Assessment of lipid response to acute olanzapine administration in healthy adults

BACKGROUND: Atypical antipsychotics (AAP) can induce hypertriglyceridaemia and type 2 diabetes. Weight gain contributes to these effects, but there is evidence that AAP can have acute metabolic effects on glycaemia independent of weight change. AIMS: We undertook a single‐blind crossover study in eight healthy volunteers to assess whether the AAP olanzapine acutely increases triglyceride and free fatty acid in response to a high‐fat oral load (50 g fat with no carbohydrate) and whether these effects are attenuated by the dopamine D2 receptor agonist bromocriptine. METHODS: Participants underwent three treatments in random order: Olanzapine 10 mg plus placebo (OL + PL), Olanzapine 10 mg plus bromocriptine 5 mg (OL + BR) and placebo plus placebo (PL + PL). RESULTS: Olanzapine increased plasma prolactin, an effect that was reversed by co‐administration of the D2 receptor agonist bromocriptine (P = .0002). There were no significant differences in postprandial triglyceride (P = .8), free fatty acid (P = .4) or glucose (P = .8). CONCLUSION: These results suggest that AAPs likely do not directly increase postprandial lipids but may do so indirectly via changes in body weight and/or glycaemia.