Psychological interventions for individuals with Ehlers-Danlos syndrome and hypermobility spectrum disorder: a scoping review

Ehlers-Danlos Syndrome (EDS) comprises a group of rare hereditary connective tissue disorders characterized by several shared clinical features such as joint hypermobility and hyper-extensible skin [1]. EDS is estimated to affect between 1 in 2500 and 1 in 5000 people globally [2]. Many individuals with EDS have frailty of soft tissue and blood vessels among other conditions which may contribute to chronic and severe disabilities, greatly affecting their quality of life and mortality [1]. While some individuals are asymptomatic for their entire lives, many others experience multi-systemic and multi-factorial complications, including neurological, gastrointestinal, and cardiovascular complications, breathing difficulties, organ rupture, joint dislocation, and chronic pain [2‐5]. Currently, thirteen subtypes have been officially recognized, all of which are caused by different gene variants and have different manifestations [2, 6]. The six predominant types of EDS are classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis. Classical, hypermobile and vascular EDS are the most prevalent, accounting for 79% of the EDS population [6], while hypermobile EDS (formerly EDS type III) is the most common subtype overall [7].

Hypermobility Spectrum Disorder (HSD), formerly known as Joint Hypermobility Syndrome (JHS), is diagnosed in individuals with generalized joint hypermobility, fatigue, and chronic pain [8]. HSD/JHS is occasionally classified as a milder variant of hypermobile EDS by health authorities because the two conditions share many clinical features, although this classification is not widely used [9]. The condition is prevalent in at least 3% of the general population and it is diagnosed only after other conditions, including any of the EDS subtypes, have been excluded [9]. Patients with HSD are often predisposed to soft tissue injury as well as slow and incomplete healing [10]. Complications associated with HSD may inlude central and peripheral nervous system abnormalities; for example, many experience increased pain, resistance to local anesthetics, and gastrointestinal complications [10].

There is no known cure for EDS or HSD, and they are often difficult to diagnose since clinical presentation may vary greatly between patients and there is a lack of specific genetic tests [11]. Many symptoms of EDS and HSD are also shared with other diagnoses, such as chronic fatigue syndrome, Marfan syndrome, and osteogenesis imperfecta [12, 13]. These difficulties often lead to a greater time to diagnosis compared to other diagnoses with similar symptom profiles (e.g., Marfan syndrome), which may be easily identified clinically and genetically [14, 15]. In a qualitative study of adults with EDS, it was revealed that many had shown symptoms as children that were overlooked and misdiagnosed by their families and healthcare professionals [16]. This makes EDS and HSD of concern from a lifespan perspective, as lifelong health complaints are rarely investigated but are important to address throughout a person’s development. In the qualitative study, those who were diagnosed as adults experienced unbearable pain and fatigue as their unaddressed symptoms worsened during their development into adulthood [16].

In addition to the physiological impairments mentioned above, psychiatric disorders and psychosocial impairment are also common among individuals with EDS and HSD. Specifically, EDS and HSD have been associated with increased risk of conditions such as depression and anxiety as well as interpersonal issues when compared to the general population [17‐21]. In a cohort study of 106 patients with hypermobility-type EDS, Hershenfeld et al. [22] determined that psychiatric disorders were found in 42.5% of the cohort, with 22.7% of patients affected with 2 or more psychiatric diagnoses. Anxiety and depression were the most reported, with frequencies of 23.6% and 25.5%, respectively. This is notably higher compared to 17.6% of psychiatric disorders in the general population [23]. Moreover, the presence of any pain symptom was associated with nearly 10 times greater odds of having a psychiatric disorder.

The exact reasons for the high rates of psychiatric disorders are unclear, but it is likely that the aforementioned physical symptoms (e.g., chronic pain and other medically unexplained symptoms) play a major role [20]. Notably, the high prevalence of chronic pain in the EDS population is one of the many contributing factors that are hypothesized to be associated with high rates of psychosocial impairment [19]. For example, many patients are misdiagnosed for years or accused of malingering, leading to mistrust of the medical/health care system and self-doubt [19]. Furthermore, previous research has demonstrated that individuals with joint hypermobility have an altered sense of body awareness, which may play a role in emotional response and has been shown to mediate the relationship between joint hypermobility and anxiety [21]. For example, Mallorquí-Bagué et al. [24] found that hypermobile individuals experienced significantly higher state anxiety compared to those who were not hypermobile and that this relationship was mediated by interoceptive sensitivity (i.e., enhanced body awareness).

EDS may be managed with a variety of treatment options including physical therapy, nonsteroidal anti-inflammatory drugs, acetaminophen, opioid medications, and surgery, as well as non-traditional or complementary modalities including acupuncture and massage [25]. However, previous studies by Rombaut and colleagues [26] and Grahame [27] highlighted limitations of common pharmacological and physical interventions, noting that analgesics, non-steroidal anti-inflammatory drugs, psychotropics, and physiotherapy are often ineffective to address pain among individuals with EDS. In addition, individuals with EDS experience increased side effects of pain medications [28]; orthopedic procedures are indicated for pain relief in only selected patients [29]. Thus, it has been suggested that psychological approaches [30, 31], particularly to address chronic pain observed among individuals with EDS, may be helpful for recovery and rehabilitation. In a pilot study of 12 women with EDS, Bathen and colleagues [32] investigated a multidisciplinary rehabilitation program combining physical and cognitive behavioural therapy (CBT). Decreases in self-perceived pain were reported as well as increased participation in daily life. Such findings parallel those seen in patients with chronic pain [33], suggesting that such interventions may be readily adapted to meet the needs of patients with EDS and HSD.

Despite these promising outcomes, it has been suggested that more research is needed on relevant psychosocial strategies for individuals with EDS [31]. Rombaut and colleagues [26] also emphasized the need for evidence-based recommendations for the optimal management of EDS, which includes psychological follow-up. Similarly, there is a lack of high-quality clinical guidelines for managing the psychosocial complexities associated with pain in EDS, limiting evidence-based practice [34]. Furthermore, patient partners have been previously recognized as important contributors to developing (psychosocial) treatment options in EDS, but their expertise has not been leveraged to date [34]. Overall, our study aims to examine the nature and extent of the current evidence on psychological interventions for individuals with EDS and HSD, identifying any gaps in research and providing suggestions for future research areas.

This review used the Joanna Briggs Institute methodological framework for the current scoping review with reference to Arksey and O’Malley’s framework as well [35, 36]. These frameworks outline six main stages involved in a scoping review: (1) identifying the research question; (2) identifying relevant studies; (3) selecting studies; (4) charting the data; (5) collating, summarising and reporting the results; and (6) consulting with relevant stakeholders. Scoping reviews are conducted to determine the nature of existing evidence and to analyze and identify knowledge gaps, rather than to provide a detailed appraisal and assessment of the quality of the literature [35]. Thus, a critical appraisal of the included studies is not required. The last stage of our project will be achieved via ongoing consultation with our integrated knowledge translation (iKT) Advisory Group, consisting of individuals with EDS and HSD. The overall project uses a collaborative iKT approach that engages all relevant knowledge users and stakeholders (i.e., researchers, clinicians, and patient partners) in the full spectrum of research activities such as setting the objectives and methods and implementation of the research [37]. Our patient partners also contributed to informing our search strategy development and interpretation of results. The PRISMA-ScR checklist guided the reporting of this review [38].

Studies involving the use of psychological interventions for individuals with EDS and/or HSD were included. We defined psychological interventions as those that aim to enhance coping strategies (e.g., for pain and resiliency) and address stress or low mood, either alone or in combination. This definition was previously used for a Cochrane systematic review and meta-analysis on psychological interventions for coronary heart disease [39]. Examples of psychological interventions include cognitive behavioural therapy (CBT), motivational interviewing, acceptance and commitment therapy (ACT), and mindfulness. We only included studies where the psychological interventions were delivered by health care professionals who had been trained in their delivery (including both individuals who hold a clinical degree and those whose training was described within the study). Studies with participants of all ages were included. Our scoping review included experimental studies (randomized controlled trials (RCTs), cluster RCTs, quasi-randomized trials, and controlled clinical trials), quasi-experimental studies (including interrupted time series and controlled before and after studies), observational studies, and qualitative studies. We included studies regardless of publication status, including the grey literature. Our search strategy included English-language studies only and had no restrictions with respect to publication year.

Literature search strategies using subject headings and text words related to psychological interventions for individuals with EDS and/or HSD were developed from two systematic reviews [39, 40], as well as the search strategy used by our research team on psychological interventions for adults with cerebral palsy, childhood-onset acquired brain injury, and spina bifida [41]. A sample search strategy from CINAHL can be found in Additional file 1. A librarian with extensive experience in conducting systematic and scoping reviews conducted all of the literature searches in consultation with the research team. Experts in the field of EDS and HSD, including members of our research team, were consulted to ensure that all relevant data was obtained. A comprehensive literature search was run in Ovid MEDLINE, Ovid MEDLINE Daily, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Epub Ahead of Print, OVID EMBASE, OVID PsycINFO, and EBSCOhost CINAHL on March 28, 2021. Duplicates were removed using Zotero's duplicate identification strategy as well as manually. Appropriate wildcards were used in the search to account for plurals and variations in spelling. A grey literature search was performed by searching targeted websites (i.e., Ehlers-Danlos Society, Ehlers-Danlos Support UK, Marfan Foundation) as recommended by members of our research team. The team developed inclusion and exclusion criteria screening questions and forms for the title and abstract screening (level 1 screening), full-text screening (level 2 screening), and abstraction.

To increase the reliability of screening among reviewers, a pilot test of a pre-defined screening form based on the eligibility criteria was performed on a random 1% sample, and reviewers reported 90% agreement or higher before moving on to full screening. The inclusion and exclusion criteria were discussed and clarified to promote the consistent application of the selection criteria if necessary. All title and abstract screening (i.e., level 1 screening) identified by the literature search were performed independently, in duplicate. The full text of the potentially relevant articles was acquired and screened to determine final inclusion (i.e., level 2 screening). Level 2 screening was performed independently and in duplicate. Discrepancies were resolved by discussion or by a third reviewer, if necessary. Studies excluded during the screening phase were documented along with an explanation for exclusion.

Data abstracted from the publications included study characteristics (e.g., author names, year of publication, country of study conduct, study design, sample size, setting characteristics), participant characteristics (e.g., EDS and/or HSD, age, sex, race, etc.), psychological intervention characteristics, and outcome results. We used the Template for Intervention Description and Replication (TIDieR) checklist and guide [42] to inform the data abstraction on the psychological interventions. This guide includes how, when, where, and how much the intervention was delivered, as well as whether any modifications or tailoring were made/are recommended [43]. The data abstraction form was pilot-tested and modified accordingly. Data abstraction was performed independently and in duplicate. Discrepancies were resolved by discussion or by a third reviewer, if necessary. The data from this scoping review were summarised quantitatively using numerical counts and as well as qualitatively using content analysis. Data are organized in the tables by type of psychological intervention.

Table 1 highlights the study characteristics of the ten articles included in this review. The studies were published between 2011 and 2021. There were four case reports [44‐47], five cohort studies [32, 48‐51], and one study that featured two case reports and a literature review [52]. Three were conducted in the United States [47, 50, 51], two in the United Kingdom [46, 49], two in France [45, 48], one in Australia [44], one in Norway [32], and one in Canada [52].

There were 258 total participants in the ten studies included in our review. Sample sizes ranged from 1 (case report) to 95 (cohort study), with participants ranging in age from 9 to 51 years (note that some studies only provided a mean age, rather than an age range). Most studies (80%) had a small sample size (n < 50), which may be partly attributed to the study types (i.e., many were case studies). Nine of the ten studies included a higher proportion of female participants (90–100%) compared to males, with only one case study featuring a male patient. The ten studies included participants with EDS (hypermobile [32, 44, 48, 51, 52], classic [45], vascular [47], or unspecified [46, 50, 52] subtype) and/or JHS [32, 44, 49, 51]. JHS would be presently referred to as HSD. Three of the studies reported including individuals with comorbid conditions (i.e., Cornelia de Lange syndrome [45], Emotionally Unstable Personality Disorder (EUPD) [46], and Postural Orthostatic Tachycardia Syndrome (POTS) [47]) while the other seven did not indicate whether patients with mental or physical health comorbidities were excluded from participation.

Table 2 describes the characteristics and results of the interventions. Nine of the ten studies described multidisciplinary interventions (i.e., interventions which administered more than one treatment modality) to treat EDS/JHS (all except Knowlton et al. [47]). Most of the studies (n = 8) aimed to provide patients with tools and techniques to manage pain independently and overcome functional limitations associated with their conditions, while the other studies (n = 2) focused on minimizing disruptive and harmful behaviours (i.e., self-harm) [45, 46]. CBT was a common psychological treatment used in the included interventions (n = 4) [32, 44, 46, 49]. Half (n = 5) of the studies used a combination of pharmacotherapy (e.g., medications) with some form of psychotherapy (e.g., CBT) [44‐46, 51, 52]. The multidisciplinary interventions (n = 9) used a combination of psychological therapy along with physiotherapy, occupational therapy, and/or physical exercise programming. For example, Henry et al. [46] used a combination of Dialectical Behavioural Therapy (DBT), pharmacotherapy, occupational therapy, and physiotherapy.

Interventions were administered by a multidisciplinary team for most of the studies (n = 8) [32, 44, 46, 48‐52], while one study did not clearly describe the administrators [45] and one study had only one administrator (post-master’s clinical psychology Ph.D. student) [47]. For all ten studies, the administrator of the psychological intervention specifically was not clearly described, although it could be assumed that the psychologists and therapists were the administrators for those interventions which listed these professionals as part of the team. All interventions were administered in person; six interventions were administered on an in-patient basis (in clinic or in hospital) [32, 44‐46, 48, 50], three interventions were administered on an out-patient basis [47, 49, 51], and one study did not describe whether the intervention was delivered on an in-patient or out-patient basis [52]. The duration of the interventions ranged from 5 days to 21 months for nine studies, while one study did not clearly describe the length of the intervention [52]. The intensity of the interventions was not clearly described for seven studies [32, 44‐46, 48, 49, 52]; the intensity of the other three interventions ranged from 45 min to 6 h in length per day [47, 50, 51].

In terms of outcome measures, two of the studies did not outline clear outcome measures [44, 45], while the other eight listed multiple outcome measures which included at least one that measured pain levels. All the interventions resulted in some improvements in outcome measures from admission to follow-up (i.e., decrease in pain, decrease in depression), although two studies did not report significant results [44, 46]. Three of the interventions received modifications and/or tailoring before or during their administration: Chaleat-Valayer et al. [48] altered the program to be 5 days of hospitalization instead of 5 half-days at a day hospital (reasoning unclear; the decision was made following initial evaluation of the sessions), Revivo et al. [51] individuated treatment plans based on patient need (details not provided), and Rahman, Daniel, and Grahame [49] tailored the daily program design to accommodate the needs of each group of patients receiving treatment over the years (details not provided).

Four of the studies included treatments using CBT techniques as the psychological intervention, one study investigated a DBT approach, two of the studies investigated programs focused on psychoeducation, two of the studies applied an intensive interdisciplinary pain program (IIPT), and one study used an ACT approach.

Most included studies reported significant improvements for their respective interventions in terms of pain, reduction of destructive behaviours, and/or other outcome measures including anxiety, depression, and quality of life. However, these results are inconclusive due to the lack of high-quality research surrounding psychological interventions for individuals with EDS and HSD (e.g., small sample sizes, study types with poor validity/reliability, lack of RCTs, etc.). Some interventions identified in our review have been previously explored in similar patient populations and are thus recommended for further investigation in patients with EDS and/or HSD.

Four of our included studies investigated a CBT approach. Notably, Bathen et al.’s cohort study [32] reported significant improvements in activity performance, performance satisfaction, physical strength and endurance, self-reported pain intensity, and a decrease in kinesiophobia. Rahman, Daniel, and Grahame’s cohort study [49] reported significant improvements in pain and depressive symptoms. In accordance with these results, several meta-analyses and reviews have demonstrated the efficacy of CBT for managing pain and improving daily functioning and independence in patients with chronic pain disorders [56, 57]. For example, a review by Knoerl et al. [58] investigated CBT for adults with chronic pain associated with fibromyalgia and arthritis. The CBT treatment reduced pain intensity significantly in 43% of the included RCTs, and significant improvements in other outcomes such as depression and anxiety were also noted in over 50% of the trials testing these outcomes. However, it should be noted that many trials on CBT for individuals with chronic pain have not compared CBT groups to another active control group. Williams et al.’s systematic review [59] demonstrated that when compared with active controls, some small improvements were observed for CBT in terms of pain, disability, and distress for adults with chronic pain, but these improvements were not significant. While we cannot conclude the efficacy of CBT based on our study results due to a lack of high-quality research, CBT may be further investigated as a method of improving pain and daily functioning of patients with conditions such as EDS or HSD which also cause chronic pain and disability.

Two studies investigated a psychoeducational program. Notably, Chaleat-Valayer et al.’s cohort study [48] found significant improvements in the patients’ self-image as well as the knowledge and skills of patients and their relatives. A 2021 systematic review by Gómez-de-Regil [60] on psychoeducational interventions for patients with fibromyalgia revealed that interventions were able to significantly improve patients’ pain intensity, fatigue, sleep quality, depression, anxiety, functional ability cognitive impairment, and quality of life. These results are supported by studies investigating psychoeducation for individuals with chronic pain [61, 62]. While we cannot conclude the efficacy of psychoeducational programs for those with EDS/HSD due to a lack of high-quality research, research on similar patient populations shows that psychoeducational programs may be worth investigating to improve the knowledge and skills of individuals who live with chronic pain and disability (e.g., patients with EDS and their families).

Two studies investigated an IIPT program. Randall et al.’s cohort study [50] found significant decreases in functional disability from admission to follow-up, as well as significant improvements in pain and function. Revivo et al.’s cohort study [51] found significant improvements in average pain intensity, patient/parent functioning, daily functioning, depression, and pain-related anxiety. These findings are consistent with results from a systematic review investigating IIPTs for children with chronic pain [63], which found IIPTs may significantly improve pain symptoms as well as disability short-term; however, the review revealed that there is a lack of well-designed clinical trials investigating IIPT efficacy, so these conclusions may not be reliable. An observational study published by Zernikow et al. [64] investigated IIPTs for adolescents and children with chronic pain. The authors found that participants had a significant reduction in pain-related and psychological (anxiety, depression, pain catastrophizing) outcome measures, which were sustained at the four-year follow-up. Overall, previous studies investigating IIPTs for the management of pain and other symptoms have yielded promising results for the chronic pain population. Although we again cannot conclude the efficacy of IIPT for those with EDS/HSD, this intervention warrants further investigation with high-quality studies for this population.

It is notable that some psychological interventions studied in chronic pain populations, which have demonstrated significant improvements in outcomes such as pain, depression, and anxiety, have not been studied in individuals with EDS and/or HSD, or at least were not identified in this review. For example, Motivational Interviewing (MI) is a technique focusing on resolving an individual’s ambivalence toward behavioural change by strengthening their commitment and motivation to change [65]. MI has been previously investigated for individuals struggling with chronic pain; a systematic review and meta-analysis by Alperstein and Sharpe [65] on MI for individuals with chronic pain identified that MI was able to significantly increase short-term adherence to prescribed treatment plans and significantly reduce pain in the short-term. While more research is required to validate these results, future studies may explore MI as a psychological approach for improved pain management and adherence to treatment plans for individuals with EDS and HSD.

Mindfulness-Based Stress Reduction (MBSR) is another promising psychological intervention for individuals with EDS/HSD. MBSR promotes a non-judgemental approach to pain where the physical and psychological aspects of pain are uncoupled [66]. This is typically achieved through meditation and mindfulness practices in which the patient increases their awareness of body signals and breath. Some of the studies in our review briefly outlined mindfulness techniques (e.g., relaxation), but none of the programs clearly identified or described mindfulness as the main psychological component. MBSR has been previously investigated as a treatment for pain in individuals with chronic lower back pain, headache, and fibromyalgia [66]. A 2011 systematic review [67] found that MBSR may significantly decrease anxiety, stress, and depression while improving the quality of life of patients with diseases such as cancer as well as chronic pain disorders. Another systematic review by Abbott et al. [68] found similar results for patients with vascular disease in that MBSR was effective in improving depression, anxiety, and psychosocial stress. Thus, future studies should explore MBSR in treating psychological symptoms associated with EDS and HSD as well.

Our review yielded only ten studies that investigated psychological interventions for individuals with EDS and/or HSD. Of these ten, half were single case reports; the remaining were retrospective cohort studies. Consequently, study results may not be generalizable to the overall cohort. RCTs should be conducted to reliably evaluate the effectiveness of these psychological interventions. Qualitative studies were also not identified in our review but may be a meaningful addition to the literature (i.e., to provide insight into patient experience). While it is encouraging that the existing research has focused on individually tailored programs given that research has shown the importance of tailored treatment plans in the successful management of chronic pain, future studies should investigate the efficacy of tailored treatment plans on a larger cohort for increased validity and reliability [69]. Similarly, small sample sizes may affect the reliability of the cohort study outcomes. Two of the studies [32, 51] explicitly recommended future studies use larger sample sizes to validate the results. Another notable limitation among included studies was the lack of validated outcome measures used in some studies. Branson et al.’s case report [44] relied on the patient’s self-report and physical symptoms, while Cravero et al.’s case report [45] relied on physical signs. Future studies should use standardized outcome measures for increased validity of findings. Lastly, one case report [46] included in our study focused heavily on the patient’s other comorbidity (EUPD) rather than their EDS, which may confound its findings (i.e., Henry et al.’s [46] intervention may be better suited for individuals with EUPD rather than EDS).

An important finding among our included studies is that the psychological interventions were often not well-described. Many of the interventions mentioned the underlying psychological methods in general terms (e.g., CBT techniques), but failed to describe the treatment details. It was thus often unclear where and how the technique was applied. For instance, Rahman, Daniel, and Grahame [49] stated that the administrators in their study applied principles of CBT in their interventions, but the authors did not provide further details regarding which principles were used and how those principles were integrated into the treatment plan. Furthermore, in many of the studies, the administrators of the psychological interventions were not clearly identified (e.g., described as a “multidisciplinary team”) and it was also unclear what type of training these administrators received to provide these interventions. Future studies should outline the psychological interventions in greater detail in terms of their principles, how those principles were applied to the treatment plan, and who the treatment administrators were. Similarly, many studies did not provide details on participant demographics. The race/ethnicity of participants was provided for only four of the ten studies, and all participants were white/Caucasian. Future studies should include a more detailed demographic profile of its participants to establish the external validity of the treatments for a diverse population (e.g., determine if an intervention is suitable for individuals of different ethnicities).

To our knowledge, this is the only existing scoping review that examines the literature on psychological interventions for individuals with EDS/HSD and identifies various gaps in existing research. It is strengthened by using an experienced information specialist to conduct an exhaustive literature search, as well as multiple reviewers to conduct screening and data extraction independently, in duplicate. The multidisciplinary expertise of our research team (e.g., EDS content experts, methodology experts) helped to strengthen the review, as well as our lifespan approach (e.g., we broadened our search and inclusion criteria to investigate individuals of all ages, rather than just adult or pediatric patients). We also acknowledge some limitations. Since this review included English-language studies only, there may have been a bias toward the inclusion of studies from English-speaking countries. Additionally, we limited our grey literature to three websites (Ehlers-Danlos Society, Ehlers-Danlos Support UK, and Marfan Foundation) on the recommendation of the research team; consequently, we may have excluded important and relevant studies from other sources. Another possible limitation is the search of only MEDLINE, CINAHL, EMBASE, and PsycINFO databases; a wider array of databases may have yielded more articles for inclusion. Additionally, our literature search was conducted on March 28, 2021; thus, we were only able to include articles that had been published by this date, all of which happened to investigate in-person psychological interventions. We acknowledge that we may have missed interventions that were subsequently conducted and published, such as the online RCT by Kalisch and colleagues [70]. It should also be noted that nine of the ten studies were multidisciplinary, meaning that the psychological intervention was only one part of the treatment plan. As a result, it is impossible to ascertain that the outcomes of the treatments were a result of the psychological interventions alone, meaning that the included studies in our review may not accurately reflect the effectiveness of psychological interventions (e.g., the outcomes may have been more influenced by other components of the treatment such as medication or physiotherapy). Overall, more studies are needed that focus on individuals with EDS/HSD to verify the effectiveness of such interventions.

This scoping review on psychological interventions for individuals with EDS and/or HSD identified a lack of high-quality research for this population. Only cohort studies and case reports were identified, and most of the participants were diagnosed with EDS hypermobility type or JHS/HSD. CBT, IIPT, and psychoeducation may be worth investigating further with high-quality studies, but no conclusions about their efficacy can be made presently. MI and MBSR are psychological interventions that may be effective in treating pain and symptoms associated with pain (e.g., depression, anxiety). These may be further investigated for individuals with EDS and HSD. Future studies should also investigate psychological interventions with participants with other forms of EDS, as well as with larger sample sizes and higher quality studies (e.g., RCTs). Furthermore, many of the studies included in our review lacked sufficient detail surrounding demographic information (i.e., race/ethnicity) and description of the intervention (i.e., how the principles of CBT were applied to the treatment plan). This information should be provided in future studies to account for demographic variables in determining the efficacy of a treatment plan and to provide a clearer understanding of effective psychological techniques. Ultimately, many patients with EDS and HSD experience heightened psychological distress from their conditions, yet there is a lack of high-quality research investigating psychological interventions for these individuals, both alone and as a component of a multidisciplinary treatment plan. The results of our study may guide future researchers in designing high-quality studies to determine the most effective interventions for the rehabilitation of individuals with EDS and HSD, which may later be useful in guiding clinical practice.