriate care delivery, such as that specific problem, under which set of circumstances?” [119]. excessive waiting times to access mental health care [60], low Moreover, we believe that the integration of principles from frequency of sessions [113], or inadequate follow-up care [56]. different evidence-based protocols (eg, components of the UP Moreover, the lack of training in evidence-based treatments and DBT) can be a powerful strategy that should guide future among professionals further adds to this problem [114]. Finally, research on evidence-based psychotherapy. This strategy is in in Spain, several RCTs have been conducted using the internet line with process-based CBT and the new foundational question to provide evidence-based treatments, showing that they are proposed by Hofmann and Hayes [49] ( ie, “What core effective for the treatment of ED and, in particular, depression, biopsychosocial processes should be targeted with this client in community samples [94] and primary care [115,116], and given this goal in this situation, and how can they most others are underway [117]. This study demonstrated that an efficiently and effectively be changed?”) . Second, despite the internet-delivered protocol for ED was effective in public huge advances experienced by the field of internet-delivered specialized care, a setting with a high demand, but much less treatments in the past two decades, high dropout rates remain explored, thus adding to the literature on these treatments for a major challenge in the field. To continue to improve current ED. Furthermore, the use of TAU as the control condition may and future internet-delivered interventions, future studies should help to answer the question of “whether a new treatment or an strive to include dropouts in the analysis of acceptability using evidence-based psychotherapy really surpasses in outcome both qualitative and quantitative approaches. Moreover, to effects what is ordinarily done at a given clinic” [118], thus ensure the integrity, quality, and replicability of these studies, helping to make clinicians, researchers, and policy makers aware adherence to existing research guidelines is of paramount of the limitations and aspects that should be improved in this importance in this endeavor. Third, although we did not assess specific setting. the acceptability of clinicians involved in the RCT (ie, psychiatrists, clinical psychologists, and nurses), it is worth Limitations mentioning that some of them refused to participate in the Although the results of this RCT are promising, they should be recruitment process, which might reflect negative attitudes interpreted in light of the following limitations. First, although toward internet-delivered interventions among these several measures were taken to minimize attrition (eg, guidance professionals. In this scenario, research efforts should be made was provided to all the patients participating in to inform clinicians and state holders about the benefits of EmotionRegulation), the number of patients who dropped out internet-delivered treatments, especially because they are seen of the study was high (around 35%). However, this proportion as authority figures and, therefore, their attitudes can have a was close to what is typically observed in the literature on major impact on patients’ perceptions. Finally, although the internet-delivered psychological treatments (ie, approximately need for efficacy studies is out of doubt, we believe that it is of 30%-35%) [71]. Moreover, attrition in the TAU condition was paramount importance to conduct more implementation research similar (34/108, 31.5%). Second, this RCT was not powered to [120]. These studies may provide a much deeper understanding detect differences in disorder-specific measures (ie, for GAD, of implementation variables that can either facilitate or hamper PD or AG, SAD, and OCD). Therefore, future studies that meet the effective uptake of evidence-based protocols in real clinical the minimum levels of statistical power to detect differences in practice, such as the attitudes of clinicians and other these measures are warranted. Third, although the frequency of professionals toward internet-delivered treatments, or the session in TAU was low and most patients in this condition economical and logistic aspects that are difficult to implement. were receiving only pharmacotherapy (as observed by the https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 16 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al Acknowledgments The authors would like to thank Consorcio Hospitalario Provincial de Castellón, Hospital Universitario de la Ribera, and Hospital Universitario Vall d’Hebrón for their invaluable contribution to this study. This research was conducted with the financial support of grants P1-1B2014-43 (Universitat Jaume I, Castellón), a PhD grant from the Ministry of Education, Culture and Sports (FPU13/00576), and CIBER Fisiopatología de la Obesidad y Nutrición-ISCIII CB06/03/0052. 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[doi: 10.1016/S0140-6736(18)32205-0] [Medline: 30314860] Abbreviations AG: agoraphobia ANCOVA: analysis of covariance ANOVA: analysis of variance BA: behavioral activation BAI: Beck Anxiety Inventory BAS: behavioral activation scale BDI-II: Beck depression inventory, 2nd edition BI: behavioral inhibition BIS: behavioral inhibition scale CBT: cognitive behavioral therapy CONSORT: Consolidated Standards of Reporting Trials DBT: dialectical behavioral therapy DD: dysthymic disorder DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ED: emotional disorder EQ-5D-3L: EuroQoL-5D-3L questionnaire GAD: generalized anxiety disorder ITT: intention-to-treat MCAR: missing completely at random MDD: major depressive disorder MINI: mini-international neuropsychiatric interview ML: maximum likelihood NOS: not otherwise specified OCD: obsessive compulsive disorder PD: panic disorder QoL: quality of life RCI: reliable change index RCT: randomized controlled trial SAD: social anxiety disorder https://www.jmir.org/2020/7/e18220 J Med Internet Res 2020 | vol. 22 | iss. 7 | e18220 | p. 22 (page number not for citation purposes) XSL• FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH González-Robles et al SI: societal index TAU: treatment as usual UP: Unified Protocol VAS: visual analog scale Edited by G Eysenbach; submitted 14.02.20; peer-reviewed by B Sandín, L Bücker; comments to author 24.03.20; revised version received 08.04.20; accepted 08.04.20; published 07.07.20 Please cite as: González-Robles A, Díaz-García A, García-Palacios A, Roca P, Ramos-Quiroga JA, Botella C Effectiveness of a Transdiagnostic Guided Internet-Delivered Protocol for Emotional Disorders Versus Treatment as Usual in Specialized Care: Randomized Controlled Trial J Med Internet Res 2020;22(7):e18220 URL: https://www.jmir.org/2020/7/e18220 doi: 10.2196/18220 PMID: ©Alberto González-Robles, Amanda Díaz-García, Azucena García-Palacios, Pablo Roca, Josep Antoni Ramos-Quiroga, Cristina Botella. 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