Abstract
RationaleSexual side effects are commonly associated with selective serotonin reuptake inhibitor (SSRI) treatment. Some evidence suggest that activation of 5-HT1A receptors attenuates SSRI-induced sexual dysfunction.ObjectiveThis study in male rats compared the effects of vilazodone, an antidepressant with SSRI and 5-HT1A receptor partial agonist activity, with other prototypical SSRIs (citalopram and paroxetine) on sexual behaviors and 5-HT receptors (5-HT1A and 5-HT2A) and transporter (5-HTT) levels in select forebrain regions of the limbic system using quantitative autoradiography.MethodsRats received vilazodone (1, 3, and 10 mg/kg), citalopram (10 and 30 mg/kg), or paroxetine (10 mg/kg) treatment for 14 days. Sexual behaviors (frequency and latency of mounts, intromissions, and ejaculations) were measured in the presence of an estrous female rat on days 1 (acute), 7 (subchronic), and 14 (chronic).ResultsVilazodone-treated rats exhibited no sexual dysfunction compared with controls; in contrast, the citalopram- and paroxetine-treated rats exhibited impaired copulatory and ejaculatory behaviors after subchronic and chronic treatments. Chronic vilazodone treatment markedly decreased 5-HT1A receptor levels in cortical and hippocampal regions, while the SSRIs increased levels of this receptor in similar regions. All chronic treatments reduced 5-HTT levels across the forebrain; however, the magnitude of the decrease was considerably smaller for vilazodone than for the SSRIs.ConclusionsThe current studies showed that chronic treatment with vilazodone, in contrast to citalopram and paroxetine, was not associated with diminished sexual behaviors in male rats, which may be related to the differential effects of vilazodone on 5-HT1A receptor and 5-HTT levels relative to conventional SSRIs.
Highlights
Major depressive disorder (MDD) is one of the most common mental disorders, with an estimated lifetime prevalence in the USA of 19.2 % (Kessler et al 2010)
The current studies showed that chronic treatment with vilazodone, in contrast to citalopram and paroxetine, was not associated with diminished sexual behaviors in male rats, which may be related to the differential effects of vilazodone on 5-HT1A receptor and 5-HTT levels relative to conventional selective serotonin reuptake inhibitor (SSRI)
Following acute administrations of vilazodone, citalopram, and paroxetine, there were no significant effects of treatment on any of the sexual behavior parameters (Figs. 1 and 2a–b)
Summary
Major depressive disorder (MDD) is one of the most common mental disorders, with an estimated lifetime prevalence in the USA of 19.2 % (Kessler et al 2010). Selective serotonin reuptake inhibitors (SSRIs) are efficacious in treating MDD and are the most commonly prescribed first-line therapy. Their clinical effectiveness is often limited by poor adherence and discontinuation due to lack of therapeutic response and adverse effects (Nantz et al 2009). Sexual dysfunction, which affects up to 60 % of patients treated with SSRIs (Kennedy and Rizvi 2009), is a leading cause of treatment nonadherence (Ashton et al 2005) and is reported by patients to be one of the most unacceptable side effects associated with SSRIs (Hu et al 2004).
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