The antidepressant fluoxetine (Prozac®) modulates serotonin signaling to alter maternal peripartum calcium homeostasis

Abstract Antidepressant use is two-fold greater in women compared to men; however, most studies have been performed in male subjects. We aimed to understand the impact of selective serotonin reuptake inhibitors (SSRI, most used antidepressants) on calcium homeostasis and steroid metabolism during the peripartum period. Pregnant sheep (n = 10/group) were treated with vehicle or fluoxetine (most common SSRI) during the last month of gestation. Fluoxetine treatment decreased circulating calcium prior to parturition (8.7 ± 0.1 mg/dL vs 8.2 ± 0.1 mg/dL; P = 0.07). In the control group, total calcium decreased after parturition corresponding to the onset of lactogenesis followed by increase in calcium by day 2 postpartum. Interestingly, this normal transient decrease in circulating calcium was absent in fluoxetine-treated ewes. The steroids cortisol and progesterone were not altered by fluoxetine treatment whereas estradiol was decreased after the onset of treatment (12.4 ± 1.3 vs 9.1 ± 1.2 pg/mL, P = 0.05) and prior to parturition (38.1 ± 8.1 vs 22.3 ± 4.2 pg/mL, P = 0.03). Our hypothesis was supported that fluoxetine treatment alters circulating concentrations of calcium in the peripartum period; however, we surprisingly observed a decrease in estradiol concentrations contrary to reports in in vitro studies.