Sprint interval training

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May 8, 2018 - Sprint interval training (SIT) substantially reduces depressive symptoms in major depressive disorder (MDD): A randomized controlled trial.
Psychiatry Research 265 (2018) 292–297

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Sprint interval training (SIT) substantially reduces depressive symptoms in major depressive disorder (MDD): A randomized controlled trial

T



Alice Minghettia, , Oliver Faudea, Henner Hanssena, Lukas Zahnera, Markus Gerbera, Lars Donatha,b a b

Department of Sport, Exercise and Health, University of Basel, Basel 4052, Switzerland Department of Intervention Research in Exercise Training, German Sport University Cologne, Köln, Germany

A R T I C LE I N FO

A B S T R A C T

Keywords: Exercise training Intermittent exercise Interval training Inpatient Depressive disorder Depression

Continuous aerobic exercise training (CAT) is considered a complementary treatment option in patients with major depressive disorder (MDD). Intermittent exercise training protocols, such as sprint interval training (SIT) have gained increasing popularity, but no studies on depressive symptoms following SIT in patients with MDD are available. Fifty-nine in-patients with MDD were randomly assigned to a SIT or CAT group. Medication was counterbalanced in both intervention arms. Both intervention groups received 3 weekly training sessions for 4weeks (12 sessions in total). SIT comprised 25 bouts of 30 seconds at 80% of maximal power, whereas CAT consisted of 20 minutes of physical activity at 60% of maximal power. The training protocols were isocalorically designed. Maximal bicycle ergometer exercise testing yielded maximal and submaximal physical fitness parameters. The Beck-Depression-Inventory-II (BDI-II) was filled out by the patients before and after the intervention period. BDI-II scores substantially decreased in both groups with an effect size pointing towards a large effect (p < 0.001, ηp² = 0.70) while submaximal (0.07 < d < 0.89) and maximal (0.05 < d < 0.85) fitness variables improved in both groups. Short-term SIT leads to similar results as CAT in patients with MDD and can be regarded as a time-efficient and promising exercise-based treatment strategy.

1. Introduction

been included in WHO guidelines for the standard treatment of depression (WHO 2012). Aerobic exercise intensity determination in MDD patients is nonetheless viewed as challenging since MDD has been linked to traditional cardiovascular risk factors such as hypertension, diabetes and insulin resistance (Anderson et al., 2001; Correll et al., 2017) as well as alterations in immune response and inflammation (Kop et al., 2002; Vancampfort et al., 2016) and metabolic syndrome (Vancampfort et al., 2015). Furthermore, patients suffering from MDD show a more pronounced inflammatory stress response following acute exercise than healthy controls (Boettger et al., 2010). Considering this background, determining aerobic exercise intensities in MDD patients presents itself as a complex and debated issue, particularly in terms of higher intensities and volumes (Donath et al., 2010). A meta-analysis investigating the effects of exercise on depressive symptoms revealed a pooled moderate effect (g = 0.68 with confidence limit ranging from g = 0.44 to 0.92) in favor of aerobic exercise. These exercise trials were

Major depressive disorder (MDD) is one of the leading causes of disease burden worldwide affecting health status more than somatic diseases such as diabetes, musculoskeletal and coronary artery disease (Moussavi et al., 2007) and should therefore be considered a publichealth priority. Depression causes a distinct change of mood such as sadness or irritability and is accompanied by numerous psychophysiological alterations including disturbance in appetite and sleep, loss of ability to experience pleasure, slowing of speech and action as well as suicidal thoughts (Belmaker and Agam, 2008). Effective therapy strategies to reduce disease severity and burden are of great interest (Hecksteden et al., 2013). Along a variety of promising pharmaceutical and behavioral treatment options, physical activity and exercise training evolved into an important evidence-based antidepressant therapy option (Schuch et al., 2016; Vancampfort et al., 2017) and has

Abbreviations: BDI-II, Beck Depression Inventory; BDNF, brain-derived neurotrophic factor; BMI, Body Mass Index; CAT, Continuous aerobic exercise training; f, respiratory frequency; HIT, High intensity interval training; HR, Heart rate; HRV, Heart rate variability; MDD, Major depressive disorder; RCT, Randomized controlled trial; RER, Respiratory exchange ratio; Rpm, Revolutions per minute; SIT, Sprint interval training; VCO2, Carbon dioxide output; VE/VO2, Equivalent for oxygen uptake; VE, Ventilatory efficiency; VO2, Oxygen uptake; VO2peak, Maximal oxygen uptake ⁎ Corresponding author at: Department for Sport, Exercise and Health, Birsstrasse 32B, Basel 4053, Switzerland. E-mail addresses: [email protected] (A. Minghetti), [email protected] (O. Faude), [email protected] (H. Hanssen), [email protected] (L. Zahner), [email protected] (M. Gerber), [email protected] (L. Donath). https://doi.org/10.1016/j.psychres.2018.04.053 Received 16 January 2018; Received in revised form 6 April 2018; Accepted 23 April 2018 Available online 08 May 2018 0165-1781/ © 2018 Elsevier B.V. All rights reserved.

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delivered supervised over a period of 1–16 weeks (2–4 sessions, 30–45 min each) at 60–70% of maximal oxygen uptake or 70–80% of HRmax (Kvam et al., 2016). High intensity interval training (HIT) has gained popularity and is nowadays considered a time-efficient and effective alternative to continuous aerobic exercise training (CAT) (Ramos et al., 2015). In controlled study settings in which the caloric expenditure of both exercise modalities was kept equal, high intensity interval training improved cardiovascular fitness notably more than continuous aerobic exercise (Helgerud et al., 2007). Meanwhile, high intensity interval training has been successfully applied to psychiatric patients in general (Wu et al., 2015) and depressed patients in particular (Heggelund et al., 2014). During the past decade, sprint interval training (SIT) has gained interest in the general population and has become an increasingly promising exercise treatment strategy (Gibala and McGee, 2008). Sprint interval training is a particularly potent variation of interval training which involves “all out” efforts or an intensity corresponding to ≥100% of power or speed associated with an individual's VO2max (Gibala and Hawley, 2017). The overall caloric expenditure is considerably lower than the one of continuous aerobic or high intensity training protocols, but results nonetheless in similar metabolic adaptations (Burgomaster et al., 2008). To date, supervised aerobic exercise has been applied at moderate to high intensities in patients suffering from depression and has yielded promising results (Kvam et al., 2016; Hanssen et al., 2017). To the best of our knowledge, an intermittent modality of aerobic interval exercise training in the form of sprints applied in intervals has however not yet been applied to psychiatric populations. Against this background, the present study aimed at investigating the effects of a low volume sprint interval training regime on heart rate response, perceived exertion and depression severity compared to a continuous aerobic training protocol. We hypothesized that sprint interval training leads to similar symptom reductions at lower perceived effort and heart rates compared to continuous aerobic exercise.

Fig. 1. Flow chart of the study.

Table 1 Demographic data of the patients before (pre) the 4-week intervention for SIT and CAT. Data are presented as means (M) ± standard deviations (SD).

Gender [f/m] Age [years] Height [cm] Weight [kg] BMI (kg/m2) Moderate smoking [1–10 pack years] BDI-II [score] VO2max[L min−1]

SIT (n = 29)

CAT (n = 30)

21/8 35 ± 12 172 ± 10 68 ± 14 22.8 ± 3.4 8 of 23 31 ± 10 2.1 ± 0.5

25/6 37 ± 10 170 ± 8 69 ± 14 24.9 ± 4.4 7 of 25 35 ± 10 2.1 ± 0.6

VO2peak and baseline BDI-II score) either to the sprint interval training group (SIT) or the continuous, aerobic training group (CAT) (Table 1). Both groups trained 3 times a week over the course of a 4-week intervention period, resulting in a total of 12 training sessions. Patients’ medication intake was recorded and comparable in both intervention arms (Table 2). The amount and duration of other behavioral therapies that were applied (e.g., breathing therapy, handcraft, relaxation) also did not differ between groups. The study protocol, informed consent and participants’ information were approved by the Ethical Committee of Northwestern Switzerland (approval number: 2014-374) and met the criteria of the declaration of Helsinki. The CONSORT checklist was followed during the preparation period of the study and manuscript. Participants received all study-relevant information and signed a written consent prior to enrollment.

2. Methods 2.1. Study design and participants The present study was conducted as a two-armed randomized controlled trial (RCT). Participants were stationary patients recruited from the in-patient ward of the Clinic Sonnenhalde in Riehen, Switzerland. Inclusion criteria was a clinical diagnosis of one of the following mood affective disorders according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) (WHO, 2016) criteria: F32.1: major depressive disorder, single episode, moderate; F32.2: major depressive disorder, single episode, severe without psychotic features; F33.1: major depressive disorder, recurrent, moderate; F33.2: major depressive disorder, recurrent severe without psychotic features. Exclusion criteria were any further psychiatric diagnoses including a) eating disorders such as anorexia, bulimia or binge-eating, b) addictions (including alcohol) or current detoxification treatment, c) schizophrenia, d) bipolar disorder, e) panic disorders with or without agoraphobia or somatic disorders including a) cardiovascular diseases, b) stroke or thrombosis, c) epilepsia or other neurological disorders, d) pulmonary diseases, or e) obesity (BMI ≥ 30). Of the 195 initially contacted in-patients suffering from MDD between 18 and 55 years of age, a total of 72 were included. Due to the fact that eligible patients suffered from MDD and were hospitalized for this reason, a relatively large number was not willing to undergo certain measurements or exercise training. This explains why, out of the 195 patients, 123 were not willing to participate. The study flow of the patients is depicted in Fig. 1. Patients were randomly assigned (minimization method (Pocock and Stone, 2016), strata: age, gender, BMI,

Table 2 Medication use of participants.

SNRIs Venlafaxin (75, 175, 225 mg) Mirtzapin (7.5, 15, 30 mg) Wellbutrin (150 mg) SSRIs Trittico (25, 50, 100 mg) Escitalopram (10, 20 mg) Citalopram (20 mg) Fluoxetin (20, 40 mg) Paroxetin (20 mg) Cipralex (60 mg) Seralin (50 mg) Atypical neuroleptic medication Quetiapin (25, 50, 150, 300 mg) Trimipramin (50 mg)

293

SIT (n = 29)

CAT (n = 30)

4 6 1

4 6 1

4 7 1 0 1 1 0

3 6 4 2 0 0 1

4 0

1 1

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Hypotheses of the study were not communicated to the participants in order to meet blinding criteria. Data was collected, stored and analyzed anonymously. Testing personnel consisted of clinicians as well as research assistants, whereby all were blinded to group allocation. Depressive symptoms obtained from the BDI-II served as primary outcome. For this outcome measure, small to moderate between group effects can be detected with a power of 95% and a significance level of 1%. Secondary outcomes were submaximal and maximal physical fitness variables as well as perceived effort and heart rate response.

maximal power output followed by 30 s of total rest (remaining seated on the bicycle). Training loads in terms of EE were comparable in both groups for each training session. The energy expenditure to compare both training regimes can be estimated using the American College of Sports Medicine's metabolic calculation formula for leg cycling [VO2 = (10.8 × Watt × body mass − 1) + 7] (Herbsleb et al., 2014). The estimated training VO2 (l/min) can be converted into EE (kcal/ min) by multiplying by 5 × total number of cycling minutes (Herbsleb et al., 2014). No adverse and serious adverse events were reported.

2.2. Outcome measures

2.4. Statistical analysis

2.2.1. Depressive symptoms The German translated version of the Beck Depression Inventory-II (BDI-II) was applied in order to determine individual severity of depressive symptoms (Beck et al., 1961). The BDI-II yields reliable, internally consistent and valid scores (Cronbach's alpha: 0.93) to detect depression (Arnau et al., 2001) and consists of 21 items including a range of affective, behavioral, cognitive, and somatic symptoms that are indicative of unipolar depression. Each item contains four responses that reflect increasing levels of depressive symptomatology. Possible scores range from 0 to 63 with higher scores indicating more severe depressive symptoms. According to Knaster et al., the following scores represent the severity-index of depression (Knaster et al., 2016): 0–9: no depression; 10–18: mild depression; 19–29: moderate depression; 30–63: severe depression.

Means (M) and standard deviations (SD) are reported for all outcome measures. These outcomes were checked for variance homogeneity (Levene test) and normal distribution (Kolmogorov-Smirnov test). Data were analyzed using IBM SPSS Statistics 21. A significance level of p < 0.05 was set. All outcomes were analyzed via separate 2 (group: SIT vs. CAT) × 2 (time: pre, post) repeated measures analyses of variance (rANOVA). Thereby, we included baseline values as covariates in order to adjust for potential baseline differences. To assess the overall effect sizes for rANOVA, partial eta squared (ηp²) was computed with ηp² ≥ 0.01 indicating small, ≥0.059 medium and ≥0.138 large effects for each parameter (Cohen, 1988). Effect sizes of pairwise comparisons were reported by standardized mean differences (SMD: trivial: d < 0.2, small: 0.2 ≤ d < 0.5, moderate: 0.5 ≤ d < 0.8, large d ≥ 0.8).

2.2.2. Maximal and submaximal physical fitness All subjects completed two exhausting incremental exercise tests on a sitting bicycle ergometer (Ergometrics 900®, Ergoline, Bitz, Germany) before and after the intervention. Participants started at a 25 W workload, resting heart rates (pre exercise heart rates) were measured 5 min prior to the start of cycling sitting on the ergometer using a Polar heartrate monitor (Polar RS 400, Polar® Electro, Kempele, Finland). Every minute an increase of 10 W was applied until subjective perceived exhaustion (Borg 10) was reported. (Borg, 1998) The cadence was intra-individually kept constant. The inter-individual range was between 60 and 80 revolutions per minute (rpm) due to individual pedaling comfort. After reaching previously published exhaustion levels (Boettger et al., 2009), all participants cycled at a low workload (10 W, 30 rpm) for 3 min. Respiratory gas exchange data was collected continuously every 10 s using a facemask connected to a breath-by-breath spirometric system (Metamax®, Cortex, Leipzig, Germany). Oxygen uptake (VO2, L min−1), carbon dioxide output (VCO2, L min−1), minute ventilation (VE, L min−1), respiratory exchange ratio (RER), the ventilatory equivalent for oxygen (VE/VO2) and respiratory frequency (f, min−1) were assessed. The highest oxygen uptake averaged over 30 s was regarded as VO2peak. Heart rates and perceived exertion (Borg) were collected at the end of each increment. VT1 was determined using the V-slope method (Beaver et al., 1986). The distinct deflection point of the linear relationship between VCO2 delivery and VO2 uptake was considered as VT1. The ventilatory equivalent for oxygen uptake obtained from the VE and VO2 diagram was redundantly used for a plausibility check of VT1 determination.

3. Results 3.1. Depressive symptoms No significant group × time interaction was found with regard to the BDI-II scores (p = 0.98, ηp² = 0.001). Significant time effects were observed (p < 0.001, ηp² = 0.70). The corresponding effect size for the time effect can be considered very large. Similarly, a pair-wise within group comparison revealed large effect sizes (SMD = 1.1) for both interventions (Fig. 2). 3.2. Physical fitness No significant group × time interactions were observed for submaximal (0.07 < p < 0.89) and maximal fitness parameters (0.05 < p < 0.85), and the corresponding effect sizes were small (submaximal parameters: 0.06 < ηp² < 0.001; maximal parameters: 0.07 < ηp² < 0.001). Significant time effects with large effect sizes in

2.3. Exercise training intervention The patients trained three times a week (Mondays, Wednesdays and Fridays) under supervision of an experienced exercise coach. Each training session lasted 35 min including a standardized warm-up (5 min) and cool-down (5 min) period. Training intensity was prescribed in relation to the maximal power output obtained from the incremental exercise test. Continuous aerobic training consisted of 20 min continuous exercise at a power output corresponding to 60% of the maximal power output, whereas the sprint interval training session consisted of 25 repetitions of 30 s high intensity bursts at 80% of

Fig. 2. Scores of the Beck Depression Inventory (BDI-II) at pre (grey bar) and post (dark bars) testing for sprint interval training (SIT) and continuous exercise training (CAT). Data are depicted as means (M) and standard deviations (SD). Pairwise effect sizes are provided as standardized mean differences (SMD; Cohen's d). 294

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Table 3 Performance parameters obtained during the physical fitness test. SIT

Submaximal parameter at VT1 P [W] VO2 [L min−1] VO2 [mL min−1 kg−1] HR [min−1] Peak parameter P [W] VO2 [L min−1] VO2 [mL min−1 kg−1] HR [min−1]

CAT

Time p-value; ƞp²

Time × Group p-value; ƞp²

Pre

Post

Pre

Post

59 ± 18 1.1 ± 0.2 16 ± 4 123 ± 15

65 ± 22 1.2 ± 0.2 17 ± 4 118 ± 23

50 ± 15 1.0 ± 0.2 15 ± 3 114 ± 16

58 ± 24 1.1 ± 0.2 16 ± 4 117 ± 15

0.003; 0.16 0.01; 0.12 0.006; 0.14 0.51; 0.008

0.62; 0.43; 0.67; 0.08;

0.005 0.01 0.004 0.06

161 ± 39 2.1 ± 0.5 32 ± 8 174 ± 19

167 ± 39 2.3 ± 0.5 34 ± 8 172 ± 18

148 ± 39 2.1 ± 0.6 30 ± 6 172 ± 15

158 ± 39 2.2 ± 0.5 32 ± 7 172 ± 13

0.001; 0.30 0.06; 0.06 0.01; 0.12 0.70; 0.003

0.49; 0.84; 0.56; 0.76;

0.009 0.001 0.007 0.002

endurance training (Milanovic et al., 2015). These successful concepts have been translated into clinical practice, including psychiatric care (Heggelund et al., 2014; Heggelund et al., 2011). Although selective studies observed notable acute effects of highly intense bouts of aerobic exercise in mood (Elkington et al., 2017), to date no conclusive evidence derived from RCTs or meta-analyses is available concerning depressed patients. From this perspective, sprint interval training might serve as an alternative intermittent aerobic exercise mode at the same caloric expenditures and systemic demands compared to high intensity interval training and continuous exercise, respectively. Gibala et al. (2006) as well as Burgomaster et al. (2008) observed similar metabolic and skeletal adaptations following sprint interval training at 10% of the caloric expenditure of traditional endurance training (Burgomaster et al., 2008; Gibala et al., 2006). They concluded that this exercise mode causes “a lot of gain for a little pain” (Gibala and McGee, 2008). Even few sessions in general (e.g., 2 weeks) or few bouts per session of sprint intervals have been shown to induce meaningful metabolic (e.g., citrate synthase and muscle glycogen content) and performance (e.g., cycling endurance capacity) changes (Burgomaster et al., 2005; Parra et al., 2000). These findings have been summed up in a meta-analysis showing equal effectiveness of sprint interval training compared to continuous training with reduced training volume (Gist et al., 2014). Beneficial effects of sprint interval training were also reported within recent years in clinical populations (Freese et al., 2014; Heiskanen et al., 2017; Shepherd et al., 2017). The applied bout length was predominantly 30 s at nearly maximal exercise intensities and were repeated 4–6 times. The length of the breaks differed between trials. Even though the research examining the effects of sprint interval training are very promising, studies in psychiatric patients are lacking. This training method is thus not performed in clinical settings. Up to date, only one case study of sprint interval training has been conducted in a schizophrenic patient. Herbsleb et al. (2014) observed impressively lower resting heart rates, serving as an indicator of increased parasympathetic activity, compared to the continuous exercise training regimen. However, the compared exercise protocols had similar caloric expenditure. Thus, it might be reasonable to assume that training volume on the one hand and the intermittent character of the training regime on the other hand might lead to more vagal drive. In our study, we applied a similar pattern of 25 times 30 s at 80% of maximal power output. This exercise training mode led to a net training load of 12.5 min three times a week compared to 3 × 20 min of continuous aerobic training. Our effect size of symptom reductions was large in both training regimens, with both groups successfully reducing BDI-II scores. This effect may be explained on a molecular level. Exercise induces a release of brain-derived neurotrophic factor (BDNF), a neurotrophin which has been negatively correlated to depression-related personality traits in healthy subjects (Nomoto et al., 2015). A meta-analysis confirmed the involvement of BDNF in psychiatric disorders, correlating decreased serum of BDNF to major depressive

favor of both interventions were found for the power at VT1 (p = 0.003, ηp² = 0.16), relative oxygen uptake (p = 0.006, ηp² = 0.14). All other spiroergometric variables did not change significantly. Similar results were found for maximal parameters (Table 3). 3.3. Training response ANCOVA found large effects for changes in average heart rates (p = 0.01, ƞp² = 0.16) in both groups (SIT, pre: 140 ± 14, post: 136 ± 17; CAT, pre: 147 ± 18, post: 140 ± 14). Also perceived effort (SIT, pre: 14 ± 2, post: 12 ± 2; CAT, pre: 15 ± 3, post: 13 ± 3; time: p < 0.001, ƞp² = 0.28, time × group: p = 0.88, ƞp² = 0.004) showed substantial changes from the 1st to the 12th training session. 4. Discussion To the best of our knowledge, this is the first randomized controlled trial that compared the effects of a 4-weeks sprint interval training (SIT) with continuous aerobic exercise training (CAT) on depressive symptoms and physical fitness in stationary patients with major depressive disorder (MDD). We found large reductions of BDI-II scores following both exercise modes. Improvements of submaximal and maximal physical fitness indices did not differ between either groups. Interestingly, heart rate and subjectively perceived efforts were found to be notably lower in the sprint interval group. In comparison to traditional continuous aerobic training, sprint interval training can be regarded as a promising, time-efficient and tolerable exercise training alternative at lower cardiovascular and psychological strain. No specific exercise protocol exists for MDD patients yet. Therefore, exercise prescriptions in institutional settings are mainly based on common aerobic exercise recommendation for healthy adults. These recommendations however need to be adapted in order to avoid physical overstrain of MDD patients since their submaximal metabolic response to aerobic exercise is altered (Donath et al., 2010). Health care providers may primarily target light physical activity instead of vigorous exercise performed at higher intensities (Helgadottir et al., 2015). A factor which should furthermore not be neglected, especially in depressed subjects, are individual preferences of exercise modalities. The vast majority of available RCTs on exercise and depression report a dropout rate of around 20% (Stubbs et al., 2016; Schuch et al., 1999). One fifth of the patients seems to feel uncomfortable with aerobic exercise training as a complementary treatment option. Our study is in line with these dropout reports, whereby the dropout rates between the two exercise protocols were similar (SIT: 17%, CAT: 19%). The stated reason for their dropout was lack of motivation. In future research, a comparison of a variety of different exercise protocols that have been proven to be effective should be tailored to individual needs, barriers and preferences of depressed patients. Previous studies revealed that high intensity interval training has larger effects on maximal oxygen uptake compared to continuous 295

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Acknowledgments

disorders (Sen et al., 2008). Studies have shown that physical exercise has been able to increase low serum levels in depressed patients to normal levels (Laske et al., 2010), whereby the increase of BDNF was associated to the intensity of the applied exercise (Gustafsson et al., 2009). These results indicate that regular exercise should be included as a non-pharmaceutical treatment option in MDD. Considering adherence levels of antidepressant medication, where about 30% of patients do not achieve remission after four different antidepressant treatment trials (Olchanski et al., 2013), these findings are of major importance. Patients are concerned about side effects and potential addiction to medical treatment and prefer non-pharmaceutical options which do not possess the potential side effects of regular and long-term use of medication (Hunot et al., 2007; Churchill et al., 2001). In light of these findings, we recommend health care providers to tailor exercise modes to the individual needs, preferences and potential barriers of the patients. Beside high-intensity interval training and continuous aerobic training, sprint interval training might also serve as a feasible and effective complementary exercise-based treatment option. This is of particular relevance since intermittent high-intensity sprint training can be perceived as less demanding and more enjoyable than traditional, continuous endurance training (Bartlett et al., 2011; Thum et al., 2017). Changes of affective valance in our study did not differ between either groups throughout the intervention period. However, our study also revealed lower perceived efforts during sprint interval training compared to continuous aerobic training. This finding might refer to a less strenuously perceived sprint interval training session due to the length of each interval. Further large-scale randomized controlled trials applying these exercise protocols are necessary in order to draw conclusive findings. Despite the novelty of the presented results, they must be interpreted in light of several limitations. Confidential patient data such as the number or duration of depressive episodes as well as medication intake prior to their clinical stay were not accessible to us. Although both intervention arms revealed substantial reductions of BDI-scores, we must nonetheless consider that other applied therapies may have additionally contributed to these observations. However, non-exercise treatment methods were equal in both groups and a passive control condition might be considered debatable as the effects of continuous, aerobic exercise have previously been proven to be beneficial. Thus, we did not see it fit to detain a treatment possibility from patients. Additionally, we only included patients willing to exercise regularly. Those participants might have been aware of the antidepressant effects of physical activity. Finally, we were not able to conduct an intention to treat analysis. Thus, dropping out of the study can refer to meaningful adverse effects of exercise in those patients. Future studies should try to engage drop out patients into post testing in order to compare intention to treat with as treated analyses. This step would enable more detailed drop out analyses. Unfortunately, our patients were not available for post testing after dropping out of the study.

We cordially thank all patients for their engagement. We also appreciate the support of the Clinic “Sonnenhalde” (Riehen, Switzerland) namely Anja Rogausch for recruiting patients and providing medication and secondary treatment data. Vincent Hughes, Manuel Kranich and Simon Lorenzen need to be mentioned for their study assistance throughout the training and testing procedure. Ethics approval and consent to participate The study was approved by the local ethical committee (Ethical Committee of Northwestern Switzerland, EKNZ), Approval number: 2014-374) and all patients signed an informed consent to the study after receiving all relevant study information. Consent for publication Was obtained from the participants, collaborators and co-authors. Availability of data and material Can be requested for further analyses or transparency reasons from the corresponding author. Competing interests None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions AM and LD developed the study design, conducted the statistics and wrote the manuscript; OF, HH, LZ and MG contributed to the study design and revised the manuscript. All authors contributed to the manuscript draft and approved the final draft version. References Anderson, R.J., Freedland, K.E., Clouse, R.E., Lustman, P.J., 2001. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 24 (6), 1069–1078. Arnau, R.C., Meagher, M.W., Norris, M.P., Bramson, R., 2001. Psychometric evaluation of the Beck Depression Inventory-II with primary care medical patients. Health Psychology 20 (2), 112–119. Bartlett, J.D., Close, G.L., MacLaren, D.P., Gregson, W., Drust, B., Morton, J.P., 2011. High-intensity interval running is perceived to be more enjoyable than moderateintensity continuous exercise: implications for exercise adherence. J. Sports Sci. 29 (6), 547–553. Beaver, W.L., Wasserman, K., Whipp, B.J., 1986. A new method for detecting anaerobic threshold by gas exchange. J. Appl. Physiol. 60 (6), 2020–2027. Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., Erbaugh, J., 1961. An inventory for measuring depression. Arch. Gen. Psychiatry 4, 561–571. Belmaker, R.H., Agam, G., 2008. Major depressive disorder. New Engl. J. Med. 358 (1), 55–68. Boettger, S., Muller, H.J., Oswald, K., et al., 2010. Inflammatory changes upon a single maximal exercise test in depressed patients and healthy controls. Prog. Neuropsychopharmacol. Biol. Psychiatry 34 (3), 475–478. Boettger, S., Wetzig, F., Puta, C., et al., 2009. Physical fitness and heart rate recovery are decreased in major depressive disorder. Psychosom. Med. 71 (5), 519–523. Borg, G., 1998. Perceived Exertion and Pain Scales. Human Kinetics, Champaign. Burgomaster, K.A., Howarth, K.R., Phillips, S.M., et al., 2008. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J. Physiol. 586 (1), 151–160. Burgomaster, K.A., Hughes, S.C., Heigenhauser, G.J., Bradwell, S.N., Gibala, M.J., 2005. Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans. J. Appl. Physiol. 98 (6), 1985–1990. Churchill, R., Hunot, V., Corney, R., et al., 2001. A systematic review of controlled trials

5. Conclusion Our randomized controlled trial showed that short term sprint interval training in stationary patients with MDD led to similar symptom reductions compared to traditional continuous aerobic training at notably lower training volumes and perceived efforts. Further studies have to investigate whether a combination of both exercise modalities can optimize therapeutic targets for disease severity. As a further perspective, patients will have to uphold their exercise regimen after discharge and need infrastructure to maintain adherence. It remains debated how exercise programs can be routinely implemented into clinical settings and more research is warranted to investigate feasibility of regular exercise training in a home-based setting under less or no supervision.

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