Fluoxetine increases resting energy expenditure and basal body temperature in humans

Humans lose weight when administered fluoxetine, an inhibitor of serotonin reuptake by nerve terminals. To determine whether increased energy expenditure contributes to this weight loss we admitted 20 nondepressed obese women to a metabolic unit where they were randomly assigned to 3 wk of a 1.76-MJ/d formula diet and either 60 mg fluoxetine/d or a placebo. Resting energy expenditure of the control subjects fell below normal after 5.6 +/- 0.6 d of energy restriction, whereas that of the fluoxetine-treated subjects increased by 4.4 +/- 1.8% (P < 0.005) within 3 d of commencing treatment. This increased resting energy expenditure then reversed and fell below normal after 9.8 +/- 0.9 d of energy restriction. Basal body temperature of the control subjects decreased insignificantly during the period of energy restriction, but that of the fluoxetine-treated subjects increased by 0.28 +/- 0.10 degrees C (P < 0.05) within 3 d of commencing diet and drug treatment. Urinary norepinephrine excretion and the serum triiodothyronine concentration decreased equally in both groups. Despite identical energy intakes and equal nitrogen balance, the fluoxetine-treated subjects lost weight faster than the control subjects during the final week of energy restriction (P < 0.05). We propose that serotonin reuptake inhibition increases energy expenditure by increasing basal body temperature.