Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system

Waldinger, Marcel D.; Berendsen, Hemmie H.G.; Blok, Bertil; Olivier, Berend; Holstege, Gert

doi:10.1016/s0166-4328(97)00183-6

Cited by 344 publications

(264 citation statements)

References 39 publications

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“…This is in line with clinical observations relating dopamine agonists to hypersexuality (Voon et al, 2009) and dopamine antagonists to sexual dysfunction (Baldwin and Mayers, 2003). Animal experiments clearly support the notion that modulation of central, but not peripheral, serotonergic pathways is involved in SSRI-related alteration of sexual functioning (Waldinger et al, 1998). Enhancement of central serotonergic neurotransmission with stronger activation of inhibitory postsynaptic autoreceptors (Blier et al, 1988) has been postulated as a likely SSRI effect modulating the inhibitory control of ejaculation (Giuliano and Clement, 2006).…”

Section: Introductionsupporting

confidence: 80%

Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion

Abler

Seeringer

Hartmann

et al. 2011

Neuropsychopharmacol

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Sexual dysfunction is a common side effect of selective serotonin reuptake inhibitors (SSRIs) like paroxetine in the treatment of depression, imposing a considerable risk on medication adherence and hence therapeutic success. Bupropion, a norepinephrine and dopamine reuptake inhibitor, is recommended as an alternative treatment without adverse effects concerning sexual arousal and libido. We investigated the neural bases of paroxetine-related subjective sexual dysfunction when compared with bupropion and placebo. We scanned 18 healthy, heterosexual males in a randomized, double-blind, within-subject design while watching video clips of erotic and nonerotic content under steady-state conditions after taking 20 mg of paroxetine, 150 mg of bupropion, and placebo for 7 days each. Under paroxetine, ratings of subjective sexual dysfunction increased compared with placebo or bupropion. Activation along the anterior cingulate cortex (ACC), including subgenual, pregenual, and midcingulate cortices, in the ventral striatum and midbrain was decreased when compared with placebo. In contrast, bupropion let subjective ratings and ACC activations unchanged and increased activity of brain regions including posterior midcingulate cortex, mediodorsal thalamus, and extended amygdala relative to placebo and paroxetine. Brain regions that have been related to the processing of motivational (ventral striatum), emotional, and autonomic components of erotic stimulation (anterior cingulate) in previous studies showed reduced responsiveness under paroxetine in our study. Drug effects on these regions may be part of the mechanism underlying SSRI-related sexual dysfunction. Increased activation under bupropion may point to an opposite effect that may relate to the lack of impaired sexual functioning.

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Section: Introductionsupporting

confidence: 80%

Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion

Abler

Seeringer

Hartmann

et al. 2011

Neuropsychopharmacol

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“…Selective serotonin reuptake inhibitors (SSRIs: paroxetine, fluoxetine, sertraline, and citalopram) are reported to be effective for treating PE (Waldinger et al, 2004a;Safarinejad and Hosseini, 2006), but they were not developed to treat PE. Probable mechanism of these drugs is the enhancement of net serotonergic transmission by blocking the presynaptic 5-HT (serotonin) uptake site (Waldinger et al, 1998a). A member of the well-known SSRI class of compounds, dapoxetine would become the first oral pharmacologic product indicated for the treatment of PE, but at the end of 2005 has not been approved by the FDA as an oral drug for the treatment of PE.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study

Safarinejad¹

2007

Neuropsychopharmacol

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The aim of the study was to evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) drug dapoxetine in delaying ejaculation in patients with premature ejaculation (PE). A total of 212 potent men with PE were randomly assigned to receive 30 mg orally dapoxetine (group 1, N ¼ 106) twice daily or similar regimen of placebo (group 2, N ¼ 106) during a 12-week period for each agent. Pretreatment evaluation included history and physical examination, geometric mean intravaginal ejaculatory latency time (IELT, primary outcome measure), and International Index of Erectile Function (IIEF). The efficacy of two treatments was assessed every 2 weeks during treatment, at the end of study, and in 3-month follow-up after cessation of treatment. We measured geometric mean IELT. Thus, the IELT values were logarithmically transformed before statistical analysis, and the results are reported as fold increases from baseline with associated 95% confidence intervals (CI). The independent sample two-tailed t-test was used to compare the IELTs. At the end of 12-week treatment, the dapoxetine group had a 2.9-(95% CI, 1.84-4.16) fold increase of the geometric mean IELT, while after placebo the geometric mean IELT did not increase significantly (1.4-fold increase; 95% CI, 0.84-1.63) (p ¼ 0.001). The mean weekly intercourse episodes increased from pretreatment values of 1.16 and 1.14 to 2.2 and 1.4, for dapoxetine and placebo, respectively (p ¼ 0.04). Baseline mean intercourse satisfaction domain values of IIEF, 12 and 11, reached to 16 and 10 at the 12-week treatment in groups 1 and 2, respectively (p ¼ 0.04). At the end of 3-month follow-up period, the geometric mean IELT in dapoxetine and placebo group demonstrated 1.4-(95% CI, 0.66-1.46) and 1.3-(95% CI, 0.77-1.63) fold increase, respectively (p ¼ 0.1). Three-month intercourse satisfaction domain value of IIEF was 11 in group 1 and 10 in group 2 (p ¼ 0.1). Mean number of adverse events was 19 for dapoxetine and 7 for placebo (p ¼ 0.02). Dapoxetine has moderately better results in terms of IELT and intercourse satisfaction vs placebo without long-term benefit for the patient after it is withdrawn. Further studies are necessary to draw final conclusions on the efficacy of this drug in PE.

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“…[1][2][3] Based on animal 4 and human psychopharmacological studies, Waldinger et al have postulated that lifelong premature ejaculation is a neurobiological phenomenon related to decreased central serotonergic neurotransmission, 5-HT 2C receptor hyposensitivity and/or 5-HT 1A hypersensitivity. [5][6][7] In addition, Waldinger postulates that lifelong early ejaculation is not an acquired disorder due to learned behavior, as has been suggested by Masters and Johnson, but, instead, belongs to the normal biological variability of the intravaginal ejaculation latency time (IELT) in men, with a possible familial genetic vulnerability. 1,[5][6][7][8][9] In this sense, early ejaculation is considered a neurobiological phenomenon, that may become perceived as premature ejaculation and consequently may secondarily lead to psychological distress.…”

Section: Introductionmentioning

confidence: 99%

Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis

et al. 2004

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The aim of this systematic review and meta-analysis is to evaluate whether the design and methodology of drug-treatment studies of premature ejaculation affect the efficacy outcome differently. Therefore, methodological, design and efficacy data from 79 studies (3034 males), published between 1943 and 2003, are reviewed. A meta-analysis is performed on 43 selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies (1514 males), published between 1973 and 2003; these studies were pooled to provide a summary variance-weighted effect size. The antidepressant-induced percentage increase of the intravaginal ejaculation latency time (IELT) was calculated and examined against various methodological items. A significant difference in efficacy between SSRIs was observed. Using daily treatment, paroxetine appeared more effective than the other SSRIs. Retrospective use of a questionnaire, subjective reports, single-blind and open study designs generate far greater variability of ejaculation time both at baseline and during active drug treatment than real time assessment by stopwatch. In conclusion, at daily treatment, the overall efficacy of paroxetine, clomipramine, sertraline and fluoxetine is comparable, but paroxetine exerts the strongest ejaculation delay. Only eight (18.5%) studies on antidepressant treatment fulfilled all criteria used in evidence-based medicine, for example, randomised, double-blind studies with prospective real time (stopwatch) assessment of the IELT at each intercourse. Single-blind studies, open designs, retrospective reporting, or the use of a questionnaire to assess ejaculation time should be avoided.

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Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system

Cited by 344 publications

References 39 publications

Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion

Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion

RETRACTED ARTICLE: Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study

Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis

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