Chin Med J (Taipei) 1998;61:S159.

Treatment of Depression and Related Disorders: A Decade of Progress with Selective Serotonin Re-uptake Inhibitors (SSRIs)

David T. Wong

Lilly Neuroscience, The Lilly Research Laboratories, Eli Lilly and Company Indianapolis, Indiana 46285, U.S.A.

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) was first reported in brain following its discovery in serum by Page and colleagues (Twarog and Page, Am. J. Physiol. 175: 157, 1953). The function of 5-HT as a neurotransmitter was considered (Marrazzi and Hart, J. Nerv. Mental Dis. 122: 435, 1955) and distribution of separate neuronal tracks of the three monoamines, 5-HT, norepinephrine (NE) and dopamine (DA) in brain was demonstrated (Anden et al., Life Sci., 4: 1275, 1965). Presynaptic uptake specific for the three monoamines terminates their neurotransmitter functions. Fluoxetine was reported as a selective inhibitor of 5-HT uptake and considered therapeutically useful in treatment of depression (Wong et al., Life Sci. 15: 471, 1974). In animal studies, fluoxetine selectively inhibited 5-HT uptake without inhibiting uptake of NE or DA; increased 5-HT availability in brain and in turn promoted 5-HT neurotransmission. Fluoxetine also lacks interaction with receptors of serotonin or other neurotransmitters. In clinical studies, fluoxetine and its congeners sertraline, paroxetine and citalopram as a class of drugs known as SSRIs have been demonstrated efficacious for treatment of depression and related disorders (Stokes and Holtz, Clin. Therap. 19: 1135, 1997). In depressed patients, remitted from the treatment with SSRIs, would experience relapse of depressive symptoms upon abrupt depletion of the 5-HT precursor amino acid, tryptophan (Delgado, et al., Archs Gen Psychiat. 47: 411, 1990) demonstrating the dependence on synaptic availability of 5-HT for the antidepressive efficacy of the SSRIs. Fluoxetine and other SSRIs are known for the ease of once a day medication and benign profile of side effects and safety in patients. The use of SSRIs for treatment of depression associated with other medical illness including cancer, diabetes, heart disease and HIV-infection will be presented. The SSRIs have also been demonstrated to have efficacy for treatment of obsessive compulsive disorder, bulimia and panic disorder. Thus, enhancement of serotonergic neurotransmission by the SSRIs has benefited the treatment of depression and other psychiatric disorders.

Keywords: serotonin, uptake, depression, antidepressant

[Chin Med J (Taipei) 1998;61:S159.]