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Comorbidity and diagnosis distribution in transdiagnostic treatments for emotional disorders: A systematic review of randomized controlled trials

  • Alberto González-Robles ,

    Roles Conceptualization, Formal analysis, Methodology, Writing – original draft

    vrobles@uji.es

    Affiliation Department of Basic and Clinical Psychology, and Psychobiology, Universitat Jaume I, Castellon, Spain

  • Amanda Díaz-García,

    Roles Data curation, Writing – original draft

    Affiliation Department of Basic and Clinical Psychology, and Psychobiology, Universitat Jaume I, Castellon, Spain

  • Clara Miguel,

    Roles Data curation, Writing – original draft

    Affiliation Department of Basic and Clinical Psychology, and Psychobiology, Universitat Jaume I, Castellon, Spain

  • Azucena García-Palacios,

    Roles Conceptualization, Supervision, Writing – review & editing

    Affiliations Department of Basic and Clinical Psychology, and Psychobiology, Universitat Jaume I, Castellon, Spain, CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain

  • Cristina Botella

    Roles Conceptualization, Funding acquisition, Supervision, Writing – review & editing

    Affiliations Department of Basic and Clinical Psychology, and Psychobiology, Universitat Jaume I, Castellon, Spain, CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain

Abstract

The advantages of transdiagnostic protocols for emotional disorders (ED) (anxiety and depression) include the ability to treat multiple psychological disorders using the same treatment protocol, and the capacity to better address comorbidity. Comorbidity in ED has been associated with higher rates of severity, functional impairment, and chronicity. However, no attempts have been made in the literature to systematically review whether these studies include assessments to evaluate the treatment response in comorbid diagnoses, in addition to the principal diagnosis. Moreover, transdiagnostic treatments have been developed for a range of ED, but to date no study has analyzed the real distribution of diagnoses in these studies. The current study aimed to analyze: a) whether treatment response in comorbidity is evaluated in transdiagnostic treatments for ED; b) what diagnoses are targeted in transdiagnostic treatments for ED; and c) the real distribution of the diagnoses at baseline in these studies. A systematic search of the literature was conducted in PsycINFO, PubMed, EMBASE, and the Cochrane Library. Fifty-two randomized controlled trials were identified, with a total of 7007 adult participants. The results showed that, although most of the studies reported data on comorbidity at baseline, only 40% of them examined the effects of the intervention on the comorbid disorders. The most commonly targeted diagnoses in transdiagnostic protocols were panic/agoraphobia, generalized anxiety, social anxiety, and depression. Other disorders, such as obsessive-compulsive disorder, posttraumatic stress disorder, and anxiety/depression not otherwise specified, were marginally included in these studies. Regarding the distribution of diagnoses at baseline, generalized anxiety, panic/agoraphobia, social anxiety, and depression were the most frequently observed, whereas depression not otherwise specified was the least represented. The results highlight the importance of assessing comorbidity in addition to the principal diagnoses in transdiagnostic treatments, in order to draw conclusions about the true potential of these interventions to improve comorbid symptoms. Implications of the current study and directions for future research are discussed.

Introduction

Emotional disorders (ED) (depression and anxiety disorders) are common mental health conditions and one of the main causes of suffering and impairment worldwide [1,2]. In the past few decades, a large number of disorder-specific cognitive-behavioral treatments (CBT) have been developed for ED and tested in clinical trials, with evidence found for their efficacy and effectiveness [37]. However, although disorder-specific treatment protocols have been shown to work effectively, there are still some barriers related to these protocols. One of them stems from the high comorbidity rates observed in ED, ranging between 40 and 80% for these disorders [8, 9].

Comorbidity in ED has been associated with greater severity and impairment [8], worse quality of life [10], and higher chronicity rates [11]. The literature has proposed different ways to manage comorbidity, such as combinations of treatments or the sequential application of treatments [12]. Another strategy involves applying a protocol to target one of the disorders and expecting an impact on the comorbid disorders. Nevertheless, the effective use of these strategies is not well supported by the existing empirical evidence (for a review of the evidence, see McManus et al., 2010) [12]. A more recent development to deal with comorbidity is the application of treatments based on a transdiagnostic perspective. Although the term transdiagnostic has been employed to refer to different treatment approaches [13], the common denominator of these treatments is that one protocol is applied to address various psychological disorders [14].

Research on transdiagnostic treatments for ED has increased in recent years [1517], with a noteworthy rise in the number of trials assessing the efficacy and effectiveness of transdiagnostic treatments in the past 15 years [1827]. Several advantages have been attributed to transdiagnostic treatments. The first and most important is the ability to address multiple ED using the same treatment protocol. Thus, these disorders can be treated in a more cost-effective way because clinicians only have to be trained in one protocol that addresses various psychological disorders [13, 15]. Second, training clinicians in one treatment approach, rather than in a different protocol for each ED, may facilitate the dissemination of evidence-based treatments for these specific problems [15]. This approach could be of particular interest in ecological settings such as public services, where clinicians have to treat patients with diagnostically heterogeneous presentations, which makes the adequate selection of protocols and techniques difficult [13]. Third, another important advantage is that comorbid mental disorders can be more adequately targeted because these protocols usually focus on what these disorders have in common, rather than on disorder-specific symptom variations [17, 22, 26, 28]. For instance, extensive research shows the key role played by neuroticism in the onset and maintenance of both anxiety and depressive disorders, indicating its relevance in research and clinical practice [1517, 29, 30]. In this regard, the “shared mechanisms approach”, described by Sauer-Zavala et al. [13], is based on the assumption that there are core mechanisms underlying both anxiety and depressive disorders, and that, consequently, in order for the specific symptoms to improve (e.g. symptoms of panic, symptoms of social anxiety, and so on), treatment should focus on addressing these common processes. Based on this approach, some authors have argued that a transdiagnostic treatment may be appropriate for a wide range of disorders, including all the anxiety and unipolar mood disorders, and even somatoform and dissociative disorders [15, 22], while facilitating the treatment of patients with comorbidity [12]. There are, nevertheless, other transdiagnostic approaches to the treatment of ED (including the treatment of comorbid presentations), such as individually-tailored CBT [20] or “third wave” therapies (e.g. mindfulness and acceptance and commitment therapy) [3133]. Finally, transdiagnostic treatments also have the potential to address “not otherwise specified” (NOS) diagnoses for which there are no evidence-based treatments in the literature (e.g. anxiety NOS) [13].

There is a growing body of literature on the efficacy and effectiveness of transdiagnostic treatments for ED. To date, various meta-analyses have shown the efficacy of these treatments in adults with ED, compared to control conditions, on measures of overall anxiety [3438] and disorder-specific anxiety [38], as well as depression [3538] and quality of life [3638]. Moreover, a meta-analysis of the efficacy of these protocols, compared to disorder-specific CBT, found no significant differences in the efficacy of these two treatment approaches on anxiety outcomes [39]. Nevertheless, no prior study has examined how comorbidity is reported and assessed in trials analyzing transdiagnostic protocols, despite the importance of comorbidity in aspects such as the clinical severity, the clinical course, and the rate of relapse in patients with comorbid anxiety and depressive disorders [8, 10, 11]. Some studies on transdiagnostic treatments for ED have assessed treatment effects on comorbid symptoms, as well as the symptoms primarily targeted in the study. For instance, some studies include self-reported measures to assess a range of comorbid disorder-specific symptoms [21, 40, 41], and others assess the impact of the intervention in terms of the number of comorbid disorders, in addition to the number of principal diagnoses [22]. However, this aspect has not yet been systematically analyzed in the literature on transdiagnostic treatments for ED.

Regarding the types of diagnoses targeted by transdiagnostic treatments, the transdiagnostic treatments published to date may range from those targeting only two disorders [4244] to those addressing a larger number of ED [4547]. Moreover, transdiagnostic treatments may focus on anxiety disorders alone [4850], or anxiety disorders along with depressive disorders [5153]. There is, therefore, great disparity in the types and frequencies of anxiety and depressive disorders targeted in transdiagnostic treatments. However, to our knowledge, the real distribution of specific diagnoses in these interventions, i.e. the classes of disorders and the most frequent and infrequent disorders targeted in transdiagnostic treatments for ED, has not yet been analyzed.

Taking all this into consideration, a systematic review was conducted to answer the following research questions: a) Are comorbid disorders evaluated in transdiagnostic treatments for emotional disorders? b) What diagnoses are targeted in transdiagnostic treatments for emotional disorders? and c) What is the real distribution of the diagnoses at baseline in transdiagnostic treatments for emotional disorders?

Methods

Search strategy, data extraction, and coding

A systematic search of the peer-reviewed literature was conducted through the following databases: PsycINFO, PubMed, EMBASE and the Cochrane Register of Controlled Trials. The following terms were combined to conduct the search: “transdiagnostic”, “unified”, “mixed anxiety and depression”, “mixed depression and anxiety”, “heterogeneous” “depression”, “anxiety”. The deadline for inclusion of studies was February 6th (2018) (with no limits applied for year of publication). The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42018088138). Studies were included based on the following eligibility criteria:

  1. The study was a randomized controlled trial (RCT) that was compared to one of the following conditions: a waiting list control condition, placebo, attention control condition, active control condition (i.e. other treatment), and care as usual/treatment as usual control condition.
  2. The study was written in English.
  3. Participants were adults (18 years old and older).
  4. Participants had at least a principal diagnosis of an anxiety disorder or a score above a cutoff point on an anxiety self-report scale, and/or a principal diagnosis of a depressive disorder or a score above a cutoff point on a depression self-report scale.
  5. The study evaluated a transdiagnostic treatment for anxiety disorders and/or depression (i.e. unipolar mood disorders, anxiety disorders, posttraumatic stress disorder, and obsessive-compulsive disorder). To be included in the systematic review, the intervention had to target at least two different anxiety disorders or an anxiety disorder in addition to a depressive disorder.

Two assessors (AG-R and AD-G) conducted the review and selection of studies independently. The final selection of the included studies was supervised by a third expert evaluator (CB).

The following variables were included: a) study (authors and year of publication); b) country; c) aims of the study; d) hypotheses (when available); e) setting (e.g. community, primary care) and delivery format (e.g. Internet, face-to-face, individual, group); f) inclusion criteria regarding the types of diagnoses or symptoms targeted (“or” when the participants had to have at least one of the disorders, and “+” when the participants had to have both disorders); g) groups (sample size); percentage of females; and i) the distribution of each type of diagnosis at baseline. In order to evaluate the data on comorbidity, three dichotomous variables (yes/no) were created and added to the table: a) whether a principal diagnostic or symptom complaint was reported (e.g. main complaint of generalized anxiety symptoms); b) whether comorbid disorders and/or symptoms were reported. To belong to this category, the study had to report at least the proportion of patients presenting comorbid disorders or symptoms (e.g. the number of patients with one comorbid disorder, two comorbid disorders, and so on); and c) whether treatment response on comorbid disorders/symptoms was evaluated, i.e. a diagnosis made using a diagnostic interview or the severity of the disorder or symptoms through scales. All the aforementioned variables were extracted and coded independently by AG-R and AD-G, and disagreements were solved by discussion with a third author (CB).

Definition of emotional disorders included in the study

ED were considered for this study following the criteria of the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV-TR) [54] and the definitions of these disorders adopted by previous authors [15], namely, unipolar mood disorders and anxiety disorders. Unipolar mood disorders included major depressive disorder (MDD), dysthymic disorder (D), and depression not otherwise specified (Depression NOS), whereas anxiety disorders included generalized anxiety disorder (GAD), panic disorder with or without agoraphobia (PD/AG), social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), specific phobia (SP), and anxiety disorder not otherwise specified (Anxiety NOS). Although the classification of some of these disorders has changed with the publication of the DSM-5 [55] (i.e. PTSD and OCD are no longer considered anxiety disorders), the DSM-IV-TR was followed because most of the studies analyzed had recruited participants based on this diagnostic manual.

Quality assessment

The quality of the included studies was assessed using four items from the Cochrane Collaboration Risk of bias tool [56], which estimates potential bias in randomized controlled trials, including the following domains: random sequence generation, allocation concealment, blinding of outcome assessment (if applicable), and handling of incomplete outcome data. Each item on the tool was rated as low, high, or, in the case of insufficient information, unclear risk. This process was conducted by two independent researchers (AG-R and AD-G). Disagreements were resolved through discussion and, when necessary, by asking a senior researcher (CB).

Results

Selection and inclusion of studies

The study selection process is presented in the PRISMA flowchart (Fig 1). A total of 1881 studies were identified through database searches (Pubmed = 367; PsycINFO = 327; Embase = 510; Cochrane Library = 677), and 23 additional records were identified through other sources (i.e. meta-analyses about the efficacy of transdiagnostic treatments for anxiety and depression). After removing duplicates, 1103 records were screened based on title and abstract. Of them, 128 full-articles were assessed for eligibility, of which 52 were selected for final inclusion in the systematic review.

Characteristics of included studies

Relevant characteristics of the included studies are shown in Table 1. All the studies were randomized controlled trials with a total of 7007 participants. Most of the studies were conducted in the United States (n = 19, 37%), Australia (n = 12, 23%), Sweden (n = 6, 12%), and the United Kingdom (n = 5, 10%). The most common setting was the community (37 studies, 71%), followed by primary care (6 studies, 12%), specialized care (4 studies, 8%), community/primary care (3 studies, 6%) [5759], and university students (2 studies, 4%) [60, 61]. Regarding the delivery format (i.e. face-to-face vs. web-based/computerized; individual vs. group), 24 treatments were delivered face-to-face (46%), 23 were Internet-based (44%), 4 were computerized (8%) [25, 6264], and 1 was delivered by telephone (2%) [58]. Of the 52 studies, 38 were delivered in an individual format (73%), whereas 13 were delivered in a group format (25%), and one combined individual and group formats (2%) [65]. Regarding the control conditions, 21 studies used an active control condition (of which 8 were disorder-specific treatments), 19 studies used a waiting list control, 8 employed a care as usual/treatment as usual condition, 4 used an attention control condition [20, 64, 66, 67], and 1 employed a placebo control condition [50]. Finally, only 1 cost-effectiveness study was identified [67].

Quality of the included studies

The risk of bias assessment of the included trials is represented in Fig 2. In all, 38 of the 52 studies (73%) used an adequate random sequence generation method, whereas 14 studies did not report information about the randomization method. Allocation concealment was reached in 26 of the assessed trials (50%), but it was not clearly reported in the other half (50%). With regard to blinding the outcome assessment, 23 trials (44%) reported using blinded raters, whereas 12 (23%) used only self-report measures. Almost all of the studies (92%) used an appropriate method for handling incomplete outcome data (i.e. intention-to-treat analyses). Sixteen studies (31%) met all the quality criteria, 30 studies (58%) met two or three criteria, and the six remaining trials met none or only one quality criterion.

Are comorbid disorders evaluated in transdiagnostic treatments for emotional disorders?

We were also interested in the number of studies that reported and assessed comorbidity in their samples. Of the 52 studies analyzed, 39 (75%) reported the presence of comorbid disorders (i.e. whether the sample presented comorbidity at baseline), and 13 (25%) did not. However, of the total number of studies, only 21 (40%) assessed the effects of the intervention on comorbid disorders (i.e. through scales or diagnostic interviews).

What diagnoses are targeted in transdiagnostic treatments for emotional disorders?

Fig 3 presents the number of studies that target each of the different diagnoses. In this figure, both specific diagnoses and broad diagnosis categories (i.e. anxiety, depression, and mixed anxiety-depression) are shown because we identified studies that targeted either specific diagnoses or broader categories of anxiety and depression.

thumbnail
Fig 3. Number of studies that target the different diagnoses.

Note. PD/AG: Panic disorder/agoraphobia; GAD: Generalized anxiety disorder; SAD: Social anxiety disorder; Dep: Depression; Anx: Anxiety; SP: Specific phobia; Anx NOS: Anxiety not otherwise specified; PTSD: Posttraumatic stress disorder; OCD: Obsessive-compulsive disorder; M anx-dep: mixed anxiety and depression disorder; Dep NOS: Depression not otherwise specified; SD: somatoform disorder.

https://doi.org/10.1371/journal.pone.0207396.g003

Of the 52 studies included in the review, the most commonly targeted diagnoses were PD/AG, (26 studies; 50%), GAD (24 studies; 46%), and SAD (22 studies; 42%). In addition, SP was targeted in 6 studies (12%) [31, 32, 62, 69, 76, 77], Anxiety NOS in 6 studies (12%) [20, 44, 46, 57, 58, 68], PTSD in 4 studies (8%) [32, 42, 47, 71], and OCD in 4 studies (8%) [18, 31, 32, 71]. Moreover, we identified 1 study targeting Depression NOS (2%) [46] and 1 study targeting somatoform disorders (2%) [70]. Finally, 22 studies targeted symptoms or diagnoses of depressive disorders (i.e. MDD or DD) (42%), 19 studies targeted symptoms or diagnoses of anxiety disorders (any type) (36.5%), 15 targeted depression symptoms or diagnoses (any type) (29%), 3 targeted mixed anxiety and depression (6%) [25, 52, 63], and 2 targeted stress (4%) [60, 70].

What is the real distribution of diagnoses at baseline in transdiagnostic treatments for emotional disorders?

In order to obtain the distribution of each of the different diagnoses, we classified the studies into those that reported a principal diagnosis (subsample 1) and those that did not (subsample 2). Of the 52 studies included in the review, 36 established a principal diagnosis, and 4125 patients with a principal diagnosis were identified in this subsample. The proportion of these patients for each of the different principal diagnoses can be seen in Fig 4. The most common diagnoses were GAD (n = 998; 24.1%), PD/AG (n = 935; 22.6%), SAD (n = 826; 20.0%), Dep (i.e. MDD or DD) (n = 789; 19.1%), and mixed anxiety and depression (n = 222; 5.4%). Other much less frequent diagnoses were OCD (n = 95, 2.3.%), SP (n = 86; 2.1%), Anxiety NOS (n = 61; 1.5%), and PTSD (n = 47; 1.1%).

thumbnail
Fig 4. Total number of principal diagnoses of each type in subsample 1.

Note. GAD: Generalized anxiety disorder; PD/AG: Panic disorder and/or agoraphobia; SAD: Social anxiety disorder; Dep: Depression; M anx-dep: Mixed anxiety and depression; OCD: Obsessive-compulsive disorder; SP: Specific phobia; Anx NOS: Anxiety not otherwise specified; PTSD: Posttraumatic stress disorder. “Others” included GAD + MDD (n = 47), GAD + PD (n = 25), GAD + SAD (n = 1), SAD + Anxiety NOS (n = 1), OCD + PD/AG (n = 1), and anxiety/depression NOS (n = 2).

https://doi.org/10.1371/journal.pone.0207396.g004

The proportion of different diagnoses in the studies that did not include information about a principal diagnosis (subsample 2) is shown in Fig 5. In this subsample, a total of 4926 diagnoses were identified (pertaining to 2882 patients), and the most common diagnoses were Dep (n = 1220; 24.8%), PD/AG (n = 1135; 23%), GAD (n = 1119; 22.7%), SAD (n = 855; 17.4%), and PTSD (n = 323; 6.6%). Other disorders in these studies included SP (n = 74; 1.5%), OCD (n = 28; 0.6%), and Anxiety NOS (n = 18; 0.4%).

thumbnail
Fig 5. Total number of diagnoses of each type in subsample 2.

Note. Dep: Depression; PD/AG: Panic disorder and/or agoraphobia; GAD: Generalized anxiety disorder; SAD: Social anxiety disorder; PTSD: Posttraumatic stress disorder; Anx dis: Anxiety disorders; SP: Specific phobia; OCD: Obsessive-compulsive disorder; Anx NOS: Anxiety not otherwise specified. “Others” included somatoform disorder (n = 10), adjustment disorder (n = 10), eating disorders (n = 9), alcohol use disorder (n = 4), substance use disorder (n = 4), and anxiety/depression NOS (n = 4).

https://doi.org/10.1371/journal.pone.0207396.g005

Discussion

The aim of this systematic review was to analyze the following aspects about transdiagnostic treatments for ED: first, whether treatment response in the comorbid disorders is evaluated in transdiagnostic treatments for ED; second, what disorders are targeted in these studies; and third, what the real distribution of these disorders is at baseline in these studies.

The first objective was to analyze how comorbidity is reported and whether the treatment change produced in comorbid disorders is assessed in transdiagnostic trials for ED. The results showed that the number of studies reporting comorbidity was quite high, with 39 out of 52 reporting the presence of comorbid disorders in their samples at baseline. However, the number of studies assessing comorbidity was much lower, with only 21 (40.4%) studies assessing the comorbid conditions as well as the symptoms of the principal diagnosis, using either diagnostic interviews [18, 22] or self-report questionnaires [21, 40, 41]. From a transdiagnostic perspective that addresses the common maintenance vulnerabilities across disorders (e.g. neuroticism), it makes more sense to explore the extent to which these treatments are effective in improving both principal and comorbid disorders. In order to gain insight into how transdiagnostic treatments work in patients with comorbidity, we believe this strategy should be followed in future research on transdiagnostic treatments for ED. Furthermore, future meta-analyses of transdiagnostic treatments for ED would benefit from this strategy because they could analyze the impact of these treatments on comorbidities, in addition to their effects on broader measures of anxiety and depression. To date, some studies have included measures to assess treatment response in comorbidity in addition to the principal diagnosis [e.g. 2123]. However, as the results of this systematic review show, this is not the typical approach in RCTs on transdiagnostic treatments (i.e. only 40.4% of the trials analyzed in this review assessed the impact of the intervention on comorbidity). As an example of this emphasis on comorbid diagnoses, a recent study tested the efficacy of a transdiagnostic treatment (the UP), compared to disorder-specific CBT with a specific focus on comorbid conditions, finding no differences in efficacy between the two treatment approaches [82]. These authors have also acknowledged the low number of treatments that, in general, evaluate treatment effects on comorbid disorders [82], whereas other authors have highlighted that transdiagnostic treatments should improve not only overall anxiety and depression, but also the disorder-specific comorbid psychopathology [38]. In this vein, most of the meta-analyses published to date have only analyzed the effects of transdiagnostic treatments using measures of overall anxiety and depression, except one recent meta-analysis that also explored the impact of these interventions on comorbidities [38]. To do so, the authors compared the effects of transdiagnostic treatments for ED to control conditions on disorder-specific measures of generalized anxiety, panic, and social anxiety. However, only 5 studies were included in this meta-analysis, which suggests the overall lack of attention paid to the evalution of comorbidity in transdiagnostic treatments.

It is important to note that some of the studies included in this review follow a treatment perspective that does not fall into the “shared mechanisms approach” described by Sauer-Zavala et al. [13]. Some of these approaches include tailoring the treatment to the specific disorders and comorbidities of each individual [19, 20, 73], changing the relationship of the patient with her or his own subjective experience (regardless of the specific disorder involved) through the delivery of “third wave” therapies (e.g. mindfulness, acceptance, and commitment therapy) [31, 32, 43, 51], or helping the patients to resolve their inner psychic conflicts using psychodynamic therapy [46, 69]. Regarding the usefulness of these transdiagnostic treatments for comorbid presentations, whereas tailored treatments aim to tailor the treatment according to the specific symptoms of the patient, third wave and psychodynamic therapies are considered transdiagnostic because they are usually applied indistinctly to treat different types of disorders. In sum, all of these approaches represent different strategies used to target comorbidity.

Regarding the second objective, (i.e. what diagnoses are targeted in transdiagnostic treatments for emotional disorders?) PD/AG was targeted in half of the studies, followed by GAD, SAD, and Dep, which were also targeted in almost half of the studies (46, 42, and 42%, respectively). By contrast, Anxiety NOS and Depression NOS were only targeted in 12 and 2% of the studies, respectively. Finally, the third question tried to answer what the real distribution of the diagnoses is at baseline in transdiagnostic treatments for emotional disorders. Regarding this question, the findings show that, in patients with a principal diagnosis (subsample 1), GAD was the most frequent diagnosis, followed by PD/AG, SAD, and Dep. Taken together, these disorders represented 85.8% of subsample 1, with anxiety disorders being the most common disorders targeted in transdiagnostic treatments for ED. Other ED appeared much less frequently. These disorders included OCD, SP, Anxiety NOS, PTSD, and Depression NOS. In patients with unreported principal diagnoses (subsample 2), Dep was the most common diagnosis, followed by PD/AG, GAD, SAD, and PTSD. These disorders represented 94.5% of the total number of diagnoses, and anxiety disorders were again the most frequent disorders targeted in the transdiagnostic treatments. By contrast, Anxiety NOS and OCD only represented 1% of this subsample. Overall (both subsamples), the most common disorders targeted in transdiagnostic trials were GAD, PD/AG, SAD, and Dep. These results are consistent with the high prevalence rates observed for these disorders [8, 9, 54]. For instance, according to the DSM-IV-TR [54], lifetime prevalence is 5% for GAD, 10–25% (female) and 5–12% (male) for major depression, 6% for dysthymic disorder, 1.5–3.5% for PD/AG, 2.5% for OCD, 3–13% for SAD, and 1–14% for PTSD. However, other ED, such as OCD, PTSD, Anxiety NOS, and SP, have received much less attention in the research on transdiagnostic treatments for ED, and they are usually not targeted in these protocols. On the one hand, it is worth noting that there is a low proportion of patients with OCD as the principal diagnosis included in the transdiagnostic interventions, even though this disorder can be appropriately treated from a transdiagnostic perspective, based on common maintenance vulnerabilities across ED [15, 17, 22]. In the case of PTSD, earlier studies with transdiagnostic protocols like the UP [83], which originally targeted this diagnosis, do not include this category in later studies [18, 22], in spite of the fact that this disorder might be an appropriate treatment target from a mechanistically transdiagnostic approach (i.e. a treatment approach that addresses the common underlying mechanisms across a range of disorders) [18, 84]. On the other hand, transdiagnostic treatments have the potential to target diagnoses that do not fit any specific category (e.g. Anxiety NOS) [12,15]. Although there are data indicating that there is a high proportion of these presentations [85, 86], the number of diagnoses with Anxiety NOS analyzed in this study represented less than 1% of all the patients. In this regard, one somewhat surprising result is that the overall number of patients with a diagnosis of SP is larger than the number of patients with Depression or Anxiety NOS, even though one of the advantages of the transdiagnostic perspective is the possibility of treating NOS diagnoses, clinical presentations for which there is a lack of evidence-based treatments.

Regarding the control conditions, both the waitlist control and the active control conditions were the most frequent among the analyzed studies. Of the studies that used active control conditions, only 8 were disorder-specific treatments. In order to accumulate evidence about the efficacy of transdiagnostic treatments, more studies should compare these protocols to disorder-specific treatments [21, 23]. Thus, although there is some evidence showing that a transdiagnostic approach may benefit depressive symptomatology more than disorder-specific protocols [36], overall the literature suggests that these two treatment approaches have equivalent effects [18, 3941]. However, the number of studies comparing these two approaches is still low, and so more research is warranted to more firmly establish their relative efficacy. Likewise, research comparing the cost-effectiveness of transdiagnostic treatments and disorder-specific protocols is of paramount importance, for a number of reasons. First and foremost, by using a transdiagnostic treatment, less training of clinicians is required because a single protocol is used to address multiple disorders, which is likely to facilitate its implementation in real-world settings (e.g. primary care and mental health services). Second, these treatments may be more useful for clinicians that have to address comorbid presentations, either by targeting the underlying common processes, by tailoring the treatment to the symptoms and needs of each patient [20], or by addressing how the patients relate to their own cognitive, behavioral, and emotional experiences [31, 32]. Although the aforementioned reasons are true for most transdiagnostic treatments, there are other reasons specific to the protocols that fall in the category of the “shared mechanisms approach”. For instance, transdiagnostic treatments are designed to address the underlying common vulnerabilities across ED that are hypothesized to account for the onset and maintenance of these disorders [15]. Thus, by focusing on treating these processes rather than disorder-specific variations, larger and more lasting effects on clinical outcomes would be expected [13]. These results would lead to a lower prevalence of ED, and therefore to a decreased need for treatments in the short and long term, resulting in increased cost-effectiveness. For these reasons, more research on the cost-effectiveness of transdiagnostic treatments is needed, especially in comparison with disorder-specific protocols, as evidenced by the scarcity of studies of this kind found in this review (e.g. the study by Nordgren et al.) [67]. Given the substantial burden of ED and the lack of resources to tackle these disorders, especially in public services, research on how to enhance the cost-effectiveness of psychological interventions should be a research priority. A characteristic example of a treatment strategy to further increase the efficiency of transdiagnostic protocols entails personalizing the treatment to a specific presentation, i.e. by selecting the treatment components that best fit the specific set of symptoms or “weaknesses” shown by each patient [87], thereby lowering the number of sessions required to successfully treat an individual’s symptoms.

Regarding the settings, 71% of the studies were conducted in community samples, whereas 20% were carried out in primary or specialized care, and only 4% with university students. Thus, community samples continue to be the setting of choice when conducting transdiagnostic trials for ED. Regarding the way these treatments were delivered, approximately half of the studies were face-to-face, whereas the other half were delivered through Information and Communication Technologies (web-based and computerized), and only one study was delivered by telephone. These results are not surprising because research on Internet interventions has increased enormously in recent years, and these interventions have been applied to different problems using a variety of treatment approaches [88]. As the field of Internet interventions advances, researchers are more likely to select this delivery format to explore new interventions. Finally, transdiagnostic treatments were mostly individual, with 68% of the studies conducted in an individual format and the rest in groups. These results are not surprising because most transdiagnostic treatments were originally developed to be applied individually, with some exceptions [89]. However, the potential of transdiagnostic treatments for improving the dissemination of empirically supported treatments (i.e. only one protocol is needed to address a range of psychological disorders) may be enhanced by modifying the way the treatments are delivered [90]. For example, Internet or group formats can be used to reach a larger number of people in need of psychological help [92, 93], especially in ecological settings where resources are generally scarcer, such as primary care or public mental health units [91, 93].

Finally, regarding the risk of bias assessment, the overall quality of the trials included was acceptable, especially regarding the handling of incomplete outcome data, with almost all the studies using an appropriate approach. However, it is worth noting that a large percentage of the studies did not properly report specific methodological aspects, such as the sequence random generation method and whether it was performed by an independent party, which led us to rate it as unclear. In order to improve the methodological quality of trials and reduce the different sources of bias, we encourage authors to follow guidelines for conducting and reporting on clinical trials, such as the CONSORT statement (Consolidated Standards of Reporting Trials) [94, 95] or the SPIRIT guidelines (Standard Protocol Items: Recommendations for Interventional Trials) [96, 97].

Limitations

This systematic review has several limitations that should be mentioned. First, although a comprehensive search was conducted (4 different databases were used), some important studies might have not been identified. Moreover, studies written in languages other than English were excluded, which might have affected the representativity of the findings in this study. Second, the generalizability of the results is also limited by the fact that most of the studies included in this review were conducted in Western countries. Third, although aspects of the methodology were unreported or not clear in some studies, we did not contact the authors of these studies to obtain information that might have clarified these details. Thus, aspects of the study methods that were not clear were rated as unclear. However, based on our experience in conducting prior systematic reviews, we have observed that contacting the authors of these studies is often very difficult and, therefore, impractical. Fourth, as in any systematic review, this study is vulnerable to publication bias, and so some relevant unpublished studies might have been missed.

Conclusions

In conclusion, this systematic review found that, although most of the studies reported the presence of comorbid disorders in their samples at baseline, less than half of them evaluated the effects of the intervention on the comorbid disorders. Patients with comorbid disorders normally exhibit greater rates of severity, disability, and chronicity. One main reason for using a transdiagnostic approach to the treatment of ED is better management of comorbidity. Therefore, efforts should be made to assess the impact of the intervention on the comorbid disorders, in addition to the principal diagnoses targeted in these studies. On the other hand, as the results showed, the most commonly targeted diagnoses in transdiagnostic treatments were PD/AG, GAD, SAD, and Dep. More research is needed with other diagnoses much less targeted in transdiagnostic treatments, such as PTSD, OCD, and anxiety/depression NOS, to further explore the potential of transdiagnostic treatments in treating these disorders.

Supporting information

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