Helen Millar

Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia.

People with schizophrenia are at greater risk of obesity, Type 2 diabetes, dyslipidaemia and hypertension than the general population. This results in an increased incidence of cardiovascuLar disease (CVD) and reduced Life expectancy, over and above that imposed by their mentaL illness through suicide. Several Levels of evidence from data Linkage analyses to clinical trials demonstrate that treatment-related metabolic disturbances are commonplace in this patient group, and that the use of certain second-generation antipsychotics may compound the risk of developing the metabolic syndrome and CVD. In addition, smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall CVD risk. Management and minimization of metaboLic risk factors are pertinent when providing optimal care to patients with schizophrenia. This review recommends a framework for the assessment, monitoring and management of patients with schizophrenia in the UK clinical setting.

A prospective, multicentre, open-label study of aripiprazole in the management of patients with schizophrenia in psychiatric practice in Europe: Broad Effectiveness Trial with Aripiprazole in Europe (EU-BETA)

ABSTRACT Objective: To examine the effectiveness of aripiprazole in schizophrenia in a naturalistic setting in 14 European countries. Methods: This multicentre, open-label study of aripiprazole evaluated outpatients with schizophrenia for whom a medication switch was clinically reasonable or antipsychotic initiation was required. Patients (n = 833) were randomized in a 4:1 ratio to aripiprazole (recommended starting dose 15 mg/day, permitted adjustment 10–30 mg/day) (n = 680) or another antipsychotic (safety control [SC] group) (n = 153) for 8 weeks. The control group received an antipsychotic different to their recent pre-study medication. The primary effectiveness measure was the Clinical Global Impression – Improvement (CGI – I) score of aripiprazole-treated patients at Week 8 (last observation carried forward [LOCF]). Patients’ and caregivers’ medication preference was assessed using the Preference of Medication (POM) questionnaire. The Investigator Assessment Questionnaire (IAQ) was used to record investigators’ assessments of their patients’ responses to the study antipsychotic. Adverse events (AEs) were recorded. Results: At endpoint (Week 8, LOCF), the mean CGI – I score of 3.16 (95% confidence interval, [CI]: 3.04, 3.28) demonstrated the effectiveness of aripiprazole. At endpoint, 43% of aripiprazole-treated patients showed a response (CGI – I score = 1/2). Aripiprazole was rated as slightly or much better than previous antipsychotic at endpoint by 68% of patients and 65% of caregivers. The mean CGI – I score (Week 8, LOCF) for the SC group was 3.37 (95% CI: 3.14, 3.60). No major differences in the occurrence of AEs were noted between aripiprazole- and SC-treated patients. Limitations: As this is an open-label design, there may have been a bias. Secondly, the study was not powered to show differences between treatment groups and no statistical comparisons were planned. Thirdly, 8 weeks is too short to evaluate long-term effectiveness. Conclusions: Aripiprazole was effective, well tolerated and well accepted by patients and caregivers in this naturalistic study.

Management of physical health in schizophrenia: A stepping stone to treatment success

While patients with schizophrenia are known to have an increased risk of physical health co-morbidity including coronary heart disease, diabetes, hypertension, stroke and emphysema, their physical wellbeing often goes unnoticed by health care professionals. In many cases the patients only contact with the health service is through the mental health team. However, many psychiatrists consider their primary function to be the provision of clinical care in terms of symptom control and are reluctant to switch medication despite the presence of physical health issues. Nevertheless outcomes in schizophrenia may be improved by expanding the remit of the clinician to include assessments of both physical and mental health. Simple measurements such as waist circumference, weight, height, blood pressure and blood sampling would provide the psychiatrist with useful information that could be used to optimize treatment and improve overall quality of life for patients with schizophrenia.

Practical prescribing with aripiprazole in schizophrenia: consensus recommendations of a UK multidisciplinary panel

ABSTRACT Background: The atypical antipsychotic, aripiprazole, differs from other antipsychotics in its pharmacology and clinical outcomes. Aripiprazoles clinical outcomes include beneficial effects on mood, quality of life and cognition; favourable tolerability with low potential for sedation; and a favourable physical health profile, with low potential for weight change, sexual dysfunction or adverse metabolic effects. Such outcomes, particularly cognitive improvements, may allow for greater psychosocial intervention and improved social inclusion. In accordance with the UK NICE guidance on the use of antipsychotic treatment for schizophrenia (2002), aripiprazole may be an appropriate therapeutic option for patients with schizophrenia who are newly diagnosed, in acute relapse or experiencing tolerability problems, adverse metabolic effects or dissatisfaction with their current medication. Scope: A multidisciplinary panel was convened in the UK in October 2006 to discuss and provide practical guidance regarding the potential benefits and risks of prescribing aripiprazole. This report describes the consensus recommendations agreed during the meeting and includes practical guidance on the optimal approach to prescribing aripiprazole, which patients might benefit from aripiprazole and how best to approach initiation of and switching to treatment with aripiprazole. A PubMed/MEDLINE literature search was conducted to support these recommendations. Findings: To support antipsychotic therapy, a therapeutic partnership should be established between the patient and a well-informed, multidisciplinary care team. Aripiprazole should be initiated at the minimal efficacious dose (10 mg/day) and titrated as required (usually to 15 mg/day) after a minimum of 2 weeks. The primary goal during aripiprazole initiation is to ensure the patient completes the first few days of treatment, with support from concomitant medications if required. Nausea, insomnia and agitation may occur in 10–20% of patients, but are manageable and typically resolve during the first 3–7 days of therapy. The dose of any prior antipsychotic should remain stable until the response to aripiprazole is satisfactory and then the previous antipsychotic should be tapered off slowly over several weeks or more. Conclusion: Patients are more likely to adhere to treatment with aripiprazole – and indeed any other antipsychotic – and derive long-term therapeutic benefits if they and a well-informed care team are involved in the treatment decision, establish a therapeutic partnership, are aware of the transient nature of any adverse events and understand what the potential long-term benefits are.

The physical health challenges in patients with severe mental illness: cardiovascular and metabolic risks

This supplement is the output of a roundtable discussion, attended by a multidisciplinary panel with a broad range of expertise, which includes the treatment of severe mental illness, cardiovascular disease, diabetes and pharmaceutical prescribing. The roundtable and writing of the supplement were organised and paid for by MSD, including the payment of Steve Titmarsh, a medical writer who was involved in the preparation and editing of this document

The impact on community benzodiazepine prescribing of hospitalization

To assess the impact of both general and psychiatric hospitalization on the community prescribing of benzodiazepines, we carried out an observational study using record linkage of prescribing prior to and following hospitalization along with a review of hospital case records at four Tayside General Practices. In a population of 29,672 subjects, 2628 general hospital and 254 psychiatric hospitalizations were studied. The main outcome measure was the change in community benzodiazepine prescribing following hospitalization. We found that admission to a general hospital resulted in 59 of the 2628 subjects (2.2%) commencing and 45 subjects (1.7%) discontinuing benzodiazepines. Admission to a psychiatric hospital resulted in 17 of 254 subjects (6.7%) commencing and 40 (16.7%) discontinuing benzodiazepines. When compared to benzodiazepine prescribing in the study population these effects were trivial. We conclude that hospitalization in both general and psychiatric hospitals had a minor effect on total community prescribing of benzodiazepines. In this study general hospital admission resulted in a small net increase and psychiatric hospitalization a small net decrease in benzodiazepine prescribing.

Screening for mental problems in people presenting with hypertension and comorbidities.

The authors provided good guidance on the complexities of managing hypertension with associated chronic comorbid physical conditions, such as kidney disease, diabetes, chronic obstructive pulmonary disease (COPD), and heart failure.1 However, they did not mention the mental health problems that are often seen in these people …

Psychiatric and General Medical Comorbidity

The observation that chronic disorders occur together frequently has become of increasing interest as it is now viewed as the norm and not the exception. Of concern is the increasing trend of comorbidity in younger populations especially in areas of socioeconomic deprivation and low income countries. There are reasons why comorbidity is of great importance not only in the context of diagnostic classification, aetiology and pathogenesis but also for models of health-care delivery, rationalisation of pharmacotherapy, patients’ self management and the complex simultaneous utilisation of health-care systems. There is a need, therefore, for a better understanding of the coexistence of various diseases in order to develop more effective and cost-effective interventions to improve health and social outcomes. Comorbidity in medicine is now viewed as one of the major challenges in the twenty-first century in terms of prevention and treatment. With comorbidity comes the increasing risk of mental health problems especially depression leading to potentially more complications and worse prognosis overall. It is already well established that those with severe mental illness suffer increased comorbid conditions and a reduced life expectancy due to predominantly comorbid cardiovascular problems. Fragmentation in the health-care system and the current single disease model only exacerbate the problem of effectively helping people experiencing comorbidities and especially comorbidities involving both mental and physical conditions. New ways of thinking are required to redesign healthcare systems for the development of effective early intervention and screening to treat coexisting conditions and enable clinicians to deliver more integrated person-centred care to improve health outcomes and quality of life for this population.

PMH37 UNITED KINGDOM COST-CONSEQUENCE ANALYSIS OF ARIPIPRAZOLE IN SCHIZOPHRENIA: DIABETES AND CORONARY HEART DISEASE RISK PROJECTIONS (STAR STUDY)

PMH37 UNITED KINGDOM COST-CONSEQUENCE ANALYSIS OF ARIPIPRAZOLE IN SCHIZOPHRENIA: DIABETES AND CORONARY HEART DISEASE RISK PROJECTIONS (STAR STUDY) Barnett AH, Millar H, Loze JY, L’Italien GJ, van Baardewijk M, Knapp M University of Birmingham and Heart of England NHS Foundation Trust, Birmingham,West Midlands, UK, Tayside Primary Care Division, Dundee, UK, Otsuka Pharmaceutical France, Paris, France, Bristol-Myers Squibb,Wallingford, CT, USA, Bristol-Myers Squibb, Braine l’Alleud, Belgium, London School of Economics, London, UK OBJECTIVE: Schizophrenia is associated with increased morbidity and mortality compared to the general population, largely resulting from increased incidence of cardiovascular disease and diabetes. Some atypical antipsychotics are associated with adverse metabolic symptoms, such as weight gain, dyslipidaemia and glucose dysregulation, which may further increase the risk of coronary heart disease (CHD) and diabetes. This study aimed to assess the impact of these symptoms on cost of treating patients’ physical health. METHODS: Data from the Schizophrenia Trial for Aripiprazole (STAR) study showed that metabolic side effects of aripiprazole treatment are less than those experienced by patients receiving standard-of-care (SOC) treatment (physicians’ selection of olanzapine/quetiapine/risperidone). In a post-hoc analysis, projected risks for diabetes/coronary heart disease (CHD) were calculated using the Stern and Framingham models. These risks were used to estimate the difference in direct and indirect cost consequences of diabetes and CHD in schizophrenia patients treated with aripiprazole or SOC over a 10-year period, assuming risk of diabetes onset/CHD events remained linear. Diabetes costs were estimated from UKPDS and UK T2ARDIS studies, respectively, and CHD costs were estimated using prevalence data from the Health Survey of England and published literature. All costs were inflated to 2007 costs using the UK government’s Pay and Prices Index inflation rates. RESULTS: The number of avoided diabetes cases (23.4 cases/1000 treated patients) in patients treated with aripiprazole compared with SOC was associated with estimated total (direct and indirect) cost savings of 37,261,293 over ten years for the UK population. Similarly, the number of avoided CHD events (3.9 events/ 1000 treated patients) was associated with estimated total cost savings of 7,506,770 over ten years. CONCLUSION: Compared with SOC, the favourable metabolic profile of aripiprazole treatment may provide reductions in health and economic burden to schizophrenia patients and psychiatric health care services in the UK.