Prevention of the reuptake of monoamine transmitters such as serotonin, which potentiates their action in the brain, appears to be associated with antidepressant activity. SSRIs such as fluoxetine preferentially inhibit the reuptake of serotonin compared with noradrenaline, and have limited direct action at other neurotransmitter sites, including muscarinic receptors. They therefore cause fewer antimuscarinic or sedative side-effects than the tricyclic antidepressants and are less cardiotoxic.
Fluoxetine is readily absorbed from the gastrointestinal tract with peak plasma concentrations appearing about 6 to 8 hours after oral doses. Systemic bioavailability does not appear to be affected by food. Fluoxetine is extensively metabolised, by demethylation, in the liver to its primary active metabolite norfluoxetine. Excretion is mainly via the urine. Fluoxetine is widely distributed throughout the body. Fluoxetine has a relatively long elimination half-life of about 1 to 3 days after acute use and 4 to 6 days after long-term use; that of its metabolite, norfluoxetine, is even longer, being about 4 to 16 days. These long half-lives have clinical implications. Steady-state plasma concentrations will only be attained after several weeks. Additionally, fluoxetine and its metabolites may persist for a considerable time after treatment, and this has led to precautions concerning the subsequent use of other serotonergic drugs.
Fluoxetine and norfluoxetine are distributed into breast milk.
Deprozet® provides an alternative for the treatment of depression. It is also used as part of the management of obsessive compulsive disorders with or without agoraphobia, and as part of the management of bulimia nervosa. It is also used in the treatment of premenstrual dysphoric disorder.