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Chapter 13. Fluoxetine

Janos Zahajszky, M.D.; Jerrold F. Rosenbaum, M.D.; Gary D. Tollefson, M.D., Ph.D.
DOI: 10.1176/appi.books.9781585623860.410528

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Excerpt

The introduction of fluoxetine as the first selective serotonin reuptake inhibitor (SSRI) approved in the United States, initially for the treatment of depression, represents an important advance in psychopharmacology and has been the catalyst for much subsequent basic and clinical research. Considerable evidence has demonstrated that fluoxetine, like other SSRIs, has a broad spectrum of clinical indications. There is a consensus, however, that the commercial success of fluoxetine (and subsequently marketed SSRIs) derived from its advantageous safety profile, which propelled SSRIs to dominance in the antidepressant drug market. Fluoxetine, under the brand name Prozac, became a cultural icon—a symbol of the growth in antidepressant prescribing and depression recognition. Consequently, it also became a focus of controversies about rare events attributed to side effects, such as violent acts and suicide, and a symbol of the medicalization of mental health concerns. Fluoxetine was also the first of the SSRI blockbuster drugs to become available in generic form; ironically, with decreased cost has come decreased market share, likely reflecting the reduction in marketing and availability of office samples. Although SSRIs, as a class, share several common features, individual agents, such as fluoxetine, also have unique characteristics.

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FIGURE 13–1. Serotonin (5-HT) neuron showing the main steps in the life cycle of 5-HT and the sites at which drugs act.For clarity, drugs acting at 5-HT receptors have been omitted. 5-HIAA = 5-hydroxyindoleacetic acid; 5-HTP = 5-hydroxytryptophan; MAO = monoamine oxidase; MAOI = monoamine oxidase inhibitor.Source. Reprinted from Marsden CA: "The Neuropharmacology of Serotonin in the Central Nervous System," in Selective Serotonin Re-Uptake Inhibitors. Edited by Feighner JP, Boyer WF. Chichester, England, Wiley, 1991, pp. 11–35. Copyright 1991, John Wiley and Sons Limited. Reproduced with permission.

FIGURE 13–2. Chemical structures of selective serotonin reuptake inhibitors and some tricyclic antidepressants.

FIGURE 13–3. Chemical structure of fluoxetine.
Table Reference Number
TABLE 13–1. Inhibition of [3H]monoamine uptake into rat brain synaptosomes in vitro
Table Reference Number
TABLE 13–2. A comparison of several selective serotonin reuptake inhibitors

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Sample questions:
1.
Which of the following statements concerning the structure and activity of fluoxetine is true?
2.
Fluoxetine is metabolized by the liver’s cytochrome P450 (CYP) system to its active metabolite, norfluoxetine. Based on norfluoxetine’s half-life, how long would you need to wait, after discontinuing fluoxetine, before beginning a patient on a monoamine oxidase inhibitor (MAOI)?
3.
The U.S. Food and Drug Administration (FDA) has approved fluoxetine for the treatment of all of the following disorders except
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