Yes, fluoxetine is a selective serotonin reuptake inhibitor (SSRI).
Fluoxetine is definitively classified as an SSRI, as confirmed by both FDA drug labeling and major clinical guidelines. 1
Mechanism of Action
The FDA drug label explicitly states that fluoxetine's "antidepressant, antiobsessive compulsive, and antibulimic actions are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin." 1 Clinical studies at therapeutic doses demonstrate that fluoxetine blocks serotonin uptake into human platelets, and animal studies confirm it is a much more potent inhibitor of serotonin reuptake than norepinephrine reuptake. 1
Clinical Classification
Multiple authoritative sources consistently categorize fluoxetine as an SSRI:
American College of Physicians guidelines (2008) list fluoxetine among the selective serotonin reuptake inhibitors when discussing second-generation antidepressants 2
Mayo Clinic Proceedings guidelines (2016) explicitly state: "There is no question that selective serotonin reuptake inhibitors (SSRIs) have transformed the lives of patients with major depressive disorder" and identify fluoxetine (Prozac) as the drug that "ushered in a new era of prescription pharmacology" 3
Key Distinguishing Features
Unlike tricyclic antidepressants, fluoxetine binds much less potently to muscarinic, histaminergic, and α1-adrenergic receptors, which explains its more favorable side effect profile. 1 This selective action on serotonin reuptake, rather than multiple neurotransmitter systems, is what defines it as an SSRI rather than a non-selective antidepressant.
The classification is unambiguous across FDA labeling, clinical practice guidelines, and the medical literature—fluoxetine is a prototypical SSRI.