Helene Speyer

The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity

Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. CHANGE was a randomized, parallel‐group, superiority, multi‐centre trial with blinded outcome assessment, testing the efficacy of an intervention aimed to improve cardiovascular risk profile and hereby potentially reduce mortality. A total of 428 patients with schizophrenia spectrum disorders and abdominal obesity were recruited and centrally randomized 1:1:1 to 12 months of lifestyle coaching plus care coordination plus treatment as usual (N=138), or care coordination plus treatment as usual (N=142), or treatment as usual alone (N=148). The primary outcome was 10‐year risk of cardiovascular disease assessed post‐treatment and standardized to age 60. At follow‐up, the mean 10‐year risk of cardiovascular disease was 8.4 ± 6.7% in the group receiving lifestyle coaching, 8.5 ± 7.5% in the care coordination group, and 8.0 ± 6.5% in the treatment as usual group (p=0.41). We found no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, physical activity, weight, diet and smoking. In conclusion, the CHANGE trial did not support superiority of individual lifestyle coaching or care coordination compared to treatment as usual in reducing cardiovascular risk in patients with schizophrenia spectrum disorders and abdominal obesity.

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.

Exercise for patients with major depression: a protocol for a systematic review with meta-analysis and trial sequential analysis

BackgroundThe lifetime prevalence of major depression is estimated to affect 17% of the population and is considered the second largest health-care problem globally in terms of the number of years lived with disability. The effects of most antidepressant treatments are poor; therefore, exercise has been assessed in a number of randomized clinical trials. A number of reviews have previously analyzed these trials; however, none of these reviews have addresses the effect of exercise for adults diagnosed with major depression.Methods/designThe objective of this systematic review is to investigate the beneficial and harmful effects of exercise, in terms of severity of depression, lack of remission, suicide, and so on, compared with treatment as usual with or without co-interventions in randomized clinical trials involving adults with a clinical diagnosis of major depression. A meta-analysis of the effect estimates of the individual trials, taking bias risk into consideration, will be carried out. Any heterogeneity will be explored using meta-regression and subgroup analyses. Trial sequential analysis will be carried out on the trials to control for risks of random errors. The results from the study will aid health authorities and clinicians to understand whether exercise should be offered to patients with major depression.

Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

Objectives To assess the benefits and harms of exercise in patients with depression. Design Systematic review Data sources Bibliographical databases were searched until 20 June 2017. Eligibility criteria and outcomes Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention. Results Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes. Conclusions Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes. Systematic review registration The protocol was published in the journal Systematic Reviews: 2015; 4:40.

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.

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.

Poster #T172 PROJECT CHANGE: IT IS ABOUT LIFE. A RANDOMISED CLINICAL TRIAL INVESTIGATING THE EFFECT OF A SYSTEMATIC INTERVENTION FOR IMPROVING THE PHYSICAL HEALTH OF PATIENTS WITH SCHIZOPHRENIA

In the randomized clinical trial CHANGE, we will include 450 patients with schizophrenia and a waist circumference above 88cm for women and 102 cm for men and evaluate the effect of interventions aiming to reduce risk for death from medical diseases. We will compare: 1) treatment as usual with 2) affiliation to a care coordinator who has the duty to connect the patient to general practice and primary care and 3) affiliation to a staff member from the CHANGE team who should facilitate life style changes (smoking cessation, improved diet and more physical activity) and contact with general practice.