Effects of SNS Activation on SSRI-Induced Sexual Side Effects Differ by SSRI

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are associated with significant sexual side effects. By definition, all SSRIs increase overall serotonin (5HT) by binding to serotonin autoreceptors (5HTI A); however, each SSRI has a unique portfolio of secondary binding properties to other neurotransmitters such as norepinephrine (NE). As 5HTI A receptors mediate NE neurotransmission, SSRIs that are highly selective for 5HTI A are more likely to reduce NE efficiency; however, in SSRIs that are less selective for 5HTI A, this could be counteracted by secondary binding to NE. Norepinephrine is the major neurotransmitter of the sympathetic nervous system (SNS), which has been shown to mediate genital arousal in women; thus, it is possible that increasing SNS activity in women taking SSRIs that are highly selective for 5HTI A may counteract sexual side effects in those women. To test this hypothesis, we conducted a reanalysis of Meston (2004)’s 8-week, double-blind, cross-over, placebocontrolled study of the effects of ephedrine (50 mg taken 1 h prior to sexual activity) on self-reported sexual functioning of women taking paroxetine (N = 5), sertraline (N = 7), or fluoxetine (N = 7). As predicted, women taking SSRIs, which are highly selective for 5HTI A (sertraline, paroxetine), showed improvement in sexual arousal and orgasm. By contrast, women taking SSRIs, which are less selective for 5HTI A relative to NE (fluoxetine), showed no change or decrease in sexual functioning. These findings have implications for treating certain SSRI-induced sexual side effects.

The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning

“…The CS+ was followed by a set of 21 erotic pictures (100% reinforcement). Due to the clear association of serotonin to sexual processing and sexual motivation [Abler et al, ; Ahrold and Meston, ; Hull, ; Pfaus, ], we used erotic pictures as stimuli [Both et al, b; Hoffmann et al, ; Klucken et al, ]. All pictures depicted scenes with couples (always one male and one female) practicing vaginal intercourse in different positions.…”

Acute Exercise Improves Physical Sexual Arousal in Women Taking Antidepressants

“…In this study, 19 women receiving sertraline, paroxetine, or fluoxetine participated in an 8-week, randomized, crossover, placebo-controlled, at-home trial to determine if ephedrine, an adrenergic agonist, alleviated SSRI-induced sexual side effects [25]. In a reanalysis of the data, Ahrold and Meston [26] compared the effects of ephedrine on sexual side effects in the women taking either fluoxetine, which has secondary properties as a weak norepinephrine reuptake inhibitor [27–29] with the sexual side effects seen in the women taking sertraline or paroxetine, which do not act as norepinephrine reuptake inhibitors. The women taking sertraline or paroxetine had greater improvement of genital arousal and orgasm (relative to placebo) with ephedrine than did women taking fluoxetine.…”

Evaluating relationship between sexuality and mental health with the help of computers

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