A 2022 study which examined the health insurance claims of over 2 million Americans who began taking oxycodone while using SSRIs between 2000 and 2020, found that patients taking paroxetine or fluoxetine had a 23% higher risk of overdosing on oxycodone than those using other SSRIs.There is also the potential for interaction with highly protein-bound drugs due to the potential for fluoxetine to displace said drugs from the plasma or vice versa hence increasing serum concentrations of either fluoxetine or the offending agent. Pharmacology
Pharmacodynamics
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and does not appreciably inhibit norepinephrine and dopamine reuptake at therapeutic doses. It does, however, delay the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Large doses in rats have been shown to induce a significant increase in synaptic norepinephrine and dopamine. Thus, dopamine and norepinephrine may contribute to the antidepressant action of fluoxetine in humans at supratherapeutic doses (60–80 mg). This effect may be mediated by 5HT2C receptors, which are inhibited by higher concentrations of fluoxetine.Fluoxetine increases the concentration of circulating allopregnanolone, a potent GABAA receptor positive allosteric modulator, in the brain. Norfluoxetine, a primary active metabolite of fluoxetine, produces a similar effect on allopregnanolone levels in the brains of mice. Additionally, both fluoxetine and norfluoxetine are such modulators themselves, actions which may be clinically-relevant.In addition, fluoxetine has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine.
Politics
During the 1990 campaign for Governor of Florida, it was disclosed that one of the candidates, Lawton Chiles, had depression and had resumed taking fluoxetine, leading his political opponents to question his fitness to serve as Governor. Other uses
The antibacterial effect in described above (§ Environmental effects) could be applied against multiresistant biotypes in crop bacterial diseases and bacterial aquaculture diseases. In a glucocorticoid receptor-defective zebrafish mutant (Danio rerio) with reduced exploratory behavior, fluoxetine rescued the normal exploratory behavior. This demonstrates relationships between glucocorticoids, fluoxetine, and exploration in this fish.Fluoxetine has an anti-nematode effect. Choy et al., 1999 finds some of this effect is due to interference with certain transmembrane proteins. References
Further reading
Shorter E (2014). "The 25th anniversary of the launch of Prozac gives pause for thought: where did we go wrong?". The British Journal of Psychiatry. 204 (5): 331–2. doi:10.1192/bjp.bp.113.129916. PMID 24785765. Haberman C (21 September 2014). "Selling Prozac as the Life-Enhancing Cure for Mental Woes". The New York Times. External links

"Fluoxetine". Drug Information Portal. U.S. National Library of Medicine. "Fluoxetine hydrochloride". Drug Information Portal. U.S. National Library of Medicine.