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Chapter 15. Paroxetine

Clifford J. Ehmke, M.D.; Charles B. Nemeroff, M.D., Ph.D.
DOI: 10.1176/appi.books.9781585623860.426832

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Excerpt

Paroxetine (Paxil) is classified as one of the serotonin reuptake inhibitors (SRIs) because of its potent inhibition of presynaptic serotonin (5-HT) uptake. It is also a relatively potent norepinephrine (NE) reuptake inhibitor, particularly at higher doses, leading some to argue for its inclusion in the growing class of acknowledged dual serotonin–norepinephrine reuptake inhibitors (SNRIs). Since its approval for the treatment of depression, paroxetine has been demonstrated to be effective and has been approved for a broad spectrum of anxiety disorders, including panic disorder, obsessive-compulsive disorder (OCD), social anxiety disorder, generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD). Moreover, studies have demonstrated the efficacy of paroxetine in premenstrual dysphoric disorder (PMDD), postmenopausal hot flashes, and child and adolescent OCD and social anxiety disorder. Paroxetine is still one of the most prescribed antidepressant medications in the United States because of its proven efficacy, as demonstrated in randomized, double-blind clinical trials, and its much improved tolerability compared with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Although paroxetine shares many characteristics with other members of the SRI class, its unique pharmacological characteristics and clinical database are reviewed, with particular attention to the clinical setting.

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FIGURE 15–1. Chemical structure of paroxetine.

FIGURE 15–2. Norepinephrine and serotonin uptake inhibition versus serum paroxetine concentration.Standard curves for paroxetine inhibition of NE (A) and 5-HT (B) resulting from NET and 5-HTT antagonism, respectively. Note that at 100 ng/mL of paroxetine, which represents a typical therapeutic dose, there is a 15% decrease in NE uptake and a 90% decrease in 5-HT uptake. Transporter inhibition occurs in a dose-dependent manner. 5-HT = serotonin; 5-HTT = serotonin transporter; NE = norepinephrine; NET = norepinephrine transporter.Source.Gilmor et al. 2002.

FIGURE 15–3. Paroxetine effect on interferon- (IFN-)–induced depression.Kaplan-Meier analysis of the percentage of patients in the placebo and paroxetine groups who were free of major depression (A) and of severe depression, requiring the discontinuation of IFN- (B).Source.Musselman et al. 2000.
Table Reference Number
TABLE 15–1. Inhibition constants (Ki, nmol/L) of various antidepressants for various transporters and receptors in human and animal cells
Table Reference Number
TABLE 15–2. Potential drug–drug interactions involving paroxetine

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Paroxetine is approved by the U.S. Food and Drug Administration (FDA) for treatment of which of the following anxiety disorders?
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Which of the following is a characteristic of paroxetine’s pharmacokinetic profile?
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Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 47.  >
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Paroxetine approval. Am J Nurs 2014;114(1):10.doi:10.1097/01.NAJ.0000441774.81603.dd.
Antidepressants and suicide attempts in children. Pediatrics 2014;133(2):204-10.doi:10.1542/peds.2013-0923.
 
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