Working out the worries: A randomized controlled trial of high intensity interval training in generalized anxiety disorder
Introduction
In recent years, research has progressively focused on the efficacy of physical activity in anxiety disorders. In this context, several randomised controlled trials (RCT) demonstrated that aerobic exercise (AE) is an effective treatment approach for social anxiety disorder, panic disorder (PD), specific phobia and generalized anxiety disorder (GAD) (Bischoff et al., 2018; Broocks et al., 1998; Gaudlitz, Plag, Dimeo, & Ströhle, 2015; Herring, Jacob, Suveg, Dishman, & O’Connor, 2012; Lindenberger et al., 2017; Merom et al., 2008). Although studies in this field differed to some extent regarding type, intensity, frequency and total duration of exercise, recent meta-analyses found an overall medium effect of AE on disorder-specific symptomatology as well as significantly lower drop-out rates in the exercise groups compared to different control conditions (Aylett, Small, & Bower, 2018; Stubbs et al., 2017). Former studies usually established a several-week moderate intensity training (around 70 % of the maximal oxygen uptake [VO2max]) consisting of up to seven units a week (Bischoff et al., 2018; Merom et al., 2008) and a maximum of 30 min per session (e.g. (Gaudlitz et al., 2015)). Interestingly, findings quite consistently show that aerobic training of this intensity led to a significantly larger anxiolytic effect not only in comparison to non-active control groups but also to exercise programs of lower physical strain (e.g. 30 % VO2max or less) (Bischoff et al., 2018; Gaudlitz et al., 2015; Lindenberger et al., 2017). Significant evidence for an “intensity-response relationship” of aerobe exercise in anxiety disorders is currently provided by a meta-analysis that included nine trials focusing on different entities. In this analysis, exercise of higher intensity was found to be superior to “low-intensity exercise” for reducing disorder-specific anxiety with at least a small effect size (Aylett et al., 2018).
Considering these data, we suspected that high-intensity interval training (HIIT) might be a promising tool to further improve the efficacy of AE in anxiety disorders. HIIT is a popular form of exercise that is characterized by short bouts of (sub)maximum physical strain interspersed with brief periods of lower intensity or rest (Laursen & Jenkins, 2002). Although this type of training was originally developed to optimize training programs for endurance athletes, nowadays it is also frequently applied in the general population and was found to be well tolerated by previously sedentary individuals (Reljic et al., 2019). Several clinical trials demonstrated that HIIT led to similar or stronger effects on a range of health-related parameters such as cardiorespiratory fitness (CRF), body mass, glucose utilization or blood pressure compared to a moderate-intensity continuous training. These effects were also already evident within a significantly shorter period of time (Nardi, Tolves, Lenzi, Signori, & Silva, 2018; Way, Sultana, Sabag, Baker, & Johnson, 2019; Wen et al., 2019; Wewege, van den Berg, Ward, & Keech, 2017). With respect to mental conditions, a number of RCT reported HIIT’s efficacy and good tolerability particularly in patients with depression. In this context, meta-analytic data also demonstrated that HIIT led to a significantly stronger improvement of symptoms than continuous moderately intense AE (Korman et al., 2019). To get an impression of both the therapeutic properties and the feasibility of HIIT in anxiety disorders, we recently conducted an open trial with patients suffering from PD with and without agoraphobia (AG) (Plag, Ergec, Fydrich, & Ströhle, 2019). As a result, a 12-day HIIT was associated with moderate or large effects on PD severity, agoraphobic avoidance, comorbid depression and endurance performance. Interestingly, no patient dropped out during the study period even though the training was rated as significantly exhausting by the participants (Plag et al., 2019).
The present study therefore aimed to investigate the efficacy and acceptance of HIIT in GAD within a RCT. We decided to focus on GAD because this condition was found to be associated with relatively smaller effects in guideline-based treatments compared to other anxiety disorders (Bandelow et al., 2015; Cuijpers et al., 2016). Since preliminary data also provide some evidence for intensity as an important factor for the impact of exercise on GAD (Herring et al., 2012), we hypothesized that HIIT will cause a faster and larger reduction of disorder-related worrying as well as further illness-related symptoms than a control condition of less intense exercise. Moreover, previous trials found a negative association between symptom severity and CRF in some “stress-related disorders” such as major depressive disorder (MDD) or posttraumatic stress disorder (PTSD) (Papasavvas, Bonow, Alhashemi, & Micklewright, 2016; Whitworth et al., 2020) and other studies nearly unanimously reported a significant improvement of CRF through different forms of HIIT (Wen et al., 2019). We therefore further seeked to assess the relationship between HIIT-induced changes in CRF and worrying as well as disorder-unspecific psychopathology. Therefore, we focused on pre-post effects of VO2max as the most established objective parameter of CRF (Wen et al., 2019). Finally, we also aimed to explore the role of a specific pathogenetic factor of GAD in our intervention. Individual's perceived level of control (PC) over anxiety related stimuli as a distinct cognitive function was shown to be negatively correlated to symptom severity in several anxiety disorders but particularly to worrying in GAD (Gallagher, Bentley, & Barlow, 2014). Moreover, PC was also identified as a relevant factor for recovery in this condition since it was found to be indirectly associated with the outcome of cognitive behavioural therapy (CBT) (Gallagher, Naragon-Gainey, & Brown, 2013). Since further pathogenetic factors of anxiety disorders (e.g. anxiety sensitivity) were demonstrated to be changeable by AE (LeBouthillier & Asmundson, 2015), we therefore further intended to investigate the relevance of PC for both symptom severity and disorder-specific efficacy of AE in the present sample.
Section snippets
Design and patients
The present study is a parallel-group, assessor-blinded RCT and was conducted at the outpatient center for anxiety disorders of the Department of Psychiatry and Psychotherapy of the Charité, Universitätsmedizin Berlin, Germany. We initially planned to assess 40 participants, however, due to reasons of recruitment we were only able to evaluate 33 patients. Participants were told that the goal of the study is to investigate the treatment effects of two different forms of exercise. Therefore, they
Sample characteristics
Participants were recruited from 2015 to 2018. Fig. 1 demonstrates the flow of patients. Adherence rate was 82 % for HIIT and 94 % % for the control group indicating no significant differences between the conditions. No patient dropped out for reasons related to exercise. The sample consisted of 24 women and 9 men, with 13 women (72.73 %) in HIIT and 11 women (68.76 %) in LIT. See Table 1 for baseline characteristics.
Primary clinical outcome
For HIIT and LIT, the PSWQ-D scores at baseline were higher than 60
Discussion
In the first RCT addressing HIIT in anxiety disorders, we were able to demonstrate large treatment effects on worrying, stress-related somatic symptoms, unspecific anxiety and comorbid depression in GAD. As indicated by the PSWQ-pw and SOMS-7 at post as well as at follow-up, its impact on core symptoms of GAD already took place during the intervention and was still detectable 18 days after the end of the active study period. Considering that medication and psychotherapy achieve small and medium
Conclusion
The present RCT confirmed the overall role of AE as a treatment option for GAD because we found pronounced, fast-acting and sustained effects on its hallmark symptoms as well as on comorbid depression in both study conditions. For the first time, however, HIIT was demonstrated to be particularly effective and well tolerated in these patients. HIIT therefore holds some potential to complement psychotherapy as well as medication in GAD and may provide the advantage of a relatively fast onset of
Role of the funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Contributors
Jens Plag and Andreas Ströhle designed the study. Jens Plag wrote the protocol, coordinated the trial, conducted the third-party assessments and wrote the major part of the manuscript. Moritz B. Petzold carried out the main part of the statistical analysis and wrote the result section of the paper. Paul Schmidt-Hellinger and Bernd Wolfarth performed the cardiopulmonary exercise testing. Theresa Klippstein and Jennifer L. Mumm provided support for the preparation and the analysis of the data.
Acknowledgments
The authors would like to thank Nora Jung, Tonja Leonie Kühnel, Jouline Petzka and Monique Strittmatter for the supervision of the exercise units.
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