Abnormalities in Glucose Regulation During Antipsychotic Treatment of Schizophrenia

Abstract

Antipsychotic treatment of nondiabetic patients with schizophrenia can be associated with adverse effects on glucose regulation, which can vary in severity independent of adiposity and potentially increase long-term cardiovascular risk.

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

“…Our current results confirm the previously observed olanzapineinduced changes in glucose metabolism in patients with schizophrenia for healthy volunteers. The time for these metabolic changes to develop in healthy subjects was 10 days of oral intake only, a time period that is shorter than what has been demonstrated for humans before (McIntyre et al, 2001;Newcomer et al, 2002;Simpson et al, 2004).…”

“…These data indicate a significant decrease in whole body insulin sensitivity after oral intake of olanzapine, 10 mg/day for 10 days, after 80 min (po0.015), 100 min (po0.001), and 120 min (po0.0001) of glucose clamp. Effects of olanzapine and ziprasidone J Sacher et al population but is not associated with the risk of DM2 during antipsychotic treatment does not seem very likely given the evidence for a higher rather than a lower prevalence of DM2 in patients suffering from a major mental disorder in almost all data sets published to date (Mukherjee et al, 1996;Dixon et al, 2000;Okamura et al, 2000;Mokdad et al, 2001;Haupt and Newcomer, 2002;Newcomer et al, 2002;Ryan et al, 2003;Newcomer, 2004;Haupt et al, 2007). A second metabolic effect is depicted in Figure 2 and Table 2.…”

“…Newcomer et al (2002) tested oral glucose tolerance in chronically ill BMImatched patients with schizophrenia. His group found significant glucose elevations (1.0-1.5 SD) in olanzapinetreated patients compared to patients receiving typical antipsychotics as well as to untreated healthy controls.…”

“…Despite the welldescribed effects of adiposity on glucose metabolism in the general population (Welch et al, 1990;Karter et al, 1996;Macor et al, 1997;Mayer-Davis et al, 1997), the underlying mechanisms for potential adiposity-independent effects of atypical antipsychotics on insulin sensitivity have not been identified yet. While most studies report an increased risk for the development of metabolic abnormalities like glucose intolerance, insulin-resistance, and consequentially DM2 in rodent (Houseknecht et al, 2005) or dog studies as well as in patients with schizophrenia (Hedenmalm et al, 2002;Koller and Doraiswamy, 2002;Newcomer et al, 2002;Sernyak et al, 2002;Wilson et al, 2003;Kane et al, 2004;Simpson et al, 2004;Henderson et al, 2005, 2006, Haupt et al, 2007, patients with schizoaffective disorder (Wilson et al, 2003;Simpson et al, 2004) or patients with mood disorder (Gianfrancesco et al, 2003) treated with atypical antipsychotics, other studies fail to confirm these correlations for healthy subjects (Sowell et al, 2002(Sowell et al, , 2003 or patients with schizophrenia (Kinon et al, 2001).…”

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

“…In vitro (Melkersson et al, 2001;Melkersson, 2004;Johnson et al, 2005, but Melkersson andJansson, 2005) and preclinical studies (Ader et al, 2005) demonstrated that SGAs alter insulin secretion. However, in clinical samples, SGAs appear to spare pancreatic cells function (Ebenbichler et al, 2003;Laimer et al, 2005), but to change insulin signaling (Engl et al, 2005) and produce glucose intolerance and insulin resistance (Ebenbichler et al, 2003;Newcomer et al, 2002;Graham et al, 2005;Henderson et al, 2005). Although majority of glucose metabolism irregularities associated with SGAs therapy are secondary to weight gain (Newcomer, 2005), that causality could run in the opposite direction (Figure 4).…”