Clinical Guide to the Diagnosis and Treatment of Mental Disorders by First Michael B. Tasman Allan

Author:First, Michael B., Tasman, Allan
Language: eng
Format: epub
Publisher: John Wiley & Sons
Published: 2011-08-25T16:00:00+00:00

However, higher rates of diabetes have been reported from treatment with several SGAs, including clozapine, olanzapine, risperidone, and quetiapine. In 2003, an FDA warning for hyperglycemia and diabetes mellitus was added to the package insert of all SGAs. It stated that “hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with Schizophrenia and the increasing incidence of diabetes in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemiarelated adverse events in patients treated with the atypical antipsychotics. Precise estimates for hyperglycemiarelated adverse events in patients treated with atypical antipsychotics are not available.” Additional guidance is provided to clinicians regarding monitoring and management of hyperglycemic related events. The potential risk of treatment-emergent weight gain, diabetes (type II) and metabolic syndrome may result from changes in glucose metabolism and insulin resistance. In approximately 25–40% of the cases of hyperglycemia, insulin resistance appears to occur even in the absence of significant weight gain, raising some interesting questions about how these medications may interact with the insulin-glycemic control. An alternative hypothesis that may account for some of these cases is that patients were prediabetic or undiagnosed with diabetes prior to SGA administration.

Hyperlipidemia is commonly observed with SGA treatment, especially in women. Baseline data from the CATIE study suggest that the rate of diabetes mellitus was 12.5%, hyperlipidemia at 53%, and hypertension at 37%, but a significant number of these individuals were not receiving medical treatment for the same. At baseline, significantly large groups of subjects were already obese or overweight. Patients treated with olanzapine had the highest mean weight gain of 0.9 kg/month amongst all antipsychotic studied; about 30% subjects treated with olanzapine gained 7% or more weight from baseline compared with 7% to 16% with other treatment groups. Greater increases in glycosylated hemoglobin, total cholesterol, and triglycerides were observed with olanzapine compared to other study drugs. Improvement in each metabolic variablewas reported with ziprasidone treatment. In a subgroup of 689 subjects from the CATIE study, 41% subjects met criteria for metabolic syndrome at baseline. Schizophrenia is already associated with a high mortality rate and this dramatic increase in obesity and metabolic syndrome in this group further increases risk for medical morbidity and mortality. Moreover,heavy-smokingratesandunhealthylifestyle only compound the grim picture. Metabolic issues are also evident during treatment of first-episode patients with SGAs. Sharing this concern, numerous monitoring guidelines have been recommended by various groups and countries specifically suggesting assessments to be done at the time of starting antipsychotics, especially SGAs, and promoting ongoing assessments prospectively.

Amongst the SGAs, risperidone (and paliperidone), due to its potent dopamine D2 blockade, removes the inhibitory dopaminergic tone in the tuberoinfundibular neurons, resulting in a significant increase in prolactin levels. This increase in prolactin is significantly more than usually seen with the FGAs.

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