The Selective Serotonin Reuptake Inhibitors

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In 1987, the FDA approved the drug fluoxetine (Prozac) for use in the treatment of major depression. Fluoxetine belongs to a class of agents referred to as selective serotonin reuptake inhibitors (SSRIs). The SSRIs now include sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil), and citalopram (Celexa). Fluvoxamine is approved for use only in obsessive-compulsive disorder and is not discussed in this chapter.

With the introduction of the SSRIs, the safety and tolerability of antidepressants improved remarkably. As a class, these medications have little or no affinity for cholinergic, p-adrenergic or histamine receptors and do not interfere with cardiac conduction. They are well tolerated by patients with heart disease and by the elderly, who are especially sensitive to the anticholinergic and orthostatic effects of the tricyclic antidepressant agents (TCAs) and monoamine oxidase inhibitors (MAOIs).

The high degree of selectivity of SSRIs for the nerve terminal serotonin reuptake system has supported the hypothesis that these agents produce their therapeutic action through an ability to modulate serotonin neurotransmission in the brain. Chronic studies in animals have provided evidence for a cascade of altered synap-tic events, beginning with inhibition of 5-hydroxytrypta-mine (5-HT) neuronal reuptake (Fig. 33.1). Increased 5-HT levels activate 5-HT1A autoreceptors and result in a decrease in neuronal firing. Desensitization of this receptor results in enhanced serotonin release. The terminal 5-HT1B autoreceptors normally inhibiting release of serotonin also become desensitized. These events, triggered by a sustained inhibition of the nerve terminal serotonin reuptake system, ultimately cause a potentia-tion of serotonin neurotransmission at central synaptic

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How to Stop Your Depression Now

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