Effects of olanzapine and haloperidol on the metabolic status of healthy men.
BACKGROUND
A large body of evidence suggests that antipsychotic drugs cause body weight gain and type 2 diabetes mellitus, and atypical (new generation) drugs appear to be most harmful. The aim of this study was to determine the effect of short-term olanzapine (atypical antipsychotic drug) and haloperidol (conventional antipsychotic drug) treatment on glucose and lipid metabolism.


METHODS
Healthy normal-weight men were treated with olanzapine (10 mg/d; n = 7) or haloperidol (3 mg/d, n = 7) for 8 d. Endogenous glucose production, whole body glucose disposal (by [6,6-(2)H(2)]glucose dilution), lipolysis (by [(2)H(5)]glycerol dilution), and substrate oxidation rates (by indirect calorimetry) were measured before and after intervention in basal and hyperinsulinemic condition.


RESULTS
Olanzapine hampered insulin-mediated glucose disposal (by 1.3 mg x kg(-1) x min(-1)), whereas haloperidol did not have a significant effect. Endogenous glucose production was not affected by either drug. Also, the glycerol rate of appearance (a measure of lipolysis rate) was not affected by either drug. Olanzapine, but not haloperidol, blunted the insulin-induced decline of plasma free fatty acid and triglyceride concentrations. Fasting free fatty acid concentrations declined during olanzapine treatment, whereas they did not during treatment with haloperidol.


CONCLUSIONS
Short-term treatment with olanzapine reduces fasting plasma free fatty acid concentrations and hampers insulin action on glucose disposal in healthy men, whereas haloperidol has less clear effects. Moreover, olanzapine, but not haloperidol, blunts the insulin-induced decline of plasma free fatty acids and triglyceride concentrations. Notably, these effects come about without a measurable change of body fat mass.
Vidarsdottir
Solrun
S
Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
de Leeuw van Weenen
Judith E
JE
Frölich
Marijke
M
Roelfsema
Ferdinand
F
Romijn
Johannes A
JA
Pijl
Hanno
H
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D006262:Health; D006304:Health Status; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D000077152:Olanzapine; D010084:Oxidation-Reduction / Q000187:drug effects; D055815:Young Adult
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D005947:Glucose; D006220:Haloperidol; D000077152:Olanzapine