Insulin resistance during treatment with second generation antipsychotics

An increasing number of second generation antipsychotics have been introduced during the last decade. Though good efficacy and a lower potential to induce extrapyramidal symptoms have been demonstrated, these medications have other adverse events, including metabolic disturbances. One of these is insulin resistance. The mechanisms causing insulin resistance are still unclear and may involve any step of the insulin signalling pathway including alterations in insulin receptor kinetics and intracellular signal processing. It has been hypothesised that antipsychotics lead to insulin resistance via relevant pathways in muscle cells. Another, possibly independent mechanism leading to insulin resistance is antipsychotic induced weight gain. Insulin resistance leads to an increased production of insulin in beta-cells of the pancreas as a compensatory mechanism. If this compensatory mechanism is intact, which means that pancreatic function is not impaired and enough insulin is produced, manifest alterations of glucose metabolism are unlikely, but if the function of the beta cells is impaired, which has been hypothesised to happen during antipsychotic treatment, manifest diabetes could be the consequence. Insulin resistance has been found predominantly during treatment with clozapine and olanzapine.

Further research is needed to explore the risk for insulin resistance for all the new generation antipsychotics. Frequent monitoring of metabolic parameters with subsequent interventions, which may include a switch to another antipsychotic should prevent the risk of manifest diabetes in patients on antipsychotic medication.