Felipe B. Schuch

Exercise as a treatment for depression: A meta-analysis adjusting for publication bias

The effects of exercise on depression have been a source of contentious debate. Meta-analyses have demonstrated a range of effect sizes. Both inclusion criteria and heterogeneity may influence the effect sizes reported. The extent and influence of publication bias is also unknown. Randomized controlled trials (RCTs) were identified from a recent Cochrane review and searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including those with a diagnosis of major depressive disorder (MDD) or ratings on depressive symptoms), comparing exercise versus control conditions. A random effects meta-analysis calculating the standardized mean difference (SMD, 95% confidence interval; CI), meta-regressions, trim and fill and fail-safe n analyses were conducted. Twenty-five RCTs were included comparing exercise versus control comparison groups, including 9 examining participants with MDD. Overall, exercise had a large and significant effect on depression (SMD adjusted for publication bias = 1.11 (95% CI 0.79-1.43)) with a fail-safe number of 1057. Most adjusted analyses suggested publication bias led to an underestimated SMD. Larger effects were found for interventions in MDD, utilising aerobic exercise, at moderate and vigorous intensities, in a supervised and unsupervised format. In MDD, larger effects were found for moderate intensity, aerobic exercise, and interventions supervised by exercise professionals. Exercise has a large and significant antidepressant effect in people with depression (including MDD). Previous meta-analyses may have underestimated the benefits of exercise due to publication bias. Our data strongly support the claim that exercise is an evidence-based treatment for depression.

How much physical activity do people with schizophrenia engage in? A systematic review, comparative meta-analysis and meta-regression

OBJECTIVE Physical activity (PA) improves health outcomes in people with schizophrenia. It is unclear how much PA people with schizophrenia undertake and what influences PA participation. We conducted a meta-analysis to investigate PA levels and predictors in people with schizophrenia. METHOD Major databases were searched from inception till 02/2016 for articles measuring PA (self-report questionnaire (SRQ) or objective measure (e.g. accelerometer)) in people with schizophrenia, including first episode psychosis (FEP). A random effects meta-analysis and meta-regression analysis were conducted. RESULTS 35 studies representing 3453 individuals with schizophrenia (40.0years; 64.0% male) were included. Engagement in light PA was 80.44min (95% CI 68.32-92.52, n=2658), 47.1min moderate-vigorous PA (95% CI 31.5-62.8, n=559) and 1.05min (95% CI 0.48-1.62, n=2533) vigorous PA per day. People with schizophrenia engaged in significantly less moderate (hedges g=-0.45, 95% CI -0.79 to -0.1, p=0.01) and vigorous PA (g=-0.4, 95% CI -0.60 to -0.18) versus controls. Higher light to moderate, but lower vigorous PA levels were observed in outpatients and in studies utilizing objective measures versus SRQ. 56.6% (95% CI 45.8-66.8, studies=12) met the recommended 150min of moderate physical activity per week. Depressive symptoms and older age were associated with less vigorous PA in meta-regression analyses. CONCLUSIONS Our data confirm that people with schizophrenia engage in significantly less moderate and vigorous PA versus controls. Interventions aiming to increase PA, regardless of intensity are indicated for people with schizophrenia, while specifically increasing moderate-vigorous PA should be a priority given the established health benefits.

Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression.

OBJECTIVE Exercise has established efficacy in improving depressive symptoms. Dropouts from randomized controlled trials (RCTs) pose a threat to the validity of this evidence base, with dropout rates varying across studies. We conducted a systematic review and meta-analysis to investigate the prevalence and predictors of dropout rates among adults with depression participating in exercise RCTs. METHOD Three authors identified RCTs from a recent Cochrane review and conducted updated searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including major depressive disorder (MDD) and depressive symptoms) that reported dropout rates. A random effects meta-analysis and meta regression were conducted. RESULTS Overall, 40 RCTs were included reporting dropout rates across 52 exercise interventions including 1720 people with depression (49.1 years (range=19-76 years), 72% female (range=0-100)). The trim and fill adjusted prevalence of dropout across all studies was 18.1% (95%CI=15.0-21.8%) and 17.2% (95%CI=13.5-21.7, N=31) in MDD only. In MDD participants, higher baseline depressive symptoms (β=0.0409, 95%CI=0.0809-0.0009, P=0.04) predicted greater dropout, whilst supervised interventions delivered by physiotherapists (β=-1.2029, 95%CI=-2.0967 to -0.3091, p=0.008) and exercise physiologists (β=-1.3396, 95%CI=-2.4478 to -0.2313, p=0.01) predicted lower dropout. A comparative meta-analysis (N=29) established dropout was lower in exercise than control conditions (OR=0.642, 95%CI=0.43-0.95, p=0.02). CONCLUSIONS Exercise is well tolerated by people with depression and drop out in RCTs is lower than control conditions. Thus, exercise is a feasible treatment, in particular when delivered by healthcare professionals with specific training in exercise prescription.

Aerobic Exercise Improves Cognitive Functioning in People With Schizophrenia: A Systematic Review and Meta-Analysis

Abstract Cognitive deficits are pervasive among people with schizophrenia and treatment options are limited. There has been an increased interest in the neurocognitive benefits of exercise, but a comprehensive evaluation of studies to date is lacking. We therefore conducted a meta-analysis of all controlled trials investigating the cognitive outcomes of exercise interventions in schizophrenia. Studies were identified from a systematic search across major electronic databases from inception to April 2016. Meta-analyses were used to calculate pooled effect sizes (Hedges g) and 95% CIs. We identified 10 eligible trials with cognitive outcome data for 385 patients with schizophrenia. Exercise significantly improved global cognition (g = 0.33, 95% CI = 0.13–0.53, P = .001) with no statistical heterogeneity (I2 = 0%). The effect size in the 7 studies which were randomized controlled trials was g = 0.43 (P < .001). Meta-regression analyses indicated that greater amounts of exercise are associated with larger improvements in global cognition (β = .005, P = .065). Interventions which were supervised by physical activity professionals were also more effective (g = 0.47, P < .001). Exercise significantly improved the cognitive domains of working memory (g = 0.39, P = .024, N = 7, n = 282), social cognition (g = 0.71, P = .002, N = 3, n = 81), and attention/vigilance (g = 0.66, P = .005, N = 3, n = 104). Effects on processing speed, verbal memory, visual memory and reasoning and problem solving were not significant. This meta-analysis provides evidence that exercise can improve cognitive functioning among people with schizophrenia, particularly from interventions using higher dosages of exercise. Given the challenges in improving cognition, and the wider health benefits of exercise, a greater focus on providing supervised exercise to people with schizophrenia is needed.

Neurobiological effects of exercise on major depressive disorder: A systematic review

Exercise displays promise as an efficacious treatment for people with depression. However, no systematic review has evaluated the neurobiological effects of exercise among people with major depressive disorder (MDD). The aim of this article was to systematically review the acute and chronic biological responses to exercise in people with MDD. Two authors conducted searches using Medline (PubMed), EMBASE and PsycINFO. From the searches, twenty studies were included within the review, representing 1353 people with MDD. The results demonstrate that a single bout of exercise increases atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), copepetin and growth hormone among people with MDD. Exercise also potentially promotes long-term adaptations of copeptin, thiobarbituric acid reactive species (TBARS) and total mean frequency (TMF). However, there is limited evidence that exercise promotes adaptations on neurogenesis, inflammation biomarkers and brain structure. Associations between depressive symptoms improvement and hippocampus volume and IL-1β were found. Nevertheless, the paucity of studies and limitations presented within, precludes a more definitive conclusion of the underlying neurobiological explanation for the antidepressant effect of exercise in people with MDD. Further trials should utilize appropriate assessments of neurobiological markers in order to build upon the results of our review and further clarify the potential mechanisms associated with the antidepressant effects of exercise.

Prevalence and predictors of treatment dropout from physical activity interventions in schizophrenia: a meta-analysis.

OBJECTIVE Physical activity interventions have been shown to improve the health of people with schizophrenia, yet treatment dropout poses an important challenge in this population, and rates vary substantially across studies. We conducted a meta-analysis to investigate the prevalence and predictors of treatment dropout in physical activity interventions in people with schizophrenia. METHOD We systematically searched major electronic databases from inception until August 2015. Randomized controlled trials of physical activity interventions in people with schizophrenia reporting dropout rates were included. Two independent authors conducted searches and extracted data. Random-effects meta-analysis and meta-regression analyses were conducted. RESULTS In 19 studies, 594 patients with schizophrenia assigned to exercise interventions were investigated (age=37.2 years, 67.5% male, range=37.5%-100%). Trim and fill adjusted treatment dropout rate was 26.7% [95% confidence interval (CI)=19.7%-35.0%], which is more than double than in nonactive control interventions (odds ratio=2.15, 95% CI=1.29-3.58, P=.003). In the multivariate regression, qualification of the professional delivering the intervention (β=-1.06, 95% CI=-1.77 to -0.35, P=.003) moderated treatment dropout rates, while continuous supervision of physical activity approached statistical significance (P=.05). CONCLUSIONS Qualified professionals (e.g., physical therapists/exercise physiologists) should prescribe supervised physical activity for people with schizophrenia to enhance adherence, improve psychiatric symptoms and reduce the onset and burden of cardiovascular disease.

Physical activity and sedentary behavior in people with major depressive disorder: A systematic review and meta-analysis

BACKGROUND Low levels of physical activity (PA) and sedentary behavior (SB) are independent risk factors for cardiovascular disease and premature mortality in people with major depressive disorder (MDD). AIMS Investigate levels of PA and SB and their predictors in people with MDD. METHODS Electronic databases were searched from inception till 04/2016 for articles measuring PA and SB with a self-report questionnaire (SRQ) or objective measure (e.g. accelerometer) in people with MDD. Random-effects meta-analyses and meta-regression analyses were conducted. RESULTS Twenty-four eligible studies were identified including 2901 people with MDD (78.4% female, mean age=54 years; range: 21-77 years). People with MDD spent 126.0min (95%CI=91.9-160.1) per day engaging in all types of PA and spent 8.5hours (95%CI=7.51-9.62) during their waking day being sedentary. Compared to controls, people with MDD spent less time in total PA (SMD=-0.25, 95%CI=-0.03 to 0.15) and moderate to vigorous PA (SMD=-0.30, 95%CI=-0.40 to 0.21) and engaged in higher levels of SB (SMD=0.09, 95%CI=0.01-0.18). The proportion of people with MDD not meeting the recommended PA guidelines was 67.8% (n=13 studies), which was higher in studies relying on objective versus self-report measures (85.7% v 62.1%, p=0.04). People with MDD were more likely than controls to not meeting the recommended PA guidelines (OR = 1.50, 95%CI = 1.10–2.10). LIMITATIONS Heterogeneity was evident in most analyses. CONCLUSIONS Adults with MDD engage in low levels of PA and high levels of SB. PA and SB are independent predictors of mortality, therefore, future lifestyle interventions targeting both the prevention of SB and adoption and maintenance of PA are warranted.

Sedentary behavior and physical activity levels in people with schizophrenia, bipolar disorder and major depressive disorder: a global systematic review and meta-analysis

People with severe mental illness (schizophrenia, bipolar disorder or major depressive disorder) die up to 15 years prematurely due to chronic somatic comorbidities. Sedentary behavior and low physical activity are independent yet modifiable risk factors for cardiovascular disease and premature mortality in these people. A comprehensive meta‐analysis exploring these risk factors is lacking in this vulnerable population. We conducted a meta‐analysis investigating sedentary behavior and physical activity levels and their correlates in people with severe mental illness. Major electronic databases were searched from inception up to April 2017 for articles measuring sedentary behavior and/or physical activity with a self‐report questionnaire or an objective measure (e.g., accelerometer). Random effects meta‐analyses and meta‐regression analyses were conducted. Sixty‐nine studies were included (N=35,682; 39.5% male; mean age 43.0 years). People with severe mental illness spent on average 476.0 min per day (95% CI: 407.3‐545.4) being sedentary during waking hours, and were significantly more sedentary than age‐ and gender‐matched healthy controls (p=0.003). Their mean amount of moderate or vigorous physical activity was 38.4 min per day (95% CI: 32.0‐44.8), being significantly lower than that of healthy controls (p=0.002 for moderate activity, p<0.001 for vigorous activity). People with severe mental illness were significantly less likely than matched healthy controls to meet physical activity guidelines (odds ratio = 1.5; 95% CI: 1.1‐2.0, p<0.001, I2=95.8). Lower physical activity levels and non‐compliance with physical activity guidelines were associated with male gender, being single, unemployment, fewer years of education, higher body mass index, longer illness duration, antidepressant and antipsychotic medication use, lower cardiorespiratory fitness and a diagnosis of schizophrenia. People with bipolar disorder were the most physically active, yet spent most time being sedentary. Geographical differences were detected, and inpatients were more active than outpatients and those living in the community. Given the established health benefits of physical activity and its low levels in people with severe mental illness, future interventions specifically targeting the prevention of physical inactivity and sedentary behavior are warranted in this population.

Cardiorespiratory Fitness in Severe Mental Illness: A Systematic Review and Meta-analysis.

BackgroundCardiorespiratory fitness (CRF) among people with severe mental illness (SMI) (i.e., schizophrenia, bipolar disorder, and major depressive disorder) is a critical clinical risk factor given its relationship to cardiovascular disease and premature mortality.ObjectivesThis study aimed to: (1) investigate the mean CRF in people with SMI versus healthy controls; (2) explore moderators of CRF; and (3) investigate whether CRF improved with exercise interventions and establish if fitness improves more than body mass index following exercise interventions.MethodsMajor electronic databases were searched systematically. A meta-analysis calculating Hedges’ g statistic was undertaken.ResultsAcross 23 eligible studies, pooled mean CRF was 28.7 mL/kg/min [95 % confidence interval (CI) 27.3 to 30.0 mL/kg/min, p < 0.001, n = 980]. People with SMI had significantly lower CRF compared with controls (n = 310) (Hedges’ g = −1.01, 95 % CI −1.18 to −0.85, p < 0.001). There were no differences between diagnostic subgroups. In a multivariate regression, first-episode (β = 6.6, 95 % CI 0.6–12.6) and inpatient (β = 5.3, 95 % CI 1.6–9.0) status were significant predictors of higher CRF. Exercise improved CRF (Hedges’ g = 0.33, 95 % CI = 0.21–0.45, p = 0.001), but did not reduce body mass index. Higher CRF improvements were observed following interventions at high intensity, with higher frequency (at least three times per week) and supervised by qualified personnel (i.e., physiotherapists and exercise physiologists).ConclusionThe multidisciplinary treatment of people with SMI should include a focus on improving fitness to reduce all-cause mortality. Qualified healthcare professionals supporting people with SMI in maintaining an active lifestyle should be included as part of multidisciplinary teams in mental health treatment.

Exercise and severe major depression: Effect on symptom severity and quality of life at discharge in an inpatient cohort

BACKGROUND Exercise is a potential treatment for depression. However, few studies have evaluated the role of adjunct exercise in the treatment of severely major depressed inpatients. The goal of this study was to evaluate the effects of add-on exercise on the usual treatment of severely depressed inpatients. METHODS Fifty participants were randomized to an exercise (exercise + usual treatment) or a control (usual treatment) group. Twenty-five patients were randomly allocated to each group. The participants in the exercise group performed three sessions per week throughout the hospitalization period, with a goal dose of 16.5 kcal/kg/week plus the usual pharmacological treatment. Depressive symptoms and the Quality of Life (QoL) of the participants were assessed at the baseline, the second week, and discharge. RESULTS A significant group × time interaction was found for depressive symptoms and the physical and psychological domains of QoL. Differences between groups occurred at the second week and discharge with respect to depressive symptoms and the physical and psychological domains of QoL. There was no difference in the remission rate at discharge (48% and 32% for the exercise and control group, respectively). An NNT of 6.25 was found. No significant baseline characteristics predict remission at discharge. CONCLUSION Add-on exercise is an efficacious treatment for severely depressed inpatients, improving their depressive symptoms and QoL. Initial acceptance of exercise remains a challenge.