Increased food intake and energy expenditure following administration of olanzapine to healthy men.
Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ-induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double-blind, crossover study. In periods 1 and 2, subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching PBO separated by a minimum 12-day washout. Twenty-four hour food intake (FI), resting energy expenditure (REE), activity level, metabolic markers, and insulin sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21 completed both periods. Mean age and BMI were 27 years (range: 18-49 years) and 22.6 +/- 2.2 kg/m(2), respectively. Relative to PBO, OLZ resulted in a 2.62 vs. 0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal) increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE relative to PBO (113 kcal/day, P = 0.003). Significant increases in triglycerides, plasminogen activator inhibitor-I (PAI-I), leptin, and tumor necrosis factor-alpha (TNF-alpha) were observed. No significant differences in activity level or IS were observed. This study provides evidence that OLZ pharmacology drives the early increase in weight through increased FI, without evidence of decreased energy expenditure (EE), activity level, or short-term perturbations in IS.
Pfizer Global Research and Development, New London, Connecticut, USA. robert.j.fountaine@pfizer.com
Robert J
RJ
Fountaine
Ann E
AE
Taylor
James P
JP
Mancuso
Frank L
FL
Greenway
Lauri O
LO
Byerley
Steven R
SR
Smith
Marlene M
MM
Most
David A
DA
Fryburg
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001481:Basal Metabolism / Q000187:drug effects*; D001569:Benzodiazepines / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood*; D004311:Double-Blind Method; D002149:Energy Intake / Q000187:drug effects*; D015444:Exercise; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012016:Reference Values; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain / Q000187:drug effects*; D055815:Young Adult
D014150:Antipsychotic Agents; D015415:Biomarkers; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D001569:Benzodiazepines; D000077152:Olanzapine