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15th European Congress of Psychiatry

Madrid, Spain / March 17-21, 2007

Given the 15-year shorter life expectancy of a schizophrenic patient, approximately 40% of this difference can be accounted for by accidents and a suicide rate 20 times higher than average. The remainder is explained by a higher prevalence of physical illness. According to Dr. Stefan Leucht, Assistant Professor, Psychiatry and Psychotherapy, Technische Universität, Munich, Germany, “What we had been lacking until recently was a review of the comorbidities while these patients are still alive, and this is important because it means that an intervention is possible.”

He noted, “The big health issues are nutritional and metabolic diseases and their associated cardiovascular [CV] problems.” CV disease (CVD) is more than twice as prevalent in patients with schizophrenia than in the general population. It is also the most frequent cause of death. Viral diseases (particularly HIV infection), respiratory illnesses, urological and gynecological diseases, obstetric complications and polydipsia are also more common among the mentally ill.

Some studies have found a lower incidence of certain health issues in this patient group. For example, musculoskeletal complaints such as nonspecific back pain and arthrosis were reported less frequently than in the general population. Dr. Leucht remarked that this finding was more likely due to underreporting.

Dr. Marc De Hert, University Psychiatric Center, Katholieke Universiteit Leuven, Belgium, added, “There is also a very important problem of limited access to medical care… the quality of care between people with and without mental illness can be quite different.”

Cardiovascular and Metabolic Disease

Elevated rates of CVD in patients with schizophrenia may be linked to a higher than average incidence of traditional risk factors such as obesity (42% higher prevalence of body mass index >27), lipid abnormalities, hypertension, metabolic syndrome (prevalence >50% vs. >25% in the general population), physical inactivity and smoking (more than 50% of schizophrenic patients are smokers) (Hennekens et al. Am Heart J 2005;150:1115-21). In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), approximately 20% of patients had hypertension, 14% hyperlipidemia and 10% diabetes. According to data from Belgium presented by Dr. De Hert, diabetes is four to five times more prevalent in schizophrenic patients aged 15 to 65 compared with age-matched controls, and metabolic syndrome (the constellation of obesity, hypertension, elevated fasting plasma glucose and abnormal levels of triglycerides and HDL-C) approximately twice as prevalent. Similarly, a comparison of schizophrenic patients in CATIE with randomly selected matched subjects from the National Health and Nutrition Examination Survey (NHANES) determined that a diagnosis of metabolic syndrome was twice as likely in the former. In men, the prevalence was 36% in patients and 19.7% in controls; the figures were 51.6% and 25.1% in women (McEvoy et al. Schizophr Res 2005;80:19-32).

Dr. De Hert used data from the Framingham study to explain the gradient of risk with accumulating risk factors. While smoking approximately doubles a patient’s risk of coronary heart disease, the additive factors of obesity and hyperlipidemia quadruples the risk; the addition of diabetes and hypertension raises the relative risk to 12 (Wilson et al. Circulation 1998; 97:1837-47). He used these data to link the discussion towards pharmacological choices for schizophrenic patients and how they can affect CV risk.

Antipsychotics and Cardiovascular Risk

Second-generation or atypical antipsychotics are now widely favoured over conventional agents due to their lower propensity to cause extrapyramidal symptoms and tardive dyskinesia. However, many of the newer agents are associated with adverse effects that have CV implications, including weight gain, altered glucose metabolism (independent of changes in adiposity) and dyslipidemia.

In a study by Allison et al. (J Clin Psychiatry 2001; 62(suppl 7):22-31), weight gain 4 to 10 weeks after initiation of antipsychotic treatment was > 4 kg for clozapine or olanzapine, 2.1 kg with risperidone and <0.04 kg for ziprasidone. “You get a more frightening picture if you look at weight gain in the long run. There are agents that are associated with minimal weight gain and others that cause large weight gains,” remarked Dr. De Hert.

He also presented CATIE long-term data on the effects of various antipsychotic agents on CV risk (Lieberman et al. N Engl J Med 2005;353:1209-23). In this analysis, weight gain ranged from 15 to 25 lbs. with olanzapine to approximately 7.5 lbs. with quetiapine and <5 lbs. with risperidone, amisulpride, aripiprazole and ziprasidone (Figure 1). Patients taking olanzapine vs. the other agents were more likely to discontinue treatment due to weight gain or adverse effects consistent with the metabolic syndrome. Furthermore, among the agents evaluated, ziprasidone led to favourable changes to glycosylated hemoglobin, triglycerides and total cholesterol.

Figure 1. One-Year Weight Gain While on Treatment with an Antipsychotic

Data presented here by Dr. Emilio Sacchetti, School of Medicine, University of Brescia, Italy, and colleagues bolster the CATIE findings in their one-year, open-label extension of the double-blind, clozapine-controlled MOZART (Monitoring Oral Ziprasidone as Rescue Therapy in Neuroleptic-Resistant/Intolerant Patients) study. Original MOZART data showed that ziprasidone exhibited comparable efficacy to clozapine over 18 weeks but had a better safety profile. The efficacy observed during the primary phase of the double-blind study was generally maintained during the extension phase. Moreover, in comparison with the core study, the investigators documented favourable changes in weight, cholesterol, triglycerides and glucose levels in patients receiving ziprasidone 80 to 160 mg/day. Similarly, several published reports indicate there is weight loss and a low incidence of metabolic syndrome with aripiprazole vs. olanzapine.

Addressing the Risk

CV disease and risk factors and other physical health issues are often undermonitored and inadequately treated in patients with schizophrenia. Speakers here stressed that individuals with schizophrenia should be assessed before and monitored during treatment to ensure such modifiable risk factors as weight gain, hypertension, dyslipidemia, glucose abnormalities, metabolic syndrome or diabetes are detected and addressed with practical lifestyle measures or appropriate treatment. Interestingly, relatively few psychiatrists regularly measure or monitor their patients’ risk factors. For example, in a survey of 147 clinicians, more than 50% said they obtained a blood pressure measurement at fewer than half of patient visits; between 60 and 70% said they seldom sought evaluation of fasting blood glucose or lipids; very few measured their patients’ waist circumference at initiation of antipsychotic therapy or as part of ongoing monitoring (Buckley et al. Schizophr Res 2005;79:281-8).

Current recommendations by the American Diabetes Association/American Psychiatric Association (ADA/APA) (Diabetes Care 2004;27:596-601) also indicate that clinicians should take into account a patient’s baseline CV risk and the importance of cardiometabolic adverse effects when selecting an atypical antipsychotic. Weight gain of ³6% of baseline body weight or worsening glycemia or dyslipidemia point to the need to reassess therapy and consider switching the patient to an antipsychotic less likely to cause weight gain or diabetes.

Summary

Schizophrenic patients are far more likely to suffer from comorbid conditions that negatively affect their life expectancy. CV risk factors, including metabolic syndrome, are more prevalent among this patient group than the general population. Treating physicians should ensure adequate screening to detect modifiable CV risk factors and manage them appropriately where necessary.