Possible Interaction: Fluoxetine and Progesterone

“ Fluoxetine competitively inhibited CYP2D4-mediated PROG 21-hydroxylation and increased both Km and Vmax values of CYP2D6-mediated PROG 21-hydroxylation.”

“These results indicate that psychotropic drugs including fluoxetine affected the metabolism of neurosteroids, such as PROG and ALLO in the brain, suggesting that the regulation of the neurosteroid levels is modified by central nervous system-active drugs that inhibit brain CYP2D isoforms.”

“In the third experiment, the ability of progesterone to reduce the acute response to fluoxetine was evaluated.”

“WAY100635 attenuated the effect of fluoxetine; prior treatment with fluoxetine decreased 8-OH-DPAT's potency in reducing lordosis behavior; and progesterone shifted fluoxetine's dose-response curve to the right.”

“ Fluoxetine treatment also elongated the estrous cycle, reduced blood levels of progesterone , and eliminated lordosis behavior.”

“Prior administration of GABA(A) receptor agonist muscimol or neurosteroid ALLO or progesterone , a precursor of ALLO or neurosteroidogenic drugs like FGIN 1-27, an agonist at the mitochondrial diazepam binding inhibitor receptor (MDR) or metyrapone, an 11beta-hydroxylase inhibitor, significantly potentiated the anticonvulsant effect of fluoxetine.”

“ Chronic fluoxetine treatment (5 mg/kg/day) completely blocked the increased secretion of corticosterone and progesterone in response to the acute fluoxetine challenge.”

“There was a trend for more women on fluoxetine to report improvement in luteal phase SDD compared to women on placebo (P=0.057).”