Relationship Between CYP 2D6 Metabolic Status and Sexual Dysfunction in Paroxetine Treatment

Žourková, Alexandra; Hadašová, Eva McCaskey

doi:10.1080/00926230290001565

Cited by 23 publications

(8 citation statements)

References 26 publications

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“…However, Bishop and colleagues have described evidence that genetic polymorphisms in the promoter regions of the 5‐HT 2A receptor gene or in the SERT gene may influence vulnerability to SSRI‐associated sexual dysfunction [62,63] but not all reports agree [64]. Other investigators have implicated individual differences in the effect of SSRIs on the P450 2D6 isoenzyme leading to accumulation of higher concentrations of the drugs [65]. Clearly, the ideal would be to differentiate those factors that are required for the therapeutic efficacy of SSRIs from those which lead to sexual side effects.…”

Section: Discussionmentioning

confidence: 99%

Sprague-Dawley and Fischer Female Rats Differ in Acute Effects of Fluoxetine on Sexual Behavior

Miryala

Hiegel

Uphouse

2013

The Journal of Sexual Medicine

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Introduction The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT1A receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT1A receptors holds for other rat strains is not known. Aim The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT1A receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined. Main Outcome Measures Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC50 for inhibition of lordosis behavior was determined. Methods Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI. Results In both the intact and the hormonally-primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose-dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally-primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT1A receptor agonist. Conclusions Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT1A receptor agonist. Fluoxetine’s inhibition of female rat sexual behavior may involve effects of the SSRI in addition to activation of the 5-HT1A receptor.

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Section: Discussionmentioning

confidence: 99%

Sprague-Dawley and Fischer Female Rats Differ in Acute Effects of Fluoxetine on Sexual Behavior

Miryala

Hiegel

Uphouse

2013

The Journal of Sexual Medicine

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“…Other drugs like citalopram, escitalopram, sertraline, and to a lesser extent fluoxetine and fluvoxamine are substrates for the cytochrome P450 2C19 isoenzyme and it is thought that polymorphisms encoding for this isoenzyme could also play a role in SD. However there is a lack of definitive evidence validating these findings [22][23][24].…”

Section: Pathophysiology Of Antidepressant Induced Sexual Dysfunctionmentioning

confidence: 95%

Sexual Dysfunctions in Depression

J¹,

Rao²,

Chandran³

et al. 2017

Clin Depress

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Sexual dysfunction is one of the common symptoms seen in depression. Presentations include decreased libido, erectile dysfunction, arousal difficulties and orgasm related dysfunctions. The probable causes of sexual dysfunction in such patients are complex and biological, psychological as well as psychosocial factors are likely to play an important role. Sexual dysfunction could also occur as an adverse effect of anti-depressants although it is difficult to establish whether the dysfunction is due to the illness or the medication. Awareness among professionals about sexual dysfunction is essential as it can have a profound impact in terms of relationship conflict, marital satisfaction, quality of life and compliance with treatment in patients with depression.

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“…Some have reported that UMs may have very low or undetectable concentrations of paroxetine with usual doses (Lam et al, 2002;Charlier et al, 2003). Data on the clinical implications are lacking, although one study (without pharmacokinetic assessment) suggested that sexual dysfunction was more frequent in those who were genotypically EMs, but who were phenotyped as PMs during treatment (17 of 24 patients or 71%) compared with those who were phenotyped as EMs (2 of 6 or 33%) (p ϭ 0.015) (Zourkova and Hadasova, 2002). However, it seems unlikely that knowledge of the CYP2D6 genotype will assist with dosing given the unpredictable phenocopying that occurs.…”

Section: Doxepin (Tertiary)/desmethyldoxepin (Secondary)mentioning

confidence: 99%