Lifestyle Interventions for Weight Management in People with Serious Mental Illness: A Systematic Review with Meta-Analysis, Trial Sequential Analysis, and Meta-Regression Analysis Exploring the Mediators and Moderators of Treatment Effects.

BACKGROUND: Serious mental illness (SMI) reduces life expectancy, primarily due to somatic comorbidity linked to obesity. Meta-analyses have found beneficial effects of lifestyle interventions in people with SMI and recommended their implementation to manage obesity. OBJECTIVE: The objective of this systematic review was to assess the benefits and harms of individualized lifestyle interventions for weight in people diagnosed with SMI and to explore potential mediators and moderators of the effect. METHODS: The protocol was registered at PROSPERO (CRD42016049093). Randomized clinical trials (RCTs) assessing the effect of individualized lifestyle interventions on weight management in people with SMI were included. Primary outcomes were differences in endpoint body mass index (BMI) and the proportion achieving clinically relevant weight loss (≥5%). Secondary outcomes included quality of life, cardiometabolic risk factors, and adverse effects. RESULTS: We included 41 RCTs (n = 4,267). All trials were at high risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. The experimental interventions reduced the mean difference in BMI by -0.63 kg/m2 (95% confidence interval [CI] = -1.02 to -0.23; p = 0.002; I2 = 70.7%) compared to the control groups. At postintervention follow-up (17 RCTs), the effect size remained similar but was no longer significant (BMI = -0.63 kg/m2; 95% CI = -1.30 to 0.04; p = 0.07; I2 = 48.8%). The risk ratio for losing ≥5% of baseline weight was 1.51 (95% CI = 1.07-2.13; p = 0.02) compared to the control groups. GRADE showed very low or low quality of evidence. CONCLUSION: There is a statistically significant, but clinically insignificant, mean effect of individualized lifestyle interventions for weight reduction in people with SMI.

Protocol for CHANGE: a randomized clinical trial assessing lifestyle coaching plus care coordination versus care coordination alone versus treatment as usual to reduce risks of cardiovascular disease in adults with schizophrenia and abdominal obesity.

BACKGROUND: Life expectancy in patients with schizophrenia is reduced by 20 years for males and 15 years for females compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being the single largest cause of death. METHODS/DESIGN: The CHANGE trial is an investigator-initiated, independently funded, randomized, parallel-group, superiority, multi-centre trial with blinded outcome assessment. 450 patients aged 18 years or above, diagnosed with schizophrenia spectrum disorders and increased waist circumference, will be recruited and randomized 1:1:1 to 12-months interventions. We will compare the effects of 1) affiliation to the CHANGE team, offering a tailored, manual-based intervention targeting physical inactivity, unhealthy dietary habits, and smoking, and facilitating contact to their general practitioner to secure medical treatment of somatic comorbidity; versus 2) affiliation to a care coordinator who will secure guideline-concordant monitoring and treatment of somatic comorbidity by facilitating contact to their general practitioner; versus 3) treatment as usual to evaluate the potential add-on effects of lifestyle coaching plus care coordination or care coordination alone to treatment as usual. The primary outcome is the 10-year risks of cardiovascular disease assessed at 12 months after randomization. DISCUSSION: The premature mortality observed in this vulnerable population has not formerly been addressed specifically by using composite surrogate outcomes for mortality. The CHANGE trial expands the evidence for interventions aiming to reduce the burden of metabolic disturbances with a view to increase life expectancy. Here, we present the trial design, describe the methodological concepts in detail, and discuss the rationale and challenges of the intermediate outcomes. TRIAL REGISTRATION: Clinical Trials.gov NCT01585493 . Date of registration 27(th) of March 2012.

Associations between clinical and psychosocial factors and metabolic and cardiovascular risk factors in overweight patients with schizophrenia spectrum disorders - Baseline and two-years findings from the CHANGE trial.

OBJECTIVES: People with severe mental disorders die averagely 15years earlier than people in the Western background population, cardiovascular disease being the most frequent cause of death with unhealthy eating habits and lower levels of physical activity as major contributing risk factors. Understanding possible associations and predictors of the specific cardiovascular risk may permit more targeted and effective prevention. The aim of this study was to investigate the associations between clinical and psychosocial factors and several separate cardiovascular risk factors in a cohort of 428 persons with schizophrenia and abdominal obesity enrolled in the CHANGE trial. METHODS: We used data from baseline and two-year follow-up of 428 individuals with schizophrenia spectrum disorders and abdominal overweight enrolled in the CHANGE trial. By linear regressions we explored the relationships between clinical and psychosocial factors and established cardiovascular risk factors: Dependent variables were baseline and follow-up values of the following: VO2max, waist circumference, high density lipoprotein (HDL), systolic blood pressure and HbA1c. Independent variables were baseline values of the following: negative symptoms, positive symptoms, cognition, level of functioning, antipsychotic medication, duration of illness, employment situation and whether the participants had any friend. RESULTS: Negative symptoms were associated with most baseline- as well as two-years-outcome; negatively with cardiorespiratory fitness and with dietary quality and with HDL, and with increasing values of the variables waist circumference, BMI and HbA1c. Negative symptoms were seen also to predict poorer cardiorespiratory fitness and larger waist circumference, higher HbA1c and lower HDL at two year follow-up. Level of functioning and Cognitive function correlated positively with cardiorespiratory fitness and HDL, and correlated negatively with waist circumference and HbA1c. Both parameters also predicted a better fitness, higher HDL and lower HbA1c at two year follow-up. Isolating the antipsychotic drugs known to give the worst metabolic adverse effects (olanzapine, clozapine, quetiapine), the dosage was positively associated with cholesterol, but not with any other outcome. Psychotic symptoms and duration of illness were not significantly associated with any outcome. Employment of any kind was significantly associated with cardiorespiratory fitness and negatively associated with waist circumference, BMI and systolic blood pressure. At two year follow-up associations were significant for the two year outcomes cardiorespiratory fitness and waist circumference. Friendship relations were negatively associated with waist circumference and positively with HDL cholesterol. None of the two year outcomes were predicted by friendship. CONCLUSIONS: We found various clinical and psychosocial factors to be associated with less healthy lifestyle factors and higher risk of cardiovascular disease, with negative symptoms building the strongest associations, although a possible bidirectional causality needs to be regarded. Reduction of negative symptoms should be investigated further in order to reduce the increased cardiovascular morbidity and mortality in people with schizophrenia spectrum disorders.

Dietary patterns and physical activity in people with schizophrenia and increased waist circumference.

OBJECTIVES: People with severe mental disorders die 10-25years earlier than people in the Western background population, mainly due to lifestyle related diseases, with cardiovascular disease (CVD) being the most frequent cause of death. Major contributors to this excess morbidity and mortality are unhealthy lifestyle factors including tobacco smoking, unhealthy eating habits and lower levels of physical activity. The aim of this study was to investigate the dietary habits and levels of physical activity in people with schizophrenia spectrum disorders and overweight and to compare the results with the current recommendations and with results from the general Danish population. METHODS: We interviewed a sample of 428 people with schizophrenia spectrum disorders and increased waist circumference enrolled in the CHANGE trial using a Food Frequency Questionnaire (FFQ) and a 24h recall interview, a Physical Activity Scale (PAS), scale for assessment of positive and negative symptoms (SAPS and SANS, respectively), Brief Assessment of Cognition in Schizophrenia (BACS) and Global Assessment of Functioning (GAF). We compared with information on dietary intake and physical activity in the general Danish population from the Danish National Survey of Dietary Habits and Physical Activity in 2011-2013 (DANSDA). RESULTS: The CHANGE participants reported a very low energy intake and their distribution of nutrients (i.e. fat, protein and carbohydrates) harmonized with the recommendations from the Danish Health Authorities, and were similar to the latest report on the dietary habits in the Danish general population. However, the intake of saturated fat, sugar and alcohol exceed the recommended amounts and the corresponding intake in the general population. The intake of fiber, vegetables and fruit and fish were insufficient and also less than in the general population. The overall estimated quality of the dietary habits was poor, only 10.7% of the participants had healthy dietary patterns, and the quality was poorer than in the general population. Even with a very liberal definition of the term "homecooked", only 62% of the participants had taken any part in the preparation of their food. The level of physical activity was low and only one fifth of the participants complied with the recommendations of min. 30min daily moderate-to-vigorous activity. Half of the CHANGE participants were smokers, compared to 17% in the general population. Negative symptoms were significantly associated with poorer dietary quality and less physical activity, whereas no such significant associations were found for cognition, positive symptoms or antipsychotic medication. CONCLUSIONS: Even when accounting for some error from recall - and social desirability bias, the findings point in the direction that the average energy intake in obese people with schizophrenia spectrum disorders is not exceeding that of the general population, and that overweight may to some degree be a result of physical inactivity and metabolic adverse effects of antipsychotic medication. The physical activity level is low and the rate of tobacco smoking is high, and our results suggest that negative symptoms play a significant role. Future research should focus on bringing about lifestyle changes in this fragile population in order to reduce the excess risk of CVD and mortality.

Effect of lifestyle coaching versus care coordination versus treatment as usual in people with severe mental illness and overweight: Two-years follow-up of the randomized CHANGE trial.

The objective of this trial was to assess the long-term effect of the CHANGE lifestyle coaching intervention for 428 people with abdominal obesity and schizophrenia spectrum disorders on cardiovascular risk. In this randomized, superiority, multi-center clinical trial, participants were randomized to 12 months of either lifestyle coaching plus care coordination (N = 138), care coordination alone, (N = 142) or treatment as usual (N = 148). There was no effect after 12 months, but we hypothesized that there might have been a delayed treatment effect. Our primary outcome at two-year follow-up was 10-year risk of cardiovascular disease standardized to 60 years of age. After two-years the mean 10-year cardiovascular-disease risk was 8.7% (95% confidence interval (CI) 7.6-9.9%) in the CHANGE group, 7.7% (95% CI 6.5-8.9%) in the care coordination group, and 8.9% (95% CI 6.9-9.2%) in the treatment as usual group (P = 0.24). Also, there were no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, weight, physical activity, diet and smoking. No reported adverse events could be ascribed to the intervention. We conclude that there was neither any direct nor any long-term effect of individual lifestyle coaching or care coordination on cardiovascular risk factors in people with abdominal obesity and schizophrenia spectrum disorders. The trial was approved by the Ethics Committee of Capitol Region Copenhagen, Denmark (registration number: H-4-2012-051) and the Danish Data Protection Agency (registration number: 01689 RHP-2012-007). The trial was funded by the Mental Health Services of the Capital Region of Denmark, the Lundbeck Foundation, the Tryg Foundation, the Danish Ministry of Health, and the Dæhnfeldts Foundation.

[Overweight and obesity in patients with severe mental illness].

Obesity is an increasing global problem. Individuals with severe mental illness (SMI) are no exception; on the contrary, these patients are more often obese than others and suffer from sequelae. Poor life style, poor socio-economic status and side effects to antipsychotics are well known contributors to obesity. Interventions targeting the individual have been tested with limited success. The healthcare systems and the communities have to rethink the integration of individuals with SMI as equal citizens in the society in order to prevent weight gain or for weight loss interventions to be successful.

Can exercise increase fitness and reduce weight in patients with schizophrenia and depression?

BACKGROUND: Psychiatric patients have a reduced life expectancy of 15-20 years compared with the general population. Most years of lost life are due to the excess mortality from somatic diseases. Sedentary lifestyle and medication is partly responsible for the high frequency of metabolic syndrome in this patient group and low levels of physical activity is associated with increased risk of cardiovascular disease, diabetes, and all-cause mortality. This study aimed to review trials allocating patients with either schizophrenia or depression to exercise interventions for effect on cardiovascular fitness, strength, and weight. METHODS: We searched PubMed, Embase, and PsycINFO including randomized clinical trial allocating patients with either schizophrenia or depression to isolated exercise interventions. RESULTS: We identified five trials including patients with schizophrenia (n = 94) and found little evidence that exercise could increase cardiovascular fitness or decrease weight. Nine exercise trials for patients with depression (n = 892) were identified increasing cardiovascular fitness by 11-30% and strength by 33-37%. No evidence in favor of exercise for weight reduction was found. CONCLUSION: Based on the current evidence isolated exercise interventions are unlikely to improve cardiovascular fitness or induce weight loss in patients with schizophrenia. In patients with depression, exercise interventions are likely to induce clinically relevant short term effects, however, due to lack of reporting, little is known about the effect on weight reduction and cardiovascular fitness. Future exercise trials regarding patients with mental illness should preferably measure changes in cardiovascular strength, repetition maximum, and anthropometric outcomes. Ideally, participants should be assessed beyond the intervention to identify long lasting effects.