Structured lifestyle education for people with schizophrenia, schizoaffective disorder and first-episode psychosis (STEPWISE): randomised controlled trial.

BACKGROUND: Obesity is a major challenge for people with schizophrenia.AimsWe assessed whether STEPWISE, a theory-based, group structured lifestyle education programme could support weight reduction in people with schizophrenia. METHOD: In this randomised controlled trial (study registration: ISRCTN19447796), we recruited adults with schizophrenia, schizoaffective disorder or first-episode psychosis from ten mental health organisations in England. Participants were randomly allocated to the STEPWISE intervention or treatment as usual. The 12-month intervention comprised four 2.5 h weekly group sessions, followed by 2-weekly maintenance contact and group sessions at 4, 7 and 10 months. The primary outcome was weight change after 12 months. Key secondary outcomes included diet, physical activity, biomedical measures and patient-related outcome measures. Cost-effectiveness was assessed and a mixed-methods process evaluation was included. RESULTS: Between 10 March 2015 and 31 March 2016, we recruited 414 people (intervention 208, usual care 206) with 341 (84.4%) participants completing the trial. At 12 months, weight reduction did not differ between groups (mean difference 0.0 kg, 95% CI -1.6 to 1.7, P = 0.963); physical activity, dietary intake and biochemical measures were unchanged. STEPWISE was well-received by participants and facilitators. The healthcare perspective incremental cost-effectiveness ratio was £246 921 per quality-adjusted life-year gained. CONCLUSIONS: Participants were successfully recruited and retained, indicating a strong interest in weight interventions; however, the STEPWISE intervention was neither clinically nor cost-effective. Further research is needed to determine how to manage overweight and obesity in people with schizophrenia.Declaration of interestR.I.G.H. received fees for lecturing, consultancy work and attendance at conferences from the following: Boehringer Ingelheim, Eli Lilly, Janssen, Lundbeck, Novo Nordisk, Novartis, Otsuka, Sanofi, Sunovion, Takeda, MSD. M.J.D. reports personal fees from Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceuticals International Inc.; and, grants from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Janssen. K.K. has received fees for consultancy and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Servier and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. K.K. has received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme and Novo Nordisk. D.Sh. is expert advisor to the NICE Centre for guidelines; board member of the National Collaborating Centre for Mental Health (NCCMH); clinical advisor (paid consultancy basis) to National Clinical Audit of Psychosis (NCAP); views are personal and not those of NICE, NCCMH or NCAP. J.P. received personal fees for involvement in the study from a National Institute for Health Research (NIHR) grant. M.E.C. and Y.D. report grants from NIHR Health Technology Assessment, during the conduct of the study; and The Leicester Diabetes Centre, an organisation (employer) jointly hosted by an NHS Hospital Trust and the University of Leicester and who is holder (through the University of Leicester) of the copyright of the STEPWISE programme and of the DESMOND suite of programmes, training and intervention fidelity framework that were used in this study. S.R. has received honorarium from Lundbeck for lecturing. F.G. reports personal fees from Otsuka and Lundbeck, personal fees and non-financial support from Sunovion, outside the submitted work; and has a family member with professional links to Lilly and GSK, including shares. F.G. is in part funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research & Care Funding scheme, by the Maudsley Charity and by the Stanley Medical Research Institute and is supported by the by the Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Lifestyle factors and the metabolic syndrome in Schizophrenia: a cross-sectional study.

BACKGROUND: Cardiometabolic disease is more common in patients with schizophrenia than the general population. AIM: The purpose of the study was to assess lifestyle factors, including diet and exercise, in patients with schizophrenia and estimate the prevalence of metabolic syndrome. METHODS: This is a cross-sectional study of a representative group of outpatients with schizophrenia in Salford, UK. An interview supplemented by questionnaires was used to assess diet, physical activity, and cigarette and alcohol use. Likert scales assessed subjects' views of diet and activity. A physical examination and relevant blood tests were conducted. RESULTS: Thirty-seven people were included in the study. 92% of men had central adiposity, as did 91.7% of women (International Diabetes Federation Definition). The mean age was 46.2 years and mean illness duration was 11.6 years. 67.6% fulfilled criteria for the metabolic syndrome. The mean number of fruit and vegetable portions per day was 2.8 ± 1.8. Over a third did not eat any fruit in a typical week. 42% reported doing no vigorous activity in a typical week. 64.9% smoked and in many cigarette use was heavy. The Likert scale showed that a high proportion of patients had insight into their unhealthy lifestyles. CONCLUSIONS: Within this sample, there was a high prevalence of poor diet, smoking and inadequate exercise. Many did not follow national recommendations for dietary intake of fruit and vegetables and daily exercise. These factors probably contribute to the high prevalence of metabolic syndrome. Many had insight into their unhealthy lifestyles. Thus, there is potential for interventions to improve lifestyle factors and reduce the risk of cardiometabolic disease.

Weight Gain Risk Factor assessment checklist: overview and recommendation for use.

OBJECTIVES: Patients with mental illness are at risk for weight gain. Evidence-based risk assessment checklists have the potential to identify patients at risk early in treatment and improve patient outcomes. METHODS: The 16-item Weight Gain Risk Factor (WGRF-16) checklist has been developed as a simple brief assessment of key weight gain risk factors during antipsychotic treatment. It consists of factors that were collected on the basis of published research on predictors to be assessed at initiation of, and early in treatment with antipsychotics. RESULTS: The factors in the WGRF-16 checklist included age, sex, body mass index, race, appetite, energy intake, a diagnosis of undifferentiated schizophrenia, early clinical response, comorbiditites, social activity, patient insight, housing conditions, weight satisfaction, eating habits, and physical activity level. The WGRF-16 is designed to be repeated 2-3 weeks after initiation of treatment to help to predict an individual's risk of clinically significant weight gain (>7%) during long-term treatment. Further research is required to assess the predictive validity of the checklist. CONCLUSIONS: The WGRF-16 checklist is not intended to replace other required monitoring of patients with severe mental disorders but is a facilitator of weight monitoring in conjunction with clinical guidelines.

Antipsychotics and hyperprolactinaemia: clinical recommendations.

A group of international experts in psychiatry, medicine, toxicology and pharmacy assembled to undertake a critical examination of the currently available clinical guidance on hyperprolactinaemia. This paper summarises the group's collective views and provides a summary of the recommendations agreed by the consensus group to assist clinicians in the recognition, clinical assessment, investigation and management of elevated plasma prolactin levels in patients being treated for severe mental illness. It also deals with the special problems of particular populations, gives advice about information that should be provided to patients, and suggests a strategy for routine monitoring of prolactin. The recommendations are based upon the evidence contained in the supplement 'Hyperprolactinaemia in schizophrenia and bipolar disorder: Clinical Implications' (2008). The guidance contained in this article is not intended to replace national guidance (such as that of the National Institute of Clinical Excellence), however, it does provide additional detail that is unlikely to be covered in existing guidelines, and focuses on areas of uncertainty and disagreement. We hope it will add to the debate about this topic.

Reducing weight gain in people with schizophrenia, schizoaffective disorder, and first episode psychosis: describing the process of developing the STructured lifestyle Education for People With SchizophrEnia (STEPWISE) intervention.

BACKGROUND: Obesity is twice as common in people with schizophrenia as the general population and associated with significantly worsened psychiatric and physical health. Despite National Institute for Health and Care Excellence guidelines for the management of psychosis recommending that mental health services offer lifestyle programmes to people with schizophrenia to improve physical health, this is not currently occurring. The aim of the STEPWISE research programme was to develop a lifestyle intervention addressing obesity and preventing weight gain in people with schizophrenia, schizoaffective disorder, or first episode psychosis taking antipsychotic medication, through an approach and fundamental principles drawn from existing diabetes and diabetes prevention interventions. This paper describes the often under-reported process of developing such an intervention from first principles. METHODS: Following an extensive literature review, an iterative cycle of development with input from people with schizophrenia, mental healthcare professionals, facilitators, and other stakeholders, a new weight management intervention for the target group was developed. A set of four core weekly sessions was piloted in Sheffield, followed at 3-monthly intervals by three booster sessions and telephone support contact once every 2 weeks, to form an intervention lasting 12 months. Facilitators were provided with a 4-day training package to support delivery of the intervention. RESULTS: This paper reports the process of development, including challenges and how these were addressed. It describes how user input influenced the structure, topics, and approach of the intervention. The outcome of this process was a feasible and acceptable lifestyle intervention to support people with schizophrenia, schizoaffective disorder, or first episode psychosis to manage their weight. This pilot provided opportunities for refinement of the intervention and facilitator training prior to testing in a multi-centre randomised controlled trial. Key findings from the pilot were linked to accessibility, focus, uptake, and retention, which influenced session length, travel arrangements, refreshment, breaks, and supporting tools to incentivise participants. CONCLUSIONS: The STEPWISE intervention has been evaluated in a randomised controlled trial in 10 mental health trusts in England, and the results will be published in the British Journal of Psychiatry and the NIHR Journals Library. TRIAL REGISTRATION: ISRCTN19447796. Date registered: 20/03/2014.

Structured lifestyle education to support weight loss for people with schizophrenia, schizoaffective disorder and first episode psychosis: the STEPWISE RCT.

BACKGROUND: Obesity is twice as common in people with schizophrenia as in the general population. The National Institute for Health and Care Excellence guidance recommends that people with psychosis or schizophrenia, especially those taking antipsychotics, be offered a healthy eating and physical activity programme by their mental health care provider. There is insufficient evidence to inform how these lifestyle services should be commissioned. OBJECTIVES: To develop a lifestyle intervention for people with first episode psychosis or schizophrenia and to evaluate its clinical effectiveness, cost-effectiveness, delivery and acceptability. DESIGN: A two-arm, analyst-blind, parallel-group, randomised controlled trial, with a 1 : 1 allocation ratio, using web-based randomisation; a mixed-methods process evaluation, including qualitative case study methods and logic modelling; and a cost-utility analysis. SETTING: Ten community mental health trusts in England. PARTICIPANTS: People with first episode psychosis, schizophrenia or schizoaffective disorder. INTERVENTIONS: Intervention group: (1) four 2.5-hour group-based structured lifestyle self-management education sessions, 1 week apart; (2) multimodal fortnightly support contacts; (3) three 2.5-hour group booster sessions at 3-monthly intervals, post core sessions. Control group: usual care assessed through a longitudinal survey. All participants received standard written lifestyle information. MAIN OUTCOME MEASURES: The primary outcome was change in weight (kg) at 12 months post randomisation. The key secondary outcomes measured at 3 and 12 months included self-reported nutrition (measured with the Dietary Instrument for Nutrition Education questionnaire), objectively measured physical activity measured by accelerometry [GENEActiv (Activinsights, Kimbolton, UK)], biomedical measures, adverse events, patient-reported outcome measures and a health economic assessment. RESULTS: The trial recruited 414 participants (intervention arm: 208 participants; usual care: 206 participants) between 10 March 2015 and 31 March 2016. A total of 341 participants (81.6%) completed the trial. A total of 412 participants were analysed. After 12 months, weight change did not differ between the groups (mean difference 0.0 kg, 95% confidence interval -1.59 to 1.67 kg; p = 0.964); physical activity, dietary intake and biochemical measures were unchanged. Glycated haemoglobin, fasting glucose and lipid profile were unchanged by the intervention. Quality of life, psychiatric symptoms and illness perception did not change during the trial. There were three deaths, but none was related to the intervention. Most adverse events were expected and related to the psychiatric illness. The process evaluation showed that the intervention was acceptable, with participants valuing the opportunity to interact with others facing similar challenges. Session feedback indicated that 87.2% of participants agreed that the sessions had met their needs. Some indicated the desire for more ongoing support. Professionals felt that the intervention was under-resourced and questioned the long-term sustainability within current NHS settings. Professionals would have preferred greater access to participants' behaviour data to tailor the intervention better. The incremental cost-effectiveness ratio from the health-care perspective is £246,921 per quality-adjusted life-year (QALY) gained and the incremental cost-effectiveness ratio from the societal perspective is £367,543 per QALY gained. CONCLUSIONS: Despite the challenges of undertaking clinical research in this population, the trial successfully recruited and retained participants, indicating a high level of interest in weight management interventions; however, the STEPWISE intervention was neither clinically effective nor cost-effective. Further research will be required to define how overweight and obesity in people with schizophrenia should be managed. The trial results suggest that lifestyle programmes for people with schizophrenia may need greater resourcing than for other populations, and interventions that have been shown to be effective in other populations, such as people with diabetes mellitus, are not necessarily effective in people with schizophrenia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19447796. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 65. See the NIHR Journals Library website for further project information.

STEPWISE - STructured lifestyle Education for People WIth SchizophrEnia: a study protocol for a randomised controlled trial.

BACKGROUND: People with schizophrenia are two to three times more likely to be overweight than the general population. The UK National Institute of Health and Care Excellence (NICE) recommends an annual physical health review with signposting to, or provision of, a lifestyle programme to address weight concerns and obesity. The purpose of this randomised controlled trial is to assess whether a group-based structured education programme can help people with schizophrenia to lose weight. METHODS: Design: a randomised controlled trial of a group-based structured education programme. SETTING: 10 UK community mental health trusts. PARTICIPANTS: 396 adults with schizophrenia, schizoaffective, or first-episode psychosis who are prescribed antipsychotic medication will be recruited. Participants will be overweight, obese or be concerned about their weight. INTERVENTION: participants will be randomised to either the intervention or treatment as usual (TAU). The intervention arm will receive TAU plus four 2.5-h weekly sessions of theory-based lifestyle structured group education, with maintenance contact every 2 weeks and 'booster' sessions every 3 months. All participants will receive standardised written information about healthy eating, physical activity, alcohol and smoking. OUTCOMES: the primary outcome is weight (kg) change at 1 year post randomisation. Secondary outcomes, which will be assessed at 3 and 12 months, include: the proportion of participants who maintained or reduced their weight; waist circumference; body mass index; objectively measured physical activity (wrist accelerometer); self-reported diet; blood pressure; fasting plasma glucose, lipid profile and HbA1c (baseline and 1 year only); health-related quality of life (EQ-5D-5L and RAND SF-36); (adapted) brief illness perception questionnaire; the Brief Psychiatric Rating Scale; the Client Service Receipt Inventory; medication use; smoking status; adverse events; depression symptoms (Patient Health Questionnaire-9); use of weight-loss programmes; and session feedback (intervention only). Outcome assessors will be blind to trial group allocation. Qualitative interviews with a subsample of facilitators and invention-arm participants will provide data on intervention feasibility and acceptability. Assessment of intervention fidelity will also be performed. DISCUSSION: The STEPWISE trial will provide evidence for the clinical and cost-effectiveness of a tailored intervention, which, if successful, could be implemented rapidly in the NHS. TRIAL REGISTRATION: ISRCTN19447796 , registered on 20 March 2014.

A review of hyperprolactinaemia and severe mental illness: are there implications for clinical biochemistry?

Hyperprolactinaemia is a common adverse event reported in association with treatments used in schizophrenia and bipolar disorder. Recent data are suggestive that hyperprolactinaemia may have a range of significant short-and long-term clinical consequences. The objective of this review is to examine the causes, frequency and clinical consequences of hyperprolactinaemia in the severely mentally ill (SMI) with a focus on patients taking antipsychotic medications. A Medline search was carried out to identify relevant publications. Reference lists from previous review articles were also examined to search for additional data. Hyperprolactinaemia may be one of the most common adverse events associated with some antipsychotic medications. Precise rates with individual drugs had however until recently been poorly categorized. The relationship between hyperprolactinaemia and adverse outcomes in the SMI population appears similar to that in the general population. Adverse outcomes (such as sexual dysfunction) can occur acutely and in the longer term (bone fractures and possibly breast cancer), but the precise link between degree and length of hyperprolactinaemia and adverse outcome remains to be established. In conclusion, hyperprolactinaemia is a common treatment-emergent adverse event of some antipsychotic medications and may have clinical consequences. Physicians must balance the benefits and risks of treatment when determining appropriate therapy for individual patients.

Intentional weight loss in overweight and obese patients with severe mental illness: 8-year experience of a behavioral treatment program.

OBJECTIVE: Obesity is 2 to 3 times more common among people with severe mental illness and has adverse effects on physical and psychological health. We report the experience from the first 8 years of a self-referring weight management clinic. METHOD: From 2000 to 2008, 113 patients with severe mental illness (according to ICD-10 criteria) with a mean +/- SE age of 43.8 +/- 1.7 years (range, 22-71 years) referred themselves to this clinic. The patients were seen in weekly group sessions lasting 1 hour that involved weight measurement, discussion, and education. The response to the program was assessed by the paired Student t test and linear analysis corrected for repeated measures. RESULTS: Mean +/- SE baseline weight was 90.1 +/- 1.6 kg (body mass index [BMI] = 32.2 +/- 0.5 kg/m(2)). Fifty subjects of the 142 total patient episodes (35%) dropped out within the first 3 months. Sixty-four subjects completed 1 year of the program, and 35 have attended for 2 years or longer. There were progressive statistically significant reductions in mean weight and BMI throughout the duration of monitoring, with no suggestion of a plateau. The mean +/- SE final weight loss was 7.2 +/- 0.6 kg. Weight loss was correlated only with the number of sessions attended (r = 0.42, P < .0001). CONCLUSIONS: Lifestyle advice within a group setting may be effective in long-term management of obese and overweight patients with severe mental illness.

Evaluation of a behavioural weight management programme for patients with severe mental illness: 3 year results.

Excess weight is a common problem in the general population and in those with severe mental illness and is associated with a range of adverse consequences. The evidence base for managing excess weight in those with severe psychiatric illness is small. We report the outcome of a weight management programme provided in a community mental health centre. The programme consisted of group sessions, held weekly and lasting one hour. Participants self-referred and attended as many sessions as they wished. Sessions included weighing, feedback from participants and education on a range of issues including healthy eating and exercise. Over a 3-year period 70 patients, predominantly with schizophrenia, attended the programme. Length of follow-up ranged from 2 weeks to 3 years. Data for all 70 patients was evaluated. The mean BMI at entry to the programme was 32.5 kg/m2. The mean number of sessions attended was 34. Patients achieved a mean weight loss of 4.97 kg. The mean BMI at last attendance was 30.7 kg/m2. Weight loss correlated with number of sessions attended (p = 0.0001). This study demonstrates the long-term value of a weight management programme at 3 years and supports the hypothesis that weight loss can be achieved using a simple behavioural intervention in motivated psychiatric patients.

The role of lifestyle interventions and weight management in schizophrenia.

The recognition that schizophrenia is associated with metabolic comorbidity and a subsequent greater risk of cardiovascular events compared to the general population has led to attempts to reduce this metabolic burden. Increased weight, and smoking rates combined with less exercise and poor dietary choices, have led to a variety of behavioural programmes and pharmacological agents being evaluated with the aim of improving lifestyle and managing weight. Adjunctive pharmacological strategies for weight management have not been shown to be consistently effective and remain contraindicated in many schizophrenia subjects. However some novel compounds with recent promising data suggest that research should not be abandoned. In contrast a variety of behavioural interventions have shown a consistent degree of success not only with weight management but also in achieving lifestyle changes. Many reported data-sets are naturalistic or open-label indicating that there is a difficulty in performing traditional randomized controlled studies in this area. The long-term naturalistic studies and holistic approaches show that weight management and significant lifestyle changes are attainable goals in schizophrenia patients. Weight management and lifestyle advice should be routinely offered to all schizophrenia subjects.