John Pendlebury

Long-term maintenance of weight loss in patients with severe mental illness through a behavioural treatment programme in the UK

Objective:  Obesity is common among people with severe mental illness (SMI). We report our experience from the first 4 years of The Cromwell House weight management clinic.

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.

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.

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.

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. Aims We 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 interest R.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 Kings College London.

Prolactin and Schizophrenia, an Evolving Relationship

Prolactin is a polypeptide hormone originally discovered from the crop glands of pigeons in 1933 (Riddle et al, 1933; Bushe and Pendlebury, 2010), however there was some scepticism that prolactin even existed in humans until the 1970s as human prolactin was considered identical to growth hormone (GH). During the 1970s, the development of radioimmunoassay techniques allowed the isolation of prolactin and its subsequent measurement (Kohen and Wildgust, 2008). Since that time, awareness of the consequences of hyperprolactinaemia in psychiatry has been less than rapid despite clear evidence that many psychotropic agents, in particular antipsychotics, elevate prolactin levels to some degree in many patients. As a result, prolactin monitoring is not commonplace and many clinicians remain unsure of its utility. In part, this may relate to lack of knowledge regarding pathological endpoints caused by hyperprolactinaemia. In the last decade, however, awareness has begun to emerge of the potential consequences of untreated hyperprolactinaemia including short-term adverse events of sexual dysfunction, amenorrhoea and infertility and longer term consequences that may include bone fractures and breast cancer. This has been due in part to a number of reviews focussing on the potential consequences of hyperprolactinaemia and the relatively high prevalence of this adverse event (Haddad and Wieck, 2004; Bostwick et al, 2009; Bushe and Pendlebury, 2010), ). In 2008 the first set of prolactin monitoring guidelines was published and more recent data have begun to evaluate the use of specific polypharmacy to reduce prolactin levels (Peveler et al, 2008). There remain, however, many unanswered questions; most relate to the need to establish the true incidence of longer term sequelae of hyperprolactinaemia and to the simple questionwhat level of prolactin actually carries consequences and when? When one considers that prolactin has at least 300 biological actions it may be that this diversity of function will lead to research that further defines the precise role of and subsequent pathology induced by hyperprolactinaemia (Fitzgerald and Dinan, 2008).