Antipsychotic therapy forms the cornerstone of treatment for people with severe mental illness. Second-generation (atypical) antipsychotics are associated with a significantly lower incidence of extrapyramidal symptoms than the typical, first-generation agents; however, changes in metabolic variables -- including impaired glucose metabolism, diabetes mellitus, weight gain and dyslipidaemia -- have been reported during treatment with second-generation antipsychotics. Understanding any potential link between antipsychotic treatment and the incidence of these events is complicated by the increasing prevalence of obesity and diabetes occurring in the general population and the increased risk of diabetes and changes in metabolic variables in people with schizophrenia. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose level appears to fall on a continuum, with olanzapine appearing to have a greater association than some other atypical antipsychotics. The PubMed database was used to search for publications that included any information on measures of changes in weight, body mass index (BMI) and/or metabolic variables in randomized studies of olanzapine published between 1992 and 2010. In long-term (≥48 weeks) studies of olanzapine, the mean weight gain was 5.6 kg (last observation carried forward; median exposure 573 days). The proportions of patients who gained at least 7%, 15% or 25% of their baseline weight with long-term exposure were 64%, 32% and 12%, respectively. Some studies have suggested that weight gain early during the course of olanzapine treatment may predict clinically significant weight gain following long-term exposure to the drug. Changes in metabolic variables, such as elevated indices of glucose metabolism and triglyceride level, have also been observed during treatment with olanzapine. Consensus guidelines emphasize the importance of appropriate baseline screening and ongoing monitoring of weight gain and metabolic variables for people receiving all antipsychotic treatments. Long-term weight management programmes have been shown to reduce weight gain in some patients.

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