Fluoxetine: a five-year review

Depression is associated with significant morbidity, mortality, and economic cost. Although effective pharmacologic therapy has been available for nearly 40 years, most patients have been treated inadequately. The side effects associated with available antidepressants usually led to subtherapeutic dosing, premature discontinuation of therapy, or lack of patient compliance. The introduction in 1988 of fluoxetine hydrochloride, the first selective serotonin uptake inhibitor (SSUI) or selective serotonin reuptake inhibitor (SSRI) available in the United States, represented a major advance in the pharmacologic management of depression. Large-scale trials showed fluoxetine to be as effective as existing agents, but because of its selectivity, the side effects of fluoxetine treatment are generally mild and transient and rarely cause premature discontinuation of therapy. In clinical trials approximately twice as many patients discontinue treatment because of side effects with tricyclic antidepressants (TCAs) as with fluoxetine. In contrast to older agents fluoxetine requires no titration and can be dosed once daily. It is also safer in overdose than TCAs. Numerous clinical trials and widespread postintroduction clinical experience have demonstrated the advantages of fluoxetine compared with older antidepressants. It may also have some advantages over the two SSUIs that have followed thus far, sertraline and paroxetine, although comparative trials will be required to resolve this issue.