Fluoxetine: A Serotonin‐specific, Second‐generation Antidepressant

Fluoxetine is a bicyclic antidepressant that is a specific and potent inhibitor of the presynaptic reuptake of serotonin. It has essentially no effect on the reuptake of norepinephrine or other neurotransmitters. Similarly, it has negligible binding affinity for neurotransmitter receptor sites. It is well absorbed after oral administration, with absolute bioavailability in dogs of approximately 72 ± 27.6%. The mean T_max is between 4 and 8 hours, and it is approximately 94% protein bound. After a single dose, the elimination half‐life is 1–3 days. After long‐term administration, the elimination half‐life averages 4 days. Its pharmacokinetics appear nonlinear. It is metabolized to an active metabolite norfluoxetine, which is also specific for the inhibition of serotonin reuptake. Norfluoxetine's elimination half‐life averaged 7 days after long‐term administration. Little is known about potential drug interactions; however, fluoxetine appears to have minimal clinically relevant interactions. Fluoxetine is indicated in the treatment of major depression. Its efficacy is comparable to the tricyclics and it has a similar onset of action. Although doses as high as 80 mg/day have been used, the optimal dosage range appears to be 20–40 mg once daily. Fluoxetine has been used with success in obsessive‐compulsive disorder and intention myoclonus, however, its use in these disorders remains investigational. The frequency of side effects is low and dose related; the most common effects are nausea, anxiety, insomnia, anorexia, diarrhea, nervousness, and headache. Eight reports of intentional overdose with fluoxetine alone resulted in no deaths and mild adverse effects. It will be marketed as 20‐mg capsules under the brand name of Prozac. Although fluoxetine should be added to formularies, its use should be reserved for treatment of those who do not respond to or do not tolerate tricyclic agents. 1987 Pharmacotherapy Publications Inc.