Use of antipsychotic medication, benzodiazepines, and psychiatric hospitalization in cannabis-related versus cannabis-unrelated schizophrenia - a nationwide, register-based cohort study.

BACKGROUND: Evidence suggests that cannabis may be a causal factor for development of schizophrenia. We aimed to investigate whether use of antipsychotic medication, benzodiazepines, and psychiatric service use differs among patients with schizophrenia depending on whether psychosis was precipitated by a diagnosis of cannabis use disorder (CUD). METHODS: We utilized the nationwide Danish registries to identify all individuals with an incident diagnosis of schizophrenia from 1995 to 2016. We also collected information on whether first CUD diagnosis preceded schizophrenia and thus defined a group of potentially cannabis-related schizophrenia. We compared the cannabis-related schizophrenia group both with all non-cannabis-related patients with schizophrenia and with non-cannabis-related patients with schizophrenia that were propensity-score matched to cases using a range of potentially confounding variables. RESULTS: We included 35 714 people with incident schizophrenia, including 4116 (11.5%) that were cannabis-related. In the unmatched-comparison analyses, there were no clear differences over time in use of antipsychotics and benzodiazepines related to whether the diagnosis of schizophrenia was cannabis-related. After propensity-score matching, use of antipsychotics and benzodiazepines was significantly lower among cannabis-related cases of schizophrenia. In the unmatched comparison, the cannabis-related group had significantly more days admitted than the non-cannabis-related group. This was markedly attenuated after propensity-score matching. CONCLUSIONS: Our findings indicate the importance of considering cannabis-related cases of schizophrenia as a potentially distinct disorder in terms of prognosis. It is unclear, however, if these differences are due to different biological types of schizophrenia being compared or if they rather indicate behavioral differences such as reduced adherence and treatment-seeking.

The bidirectional association between psychiatric disorders and sheltered homelessness.

BACKGROUND: Psychiatric disorders and homelessness are related, but temporal associations are unclear. We aimed to explore the overlap between hospital-based psychiatric disorders and sheltered homelessness. METHODS: This population-based cohort study was conducted using the Danish registers e.g., the Danish Homeless Register and the Danish National Patient Register. The study cohort included all individuals aged 15 years or older, living in Denmark at least one day during 2002-2021 (born 1984-2006). First psychiatric diagnosis was used to define psychiatric disorder and first homeless shelter contact to define homelessness. Adjusted incidence rate ratios (IRRs) and cumulative incidences were estimated. RESULTS: Among 1 530 325 individuals accounting for 16 787 562 person-years at risk aged 15-38 years, 11 433 (0.8%) had at least one homeless shelter contact. Among 1 406 410 individuals accounting for 14 131 060 person-years at risk, 210 730 had at least one psychiatric disorder. People with any psychiatric disorder had increased risk of sheltered homelessness relative to individuals with no psychiatric disorder [IRR 9.2, 95% confidence interval (CI) 8.8-9.6]. Ten years after first psychiatric disorder, 3.0% (95% CI 2.9-3.1) had at least one homeless shelter contact. Individuals experiencing homelessness had increased risk of any psychiatric disorder compared to individuals with no homeless shelter contact (IRR 7.0, 95% CI 6.7-7.4). Ten years after first homeless shelter contact, 47.1% (45.3-48.0) had received a hospital-based psychiatric diagnosis. CONCLUSION: Strong bidirectional associations between psychiatric disorders and homelessness were identified. Health and social care professionals should be aware of and address these high risks of accumulated psychiatric and social problems.

Association of maternal and paternal personality disorders with risk of mental disorders in children: A nationwide, register-based cohort study of 1,406,965 children.

BACKGROUND: Knowledge of the association between parental personality disorders and mental disorders in children is limited. To examine the association between parental personality disorders and the risk of mental disorders in offspring. METHODS: We linked Danish health registers to create a cohort of children born from January 1, 1995, to December 31, 2016. Children were followed until their 18th birthday, diagnosis set, emigration, death, or December 31, 2016. Parental personality disorders according to the International Classification of Diseases (ICD) Eighth or 10th Revision. Poisson regression analyses were used to estimate the incidence risk ratio (IRR) and cumulative incidence of ICD 10th mental disorders in offspring (age 0-17). RESULTS: The study cohort included 1,406,965 children. For girls, maternal or paternal personality disorder (MPD/PPD) was associated with mental disorders: MPD girls (IRR, 2.74; 95% CI, 2.59-2.89) and PPD girls (IRR, 2.10; 95% CI, 1.94-2.27). Likewise, the risk was increased for both MPD boys (IRR, 2.44; 95% CI, 2.33-2.56) and PPD boys (IRR, 2.04; 95% CI, 1.91-2.18). For girls and boys combined, exposure to two parents with a personality disorder was associated with the highest risk (IRR, 3.69; 95% CI, 3.15-4.33). At age 18, the cumulative incidence of any mental disorder in children of one or two parents with a personality disorder was 34.1% (95% CI, 33.0-35.1), which was twice the cumulative incidence of mental disorders in nonexposed children (15.2% [95% CI, 15.1-15.3]). CONCLUSION: Children of parents with a personality disorder were at a 2 to 3.5 times higher risk of mental disorders compared with nonexposed offspring. Possible mechanisms of transmission of mental disorders from parent to child involve genetic, environmental, and gene-environment pathways. More research into these mechanisms and research into preventive interventions is warranted.

Predictors of Mortality Following a Schizophrenia Spectrum Diagnosis: Evidence From the 20-Year Follow-up of the OPUS Randomized Controlled Trial.

BACKGROUND AND HYPOTHESIS: The life expectancy of patients diagnosed with schizophrenia is 10-12 years lower than in the general population and the mortality gap seems to be worsening. Many of these deaths might be avoidable. We aimed to determine mortality rates and causes of death after a first-episode psychosis, and to examine if clinical characteristics at baseline or during illness could predict mortality. STUDY DESIGN: The OPUS study was a randomized controlled trial of 578 patients first diagnosed with schizophrenia spectrum disorders. Patients were clinically assessed after 2, 5, 10, and 20 years. Information about time and cause of death was obtained from the Danish Cause of Death Register. Hazard ratios were used to assess predictors of death. STUDY RESULTS: In total, 82 (14.4%) participants died during 20 years of follow-up. The most common cause of death was suicide (27%). At baseline employment (HR 0.47 P = .049), psychotic disorder other than schizophrenia (HR 0.36, P = .017), and longer duration of untreated psychosis (HR 0.57 P = .042) predicted lower mortality while substance use predicted higher mortality (HR 2.56, P < .001). During follow-up, symptom remission without antipsychotic medication and recovery predicted lower mortality (HR 0.08 P = .013 and HR 0.21, P = .028) while substance use (HR 3.64 P < .001), and all chronic illnesses predicted increased risk. CONCLUSIONS: There is an increased risk of early mortality in schizophrenia compared to the background population, and there is an urgent need for new efforts to improve the disparities in health that lead to this increased mortality.

Alteration of Gut Microbiome in Patients With Schizophrenia Indicates Links Between Bacterial Tyrosine Biosynthesis and Cognitive Dysfunction.

Background: Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. Methods: In this case-control study, gut microbiota of 132 patients with SCZ and increased waist circumference were compared with gut microbiota of two age- and sex-matched control groups, composed of 132 healthy individuals and 132 individuals with metabolic syndrome. Shotgun sequencing was used to characterize fecal samples at the taxonomic and functional levels. Cognition of the patients with SCZ was evaluated using the Brief Assessment of Cognition instrument. Results: SCZ gut microbiota differed significantly from those of healthy control subjects and individuals with metabolic syndrome in terms of richness and global composition. SCZ gut microbiota were notably enriched in Flavonifractor plautii, Collinsella aerofaciens, Bilophila wadsworthia, and Sellimonas intestinalis, while depleted in Faecalibacterium prausnitzii, Ruminococcus lactaris, Ruminococcus bicirculans, and Veillonella rogosae. Functional potential of the gut microbiota accounted for 11% of cognition variability. In particular, the bacterial functional module for synthesizing tyrosine, a precursor for dopamine, was in SCZ cases positively associated with cognitive score (ρ = 0.34, q ≤ .1). Conclusions: Overall, this study shows that the gut microbiome of patients with SCZ differs greatly from that of healthy control subjects or individuals with metabolic syndrome. Cognitive function of patients with SCZ is associated with the potential for gut bacterial biosynthesis of tyrosine, a precursor for dopamine, suggesting that gut microbiota might be an intervention target for alleviation of cognitive dysfunction in SCZ.

Discontinuation of antipsychotics in individuals with first-episode schizophrenia and its association to functional outcomes, hospitalization and death: a register-based nationwide follow-up study.

BACKGROUND: Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death. METHODS: Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995-2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2-5. Outcomes year 5-6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression. RESULTS: Among 21 351, 9.3% took antipsychotics continuously year 2-5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53-2.56 and OR 2.60, 95% CI 1.91-3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05-1.48 and 2.04, 95% CI 1.64-2.53) and no antipsychotics (OR 2.00, 95% CI 1.69-2.38 and 5.64, 95% CI 4.56-6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10-1.47) and longer admissions (IRR 1.68, 95% CI 1.30-2.16) year 5-6 compared to continuous users. Mortality during year 5-6 did not differ between groups. CONCLUSION: Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.

Clinical Recovery Among Individuals With a First-Episode Schizophrenia an Updated Systematic Review and Meta-Analysis.

BACKGROUND AND HYPOTHESIS: Through decades the clinical recovery outcomes among individuals diagnosed with schizophrenia have been highly inconsistent ranging from 13.5% to 57%. The primary objective of this updated examination was to report the pooled estimate and explore various moderators to improve the understanding of the course of schizophrenia. STUDY DESIGN: A systematic literature search was set up on PubMed, PsycInfo, and EMBASE until January 13th, 2022. Both observational and interventional studies among cohorts of individuals with the first episode of schizophrenia reporting on clinical recovery were included. The PRISMA 2020 statement was used and data was extracted for a random-effects meta-analysis, meta-regression, and sensitivity analyses. Risk of bias was assessed using The Newcastle-Ottawa Scale. STUDY RESULTS: A 20.8% (95% CI = 17.3 to 24.8) recovery rate was found among 26 unique study samples (mean trial duration, 9.5 years) including 3877 individuals (mean age, 26.4 years). In meta-regression none of the following study characteristics could uncover the diverse reported recovery rates; age at inclusion (P = .84), year of inclusion (P = .93), follow-up time (P = .99), drop-out rate (P = .07), or strictness of the recovery criteria (P = .35). Furthermore, no differences in recovery were found between early intervention services (EIS; 19.5%; 95% CI = 15.0 to 24.8) compared to other interventions (21%; 95% CI = 16.9 to 25.8), P = .65. CONCLUSIONS: A clinical recovery rate of approximately 21% was found with minimum impact from various moderators. The rate was not different comparing EIS with other interventions implying that new initiatives are needed to improve the rate of recovery.

Tapered discontinuation vs. maintenance therapy of antipsychotic medication in patients with first-episode schizophrenia: Obstacles, findings, and lessons learned in the terminated randomized clinical trial TAILOR.

Aim: Evidence is insufficient regarding the consequences of discontinuing vs. maintaining antipsychotic medication in patients with first-episode schizophrenia. Our aim was to examine tapered discontinuation vs. maintenance treatment regarding remission of psychotic symptoms and impact on other areas. Methods: Patients included had a diagnosis of schizophrenia, were treated with antipsychotic medication, and were in remission of psychotic symptoms. Participants were randomized to tapered discontinuation or maintenance treatment with antipsychotic medication. Assessments were undertaken at baseline and after 1-year. The primary outcome was remission of psychotic symptoms without antipsychotic medication. Results: The trial was terminated due to insufficient recruitment. In total, 29 participants were included: 14 in the tapering/discontinuation group and 15 in the maintenance group. Adherence to maintenance treatment was poor. At 1-year follow-up, remission of psychotic symptoms without antipsychotic medication for 3 months was observed in five participants in the tapering/discontinuation group and two in the maintenance group. Conclusion: Due to insufficient recruitment this study does not provide a conclusion on whether unfavorable outcomes or advantages follow tapering of antipsychotic medication. Recruitment and adherence to maintenance treatment encountered obstacles. Based on experiences from this trial, we discussed alternative study designs as consistent evidence is still needed on whether to continue or discontinue antipsychotic medication in remitted patients with first-episode schizophrenia. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000565-23/DK, EU Clinical Trials Register-EudraCT no. 2016-000565-23.

Reversibility of Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis.

Background and Aims: Weight gain is a major adverse effect of antipsychotic medication, negatively affecting physical and mental well-being. The objective of this study was to explore if dose reduction, discontinuation, switch to a partial agonist, or switch from polypharmacy to monotherapy will lead to weight loss. Methods: Controlled and uncontrolled studies reporting the effects of discontinuation, dose reduction, switch to a partial agonist, or switch from polypharmacy to monotherapy on weight were included. Primary outcome was difference in weight compared to maintenance groups based on controlled studies. Secondary outcome was change in weight from initiation of one of the included interventions until follow-up in a pre-post analysis. Results: We identified 40 randomized controlled trials and 15 uncontrolled studies including 12,279 individuals. The effect of the interventions, i.e. dose reduction, drug discontinuation, or switch to a partial agonis, reduced the weight with 1.5 kg (95% CI -2.03 to -0.98; P < 0.001) compared to maintenance treatment. The weight change from pre to post was a reduction of 1.13 kg (95% CI -1.36 to -0.90; P < 0.001). Conclusion: We found a significant but small reduction in weight, suggesting that antipsychotic-induced weight gain can be reversed to some degree. Only a few studies were designed to address the question as primary outcome, which limits the generalizability of our findings.

Gut microbial changes of patients with psychotic and affective disorders: A systematic review.

BACKGROUND: Many diverse inflammatory pathophysiologic mechanisms have been linked to mental disorders, and through the past decade an increasing interest in the gut microbiota and its relation to mental health has been arising. We aimed to systematically review studies of alterations in gut microbiota of patients suffering from psychotic disorders, bipolar disorder or depression compared to healthy controls. METHODS: We systematically searched the databases CENTRAL, PubMed, EMBASE, PsycINFO and LILACS. Primary outcome was to compare the gut microbiota of patients suffering from psychotic disorders, bipolar disorder or depression with healthy controls. RESULTS: We identified 17 studies, covering 744 patients and 620 healthy controls. The most consistent microbiota changes were a tendency towards higher abundance of Actinobacteria and lower abundance of Firmicutes at the phylum level, lower abundance of Lachnospiraceae at family level and lower abundance of Faecalibacterium at genus level for the mental disorders overall. However, we found that all studies had risk of bias and that the included studies displayed great variability in methods of storage, analysis of the fecal samples, reporting of results and statistics used. CONCLUSION: Due to the many limitations of the included studies the findings should be interpreted with caution. Larger studies (especially of schizophrenia and major depressive disorder) are needed, but it is also of great importance to gather information of and control for factors that influence the result of a microbiota analysis including body mass index (BMI), smoking, alcohol consumption, diet habits, antibiotics, sample handling, wet laboratory methods and statistics.

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.

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.

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.

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.

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.