Introduction
Anxiety disorders are the most common psychiatric disorders in youth (McKay & Storch, Reference McKay, Storch, McKay and Storch2023; Merikangas et al., Reference Merikangas, He, Burstein, Swanson, Avenevoli, Cui and Swendsen2010). Approximately 30% of youth around the world meet criteria for an anxiety disorder (Merikangas et al., Reference Merikangas, He, Burstein, Swanson, Avenevoli, Cui and Swendsen2010). Generalized anxiety disorder (GAD) is known as one of the most common anxiety disorders, carrying significant comorbidity, impairment, and disability (Mohammadi et al., Reference Mohammadi, Pourdehghan, Mostafavi, Hooshyari, Ahmadi and Khaleghi2020; Wittchen, Reference Wittchen2002), and if left untreated persist over time and run a chronic course (Bhatia & Goyal, Reference Bhatia and Goyal2018; Morales et al., Reference Morales, Rodríguez-Menchón, Tomczyk, Fernández-Martínez, Orgilés and Espada2020; Zemestani, Beheshti, Rezaei, van der Heiden, & Kendall, Reference Zemestani, Beheshti, Rezaei, van der Heiden and Kendall2021).
Youth living in low and middle income countries (LMICs) are at higher risk to develop anxiety disorders (Caqueo-Urízar, Flores, Escobar, Urzúa, & Irarrázaval, Reference Caqueo-Urízar, Flores, Escobar, Urzúa and Irarrázaval2020; Uppendahl, Alozkan-Sever, Cuijpers, de Vries, & Sijbrandij, Reference Uppendahl, Alozkan-Sever, Cuijpers, de Vries and Sijbrandij2020; Yatham, Sivathasan, Yoon, da Silva, & Ravindran, Reference Yatham, Sivathasan, Yoon, da Silva and Ravindran2018). Iran is considered as a LMIC based on the last World Bank classifications by income level with per capita income of less than $4255 per year (World Bank Group, 2023). Environmental stressors including poverty, unemployment, rapid socioeconomic changes, uncontrollability and unpredictability of situations, and uncertainty about future events tend to be endemic in LMICs and contribute to the development of anxiety disorders in youth (Caqueo-Urízar et al., Reference Caqueo-Urízar, Flores, Escobar, Urzúa and Irarrázaval2020; Uppendahl et al., Reference Uppendahl, Alozkan-Sever, Cuijpers, de Vries and Sijbrandij2020; Yatham et al., Reference Yatham, Sivathasan, Yoon, da Silva and Ravindran2018). In Iran, for example, a recent national epidemiological survey of youth 6–18 years, found a 14.13% prevalence of anxiety disorders (Mohammadi et al., Reference Mohammadi, Ahmadi, Khaleghi, Mostafavi, Kamali, Rahgozar and Molavi2019).
Although the prevalence rate of youth anxiety disorders in LMICs is high, the majority of these youth do not receive treatment and, of those that do, only a small minority receive treatment that is evidence-based (Cuijpers, Eylem, Karyotaki, Zhou, & Sijbrandij, Reference Cuijpers, Eylem, Karyotaki, Zhou, Sijbrandij, Stein, Bass and Hofmann2019; Ribeiro et al., Reference Ribeiro, Grande, Hoffmann, Ziebold, McDaid, Fry and Tomasi2022; Uppendahl et al., Reference Uppendahl, Alozkan-Sever, Cuijpers, de Vries and Sijbrandij2020; Yatham et al., Reference Yatham, Sivathasan, Yoon, da Silva and Ravindran2018). Low mental-health literacy, stigma relating to mental health problems, lack of accessibility to interventions due to availability of training and supervision, and the small number of available mental health professionals and expertise, outlined as the notable barriers contributing to this high non-treatment rate (Mascayano, Armijo, & Yang, Reference Mascayano, Armijo and Yang2015; Mohammadzadeh, Awang, & Mirzaei, Reference Mohammadzadeh, Awang and Mirzaei2020). There is also a growing concern that most evidence-based treatments have been developed and examined in Western countries and only a small number of these treatments has been examined in well-designed randomized controlled trials in non-western countries. Without such trials, it is uncertain whether these treatments are indeed effective in reducing mental health problems in non-Western countries (Cuijpers et al., Reference Cuijpers, Eylem, Karyotaki, Zhou, Sijbrandij, Stein, Bass and Hofmann2019; Ribeiro et al., Reference Ribeiro, Grande, Hoffmann, Ziebold, McDaid, Fry and Tomasi2022). There is a need for adaptation and dissemination of evidence-based treatments for youth with anxiety disorders in LMICs.
Several evidence-based treatments, particularly with the cognitive-behavioral therapy (CBT) approach, have been developed to address youth anxiety disorders. However, many of these treatments have been disorder-specific focusing on treating youth with a single diagnosis at a time and may lack the flexibility to adequately address comorbidity and incorporate the multitude of sometimes frequently shifting problem areas experienced by youth with anxiety disorders (e.g. emotion dysregulation, negative affectivity, intolerance of uncertainty). Developing flexible, adaptive treatment approaches (e.g. flexibility within fidelity; Kendall, Reference Kendall2022) that address the varying diagnostic profiles in youth is essential to furthering dissemination (Karlovich, Halliday, & Ehrenreich-May, Reference Karlovich, Halliday, Ehrenreich-May, McKay and Storch2023; Tonarely, Lanier, Salloum, Ehrenreich-May, & Storch, Reference Tonarely, Lanier, Salloum, Ehrenreich-May and Storch2022).
Some progress has been observed; there is some evidence suggesting that models of CBT that focus on shared underlying features of youth anxiety disorders can improve treatment outcomes (Cepeda, Grassie, & Ehrenreich-May, Reference Cepeda, Grassie and Ehrenreich-May2022; García-Escalera et al., Reference García-Escalera, Valiente, Sandín, Ehrenreich-May, Prieto and Chorot2020; Karlovich et al., Reference Karlovich, Halliday, Ehrenreich-May, McKay and Storch2023). For example, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A; Ehrenreich-May et al. Reference Ehrenreich-May, Kennedy, Sherman, Bilek, Buzzella, Bennett and Barlow2017a, Reference Ehrenreich-May, Rosenfield, Queen, Kennedy, Remmes and Barlow2017b; Ehrenreich-May & Kennedy, Reference Ehrenreich-May and Kennedy2021), targets core underlying factors that are present across different anxiety disorders and may be effective for youth with varying diagnostic profiles of anxiety disorders in LMICs due to its flexible format and transdiagnostic approach. Addressing anxiety disorders' shared underlying risk and maintenance factors during adolescence may help prevent the development of anxiety and related disorders later in life (Sandín, García-Escalera, Valiente, Espinosa, & Chorot, Reference Sandín, García-Escalera, Valiente, Espinosa and Chorot2020; Zemestani, Heshmati, Comer, & Kendall, Reference Zemestani, Heshmati, Comer and Kendall2022b).
UP-A is similar to disorder-specific CBT, but differs in that UP-A simultaneously targets the core underlying and transdiagnostic processes such as features of neuroticism including emotion dysregulation, negative affectivity, and intolerance of uncertainty rather than disorder-specific processes such as excessive worry or panic attacks. UP-A includes some of the efficacious CBT techniques traditionally found within disorder-specific protocols; however, they are conceptualized in a way that does not differentiate by specific disorders (e.g. Barlow et al., Reference Barlow, Farchione, Sauer-Zavala, Latin, Ellard, Bullis and Cassiello-Robbins2017b). For example, exposure techniques in the UP-A are focused on intense emotional experience itself more than situational cues. Compared to a disorder-specific modality, the advantage of transdiagnostic treatments is that they address comorbid presentations and can build on the similar etiological and maintenance processes underlying psychopathology shared across emotional disorders (Cuijpers et al., Reference Cuijpers, Miguel, Ciharova, Ebert, Harrer and Karyotaki2023; Pearl & Norton, Reference Pearl and Norton2021). Transdiagnostic treatments may be preferable in settings with a high demand for services and limited resources for providing diagnosis-specific treatments (Norton & Barrera, Reference Norton and Barrera2012). It can be argued that the dissemination of empirically supported treatments for youth anxiety in LMICs may be facilitated with UP-A because therapists could receive training in a single treatment for a variety anxiety and related emotional disorders rather than multiple, disorder-specific treatments.
The efficacy of UP-A has been shown across several randomized controlled trials (Ehrenreich-May et al., Reference Ehrenreich-May, Rosenfield, Queen, Kennedy, Remmes and Barlow2017b; García-Escalera et al., Reference García-Escalera, Valiente, Sandín, Ehrenreich-May, Prieto and Chorot2020; Kennedy, Bilek, & Ehrenreich-May, Reference Kennedy, Bilek and Ehrenreich-May2019; Tonarely, Sherman, Grossman, & Ehrenreich-May, Reference Tonarely, Sherman, Grossman and Ehrenreich-May2021). Although there is accumulating support, considerable ongoing work is required in to adapt to different populations (Barlow et al., Reference Barlow, Farchione, Bullis, Gallagher, Murray-Latin, Sauer-Zavala and Boswell2017a; García-Escalera et al., Reference García-Escalera, Valiente, Chorot, Ehrenreich-May, Kennedy and Sandín2017; Norton & Paulus, Reference Norton and Paulus2017; Tonarely et al., Reference Tonarely, Lanier, Salloum, Ehrenreich-May and Storch2022). Following calls for further research on the dissemination of evidence-based treatments for youth in LMICs (Murray et al., Reference Murray, Dorsey, Skavenski, Kasoma, Imasiku, Bolton and Cohen2013; Ribeiro et al., Reference Ribeiro, Grande, Hoffmann, Ziebold, McDaid, Fry and Tomasi2022) we examined the effectiveness of culturally-adapted UP-A for Iranian youth with anxiety disorders v. a waitlist control (WLC) condition. We hypothesized that culturally-adapted UP-A would show superior efficacy in comparison to WLC for reducing (a) comorbid anxiety symptoms, (b) emotion dysregulation, and (c) intolerance of uncertainty.
Method
Study design
A CONSORT compliant (Schulz, Altman, & Moher, Reference Schulz, Altman and Moher2010) RCT design compared a group who received culturally-adapted UP-A to a WLC. The trial was registered at Iranian Registry of Clinical Trials [IRCT20220303054173N1; https://www.irct.ir/trial/62329], and ethical approval was obtained from the University of Kurdistan Research Ethics Committee [IR.UOK.REC.1400.033] which followed the Declaration of Helsinki for the ethical principles of medical research involving humans.
Participants and procedure
Participants included 60 adolescents aged between 15 and 17 with anxiety symptoms who were recruited from the high school counsceling centers in the Sanandaj (Iran) between September and December 2021 through referrals from the school counseling centers. The required sample size was calculated a priori based on a medium effect size using the G*Power program and resulted in a minimum total sample size of 38 (repeated measures between factorial design, f = 0.50, α = 0.05, power = 0.95). Information about the study was given to the school psychologists/counsellors and they were encouraged to refer potentially eligible students with anxiety symptoms, with the permission of their family, to the research team. Adolescents interested in the study were screened for anxiety usiung the Youth Anxiety Measure for DSM-5 (YAM-5; Muris et al., Reference Muris, Simon, Lijphart, Bos, Hale and Schmeitz2017b), and those reporting anxiety symptoms were subsequently contacted and invited to take part in a face-to-face eligibility and clinical assessment in an outpatient clinic, with the permission of their family. The clinical assessment included the Persian version of the anxiety and related disorders interview schedule for DSM-5, (ADIS-5-C/P; Albano & Silverman, Reference Albano and Silverman2016). Interviews were carried out by a qualified, master's-level clinical psychologist with extensive training in the assessment of anxiety disorders.
Participants had to meet the following inclusion criteria: DSM-5 (American Psychiatric Association, 2013) criteria for a principal anxiety disorder diagnosis and one comorbid anxiety disorder symptoms using the Persian version of the ADIS-5-C/P (Albano & Silverman, Reference Albano and Silverman2016), being aged between 15 and 17, voluntary participation and provide informed consent. Severe psychiatric or physical illness, prominent active suicidal ideation, substance abuse or dependence, completion of a course of CBT (eight or more sessions) in the past six months were exclusion criteria. Of the 186 referrals, 107 students did not meet the inclusion criteria, and 19 students declined to participate. The remaining of 60 eligible and interested adolescents were randomized to either the UP-A (n = 30) or WLC (n = 30). Randomization, in ratio of 1:1, was conducted using a computer-generated algorithm in a parallel study design to ensure balanced groups. The CONSORT diagram is presented in Fig. 1.
CONSORT diagram of participants’ flow.
Intervention
Culturally-adapted unified protocol for transdiagnostic treatment of emotional disorders in adolescents (UP-A)
The UP-A (Ehrenreich-May et al., Reference Ehrenreich-May, Kennedy, Sherman, Bilek, Buzzella, Bennett and Barlow2017a; Ehrenreich-May & Kennedy, Reference Ehrenreich-May and Kennedy2021) is a youth adaptation of the original adult UP protocol (Barlow et al., Reference Barlow, Ellard, Fairholme, Farchione, Boisseau, Allen and Ehrenreich-May2011). Similar to the UP, the UP-A is a flexibly administered transdiagnostic, emotion-focused treatment protocol with the goal of targeting shared underlying and maintenance factors across emotional disorders. The protocol is designed to improve emotion reactivity and regulation and ameliorate anxiety and depressive symptoms using an array of evidence-based treatment techniques (e.g. psychoeducation, motivational enhancement, cognitive restructuring, exposure, behavioral activation, mindfulness, relapse prevention, etc.). The flexible format of protocol allows therapists to use traditional therapeutic techniques in various cultural contexts.
The culturally adapted UP-A manual includes the same eight core modules of the original UP-A protocol (Ehrenreich-May et al., Reference Ehrenreich-May, Kennedy, Sherman, Bilek, Buzzella, Bennett and Barlow2017a; Ehrenreich-May & Kennedy, Reference Ehrenreich-May and Kennedy2021) and participants are advised to complete one module per week (except for module seven, which usually takes one more week to complete). Participants were scheduled for nine weekly 60-min group in-person sessions following a language and culturally adapted manual for Persian speaking adolescents, developed for purposes of the present study. Treatment rationale, model, and objectives followed the original UP-A. In addition, the sessions included language and cultural adaptations with tailoring the language to be culturally appropriate. Adaptations were based on results from related empirical studies (e.g. Acarturk et al., Reference Acarturk, Alyanak, Cetinkaya, Gulen, Jalal and Hinton2019; Zemestani, Imani, & Ottaviani, Reference Zemestani, Imani and Ottaviani2017) as well as the experiences of the therapists who have treated anxious Iranian adolescents.
In general, the most common language and cultural adaptations were related to the Irani Persian language as well as local meanings of mental health and psychotherapy, local conceptualizations of the mental and somatic symptoms and workings of the mind and body, local meaning of emotions and anxiety, local meaning of cognitive flexibility, exposure exercises, tolerating and accepting uncomfortable emotions, and other integration of culturally relevant, locally accepted vocabulary, terms, concepts, phrases, idioms, images, stories, poems, and songs to engage the adolescents in treatment.
First session included enhancing motivation and psychoeducation regarding mental health problems and barriers in receiving psychotherapy in Iran due to the low mental health literacy and high stigma (e.g. being mad or crazy). The middle sessions included psychoeducation regarding uncomfortable emotions (e.g. cognitive, emotional, and somatic presentations of uncomfortable emotions particularly anxiety), how to experience these emotions and how to respond to them in more flexible, adaptive, non-avoidant ways, with Iranian language and cultural adaptions. The language and culturally adapted UP-A manual specifically elicits and addresses the adolescent's understanding of somatic symptoms of different emotional states and specifically addresses understanding of the physiology of these states, and the Iranians' idioms of anxiety, depression, stress, distress, crying, laughing, calming: in the case of Persian language, concerns about ‘anxiety’ or ‘ezterab’, ‘depression’ or ‘afsordegi’, ‘stress’ or ‘tanesh’, ‘distress’ or ‘parishani’, ‘crying’ or ‘geryeh’, ‘laughing’ or ‘xande’, ‘calming’ or ‘aramesh’.
Because emotion regulation, emotional flexibility, and acceptance are key components of UP-A, the language and culturally adapted UP-A manual placed particular emphasis on these components, and helped adolescents learn how to experience uncomfortable emotions and how to respond to them in more flexible, adaptive, non-avoidant ways. All sessions had essential objectives that included reviewing homework assignments and discussion of events between sessions, in-session exposure and mindfulness practices, and metaphors adapted to Iranian culture. Within the in-session exposure and mindfulness practices, after eliciting recent uncomfortable emotional experience we asked each adolescent to practice an exposure protocol that involved a series of steps, each of which was an emotion regulation technique: acceptance, decentering/distancing, loving-kindness meditation, living-in-the-present, mindfulness meditation, and applied muscle relaxation with a visualization encoding psychological and emotional flexibility. Please see Table 1 for a summary of adapted UP-A content.
Culturally adapted UP-A for Iranian adolescents with anxiety disorders: A brief overview
The therapist for the study was a master's-level clinical psychologist with 2 years experience. The therapist underwent extensive training in the UP protocol and certification prior to treating study patients. The administration of treatment was completely separate from research assessments and data analysis. All therapy sessions were audiotaped and files were saved using the session number to protect participants' confidentiality. Supervisors listened to audiotaped sessions and monitored treatment adherence during weekly supervision. The supervisor was an associate professor in psychology with a certified specialty in transdiagnostic CBT.
Waitlist Control (WLC)
Adolescents in the WLC condition were asked to come in to the clinic to review their mental health status and complete study self-report measures in-person at baseline, 9-weeks (equivalent to posttreatment), and 13-weeks (equivalent to one-month follow-up), in the 30–45 min duration sessions. Following completion of the WLC, participants were offered nine group sessions of UP-A.
Outcome measures
Screening and eligibility
The Anxiety Disorders Interview Schedule for DSM-5, Child and Parent Version (ADIS-5-C/P; Albano & Silverman, Reference Albano and Silverman2016). The ADIS-5-C/P is a semi-structured diagnostic interview designed to assess children and adolescents in accordance with the DSM-5 based upon child and parent report. All participants, and at least one parent, were interviewed separately with ADIS-C/P and the information combined for diagnosis. For each diagnosis, a clinical severity rating (CSR) is assigned ranging from 0 to 8 (0 = none, 8 = very severely disturbing/disabling), where a score of 4 or greater indicates that a disorder meets DSM-5 criteria. Principal diagnosis is the most impairing diagnosis, as determined by a CSR at least one point above the CSR for other diagnoses. Other co-occurring diagnoses are referred to as additional diagnoses. Previous research indicates that the ADIS-IV-C/P has demonstrated excellent interrater and retest reliability, good concurrent validity, and adequate convergent validity (Lyneham, Abbott, & Rapee, Reference Lyneham, Abbott and Rapee2007; Wood, Piacentini, Bergman, McCracken, & Barrios, Reference Wood, Piacentini, Bergman, McCracken and Barrios2002). In a recent study, the ADIS-5-C/P evidenced interrater reliability of 0.87 for the child interview and 0.96 for the parent interview (Rifkin & Kendall, Reference Rifkin and Kendall2020). Research on psychometric properties of the Persian version of ADIS-5-CP is not available, however, the instrument is widely used by clinicians in specialist health services.
Primary outcome measure
Youth Anxiety Measure for DSM-5 (YAM-5; Muris et al., Reference Muris, Simon, Lijphart, Bos, Hale and Schmeitz2017b). The YAM-5 is a 50-item self- and parent-report questionnaire assessing anxiety disorder symptoms in children and adolescents aged 8 to 18 years. The YAM-5 consisted of two parts: Part I (28 items) taps symptoms of the major DSM-5 anxiety disorders, and contains the following subscales: separation anxiety disorder (6 items), selective mutism (4 items), social anxiety disorder (6 items), panic disorder (6 items), and GAD (6 items). Part II (22 items) also contains 5 subscales covering the phobia types: animal (5 items), natural environment (4 items), blood-injection-injury (3 items), other (4 items), and situational which in terms of fear content resembles agoraphobia (6 items). Each item is scored on a 4-point Likert scale, ranging from 0 (never) to 3 (always), yielding a total score ranging from 0 to 150, with higher scores indicating greater level of anxiety symptoms. This measure has been studied in clinical and community samples and has demonstrated psychometric properties including internal consistency, retest reliability, concurrent and construct validity (Garcia-Lopez, Saez-Castillo, & Fuentes-Rodriguez, Reference Garcia-Lopez, Saez-Castillo and Fuentes-Rodriguez2017; Muris, Mannens, Peters, & Meesters, Reference Muris, Mannens, Peters and Meesters2017a; Simon, Bos, Verboon, Smeekens, & Muris, Reference Simon, Bos, Verboon, Smeekens and Muris2017). We used the Persian self-report version of YAM-5 (Soltani, Bazrafshan, Sarani, Hedayati, & Sheikholeslami, Reference Soltani, Bazrafshan, Sarani, Hedayati and Sheikholeslami2020), which has demonstrated psychometric properties with a Cronbach's alpha coefficient of 0.84 and 0.78 for YAM-I and YAM-II, respectively. Internal consistency reliability for the total items in the current study was α = 0.79.
Process of change measures
Emotion Regulation Questionnaire-Children and Adolescents (ERQ-CA; Gullone & Taffe, Reference Gullone and Taffe2012). The ERQ-CA is a 10-item self-report measure assessing two emotion regulation strategies of cognitive reappraisal (CR, 6 items) and expressive suppression (ES, 4 items) in youth aged 10 to 18 (Gullone & Taffe, Reference Gullone and Taffe2012). Items are scored on a 5-point Likert-type response scale ranging from 1 (strongly disagree) to 5 (strongly agree), with higher scores on each scale reflecting greater use of the corresponding emotion regulation strategy. The range of scores for each subscale is 6 to 30 for the CR and 4 to 20 for the ES. This measure has demonstrated good psychometric properties. Gullone and Taffe (Reference Gullone and Taffe2012) reported internal consistency for the ERQ-CA strategies (α = 0.82 to 0.86 for CR scale and α = 0.69 to 0.79 for ES scale). Sound convergent and construct validity for the ERQ-CA was also reported. The Persian version of the ERQ-CA (Lotfi et al., Reference Lotfi, Bahrampouri, Amini, Fatemitabar, Birashk, Entezari and Shiasy2019) was used in the present study, which has demonstrated a Cronbach's alpha coefficient of 0.79 and 0.68 for CR and ES, respectively. In the current study, internal consistency reliability for the CR and ES scales were α = 0.73 and 0.76, respectively.
Intolerance of Uncertainty Scale for Children (IUSC; Comer et al., Reference Comer, Roy, Furr, Gotimer, Beidas, Dugas and Kendall2009; Cornacchio et al., Reference Cornacchio, Sanchez, Coxe, Roy, Pincus, Read and Comer2018). The IUSC is a 12-item self- and parent-report measure assessing two dimentions of IU (prospective IU, 6 items and inhibitory IU, 6 items) in youth aged 8 to 18 years. Items are scored on a 5-point scale ranging from 1 (not at all) to 5 (very much). A total IU score, consisting of the sum of the two subscales, assess overall IU, with higher scores indicating greater IU. This scale has demonstrated good psychometric properties in youth with and without anxiety disorders. Cornacchio et al. (Reference Cornacchio, Sanchez, Coxe, Roy, Pincus, Read and Comer2018) reported internal consistency for the IUSC-12 total score (α = 0.87 for child-report and α = 0.97 for parent-report). The Persian self- report version of the IUSC-12 (Zemestani, Didehban, Comer, & Kendall, Reference Zemestani, Didehban, Comer and Kendall2022a) was used in the present study, which has demonstrated a Cronbach's alpha coefficient of 0.85, 0.84, and 0.87 for prospective-IU, inhibitory-IU, and total scores respectively. In the present study, internal consistency reliability for the total scores of scale was α = 0.89.
Statistical analyses
All statistical analyses were conducted using IBM Statistical Package for the Social Sciences (SPSS) for Windows, Version 27 (SPSS Inc., New York, USA). Independent two-samples t tests (for continuous variables) and χ2 (for categorical variables) were used to compare the group differences at baseline. The effects of treatment on the primary outcomes (YAM-5), and process of change measures (ERQ-CA and IUSC-12) were examined using the repeated measures ANOVA with time (pre-, post-, follow-up) as the within-subject factor and group (UP-A v. WLC) as the between-subject factor. Mauchly's test was used to evaluate the sphericity of the data before performing the repeated measures ANOVA. Within- and between-group effect sizes were reported based on Cohen's d using the SPSS-27, which uses the sample standard deviation of the mean difference for within group effect sizes and the pooled standard deviation for between-group effect sizes. By convention, a Cohen's d effect size of 0.2 is considered ‘small’, 0.5 ‘medium’, 0.8 and up ‘large’ (Cohen, Reference Cohen1992). These effects may be useful for estimation of the range of potential effect sizes in subsequent studies and comparison to effect sizes of other interventions. Significant results were followed by pairwise comparisons for pre- to post-treatment, pretreatment to follow-up, and posttreatment to follow-up with Bonferroni corrections applied. p < 0.05 (2-tailed) was considered statistically significant.
Results
Sixty participants were randomly assigned to the UP-A (N = 30; Mage = 16.16, s.d. = 0.74), or WLC (N = 30; Mage = 16.03, s.d. = 0.71) groups. The total sample included 34 males (56.7%) and 26 females (43.3%), with a mean age of 16.10 years (±s.d. = 0.72), range 15–17 years. Table 2 shows the demographic and clinical characteristics of the total sample. All participants had one principal anxiety disorder diagnosis and one comorbid anxiety disorder symptoms. Results from the independent sample t tests and χ2 analyses showed no significant differences (p > 0.05) between two groups with respect to sociodemographic or clinical characteristics, indicating successful randomization.
Demographic and clinical characteristics of the all participants
Note. UP-A, Unified Protocol for transdiagnostic treatment of emotional disorders in adolescents; WLC, Wait-list control.
a Based on t test for age and χ2-test for all other demographic variable.
Means, standard deviations, and effect size estimates reflecting between-condition (UP-A v. WLC) differences at post-treatment and follow-up are shown in Table 3. Results of the between-condition effects on the primary outcome measure showed significant differences between the UP and WLC conditions at post-treatment and follow-up in the major DSM-5 anxiety disorder symptoms [YAM-5-Part I; t post = −11.41, p < 0.001, Cohen's d = −2.00, 95% CI (−2.64 ± −1.35); t follow = −10.67, p < 0.001, Cohen's d = −1.82, 95% CI (−2.45 ± −1.18)], phobia type symptoms [YAM-5-Part II; t post = −16.64, p < 0.001, Cohen's d = −2.10, 95% CI (−2.74 ± −1.44); t follow = −14.94, p < 0.001, Cohen's d = −1.94 (−2.59 ± −1.28)], and overall anxiety symptoms [YAM-5-Total; t post = −29.40, p < 0.001, Cohen's d = −2.31, 95% CI [−2.98 ± −1.63); t follow = −25.62, p < 0.001, Cohen's d = −2.61, 95% CI (−3.33 ± −1.87)].
Symptoms and functioning over time: means, standard deviations and between-condition effect sizes
Note. UP-A, Unified Protocol for transdiagnostic treatment of emotional disorders in adolescents; WLC, Wait-list control; YAM-5, Youth Anxiety Measure for DSM-5; ERQ-CA, Emotion Regulation Questionnaire-Children and Adolescents; IUSC, Intolerance of Uncertainty Scale for Children.
a Between condition effect size uses the pooled standard deviation.
Results of the pairwise comparision and within-condition effects demonstraited that scores on the major anxiety disorder symptoms [YAM-5-Part I; t pre-post = 13.82, p < 0.001, Cohen's d = 2.46, 95% CI (1.72 ± 3.20); t pre-follow = 13.00, p < 0.001, Cohen's d = 2.13, 95% CI (1.45 ± 2.80)], phobia type symptoms [YAM-5-Part II; t pre-post = 16.66, p < 0.001, Cohen's d = 2.10, 95% CI (1.45 ± 2.74); t pre-follow = 15.07, p < 0.001, Cohen's d = 2.06, 95% CI (1.39 ± 2.70)], and overall anxiety symptoms [YAM-5-Total; t pre-post = 31.86, p < 0.001, Cohen's d = 2.19, 95% CI (1.52 ± 2.58); t pre-follow = 28.07, p < 0.001, Cohen's d = 2.76, 95% CI (1.93 ± 3.57)], significantly decreseed from pre- to post-treatment and from pre to follow-up in the UP-A, but not the WLC group (See Table 4).
Results of the pairwise comparisons and within-condition effect sizes
Note. UP-A, Unified Protocol for transdiagnostic treatment of emotional disorders in adolescents; WLC, Wait-list control; YAM-5, Youth Anxiety Measure for DSM-5; ERQ-CA, Emotion Regulation Questionnaire-Children and Adolescents; IUSC, Intolerance of Uncertainty Scale for Children.
a positive values denote a decrease between timeframes.
b Within condition effect size uses the sample standard deviation of the mean difference.
* p < 0.05.
A repeated measure ANOVA tested for an overall time by group effect on the primary outcome measure between two groups (UP-A v. WLC) and over three time points (pre, post, follow-up). A significant interaction effect of Time × Group was observed for major anxiety disorder symptoms (YAM-5-part I; F (2, 51) = 117.09, p < 0.001), phobia type symptoms (YAM-5-part II; F (2, 51) = 100.67, p < 0.001), and overall anxiety symptoms (YAM-5-Total; F (2, 51) = 196.29, p < 0.001), in favor of UP-A over WLC (See Table 5; Fig. 2 panels A-C).
Results of the repeated measure ANOVA on outcome measures
Note. UP-A, Unified Protocol for transdiagnostic treatment of emotional disorders in adolescents; WLC, Wait-list control; YAM-5, Youth Anxiety Measure for DSM-5; ERQ-CA, Emotion Regulation Questionnaire-Children and Adolescents; IUSC, Intolerance of Uncertainty Scale for Children.
Plots of mean outcome scores over time by treatment condition. This figure shows the trajectories of the mean scores for UP-A and WLC conditions: Youth Anxiety Measure for DSM-5 (YAM-5; panels A-C), Emotion Regulation Questionnaire-Children and Adolescents (ERQ-CA; panels D-E), Intolerance of Uncertainty Scale for Children (IUSC; panels F-H).
Results of the between-condition effects on the process of change outcomes also showed significant differences between the UP and WLC conditions at post-treatment and follow-up in the emotion regulation strategies of reappraisal [t post = 4.85, p < 0.001, Cohen's d = 1.30, 95% CI (0.72 ± 1.87); t follow = 3.86, p < 0.001, Cohen's d = 1.07, 95% CI (0.50 ± 1.64)], and suppression [t post = −2.85, p < 0.001, Cohen's d = −1.11, 95% CI (−1.68 ± −0.55); t follow = −2.76, p < 0.001, Cohen's d = −1.07 (−1.64 ± −0.49)], as well as intolerance of uncertainty dimensions of prospective IU [t post = −6.28, p < 0.001, Cohen's d = −1.36, 95% CI (−1.94 ± −0.77]; t follow = −6.03, p < 0.001, Cohen's d = −1.35, 95% CI (−1.94 ± −0.75)], inhibitory IU [t post = −5.11, p < 0.001, Cohen's d = −1.57, 95% CI (−2.16 ± −0.96); t follow = −4.68, p < 0.001, Cohen's d = −1.37, 95% CI (−1.96 ± −0.77)], and total IU [t post = −11.40, p < 0.001, Cohen's d = −1.66, 95% CI (−2.27 ± −1.05); t follow = −10.71, p < 0.001, Cohen's d = −1.54, 95% CI (−2.14 ± −0.92)] (See Table 3).
Results of the pairwise comparision and within-condition effects on the process of change outcomes demonstraited that scores on the emotion regulation strategies of reappraisal [t pre-post = −4.41, p < 0.001, Cohen's d = −1.14, 95% CI (−1.60 ± −0.66); t pre-follow = −3.71, p < 0.001, Cohen's d = −1.04, 95% CI (−1.49 ± −0.57)], and suppression [t pre-post = 3.65, p < 0.001, Cohen's d = 1.27, 95% CI (0.77 ± 1.76); t pre-follow = 3.21, p < 0.001, Cohen's d = 1.12, 95% CI (0.64 ± 1.59)], as well as intolerance of uncertainty dimensions of prospective IU [t pre-post = 6.37, p < 0.001, Cohen's d = 2.02, 95% CI (1.38 ± 2.66); t pre-follow = 6.03, p < 0.001, Cohen's d = 1.82, 95% CI (1.20 ± 2.42)], inhibitory IU [t pre-post = 5.31, p < 0.001, Cohen's d = 1.50, 95% CI (0.96 ± 2.03); t pre−follow = 4.96, p < 0.001, Cohen's d = 1.35, 95% CI (0.82 ± 1.85)], and total IU [t pre-post = 11.68, p < 0.001, Cohen's d = 2.11, 95% CI (1.44 ± 2.76); t pre-follow = 11.00, p < 0.001, Cohen's d = 1.86, 95% CI (1.42 ± 2.73)], significantly changed from pre- to post-treatment and from pre to follow-up in the UP-A, but not the WLC group (See Table 4).
Another set of repeated measure ANOVA tested for Time × Group effects on the process of change variables for assessing transdiagnostic processes underlying anxiety disorders. Results indicated a significant interaction effect of time × group for emotion regulation strategies of reappraisal (F (2, 51) = 17.03, p < 0.001), and suppression (F (2, 51) = 21.13, p < 0.001), as well as intolerance of uncertainty dimensions of prospective IU (F (2, 51) = 74.49, p < 0.001), inhibitory IU (F (2, 51) = 45.94, p < 0.001), and total IU (F (2, 51) = 84.42, p < 0.001), in favor of UP-A over WLC (See Table 5; Fig. 2 panels A–C).
Discussion
This study examined the outcomes/efficacy of a culturally adapted UP-A for the treatment of Iranian adolescents with anxiety disorders. As predicted, results showed UP-A was efficacious for anxiety disorders with significantly greater reductions in symptom severity for those in the UP-A treatment compared to those in the WLC at both posttreatment and follow-up. This RCT was conducted in a LMIC Middle East country whereas much of the transdiagnostic treatment literature arises from North America and Europe. Most psychological treatments that are evidence-based have been developed in Western countries and these treatments are rarely examined in RCTs in non-Western countries (Cuijpers et al., Reference Cuijpers, Eylem, Karyotaki, Zhou, Sijbrandij, Stein, Bass and Hofmann2019). Results from this RCT provide a cultural application of the UP-A for the treatment of anxiety disorders at non-Western countries and the findings suggest that the culturally adapted UP-A is an efficacious treatment for anxiety disorders in Iranian adolescents.
It is plausible that the achieved significant reduction in symptoms of anxiety may be the result of change in underlying transdiagnostic mechanisms related to anxiety. We investigated core transdiagnostic factors and, as expected, UP-A had a positive effect on reducing transdiagnostic factors: results indicated changes in both emotion regulation strategies and intolerance of uncertainty, so for those treated than those in the WLC at posttreatment and at follow-up. These findings support the general framework of a unified protocol (Barlow et al., Reference Barlow, Farchione, Sauer-Zavala, Latin, Ellard, Bullis and Cassiello-Robbins2017b; Barlow, Allen, & Choate, Reference Barlow, Allen and Choate2016; Zemestani, Ommati, Rezaei, & Gallagher, Reference Zemestani, Ommati, Rezaei and Gallagher2022), which states that changes in underlying mechanisms (e.g. emotion dysregulation, negative affectivity, intolerance of uncertainty) will simultaneously improve an individual's emotional disorder symptoms. Indeed, consistent with the present findings, changes in shared mechanisms during treatment were associated with symptom reductions. These findings are consistent with conceptual models and recent findings (Cepeda et al., Reference Cepeda, Grassie and Ehrenreich-May2022; Ehrenreich-May et al., Reference Ehrenreich-May, Rosenfield, Queen, Kennedy, Remmes and Barlow2017b; García-Escalera et al., Reference García-Escalera, Chorot, Sandín, Ehrenreich-May, Prieto and Valiente2019; Kennedy et al., Reference Kennedy, Bilek and Ehrenreich-May2019; Kennedy, Tonarely, Halliday, & Ehrenreich-May, Reference Kennedy, Tonarely, Halliday and Ehrenreich-May2022; Tonarely-Busto et al., Reference Tonarely-Busto, Phillips, Saez-Clarke, Karlovich, Kudryk, Lewin and Ehrenreich-May2022).
The present findings showed that directly targeting emotions in treatment can lead to improvements in anxiety symptoms. These findings are consistent with conceptualization that emotion regulation strategies are associated with emotional disorder symptoms (Aldao, Gee, De Los Reyes, & Seager, Reference Aldao, Gee, De Los Reyes and Seager2016; Cludius, Mennin, & Ehring, Reference Cludius, Mennin and Ehring2020; Gross & Jazaieri, Reference Gross and Jazaieri2014; Sloan et al., Reference Sloan, Hall, Moulding, Bryce, Mildred and Staiger2017). UP-A is an emotion-focused approach coupled with CBT skills in a unified intervention. As such, a unified protocol is a potential treatment for addressing underlying deficits in emotion regulation as a core transdiagnostic and maintaining risk factor.
Another mechanism that perpetuates youth anxiety disorders is intolerance of uncertainty (Dugas, Laugesen, & Bukowski, Reference Dugas, Laugesen and Bukowski2012; Rifkin & Kendall, Reference Rifkin and Kendall2020; Rosser, Reference Rosser2019). Findings of this study showed that UP-A had a beneficial effect on reducing IU and symptoms of anxiety. Within a CBT framework, IU is considered a dispositional characteristic that results from a set of dysfunctional negative beliefs about uncertainty and its implications (Carleton, 2012; Dugas & Robichaud, Reference Dugas and Robichaud2007; Hebert & Dugas, Reference Hebert and Dugas2018; Jacoby, Reference Jacoby, Abramowitz and Blakey2020). A growing body of evidence highlights the role of IU as a transdiagnostic risk factor that underlies a range of anxiety disorders in youth (Cornacchio et al., Reference Cornacchio, Sanchez, Coxe, Roy, Pincus, Read and Comer2018; Correa, Liu, & Shankman, Reference Correa, Liu and Shankman2019; Osmanağaoğlu, Creswell, & Dodd, Reference Osmanağaoğlu, Creswell and Dodd2018; Zemestani, Heshmati, et al., Reference Zemestani, Heshmati, Comer and Kendall2022b). Recent evidence supports the notion that IU is a mechanism of change in treatments for anxiety (Bomyea et al., Reference Bomyea, Ramsawh, Ball, Taylor, Paulus, Lang and Stein2015; Perrin, Bevan, Payne, & Bolton, Reference Perrin, Bevan, Payne and Bolton2019; Talkovsky & Norton, Reference Talkovsky and Norton2016; Wahlund et al., Reference Wahlund, Andersson, Jolstedt, Perrin, Vigerland and Serlachius2019; Zemestani et al., Reference Zemestani, Beheshti, Rezaei, van der Heiden and Kendall2021). These findings have positioned IU as a transdiagnostic and trans-therapy mechanism of change (Boswell, Thompson-Hollands, Farchione, & Barlow, Reference Boswell, Thompson-Hollands, Farchione and Barlow2013). Therefore, targeting IU could have the potential for reducing symptoms of comorbid anxiety disorders.
Some limitations warrant mention. The study's relatively small sample size limits the precision of the reported effect sizes. A larger study with greater statistical power is needed to obtain more precise estimates of the effects of treatment on outcome variables. A comparison of the treatment to a condition other than waitlist will add to the confidence one can have in its efficacy. The outcome measures were self-report, highlighting the need for multimethod assessment to reduce reporter bias. Although ADIS-5-CP is a widely used instrument in Iranian health services, research on psychometric properties of the Persian version of this instrument is not available. Another limitation was the follow-up period. Future studies are needed to assess the longer durability of treatment effects. Moreover, almost 10 percent of the initial sample was lost to drop-out with higher rate in boys. Although drop-out from treatment outcome studies is common and the rate of attrition in our study was lower than what was reported in both a recent meta-analysis of transdiagnostic CBT for anxiety disorders (28%; Pearl & Norton, Reference Pearl and Norton2017) and in a recent RCT in this field (35%; Plamondon & Provencher, Reference Plamondon and Provencher2022), a better understanding of factors contributing to drop-out has the potential to prevent it and strengthen the treatment outcomes (Bentley et al., Reference Bentley, Cohen, Kim, Bullis, Nauphal, Cassiello-Robbins and Barlow2021). Although drop-out rate was higher in boys and reasons for drop-out were not available in our study, results from previous studies (Bentley et al., Reference Bentley, Cohen, Kim, Bullis, Nauphal, Cassiello-Robbins and Barlow2021; Pearl & Norton, Reference Pearl and Norton2017; Plamondon & Provencher, Reference Plamondon and Provencher2022) suggest that considering both treatment-related factors (treatment credibility, therapist training, sessions timing) and child-related factors (gender, age, education, severity of symptoms) in transdiagnostic CBT. Future studies in LMICs are needed to assess the potential reasons for drop-out in delivering UP-A in these countries to prevent it and augment the treatment outcomes. Lastly, the UP-A protocol was administered by a master's-level clinical psychologist, calling into question whether the treatment might be effectively administered by providers with less formal training. As the time and costs required for training professional clinicians are two of the largest barriers to the dissemination of empirically supported treatments in LMICs (Cuijpers et al., Reference Cuijpers, Eylem, Karyotaki, Zhou, Sijbrandij, Stein, Bass and Hofmann2019; Mascayano et al., Reference Mascayano, Armijo and Yang2015), this question warrants further exploration. Future research should use multiple Ph.D. level therapists to increase generalizability of findings.
The above limitations notwithstanding, the current RCT was conducted in a LMIC Middle East country. Results from this RCT adds to the growing body of literature and provide a cultural application of the UP-A for the treatment of anxiety and related disorders in non-Western countries. While further research on UP-A for anxiety disorders is warranted, findings suggest that the culturally adapted UP-A is an efficacious treatment for anxiety disorders in Iranian adolescents. The results of this RCT will be disseminated through convincing mental health policy makers for implementing the UP-A in clinical settings. Although evidence from LMICs suggests that enforcement of mental health policies and dissemination of updated clinical guidelines in this countries is generally difficult, given the low mental health literacy and stigma about receiving psychotherapy, economic problems, lack of accessibility to interventions due to availability of training and supervision, and the small number of available mental health professionals and expertise (Mascayano et al., Reference Mascayano, Armijo and Yang2015; Mohammadzadeh et al., Reference Mohammadzadeh, Awang and Mirzaei2020), which may limit dissemination of UP-A. Using web-based transdiagnostic interventions with limited mental health professionals training to deliver self-help and guided therapies (Bernecker, Williams, Caporale-Berkowitz, Wasil, & Constantino, Reference Bernecker, Williams, Caporale-Berkowitz, Wasil and Constantino2020; Bockting, Williams, Carswell, & Grech, Reference Bockting, Williams, Carswell and Grech2016; Carter, Araya, Anjur, Deng, & Naslund, Reference Carter, Araya, Anjur, Deng and Naslund2021) is likely to be an alternative and/or additional low-cost strategy to improve access to evidence-based therapies and increase the number of individuals that receive mental health services in LMICs.
Acknowledgments
The authors would like to gratefully acknowledge the commitment of individuals who participated in the study.
Authors’ contributions
Mehdi Zemestani: Conceptualization, Methodology, Supervision, Writing-original draft- Review & Editing. Saman Ezzati: Literature searches, Investigation, Project administration, Data curation, Formal analysis. Farzad Nasiri: Adviser, Review & Editing, Technical suggestions, Validation. Matthew W. Gallagher: Methodology, Data curation, Review & Editing. David H. Barlow: Conceptualization, Review & Editing, Technical suggestions, Validation. Philip C. Kendall: Review & Editing, Technical suggestions, Validation. All authors contributed significantly to the study and approved the final version of the manuscript.
Financial support
None.
Competing interest
The authors declare that they have no conflicts of interest.
Ethical standards
The trial was registered at Iranian Registry of Clinical Trials [IRCT20220303054173N1; https://www.irct.ir/trial/62329], and ethical approval was obtained from the University of Kurdistan Research Ethics Committee [IR.UOK.REC.1400.033] which followed the Declaration of Helsinki for the ethical principles of medical research involving humans.
Informed consent
Informed consent was obtained from all participants.
Data availability
The data that support the findings of this study are available on request from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.
