European Neuropsychopharmacology (v.16, #S3)

Contents (iii).

Patients with schizophrenia have increased rates of morbidity and mortality compared with the general population, primarily due to cardiovascular disease. Thus there is an increasing need for clinicians in the psychiatric field to recognise and address cardiovascular risk factors such as abdominal obesity, dyslipidaemia, high blood pressure and elevated fasting blood glucose levels that contribute to this long-term health burden. The combination of three or more of these risk factors leads to a diagnosis of metabolic syndrome, further predisposing individuals to cardiovascular disease. A cluster of risk factors, such as in the metabolic syndrome, is being increasingly seen in patients with schizophrenia. Abdominal obesity is a key contributor to overall cardiovascular risk and is a particularly important consideration in schizophrenia as some atypical antipsychotics are associated with drug-induced weight gain. Lifestyle factors such as smoking, lack of exercise and poor diet undoubtedly contribute further. Psychiatrists need to be aware of metabolic risk when initiating treatment in patients with schizophrenia and should take steps to identify and monitor patients. A first step is to establish a risk profile for the patient based on medical, lifestyle and genetic factors, and measurement of waist circumference is a good indicator of overall cardiovascular and metabolic risk. Strategies recommended to reduce risk include promoting healthy lifestyle/behavioural habits and close monitoring of weight, glucose, and lipid profiles both before and during treatment. Established risk factors should also be considered when selecting the most appropriate antipsychotic medication for an individual patient, based on differences in the potential effect of individual medications to induce weight gain, risk of diabetes or worsening lipid profile.
Keywords: Abdominal adiposity; Atypical antipsychotic; Cardiovascular disease; Metabolic syndrome; Schizophrenia;

Treatment dissatisfaction and discontinuation continue to limit the long-term treatment of patients with schizophrenia. Schizophrenia comprises a wide spectrum of symptoms, including hallucinations, delusions, hostility, cognitive deficits, and depression and anxiety symptoms. Medication is often effective in the treatment of the positive and hostility symptoms of schizophrenia, but less effective on other symptoms of the disease i.e. negative, affective and cognitive symptoms. However, each one of these symptoms can impinge on the functionality of the patient and decrease their quality of life. For example, negative and affective symptoms may lead to low self-esteem and depression, while cognitive deficits are a major impediment to social and vocational rehabilitation. Even when therapy does address the spectrum of symptoms, often the side effects are severe and may contribute to patient non-compliance or withdrawal of therapy, as patients prefer to experience their disease symptoms rather than drug-induced adverse effects. Optimisation of long-term therapy to overcome these issues is now the challenge for antipsychotic therapy. Recent advances in the development of newer atypical antipsychotics bring us closer to achieving the correct balance between long-term efficacy, tolerability and patient function. Atypical antipsychotics have been shown to be effective for the treatment of positive, negative, affective and cognitive symptoms of schizophrenia. In addition, their advancing mechanisms of action provide advantages over the older agents in terms of long-term tolerability. The use of atypical agents to address the full range of psychotic symptoms with minimal adverse effects should ensure improved functionality and an improved patient quality of life in patients with schizophrenia: both can be regarded as positive reinforcers for long-term compliance.
Keywords: Atypical antipsychotic; Psychotic symptoms; Schizophrenia; Treatment optimisation;

Patients with schizophrenia and their physicians face a number of challenges, such as long-term control of symptoms, maintaining cognitive function and subjective well-being, and preventing relapse. While randomised, placebo-controlled trials and open-label extensions can provide valuable information about the long-term efficacy and tolerability of newer antipsychotic agents, they cannot address all the variables that may affect treatment outcome. Factors such as cognitive function, antipsychotic side effects, patients' attitudes to medication and subjective well being can all affect the results of treatment in real-life clinical practice. Moreover, the patient cohorts enrolled in clinical trials are often not reflective of the wider population with schizophrenia. For example, patients with conditions such as anxiety and panic disorders or comorbid substance abuse, as well as those with severe illness and patients from certain ethnic or age groups, may often be excluded from clinical trials. In addition, patients themselves may refuse to participate in placebo-controlled studies because of a fear of being under-treated. Naturalistic studies are, therefore, an important means of providing additional data on the safety and effectiveness of antipsychotic agents in ‘real-world’ settings. Studies such as the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, the Schizophrenia Outpatient Health Outcomes (SOHO) study and the Broad Effectiveness Trial with Aripiprazole (BETA) studies, together with large-scale database analyses, are now producing results supplementary to those observed in long-term, open-label extension studies. Such naturalistic studies will continue to provide important data on the real-world effectiveness of atypical antipsychotics with respect to key outcomes such as treatment continuation and prolonged recovery.
Keywords: Schizophrenia; Naturalistic; Atypical antipsychotics; Outcomes;

Metabolic abnormalities such as obesity, diabetes and dyslipidaemia increase the risk of cardiovascular disease, as well as a number of other adverse long-term health consequences. There is increasing evidence from case studies, retrospective analyses and clinical trials to suggest that second-generation antipsychotics can increase the risk of metabolic abnormalities in patients with schizophrenia, with indications that the level of risk may vary among antipsychotic medications. Comparison of weight gain data for the second-generation antipsychotics provides strong evidence to indicate differences in the weight gain liability, with clozapine and olanzapine being associated with the greatest weight gain over 1 year. Data suggest that these treatment-induced changes in weight are primarily responsible for treatment-related changes in glucose metabolism; however, there is also evidence to suggest that some impairments in glucose metabolism may be independent of adiposity. Studies investigating the effects of atypical antipsychotics on glucose metabolism have used a number of techniques of varying sensitivity and quality in an attempt to assign causality. Recent studies using gold standard methodologies, for both insulin sensitivity and adiposity, have shown that psychiatric patients receiving antipsychotics are at least as sensitive to the adverse effects of adiposity on glucose and lipid metabolism as non-psychiatric controls. This demonstrates the importance of weight gain prevention in psychiatry to help reduce long-term risk. There is also growing evidence to suggest that the differential effects of second-generation antipsychotics on metabolic parameters also result in differences in the risk of metabolic syndrome, with olanzapine having a significantly higher risk than either aripiprazole or ziprasidone. This differential risk highlights the need for adequate monitoring in patients receiving treatment with second-generation antipsychotics and careful selection of treatment in high-risk patients.
Keywords: Atypical antipsychotic; Glucose metabolism; Metabolic syndrome; Schizophrenia; Weight gain;

Foreword by René Kahn (v).