Journal of Psychopharmacology

Holt, Richard I. G.

doi: 10.1177/0269881105058377pmid: 16280333

Obesity is a chronic relapsing condition associated with significant morbidity andpremature mortality. The prevalence of obesity has increased dramatically over thelast 20 years and continues to do so, primarily as a result of changes in dietaryintake and exercise patterns. There are considerable challenges associated with themanagement of the obesity epidemic involving both public health policies andindividual treatment. Management of the obese individual involves lifelong lifestylechange for all, drugs for some, and surgery for a few. Appropriate selection ofpatients and the setting of realistic goals are crucial to the success of anyweight-reducing programme. The aim of obesity management is to reduce associatedmorbidity and mortality, not necessarily to restore normal body weight. While thecurrent trends in obesity are depressing, a better understanding of thepathophysiology and treatment of the condition should allow the clinician to be moreoptimistic for the future.

Haddad, Peter

doi: 10.1177/0269881105058378pmid: 16280334

Weight gain is a common complication of antipsychotic treatment. Its consequencesinclude decreased self-esteem, reduced quality of life, reduced adherence withmedication and increased morbidity and mortality. Most studies that assess weightchange are short term. Among the atypicals mean weight gain is greatest witholanzapine and clozapine and least with aripiprazole and ziprasidone. Mean weightchange obscures the marked individual variation in weight change that occurs duringantipsychotic treatment i.e. irrespective of the antipsychotic, some subjects loseweight, some maintain their weight and some gain weight. In several long-termnaturalistic studies (>6 months) mean weight gain is less marked than inrandomised controlled trials of a shorter or comparable duration. This may reflectselective prescribing, the effect of weight management interventions and differencesin the statistical analysis employed. With most antipsychotics weight stabilizes inthe short to medium term but with clozapine it may continue beyond the first year.With some drugs clinical improvement is associated with short-term weight gain.Predictors of long-term weight gain include lower body mass index, increasedappetite and rapid initial weight increase. Weight gain is greater in first onsetpatients due to the lack of prior antipsychotic exposure and associated weight gain.The potential for weight gain should be discussed with patients before startingantipsychotic treatment and weight monitored regularly during treatment. It may bepossible to predict weight gain before an antipsychotic is started or early on intreatment enabling high-risk patients to receive more intensive strategies to reduceweight gain.

Bushe, Chris; Haddad, Peter; Peveler, Robert; Pendlebury, John

doi: 10.1177/0269881105058682pmid: 16280335

The recognition that schizophrenia is associated with metabolic comorbidity and asubsequent greater risk of cardiovascular events compared to the general populationhas led to attempts to reduce this metabolic burden. Increased weight, and smokingrates combined with less exercise and poor dietary choices, have led to a variety ofbehavioural programmes and pharmacological agents being evaluated with the aim ofimproving lifestyle and managing weight. Adjunctive pharmacological strategies forweight management have not been shown to be consistently effective and remaincontraindicated in many schizophrenia subjects. However some novel compounds withrecent promising data suggest that research should not be abandoned. In contrast avariety of behavioural interventions have shown a consistent degree of success notonly with weight management but also in achieving lifestyle changes. Many reporteddata-sets are naturalistic or open-label indicating that there is a difficulty inperforming traditional randomized controlled studies in this area. The long-termnaturalistic studies and holistic approaches show that weight management andsignificant lifestyle changes are attainable goals in schizophrenia patients. Weightmanagement and lifestyle advice should be routinely offered to all schizophrenia subjects.

Tighe, Sheila; Dinan, Timothy

doi: 10.1177/0269881105058679pmid: 16280336

Weight regulation is a complex system necessary for maintaining health. Obesity andcachexia are consequences of dysregulation and cause significant physical morbidityand mortality. In the developed world, obesity is a growing epidemic. A greaterunderstanding of the neuroanatomy of weight regulation has been gained throughadvances in imaging and neural mapping techniques. The neural connections betweenkey hypothalamic and other central nuclei have been elucidated. Advances inmolecular biology have led to the identification and cloning of important peripheraland central weight regulating peptides. Weight gain as a consequence ofantipsychotic use is increasingly being recognized as a serious clinical issue. Theweight regulation system provides a framework upon which antipsychotics exert theirweight-inducing effects. Some studies have sought, with inconsistent results, toestablish associations between antipsychotic use and levels of weight regulatingmediators. The receptor pharmacology of antipsychotics known to increase weight canbe studied with a view to establishing genetic variants contributing to the risk. Todate, the 5-HT2C receptor 759C/T polymorphism shows most promise. Furtherstudies are required to replicate previous findings and establish new associations.

Gough, Stephen C. L.; O’Donovan, Michael C.

doi: 10.1177/0269881105058380pmid: 16280337

People with schizophrenia are more likely to develop type 2 diabetes than the generalpopulation. Although an increased risk of diabetes has been attributed toenvironmental determinants such as diet, lifestyle and antipsychotic drugs, theassociation between these two disorders was noticed well before the advent ofcurrent lifestyles and pharmacological interventions, raising the possibility of ashared genetic basis. Schizophrenia and type 2 diabetes are common diseases with acomplex mode of inheritance which includes both genetic factors and environmentaldeterminants. As susceptibility genes for both type 2 diabetes and schizophrenia arebeginning to be identified there is increasing interest in the possibility of sharedsusceptibility loci between the two conditions. This article reviews the geneticbasis to schizophrenia and type 2 diabetes and discusses the potential for sharedloci between both conditions.

Holt, Richard I. G.; Bushe, Chris; Citrome, Leslie

doi: 10.1177/0269881105058379pmid: 16280338

The association between schizophrenia and diabetes has been recognized for well overa century, but the underlying reasons for this association are unclear. In October2003, an international group of diabetologists and psychiatrists met to review theliterature relating to the association, and to create pragmatic guidelines for themanagement of diabetic risk in patients with severe mental illness. Since thatmeeting, over 100 additional papers have been published on the association betweenglucose abnormalities and schizophrenia, and this is a clear reflection of the levelof interest in this clinically important area. Diabetes is highly prevalent amongthe schizophrenia population, but most sufferers remain undiagnosed in thecommunity. The reasons why individuals with schizophrenia are more prone todeveloping diabetes than the general population are poorly defined, but likely to bemultifactorial. The role of antipsychotic medications in the development of diabetesand other pre-diabetic states remains controversial, but it appears that theattributable risk is low. Traditional risk factors most probably account for much ofthe diabetes seen in schizophrenia populations, suggesting that routine screeningand aggressive risk factor management are especially important in this patient group.

Bushe, Chris; Paton, Carol

doi: 10.1177/0269881105058719pmid: 16280340

Lipid abnormalities are common in the general population and early data suggests thatthey may be more common in people with schizophrenia. Little data exist fromtreatment-naive patients making it difficult to differentiate any geneticcontribution associated with a diagnosis of schizophrenia from the lifestyle risksassociated with this diagnosis. Additional potential risks associated withantipsychotic drug treatment have been noted in the literature since 1971. Themajority of the existing data on lipids derive from retrospective andcross-sectional analyses of datasets that have been designed for other purposes.Specifically screening bias for lipid testing and treatment selection bias areimportant potential confounders. Prospective clinical trials are difficult tointerpret, as many are short-term, report on non-fasting data and were neverdesigned to evaluate the differential effects of antipsychotic drugs on lipids as aprimary endpoint. There is little reported data on lipid fractions such as LDL andHDL. Nevertheless there is some evidence from placebo-controlled studies thatantipsychotics may be differentially associated with a small, clinicallyinsignificant increase in cholesterol and a larger, potentially clinicallysignificant increase in triglycerides.Further prospective randomized trials, using fasting data and controlling forestablished risk factors such as diet and exercise are essential to determine ifthere are clinically meaningful differential effects on lipids associated withindividual antipsychotic drugs.

Citrome, Leslie

doi: 10.1177/0269881105058375pmid: 16280341

Metabolic syndrome is a constellation of clinical findings that identify individualsat higher than normal risk of developing diabetes mellitus or cardiovasculardisease. There are two principal definitions, one emerging from the AmericanNational Cholesterol Education Program Expert Panel on Detection, Evaluation, andTreatment of High Blood Cholesterol in Adults, and the other from the World HealthOrganization. Both definitions share the common elements of abdominal obesity,hypertriglyceridaemia, low HDL-cholesterol, hypertension and abnormal glucoseregulation. The syndrome is relatively common across continents, and also amongthose without marked obesity. It is even more common among patients with majormental health disorders such as schizophrenia. Metabolic syndrome can be used toassess risk for cardiovascular disorder and death, and is an alternative toFramingham Risk Calculations. C-reactive protein may play an additional role in riskprediction. Ongoing monitoring for all components of the metabolic syndrome isnecessary. Individuals at high risk require multimodal interventions, includinglifestyle interventions and targeted medications as appropriate.

Morriss, Richard; Mohammed, Faizal Amir

doi: 10.1177/0269881105058678pmid: 16280342

Lifestyle, illness and treatment factors in people with bipolar disorder (BD) mayconfer additional risk of morbidity and mortality to the increasing rates ofobesity, metabolic syndrome, diabetes mellitus and cardiovascular mortality in thegeneral population.The aim of this review is to examine whether the risk of obesity and relatedmorbidity and mortality are raised in BD, and possible contributory effects oflifestyle, illness and treatment factors to this risk.Systematic search of Medline and Cochrane Collaboration for relevant studies followedby a critical review of literature was carried out.Mortality from cardiovascular causes and pulmonary embolism (standardized mortalityratio approximately 2.0), and morbidity from obesity and type 2 diabetes mellitusmay be increased in BD compared to the general population. Reduced exercise and poordiet, frequent depressive episodes, comorbidity with substance misuse and poorquality general medical care contribute to the additional risk of these medicalproblems in people with BD. There is no evidence that patients with BD are moresensitive than other patients to weight gain and medical problems associated withlong-term use of psychotropic medication; in fact long-term treatment with lithium,antipsychotics and tricyclic antidepressants may reduce overall mortality.Psychiatrists, general practitioners and other health professionals should worktogether to systematically assess and manage weight gain and related medicalproblems to reduce the morbidity and mortality associated with obesity in BD. Thereis insufficient evidence to associate any of these factors with specific drugtreatments. More research is required to understand how BD changes the risk forphysical health comorbidity.

Ascher-Svanum, Haya; Stensland, Michael D.; Kinon, Bruce J.; Tollefson, Gary D.

doi: 10.1177/0269881105058978pmid: 16280344

Treatment-emergent weight gain may be a general marker of therapeutic improvement,even when improvements occur in the absence of active antipsychotic treatment.To investigate the association between treatment-emergent weight gain and therapeuticimprovement across placebo and active treatments, and to examine the associationbetween reported treatment-emergent weight changes and the treatments’reported efficacy.Data from a randomized, double-blind trial comparing treatment of schizophrenia withplacebo and olanzapine were used to correlate weight change and change inpsychopathology. Additionally, we correlated effect sizes of the efficacy ofclozapine, olanzapine, risperidone, haloperidol and placebo (reported inmeta-analytical reviews), with their reported weight changes.Weight gain significantly correlated with clinical improvements for placebo andolanzapine. The correlation between treatments’ efficacy and correspondingweight changes was high (r 0.88, p 0.05).Treatment-emergent weight gain appears to be an important marker of symptomreduction, and may not be exclusively attributable to pharmacological perturbations.