Exercise improves cardiorespiratory fitness in people ...

SCHRES-06558; No of Pages 5 Schizophrenia Research xxx (2015) xxx–xxx

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Exercise improves cardiorespiratory fitness in people with schizophrenia: A systematic review and meta-analysis Davy Vancampfort a,b,⁎, Simon Rosenbaum c, Philip B. Ward c, Brendon Stubbs d,e a

KU Leuven Department of Rehabilitation Sciences, Leuven, Belgium KU Leuven Department of Neurosciences, UPC KU Leuven, Campus Kortenberg, Kortenberg, Belgium School of Psychiatry, University of New South Wales, Sydney, Australia d Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, United Kingdom e Health Service and Population Research Department, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom b c

a r t i c l e

i n f o

Article history: Received 16 May 2015 Received in revised form 17 September 2015 Accepted 21 September 2015 Available online xxxx Keywords: Schizophrenia Psychosis Physical activity Exercise Cardiorespiratory fitness

a b s t r a c t Objective: To determine if exercise can improve cardiorespiratory fitness in people with schizophrenia. Methods: Major electronic databases were searched systematically until May 2015. A meta-analysis calculating Hedges' g statistic was undertaken. Results: Engaging in exercise improves cardiorespiratory fitness in people with schizophrenia (g = 0.40, 95% CI = 0.16–0.64, p = 0.001, N = 7, n = 77). Data from four controlled studies demonstrated that exercise (n = 53) significantly improves cardiorespiratory fitness compared to control groups (n = 48) (g = 0.43, 95% CI = 0.05–0.82, p = 0.028). Conclusions: Considering the current findings, the multidisciplinary treatment of schizophrenia should include a focus on both, improving “fitness” and reducing “fatness”, in order to reduce all-cause mortality. © 2015 Elsevier B.V. All rights reserved.

1. Introduction People with schizophrenia have consistently higher levels of premature mortality than the general population (Walker et al., 2015), mainly due to an increased risk of cardio-metabolic diseases (Stubbs et al., 2015; Vancampfort et al., 2013). Although genetic factors (Andreassen et al., 2013) and shared pathophysiological mechanisms (Manu et al., 2014) contribute, treatment-related factors and unhealthy lifestyle habits play a particularly prominent role (Correll et al., 2014). In the general population there is robust evidence demonstrating that low cardiorespiratory fitness (the ability of the circulatory and respiratory systems to supply oxygen to working muscles during sustained physical activity) is a strong and independent predictor of cardiovascular diseases (relative risk (RR) 1.56 (95% CI = 1.39–1.75; p b 0.001) and all-cause mortality (RR 1.70 (95% CI = 1.51–1.92; p b 0.001)) (Kodama et al., 2009). Exercise interventions that seek to improve cardiorespiratory fitness are the cornerstone to prevent cardiovascular disease and associated mortality (Barry et al., 2014). A recent meta-analysis (Vancampfort et al., 2015) demonstrated that cardiorespiratory fitness is significantly reduced in people with schizophrenia (n = 154) (standard mean difference of − 0.96 (95% CI − 1.29 to −0.64; N = 5) compared to healthy controls (n = 182)). Research in the general population has demonstrated that improvements in ⁎ Corresponding author at: Leuvensesteenweg 517, 3070 Kortenberg, Belgium. E-mail address: [email protected] (D. Vancampfort).

cardiorespiratory fitness are associated with a lower risk of mortality from cardiovascular disease independent of age, smoking and body composition (Lee et al., 2010). To our knowledge, meta-analytic data on the effect of exercise on cardiorespiratory fitness are lacking in people with schizophrenia. If exercise is able to improve cardiorespiratory fitness, the implications for tackling cardiovascular disease and mortality could be important. The aim of this brief report is to conduct a systematic review and meta-analysis to quantify effects of exercise interventions on cardiorespiratory fitness in people with schizophrenia, and where possible, to compare this effect with control interventions. 2. Methods 2.1. Search procedure Two researchers (BS, DV) searched Medline, PsycARTICLES, Embase and CINAHL from database inception to May 2015. Key words used were “cardiorespiratory” OR “aerobic fitness” AND “schizophrenia” OR “psychosis” in the title, abstract or index term fields. Manual searches were also conducted using the reference lists from recovered articles. The eligibility criteria were as follows. 2.2. Participants Only studies with a confirmed diagnosis of schizophrenia spectrum according to Diagnostic and Statistical Manual (DSM) (American

http://dx.doi.org/10.1016/j.schres.2015.09.029 0920-9964/© 2015 Elsevier B.V. All rights reserved.

Please cite this article as: Vancampfort, D., et al., Exercise improves cardiorespiratory fitness in people with schizophrenia: A systematic review and meta-analysis, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.09.029

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D. Vancampfort et al. / Schizophrenia Research xxx (2015) xxx–xxx

Psychiatric Association, 2013) or the International Classification of Disease (ICD) (World Health Organisation, 1993) were included.

2.8. Study selection

We investigated the effect of aerobic exercise interventions defined as physical activity that is planned, structured, repetitive and purposive, in the sense that improvement or maintenance of physical fitness is an objective (Caspersen et al., 1985).

After the removal of duplicates, both reviewers screened the titles and abstracts of all potentially eligible articles. Both authors applied the eligibility criteria, and a list of full text articles was developed through consensus. The two reviewers then applied the eligibility criteria and a final list of included articles was reached through consensus. When necessary, the corresponding author was contacted up to two times in a 3-week period to request data to enable inclusion.

2.4. Control conditions

2.9. Statistical analyses

All non-aerobic interventions, usual-care or wait-list control conditions were included.

Random-effects meta-analyses were conducted using Comprehensive Meta-Analysis software (Version 3, Biostat, Englewood, New Jersey). We investigated the influence of exercise in schizophrenia participants using predicted VO2max or VO2peak by (a) pooling pre- and posttest changes in schizophrenia participants, and (b) comparing changes in predicted VO2max or VO2peak in the exercise versus controls. We included both RCTs and CCTs in the comparative meta-analysis due to the paucity of data but present the results with appropriate caution. We calculated Hedges' g statistic, and 95% confidence intervals (CIs) for each analysis. Statistical heterogeneity was assessed using the I2 statistic. Publication bias was assessed with the Begg–Mazumdar (Begg and Mazumdar, 1994) and Egger (Egger et al., 1997) tests.

2.3. Interventions

2.5. Outcome measure The outcome measure was cardiorespiratory fitness expressed as predicted maximal oxygen uptake (VO2max predicted) or peak oxygen uptake (VO2peak). 2.6. Study design We included pre- and post-test studies without a control group and randomized (RCTs) or non-randomized clinical controlled trials (CCTs) in which the experimental and control intervention were of similar duration.

3. Results 3.1. Search results and flow of trials through the review

2.7. Further eligibility and exclusion criteria No additional exclusion criteria were applied.

A total of 170 records were identified. After screening and the application of the eligibility criteria, seven studies (Bredin et al., 2013;

Fig. 1. Flow diagram for the search results.



Heggelund et al., 2011; Kimhy et al., 2015; Pajonk et al., 2010; Rosenbaum et al., 2015; Scheewe et al., 2012; Strassnig et al., 2012) were identified and included in the meta-analysis. We requested and received additional data from one research group (Pajonk et al., 2010). Fig. 1 presents the flow of studies through the review. 3.2. Characteristics of included trials Four of the included studies were controlled studies (of which 3 were RCTs) and the other three were pre- and post-test studies (see Table 1). Across the seven studies there were 77 people with schizophrenia that underwent exercise interventions (mean age = 31.0 ± 5.6 years) and 48 participants assigned to a control condition (35.9 ± 3.9 years). 3.3. Meta-analysis of pre- and posttest changes in cardiorespiratory fitness Data from seven studies found that exercise significantly improved cardiorespiratory fitness in 77 people with schizophrenia following an exercise intervention (hedges g = 0.40, 95% CI = 0.16 to 0.64, p = 0.001; Fig. 2). There was some heterogeneity (I2 = 65%) but no evidence of publication bias (Kendall tau = 0.14, p = 0.33, Eggers regression = 3.22, p = 0.21). The pooled mean increase in relative predicted VO2max or VO2peak was 2.87 ml/kg/min (95% CI 1.47–4.27, p b 0.0001). 3.4. Exercise versus control conditions It was possible to pool data from 4 controlled studies to compare the influence of aerobic exercise on predicted VO2max or VO2peak versus

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control interventions (Pajonk et al., 2010; Heggelund et al., 2011; Scheewe et al., 2012; Kimhy et al., 2015). Exercise significantly improved cardiorespiratory fitness compared to the control group (hedges g = 0.43, 95% CI = 0.05 to 0.82, p = 0.02; n = 101, Fig. 3). There was no heterogeneity (I2 = 0%) nor any evidence of publication bias (Kendall tau = − 0.33, p = 0.25, Eggers regression = −1.89, p = 0.33). Compared to control, schizophrenia participants who exercised experienced gains of 2.79 ml/kg/min (95% CI 0.46–5.14, p = 0.02). 4. Discussion This is the first quantitative synthesis investigating the effect of aerobic exercise interventions on cardiorespiratory fitness among people with schizophrenia. Our review identified seven studies and found that aerobic exercise significantly increased predicted VO2max or VO2peak at a clinically meaningful level, and was significantly better than any control condition. Exercise participation results in a pooled mean increase in predicted VO2max or VO2peak of 2.87 ml/kg/min (95% CI = 1.47–4.27, p b 0.0001). Compared to control conditions, those exercising experienced gains of 2.79 ml/kg/min (95% CI = 0.46– 5.14, p = 0.02). The effect sizes are in the top end of the small to moderate range and such improvements in cardiorespiratory fitness are of high clinical relevance. For example, among the general population, it has been demonstrated that every 3.5 ml/kg/min incremental increase in VO2peak is associated with 13% and 15% decrements in risk of allcause mortality and CVD, respectively (Kodama et al., 2009). Recent debate over the importance of ‘fitness vs. fatness’ has led to increasing consensus regarding the superiority of poor fitness as a better predictor of morbidity and mortality as opposed to fatness (Lee et al.,

Table 1 Cardiorespiratory fitness outcomes following cardiorespiratory exercise interventions in people with schizophrenia. Study

Design

Participants

Pajonk et al. (2010)

RCT

16♂ outpatients with schizophrenia (DSM-IV); 32.9 ± 10.6 years

Heggelund et al. (2011)

Scheewe et al. (2012)

Strassnig et al. (2012) Bredin et al. (2013)

Kimhy et al. (2015)

Rosenbaum et al. (2015)

Intervention characteristics (versus controls)

12 weeks, 3/week, 30 min ergometer cycling at heart rate (±10 beats/min) corresponding to a blood lactate concentration of about 1.5 to 2 mmol/L versus table top football with comparable levels of stimulation to that provided for cardiorespiratory exercise 8-week HIT 3/week: 4 × 4-min walking or running CCT 17 (13♂) inpatients with with a minimum of 5% inclination on a treadmill at schizophrenia 1 delusional disorder, 1 schizo-affective disorder (ICD-10); 85–95% HR peak at a work load corresponding to 70% HR peak between each interval versus computer 33.6 ± 10.3 years; BMI = 28.3 game (Tetris) same amount of time 6 months, 2/week, 1 h cardiorespiratory (week 1–3: RCT 63 (46♂) outpatients with 45%, week 4–12:65%, week 13–26:75% HRR) and schizophrenia spectrum (DSM-IV) (29.6 ± 7.4 years; BMI = 26.3 ± 6.0) muscle exercises (6 exercises weekly; 3 × 10–15 repetitions maximum for biceps, triceps, abdominal, quadriceps, pectoral, deltoid muscles) versus same amount of occupation therapy (creative and recreational activities) 6 weeks, 3/week, 30 min at a treadmill; target PE 6(4♂) outpatients with training heart rate was set at 65% of maximum schizophrenia spectrum (DSM-IV) (36.8 ± 10.4 years; BMI = 35.1 ± 3.8) (220-age) 12 weeks, 3/week, 30 min moderate to vigorous PE (pilot 13(7♂) patients with schizophrenia data of RCT) or schizoaffective disorder (DSM-IV); cardiorespiratory exercise (progression based on HR changes +5%/week) OR 12 weeks, 3/week, 30.9 ± 7.2 years; BMI = 29.0 ± 6.0 30 min resistance training (50%–70% 1RM) 2 sets of 10–15 repetitions using 8–10 exercises (i.e., chest press, shoulder press, latissimus dorsi pulldown, leg press, leg extension, leg curl, triceps push down, and arm curls). RCT 33(21♂) outpatients with 12 weeks, 3/week, 60 min cardiorespiratory (week schizophrenia (DSM-IV); 18–55 years 1: 65%, week 2: 70%, week 4–12:75% HR max) using active-play video games (e.g., Xbox Kinect) and traditional exercise equipment versus care as usual PE 5♂ outpatients with schizophrenia 12 weeks, 2/week, 45 min ergometer cycling at HR (DSM-IV); 15–25 years (±10 beats) corresponding to 65% of VO2 peak

Cardiorespiratory outcomes (VO2) (versus controls) No significant change in VO2 max from before (28 ± 7 mlO2/min/kg) to after exercise (27.6 ± 6.5 mlO2/min/kg) or compared to controls (23.9 ± 3.7 to 23.3 ± 2.9 mlO2/min/kg)

12% increase in VO2 peak in HIT-group (from 36.0 ± 7.4 to 40.2 ± 6.6 mlO2/min/kg, p b 0.001) versus no change in control group

Deterioration in VO2 peak only in controls (from 33.3 ± 12.3 to 31.1 ± 9.3 mlO2/min/kg) and not in exercisers (from 32.6 ± 8.9 to 32.9 ± 9.7 mlO2/min/kg)

16% increase in VO2 max predicted (26.5 ± 5.4 to 31.0 ± 4.4 mlO2/kg/min; Z = −2.1, p = 0.028) 12% increase in VO2 peak or 2.8 ± 3.4 mlO2/min/kg (both, cardiorespiratory and resistance group included).

18.0% increase in VO2 peak versus −0.5% in controls (p = 0.002)

20.1% increase in VO2 peak (31.8 ± 9.5 to 38.2 ± 12.6 ml/kg/min (p = 0.002)

CCT = controlled clinical trial, RCT = randomized controlled trial, PE = pre-experimental, HR = heart rate, HRR = heart rate reserve, VO2 = oxygen uptake, HIT = high intensity training, 1RM = one-repetition maximum.


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Fig. 2. Pre- and post-test changes in V02 max or VO2 peak in schizophrenia only.

2010). This is of particular relevance in schizophrenia, given the growing interest in lifestyle interventions aiming to reduce cardiovascular disease risk. Reducing weight and body mass index (BMI) is notoriously challenging in people with schizophrenia and the general population alike (Chwastiak, 2015). However, even in the absence of a reduction in BMI, improvements in cardiorespiratory fitness following exercise can significantly improve health and reduce mortality (Church et al., 2005; Hainer et al., 2009; Lee et al., 2010). Given that a recent meta-analysis demonstrated that the BMI does not appear to be reduced with exercise alone in people with schizophrenia (Firth et al., 2015), results of the current study are of great interest. Since cardiorespiratory fitness improves with exercise, we advocate that a shift in exercise interventions away from ‘fatness’ and towards “fitness” is justified. Improving cardiorespiratory fitness may be a more feasible, realistic and clinically meaningful outcome for exercise interventions in people with schizophrenia. Overall the trials identified in this review were of short to moderate length and demonstrate improvements can occur over a short period (most up to 12 weeks). Cardiorespiratory fitness is relatively straight forward to measure in clinical practice and clinicians should consider monitoring this as a ‘vital-sign’, given its significant relationship with all-cause morbidity and mortality. In addition, achieving success in changes in cardiorespiratory fitness will provide valuable feedback to patients and clinicians, many of whom experience seemingly inevitable weight gain following treatment. Future research is required to determine how to maximise adherence to exercise in order to maximise the potential benefits on cardiorespiratory fitness. Whilst the results are novel, some caution should be attached due to small number of participants and limitations in reporting of other important variables such as psychotropic medication. In addition, in our comparative meta-analysis comparing exercise

versus control interventions we included 1 CCT with 3 RCTs. Whilst we observed no significant publication bias or heterogeneity, one should note that CCT are methodologically weaker and some caution should be attached to this analysis. Nevertheless, our meta-analysis demonstrates that aerobic exercise results in significant improvements in cardiorespiratory fitness, an important predictor of mortality. Whilst achieving reductions in BMI and weight are important exercise goals that should not be abandoned, our results suggest that exercise interventions should be developed that aim to improve cardiorespiratory fitness, with BMI and weight reduction considered as secondary outcomes. Improvements in cardiorespiratory fitness appear to be achievable, and may provide a novel and valid exercise target that could lead to reductions in premature mortality in people with schizophrenia. Funding None.

Contributors DV and BS conceived and developed the study design. DV and SR wrote the study protocol in consultation with BS and PBW. DV and BS undertook the searches and collated data. BS conducted the data analysis in consultation with PBW. DV and BS wrote the manuscript. SR and PBW provided critical comments and developed the manuscript into its submitted form. All authors approved the final version.

Conflict of interest DV, SR, PBW and BS have no conflict of interest to declare.

Acknowledgments Davy Vancampfort is funded by the Research Foundation — Flanders (FWOVlaanderen).

Fig. 3. Aerobic exercise versus control condition changes in V02 max or VO2 peak in schizophrenia only.



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