Article

Dapoxetine for the Treatment of Premature Ejaculation: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial in 22 Countries

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Abstract

Dapoxetine is being developed for the on-demand treatment of premature ejaculation (PE). Previous clinical trials have demonstrated its safety and efficacy. To evaluate the long-term efficacy and safety of dapoxetine in men with PE. This randomized, double-blind, parallel-group, placebo-controlled, phase 3 trial, conducted in 22 countries, enrolled men (N=1162) > or = 18 yr of age who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE for > or = 6 mo, with an intravaginal ejaculatory latency time (IELT) < or = 2 min in > or = 75% of intercourse episodes at baseline. Dapoxetine 30 mg or dapoxetine 60 mg or placebo on demand (1-3 h before intercourse) for 24 wk. Stopwatch-measured IELT, Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change, adverse events (AEs). The study was completed by 618 men. Mean average IELT increased from 0.9 min at baseline (all groups) to 1.9 min, 3.2 min, and 3.5 min with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively, at study end point; geometric mean IELT increased from 0.7 min at baseline to 1.1 min, 1.8 min, and 2.3 min, respectively, at study end point. All PEP measures and IELTs improved significantly with dapoxetine versus placebo at week 12 and week 24 (p<0.001 for all). The most common AEs were nausea, dizziness, diarrhea, and headache. AEs led to discontinuation in 1.3%, 3.9%, and 8.2% of subjects with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively. Limitations of this study included the exclusion of men who were not in long-term monogamous relationships. Dapoxetine significantly improved all aspects of PE and was generally well tolerated in this broad population.

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... In a phase III study including 1,162 men with PE from 22 different countries, patients received dapoxetine 30 and 60 mg on-demand or a placebo 1-3 h before sexual intercourse. After 6 months of treatment, geometric mean IELT in patients receiving dapoxetine 30 mg, dapoxetine 60 mg and placebo increased from 0.7 min at the baseline (in all groups) to 1.1,1.8 and 2.3 min, respectively 133 . The average IELT was significantly greater with dapoxetine than with placebo after the first dose and at all subsequent time points (P < 0.001; all); however, this improvement might not be clinically meaningful for many patients with PE 133 . ...
... After 6 months of treatment, geometric mean IELT in patients receiving dapoxetine 30 mg, dapoxetine 60 mg and placebo increased from 0.7 min at the baseline (in all groups) to 1.1,1.8 and 2.3 min, respectively 133 . The average IELT was significantly greater with dapoxetine than with placebo after the first dose and at all subsequent time points (P < 0.001; all); however, this improvement might not be clinically meaningful for many patients with PE 133 . The most frequently reported adverse effects were headache, dizziness and diarrhoea, but the most common adverse effect that caused cessation of medication was nausea. ...
... Serious adverse effects such as ventricular tachycardia (n = 1) and transient ischaemic attack (n = 1) were observed in a few patients treated with dapoxetine 30 mg, and syncope owing to transient sinus arrest and sinus bradycardia was reported in one patient receiving dapoxetine 60 mg (reF. 133 ). ...
Article
Premature ejaculation (PE) is a prevalent male sexual dysfunction. Current standard treatment regimens include behavioural therapies, topical anaesthetics, dapoxetine and other selective serotonin reuptake inhibitors (SSRIs). Most of the pharmacotherapeutic options target neurotransmitters (such as serotonin and oxytocin) that have a role in the ejaculation mechanism. However, these treatments are mildly effective and only provide a temporary delay in the ejaculation latency time, and PE recurs when the treatment is stopped. Thus, a treatment for PE is urgently needed and research is ongoing to find the ideal PE therapy. The efficacy and safety of topical anaesthetics and SSRIs in delaying ejaculation have been confirmed in many well-designed controlled trials. Both preclinical and clinical studies on new-generation SSRIs are ongoing. Moreover, promising results came from clinical trials in which the efficacy of on-demand PE therapies targeting neurotransmitters other than serotonin, such as α1-adrenoceptor antagonists and oxytocin antagonists, was assessed. Surgical intervention and neuromodulation have been proposed as potential treatment options for PE; however, current PE guidelines do not recommend these treatments owing to safety concerns.
... hours) and rapidly achieves peak plasma concentration (C max : 1−3 hours). [12][13][14] The mean half-life of dapoxetine after a single dose was reportedly 1.3−1.5 hours, while the terminal half-life of dapoxetine was 15−19 h after a single dose. 12,13 Moreover, dapoxetine has a dose-proportional pharmacokinetic profile, and its efficacy is not affected by food 14 . ...
... [12][13][14] The mean half-life of dapoxetine after a single dose was reportedly 1.3−1.5 hours, while the terminal half-life of dapoxetine was 15−19 h after a single dose. 12,13 Moreover, dapoxetine has a dose-proportional pharmacokinetic profile, and its efficacy is not affected by food 14 . These characteristics and the drug's mild AEs suggest that dapoxetine is a good candidate for on-demand treatment of PE. ...
... CGIC is a self-evaluation assay based on patients' subjective feelings; so, it is not as objective a measure as IELT and may be influenced by physical or psychological factors. However, somehow, PE itself is a kind of subjective concept based on the PE diagnostic criteria 14 , and we should understand that patients' satisfaction is our primary treatment target, especially among patients with PE. Therefore, we used the CGIC as the standard to evaluate the PE therapeutic effect. ...
Article
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Introduction Before dapoxetine was approved for the treatment of lifelong premature ejaculation (LPE) in China, daily dosing with off-label sertraline was common. Aim To investigate the efficacy of dapoxetine in the treatment of patients with LPE as an alternative to sertraline therapy. Methods This prospective study included LPE patients who previously attempted treatment with sertraline and who agree to receive dapoxetine therapy in our hospital from January 2020 to March 2021. Patients who received any PE therapy in the two months prior to the dapoxetine therapy were excluded. All patients received dapoxetine 30 mg (taken 1–3 hours before sexual intercourse) for 12 weeks, and they were not taking sertraline during the trial. Main Outcome Measure Data on their intravaginal ejaculatory latency time and premature ejaculation profile were recorded before and after the dapoxetine treatment. Clinical Global Impression of Change scores and data on Treatment-Emergent adverse events were collected after treatment. Results A total of 144 patients with LPE completed this study; including 64 patients who reported that previous sertraline treatment was satisfactory (group A) and 80 patients for whom previous sertraline therapy was unsatisfactory in treating PE (group B). Both groups experienced significantly increased intravaginal ejaculatory latency time. Dapoxetine therapy was reported satisfactory by 67.5% of patients with LPE in whom sertraline therapy unsatisfactory according to their Clinical Global Impression of Change score, which was not different from those who reported this result in group A (62.5%). Similar outcomes were also reported for premature ejaculation profile and treatment-emergent adverse events. Conclusion : Although both dapoxetine and sertraline are selective serotonin re-uptake inhibitors, dapoxetine therapy is satisfactory in 67.5% of patients with LPE in whom sertraline treatment unsatisfactory, and the effect of dapoxetine was independent of the effect of sertraline. Liu G, Yin Y, Zhang L. et al., Efficacy of Dapoxetine in the Treatment of Patients With Lifelong Premature Ejaculation as an Alternative to Sertraline Therapy. Sex Med 2021;10:100473.
... It has been more than 12 years since the International Society of Sexual Medicine (ISSM)-and 8 years since the American Psychiatric Association (APA: DSM-5)-first laid out the three-pronged diagnostic criteria for premature ejaculation (PE): a short ejaculatory latency (EL); the inability to control, delay, or postpone ejaculation; and bother or distress about the condition [1][2][3]. The inclusion of these specific criteria relied on several seminal studies that lent preliminary support to each prong of the definition; subsequently, these criteria became benchmarks for establishing the efficacy of various treatment strategies for men with PE, e.g., [4,5]. Despite an initial flurry of research on these constructs to establish the PE criteria, once embraced, the number of studies designed to further understand and quantify two of the constructs, "ejaculatory control" and "bother/distress," dwindled to a mere handful. ...
... For the overall sample of men, straight and non-straight groups did not differ significantly on either measure of ejaculatory control (difficulty or importance), or on either measure of bother/distress (related to short latency or lack of control) (p = 0.131, 0.068, 0.412, and 0.051, respectively) ( Table 4). 5 3.8 (0.14) 3.6 (0.24) 0.374 * Bother/distress if cannot have control 5 4.0 (0.13) 3.6 (0.20) 0.061 * When only the subset of men with PE was analyzed, ejaculatory control difficulty (but not importance) was marginally greater in straight men (p = 0.015, p = 0.770, respectively). Neither bother/distress measure showed group differences (p = 0.374, 0.061). ...
... For the overall sample of men, straight and non-straight groups did not differ significantly on either measure of ejaculatory control (difficulty or importance), or on either measure of bother/distress (related to short latency or lack of control) (p = 0.131, 0.068, 0.412, and 0.051, respectively) ( Table 4). 5 3.8 (0.14) 3.6 (0.24) 0.374 * Bother/distress if cannot have control 5 4.0 (0.13) 3.6 (0.20) 0.061 * When only the subset of men with PE was analyzed, ejaculatory control difficulty (but not importance) was marginally greater in straight men (p = 0.015, p = 0.770, respectively). Neither bother/distress measure showed group differences (p = 0.374, 0.061). ...
Article
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“Ejaculatory control” and “bother/distress” are key criteria for diagnosing men with premature ejaculation (PE), yet compared with ejaculatory latency (EL), these constructs have received only minimal attention. In addition, they have not been characterized in men having different sexual orientations or subtypes of PE. This study aimed to characterize relationships among ejaculatory control, bother/distress, and EL; to assess differences across men having different sexual orientations, PE status, and PE subtypes (i.e., lifelong vs. acquired); and to determine the importance of ejaculatory control to men’s sexual partners. In total, 1071 men and sexual partners of men rated their ejaculatory control and bother/distress and estimated their EL; these measures were compared across sexual orientation, PE status, PE subtype, and male and female partners of men. Results revealed a monotonic though slightly curvilinear relationship between ejaculatory control and bother/distress. These PE criteria differed significantly between PE and non-PE men, to a lesser extent between gay and straight men, and not at all between men having lifelong vs. acquired PE. Female and male partners of men affirmed the importance of ejaculatory control during partnered sex, indicating lack of control as a potential reason for ending a relationship.
... However, the side effects of SSRIs remain an important issue, and the on-demand (OD) use of SSRIs may be helpful in decreasing these side effects, as a result of a decreased cumulative dose. Dapoxetine hydrochloride is a short-acting OD-use SSRI, but it has a modest efficacy (Buvat et al., 2009;Mirone et al., 2014). ...
... However, medical drug therapy is the gold standard-recommended treatment for lifelong PE (Serefoglu et al., 2013). The off-label use of SSRIs (including short-acting OD or long-acting daily SSRIs) is the most commonly used treatment option for lifelong PE (Alghobary et al., 2010;Arafa & Shamloul, 2006;Buvat et al., 2009). The ideal treatment should involve delaying ejaculation with minimal adverse effects. ...
... The associated literature has shown that dapoxetine produced a threefold increase in IELT after treatment (Mirone et al., 2014). A randomised controlled study and a meta-analysis showed that dapoxetine significantly improved IELT with modest efficacy in patients with lifelong PE (Buvat et al., 2009;Castiglione et al., 2016). Our findings are compatible with those in the literature (Buvat et al., 2009;Castiglione et al., 2016). ...
Article
This study compared the safety and efficacy of the on‐demand (OD) use of sertraline (50 mg), sertraline (100 mg) and dapoxetine (30 mg), and the daily use of sertraline (50 mg) in the treatment of patients with premature ejaculation (PE). This prospective randomised study involved 120 lifelong PE patients (intravaginal ejaculatory latency time [IELT]: <1 min; Arabic Index of Premature Ejaculation [AIPE] score: < 30) without secondary causes of PE, identified between March 2018 and May 2020. Patients were divided into 4 groups (30 patients per group) and treated for 8 weeks. Assessments were conducted using the AIPE form as a diagnostic tool. Sertraline (50 mg, daily; 196.7 ± 115.5 s) and sertraline (100 mg, OD; 173.3 ± 97.0 s) had similar IELT and AIPE scores. The latter groups had better results in comparison with sertraline (50 mg, OD; 100.5 ± 54.4 s) and dapoxetine (93.7 ± 53.5 s; p < 0.01). Sertraline (100 mg, OD) had a similar efficacy to that of sertraline (50 mg, daily) and was more effective than sertraline (50 mg, OD) and dapoxetine (30 mg, OD). Sertraline (100 mg, OD) can be considered in the treatment of lifelong PE treatment, having tolerable side effects.
... [9,10] Even on-demand use of the most recently developed SSRI dapoxetine, has been shown to result in a 1-3 fold increase in IELT when compared to placebo. [11,12] In a large meta-analysis, Waldinger found that on-demand SSRIs use generally exerts less ejaculation delay than daily SSRIs, but the benefit of daily use may be at the expense of greater adverse effects. [8] There is a concern that SSRI medications may increase the odds of suicide attempts by those treated with this class of drugs. ...
... [19] Another study focusing solely on on-demand dapoxetine use found discontinuation rates of up to 47%. [11] We sought to analyze our experience with drop-out rates with fluoxetine in the primary PE population and to identify predictors of continued use of this agent. ...
... In our study, dropout rates increased dramatically over subsequent months, with 56% and 72% discontinuing fluoxetine at 6 and 12 months, respectively. Except for one study looking at paroxetine that found no change in discontinuation (nearly 31%) from 3-6 months, our dropout rates are on par with the limited data available for SSRI use in PE. [11,27] Factors leading to SSRI discontinuation are not well reported in the current literature. One would expect that those men who experience the greatest improvements in IELT would be more compliant. ...
Article
Background: Premature ejaculation (PE) is a common sexual dysfunction for which selective serotonin reuptake inhibitors (SSRIs) have been used effectively for treatment. However, compliance with therapy and predictors of long-term SSRI use in the treatment of PE are not well known. Aim: To analyze our experience with drop-out rates with fluoxetine in the primary PE population and to identify predictors of continued use of this agent. Methods: Men with primary PE constituted who used fluoxetine and had at least 12 months follow-up constituted the study population. Subjects underwent a comprehensive interview to ascertain self-reported (non-stopwatch) intravaginal ejaculatory latency time (IELT), self-rated control over ejaculation, and personal and patient-reported partner distress due to PE. Patients were treated with fluoxetine 20 mg daily, with the possibility of dose titration up or down based on efficacy and side effects. Outcomes: The PE parameters of interest included self-reported IELT, self-rated control over ejaculation, personal and partner distress due to PE, and medication adherence. Results: 130 men were included in the study. Dropout rates at 6 and 12 months were 56% and 72%. Self-rated "poor" ejaculatory control decreased from 98%-41% (P < .01), high personal distress from 47%-11% (P < .01), and high partner distress rates from 72%-27% (P < .01). Predictors of continued use at 12 months included high partner distress, being unpartnered, and having a post-treatment IELT ≥5 minutes (P < .01). Overall side effects included headache (5%), dizziness (4%), nausea (5%), nervousness (5%), and sleepiness (8%); however, moderate to severe side effects reported included nausea (2%), sleepiness (2%), headache (2%), and dizziness (2%). Clinical implications: Compliance with SSRIs is a well-described problem in the depression literature, but data are sparse regarding continued use of SSRIs in the treatment of PE. Strengths and limitations: We report on 12-month compliance with SSRIs for the treatment of PE. Our early compliance rates were more encouraging than what has been reported in the past. However, IELT was self-reported and not measured objectively, and we did not use validated patient-reported outcomes but rather self-reported ejaculatory control and distress levels, which have limitations. Conclusions: Fluoxetine is an effective agent for the treatment of PE with significant improvement realized in IELT, ejaculatory control, and distress levels for both men and their partners. Despite its efficacy, continued use of fluoxetine beyond 6 months is poor. Jenkins LC, Gonzalez J, Tal R, et al. Compliance with Fluoxetine Use in Men with Primary Premature Ejaculation. J Sex Med 2020;XX:XXX-XXX.
... Similar to all other SSRIs, it inhibits serotonin reuptake in the neuronal synapses [90]. Dapoxetine is the first drug which has been approved by the EMA for the treatment of PE [91][92][93][94][95] (three level 1 studies). Dapoxetine should be taken 1-2 h before the planned sexual intercourse. ...
... Dapoxetine should be taken 1-2 h before the planned sexual intercourse. Many clinical trials have shown a 3.6 to 4.5-fold increase in IELT under on-demand dapoxetine treatment which associated with improved satisfaction and ejaculatory control in lifelong and acquired PE patients [91][92][93][94][95]. The safety of dapoxetine has also been demonstrated in those studies, with several mild side effects such as dizziness, nausea and headache [91][92][93][94][95][96]. ...
... Many clinical trials have shown a 3.6 to 4.5-fold increase in IELT under on-demand dapoxetine treatment which associated with improved satisfaction and ejaculatory control in lifelong and acquired PE patients [91][92][93][94][95]. The safety of dapoxetine has also been demonstrated in those studies, with several mild side effects such as dizziness, nausea and headache [91][92][93][94][95][96]. ...
Article
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Purpose of Review Premature ejaculation (PE) is one of the most common forms of male sexual disorder. There are still different opinions and point of view regarding its definition, classification, prevalence, pathophysiology and treatment alternatives. For these reasons, we aim to recap the recently accumulated data on definition, classification, pathophysiology and treatment alternatives of PE. The literature pertaining to PE has been reviewed by the authors. All the related articles were critically analyzed and examined. Levels of evidence (Les) and grades of recommendation (Grs) are provided based on a thorough analysis of the literature and consensus. Recent Findings After the initial evidence-based definition developed for lifelong PE, the International Society for Sexual Medicine (ISSM) advertised another unified definition for lifelong and acquired PE and confirmed the time criterion for the diagnosis of PE. The ISSM has also acknowledged the presence of the two more PE subtypes (variable and subjective PE) underlining the fact that more research is required to develop an evidence-based definition of these sexual problems. Although the pathophysiology of these four PE syndromes has not been completely elucidated yet, pharmacotherapy must be considered the treatment of choice for lifelong PE patients whereas treating the underlying pathology must be the initial goal for patients with acquired PE. To treat PE, we can use daily or on-demand use of SSRIs, on-demand use of topical anaesthetics, on-demand tramadol or phosphodiesterase type-5 inhibitors. Psychotherapy can be offered to patients who describe variable and subjective PE. Summary Despite the recent progress reached in the field of PE, there are on-going debates regarding the definition, classification, pathophysiology and treatment of this common problem. Future clinical trials must be performed to understand the actual aetiology of the four PE syndromes and develop more effective and safe treatment alternatives.
... After scanning Medline, PubMed, Embase, CNKI, Wanfang, and VIP databases, 215 potential articles were found, but most of them were excluded because they were reviews, they did not have a control group, or the contents were not relevant to our analysis. Finally, only 11 articles were included from the literature search [7][8][9][10][11][12][14][15][16][17][18]. Figure 1 presents the process of study selection. Table 1 presents the main characteristics of the included studies. ...
... They were published from 2006 to 2016, and all were RCTS. Of them, 6 reported the difference in efficacy and safety between dapoxetine and placebo in the treatment of patients with PE [7][8][9]12,14,15], 2 reported the difference between 30 mg dapoxetine and 60 mg dapoxetine [10,16], 2 reported the difference between 30 mg dapoxetine and sertraline [17,18], and 1 reported the difference between dapoxetine and fluoxetine [11]. Of them, 3 were performed in China [11,17,18]. ...
... The effect on intravaginal ejaculatory latency time (IELT) Seven included studies assessed the IELT between the dapoxetine group and control group [7,[10][11][12]14,15,18]. Our study showed that patients with PE had a longer IELT after dapoxetine intervention than with placebo or another drug intervention, and the SMD (95%CI) was 0.44 (0.40, 0.57), P<0.05. ...
Article
Full-text available
BACKGROUND The aim of this study was to assess the efficacy and safety of "on-demand" dapoxetine in the treatment of premature ejaculation (PE). MATERIAL AND METHODS We performed a meta-analysis of intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGIC), perceived control over ejaculation (PCOE), and drug-related adverse effects (AEs). We searched Medline, PubMed, Embase, CNKI, Wanfang, and VIP databases up to May 30, 2018 with the following search terms: "dapoxetine" or "SSRIs" and "premature ejaculation" or "sexual dysfunction". RESULTS Our analysis included 11 RCTs (8521 cases and 4338 controls). We found that IELT, PGIC, and PCOE in PE patients with "on-demand" dapoxetine were significantly higher than in the control group, and we observed higher proportions in 60 mg vs. 30 mg dapoxetine. The AEs were mild and tolerable. CONCLUSIONS "On-demand" dapoxetine is effective and safe for patients with PE, and a dose of 60 mg may be more effective than 30 mg.
... Учитывая тот факт, что дапоксетин 60 мг лучше перено сится, чем 100 мг дапоксетина, дозы 30 мг и 60 мг были вы браны для дальнейшего изучения в исследованиях эффек тивности и безопасности фазы III. Были проведены пять рандомизированных плацебо контролируемых клиничес ких исследований: в США [42], в 16 странах Европы, Арген тины, Бразилии, Канады, Израиля, Мексики и Южной Аф рики [43], исследование безопасности в Северной Америке [44], а также австралийского и азиатско тихоокеанского ис следований [45]. ...
... Также наблюдалось значительное снижение как лично стного расстройства, связанного с эякуляцией, так и меж личностных трудностей у женщин партнеров мужчин, по лучавших дапоксетин 30 мг и 60 мг по сравнению с плацебо (p<0,001 для обоих) [43]. ...
... В отличие от других СИОЗС, дапоксетин связан с низкими показателями сексуальной дисфункции, не име ет клинически значимых электрокардиографических эф фектов, безопасен и хорошо переносим с использованием применяемых режимов дозирования (по 30 мг и 60 мг) [43,44]. ...
Article
Full-text available
The review, devoted to the actual problems of premature ejaculation, presents the current positions of classification, etiopathogenesis and treatment of this condition. The modern representative of selective inhibitors of serotonin reuptake – dapoxetine, is the only effective drug used to correct premature ejaculation of various genesis. The article presents modern data on its mechanisms of action, in the light of new scientific research.
... In the end, 17 eligible articles were left to fit our analysis. [9,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Table 1 summarizes the characteristics of these 17 RCTs covering 5739 adults aged from 18-77. All participants in the trials were diagnosed premature ejaculation or with IVELT of about 0.5-1.5 min more than 1 year. ...
... Quality assessment were measured by Cochrane risk-of-bias tool. Details of these 17 studies are shown in Figure 3. Five studies [24,26,28,33,35] showed low risk in random sequence generation, and 4 studies [9,26,29,35] showed low risks in allocation concealment. Risk of participant blinding is high in 3 studies [24,25,32] and low in 9 studies. ...
... Risk of participant blinding is high in 3 studies [24,25,32] and low in 9 studies. [9,[26][27][28][29][30][33][34][35] Only 1 study [9] demonstrated high risk of outcome assessment blinding, while 9 studies [24,[26][27][28][29][30][33][34][35] showed low risk. Four studies [24,25,29,34] were found low risk in incomplete outcome data, accompanied with 9 studies [9,[26][27][28][30][31][32][33]35] in high risk. ...
Article
Full-text available
Background: We performed the network meta-analysis (NMA) and systematic review involved all evidence from relevant trials to compare the efficiency and safety of various types of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase-5 inhibitors (PDE5i) in patients with premature ejaculation (PE). Methods: We conducted comprehensive searches of peer-reviewed and grey literature. PubMed, the Cochrane Library Central Register of Controlled Trials, Embase were searched for randomized controlled trials published up to June 1, 2017. The primary outcome was intravaginal ejaculation latency time (IVELT) and adverse effects (AEs). We performed pairwise meta-analyses by random effects model and network meta-analysis by Bayesian model. We used the GRADE framework to assess the quality of evidence contributing to each network estimate. Results: Of 3046 titles and abstracts initially identified, 17 trials reporting 5739 participants were included. Considering IVELT in the NMA, paroxetine plus sildenafil and sildenafil alone are both superior to placebo (MD: 1.75, 95% CrI: 0.05 to 3.78; MD 1.43, 95% CrI 0.003 to 2.81). Sildenafil is superior to sertraline (MD: 1.63, 95% CrI: 0.10 to 2.79). Considering AEs, placebo demonstrated obviously lower risk comparing to paroxetine, sildenafil and paroxetine plus sildenafil (OR 0.20, 95% CI: 0.05 to 0.52; OR 0.23, 95% CI: 0.04 to 0.80; OR 0.45, 95% CI: 0.01 to 0.92). Compared with tadalafil plus paroxetine, dapoxetine showed significantly less AEs (OR 0.23, 95% CI 0.02 to 0.96). Conclusions: Our study concluded that although paroxetine plus sildenafil and sildenafil alone both demonstrated significant IVELT benefit compared with placebo, significant increase of AEs risk was also observed. Furthermore, sildenafil alone was superior to sertraline in efficacy with comparable tolerability.
... In addition, some studies were sponsored by industry. 7,22,[25][26][27] Whether the studies used intention-to-treat analysis or not may impact the result of the included studies, which may lead to differences in outcomes. Thus, the risk of potential heterogeneity was inevitable although subgroup analysis and sensitivity analysis were conducted to minimize these effects. ...
... Characteristics of studies included in the meta-analysis[22][23][24][25][26][27][28]31 ...
... Five studies evaluating dapoxetine versus placebo were enrolled in the analysis of IELT.7,[24][25][26][27] The pooled estimate presented an MD of 1.18 minutes (95% CI 1.11-1.25; ...
Article
Background: The safety and efficacy of dapoxetine for the treatment of premature ejaculation (PE) is still controversial. Thus, we decided to conduct a meta-analysis using trial sequential analysis (TSA) to determine the sufficiency of conclusions. Objective: Evaluate the efficacy and safety of dapoxetine in the treatment of patients with PE and assess the reliability of the findings. Design: Meta-analysis of randomized controlled trials (RCTs). Methods: Electronic databases including PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang data were reviewed up to July 2017. RCTs evaluating the efficacy of dapoxetine in patients with PE and reporting intravaginal ejaculatory latency time (IELT), patient global impression of change (PGIC) and/or adverse events (AEs) were included. Main outcome measures: Mean differences between trials in efficacy for IELT, and risk ratios for PGIC and treatment-emergent AEs. Sample: 8 RCTs. Results: For IELT and PGIC, significant effects were found for all doses of dapoxetine versus placebo, and similar results were obtained in subgroups of the 30-mg dose versus 60-mg dose. There were also statistically different dose-related effects on AEs. Trial sequential analysis showed that the result of our meta-analysis was confirmed and further trials are unnecessary. Conclusions: The evidence suggests that dapoxetine may be a safe and effective drug for patients with PE. Registration: Not registered, no published protocol. Conflict of interest: No relationship with manufacturer of drug.
... Produžuje IELT 2,5 do 4 puta. Usto povećava kontrolu ejakulacije, smanjuje patnju i povećava seksualno zadovoljstvo 42 (1, A). ...
... Dovode do prekida terapije u 5 -10% bolesnika. [42][43][44] Nije opisan sindrom sustezanja kod prekida uzimanja dapoksetina. ...
... 37 Ako nakon tri tjedna primjene nema učinka, doza se povisuje. 42 Primjena prema potrebi, 3 -6 sati prije odnosa, manje je učinkovita od svakodnevne primjene. 46 Jedino je klomipramin učinkovit i u doziranju prema potrebi. ...
Article
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Premature ejaculation (PE) is a sexual disorder with high prevalence, defined by three characteristics: short intravaginal ejaculation latency time, poor control over delaying ejaculation and personal and/or partner distress. The diagnosis is reached by a thorough and comprehensive history taking, which should include presence/absence of other ­co-morbid conditions (e.g. erectile dysfunction, anxiety), and assessing the type of PE (primary, secondary, variable, subjective). It is important to counsel the patient (and, if possible, the partner) about this condition and treatment options. The first line of treatment is selective serotonin reuptake inhibitors (dapoxetine, which is the only drug with an official label for this indication, paroxetine, sertraline, fluoxetine, citalopram, escitalopram). The first line of treatment also includes psychological/sexological treatment methods, such as behavioural methods (stop-start and squeeze techniques), and new functional sexological treatment. The choice of the method depends on the type of PE and on the patient preference. The second line of treatment are clomipramine and local anaesthetics, and the third line is tramadol.
... TCAs, and their derivatives, have been a cornerstone in medical treatment of depression. They are very effective, but, their use is often associated with a variety of unpleasant and sometimes dangerous sideeffects [22] (Table 4) [29,74,75,80,83,[164][165][166][167][168][169][170][171][172][173][174]. Unwanted effects of TCAs arise through interactions with several different neurotransmitter systems. ...
... A systemic review of five randomised, placebocontrolled phase III clinical trials [83][84][85][86] including 4232 men with PE from 32 countries confirmed that dapoxetine 30 and 60 mg increased the IELT and improved PROs of control, ejaculation-related distress, interpersonal distress and sexual satisfaction compared with placebo [87]. The pooled data revealed a statistically significant increase in the IELT with dapoxetine 30 mg (+2.3 min), dapoxetine 60 mg (+2.7 min) compared with placebo (+1.5 min). ...
Article
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To analyse the current therapeutic options for patients with premature ejaculation (PE) and highlight their mechanism(s) of action, effectiveness, advantages and limitations. A literature search was conducted using the PubMed database searching for articles exploring different PE treatment modalities. A Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) approach was used to report the results of the literature search. A total of 149 articles were included in this review. The currently available treatment methods for PE include behavioural therapy, local anaesthetics, tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective phosphodiesterase inhibitors. Most PE treatments are either experimental or used off-label. New treatments are certainly warranted to overcome this exasperating sexual dysfunction. Abbreviations: AIPE: Arabic Index of Premature Ejaculation; CNS: central nervous system; CYP: cytochrome P450; ED: erectile dysfunction; FDA: United States Food and Drug Administration; H1: histamine receptors; 5-HT: 5-hydroxytryptamine; IELT: The intravaginal ejaculation latency time; IPE: Index of Premature Ejaculation; M1: muscarinic receptors; OCD: obsessive–compulsive disorder; PDE5: phosphodiesterase type 5; PE: premature ejaculation; PEP: Premature Ejaculation Profile; PRO: patient-reported outcome; RCT: randomised controlled trial; SS: Severance Secret (cream); SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants
... It is administrated orally as needed (prn) 1-3 h before intercourse, indicating it may be effective as an 'on-demand' treatment for PE. The drug also shows dose-proportional pharmacokinetics, as shown in clinical trials using 30 mg and 60 mg doses [37]. In phase II and phase III clinical trials, dapoxetine has shown to be efficacious in treating all components of premature ejaculation in patients with lifelong PE [37][38][39][40][41]. ...
... The drug also shows dose-proportional pharmacokinetics, as shown in clinical trials using 30 mg and 60 mg doses [37]. In phase II and phase III clinical trials, dapoxetine has shown to be efficacious in treating all components of premature ejaculation in patients with lifelong PE [37][38][39][40][41]. This includes significantly increasing IELT, increasing perceived control over ejaculation, as well as decreasing the negative personal consequences, such as distress, surrounding PE. ...
Article
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Premature ejaculation (PE) is a highly prevalent male sexual dysfunction that is often neglected, presenting a currently unmet therapeutic need. The classification of PE has historically been varied and at times ambiguous, contributing to inaccurate prevalence estimates. This review uses the International Society for Sexual Medicine (ISSM) definition of PE, which includes reduced ejaculatory latency, lack of control and associated negative personal consequences. Patient assessment and management options differ depending on the classification of PE and it is the role of the clinician to appropriately classify patients and be aware of the correct management strategies. This review provides an overall background of PE in terms of classification and underlying physiology, patient assessment and management strategies along with the scientific rationale for treatment. Patients with lifelong and acquired PE are most likely to benefit from combination therapy of pharmacological treatment in the form of selective serotonin re-uptake inhibitor dapoxetine, psychosexual behavioural therapy and psychological therapy.
... Учитывая тот факт, что дапоксетин в дозе 60 мг лучше переносится, чем 100 мг, дозы 30 мг и 60 мг были выбраны для дальнейшего изучения в исследованиях эффективнос ти и безопасности III фазы. Фаза ІІІ проводилась в виде пяти рандомизированных плацебо контролируемых кли нических испытаний: в США [47], в 16 странах Европы, Аргентины, Бразилии, Канады, Израиля, Мексики и Юж ной Африки [48], исследование безопасности в Северной Америке [49], а также австралийского и азиатско тихооке анского исследований [50]. ...
... Опрос женщин партнеров установил, что мужской контроль над эякуляцией был «хорошим» или «очень хо рошим» с дапоксетином 30 мг (26,7%) и 60 мг (34,3%), их собственное удовлетворение половым актом было «хоро шим» или «очень хорошим» с дапоксетином 30 мг (37,5%) и 60 мг (44,7%). Также наблюдалось значительное сниже ние как личностного расстройства, связанного с эякуляци ей, так и межличностных трудностей у женщин партнеров мужчин, получавших дапоксетин 30 и 60 мг по сравнению с плацебо (p<0,001 для обоих) [48]. ...
Article
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The review, devoted to the actual problems of premature ejaculation, presents the current positions of classification, etiopathogenesis and treatment of this condition. The modern representative of selective inhibitors of serotonin reuptake - dapoxetine, is the only effective drug used to correct premature ejaculation of various genesis. The article presents modern data on its mechanisms of action, in the light of new scientific research.
... In comparative studies with dapoxetine and placebo, it was found that dapoxetine 30 mg pharmacotherapy increased IELT by about twofold while 60 mg pharmacotherapy increased 3.5 times [26]. In our study, it was found that the combination group had the longest IELT time compared to other groups and this difference was statistically significant (p < 0.001). ...
Article
Full-text available
Purpose Premature ejaculation (PE) is a common sexual dysfunction that significantly affects the quality of life of the patient and their partner. We aimed to compare the efficacy and safety of the combination therapy with biofeedback-guided pelvic floor exercise therapy (BFT) and dapoxetine 30 mg. Methods Sixty-five patients diagnosed with lifelong PE were included in the study. Patients were divided into three groups as BFT, dapoxetine 30 mg and a combination of BFT and dapoxetine 30 mg. The patients were compared with the intravaginal ejaculatory latency time (IELT) pre-treatment and post-treatment 1st and 3rd months. Results The mean IELTs of the patients in Group 1 were 40 s in pre-treatment, 115 s at the end of the 4th week and 140 s at the end of the 12th week. The IELT values of the patients in Group 2 were 40 s in pre-treatment, 145 s in the 4th week and 170 s in the 12th week. The IELT values were calculated in Group 3 as 42.5 s in pre-treatment, 185 s in the 4th week and 205 s in the 12th week When the IELT was statistically compared between the groups at 1st and 3rd months, the duration in the combination group was found to increase significantly (p < 0.001). Conclusion Combination therapy with BFT and dapoxetine 30 mg in lifelong PE treatment is a good alternative with a low side effect profile and acceptable continuous efficiency.
... Sertraline hydrochloride, as a highly selective serotonin reuptake inhibitor, can inhibit the reuptake of serotonin in ejaculatory central neurons so as to reduce the excitability of ejaculatory central neurons. On the other hand, sertraline has weak affinity for dopamine receptor, cholinergic receptor, histamine receptor, and adrenergic receptor and will not enhance the activity of catechol neurotransmitters so as to achieve the effect of treating premature ejaculation [6,7]. However, the drug takes effect 1-2 weeks after taking, often including drowsiness, dry mouth, dizziness, nausea, diarrhea, decreased sexual desire, and nonejaculation [8,9]. ...
Article
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Objective: To investigate the clinical efficacy and possible mechanism of electroacupuncture in the treatment of premature ejaculation. Methods: 50 cases of premature ejaculation patients who met the diagnostic criteria were randomly divided into 2 groups with 25 cases in each group. The observation group was treated with electroacupuncture, and the control group was treated with Longdan Xiegan decoction. The treatment period was 4 weeks. Ejaculation latency (IELT), sexual satisfaction score of patients, sexual satisfaction score of partners, testosterone test, and drug safety assessment were performed in all 4 groups before and after treatment. Results: IELT was prolonged in all groups after treatment, the difference was statistically significant (P < 0.05). At the same time, the IELT of the observation group was significantly higher than that of the control group after treatment. Life satisfaction scores of patients and spouses in 2 groups were improved after treatment compared with before treatment, the difference was statistically significant (P < 0.05). After treatment, the satisfaction scores of patients and spouses in the observation group were higher than those in the control group, and the difference was statistically significant (P < 0.05). Before treatment, there was no significant difference in serum testosterone levels among all groups (P > 0.05). Serum testosterone levels in all groups were decreased after treatment compared with before treatment, with statistical significance (P < 0.05). After treatment, the serum testosterone level of the observation group was lower than that of the control group, and the difference was statistically significant (P < 0.05). During the treatment, the adverse reactions in each group disappeared after treatment, and no obvious abnormality was observed in the safety indicators. Conclusion: Electroacupuncture can improve the symptoms of premature ejaculation, which may be related to the regulation of serum testosterone by acupuncture.
... 7 Recently, dapoxetine (Johnson & Johnson, Priligy, New Brunswick, NJ, USA) got marketing approval in some countries including Europe for the treatment of PE as a short-acting SSRI used in an on-demand manner. 8,9 However, dapoxetine showed a high prevalence of discontinuation in a clinical trial, 10 and on-demand SSRIs might be an inappropriate approach for lifelong PE and have limited effects compared to daily SSRIs. 11,12 On the other hand, the daily SSRI treatments currently used increase the risk of adverse effects such as headache, nausea, diarrhea and sexual dysfunctions (reduced libido and erectile dysfunctions) 4,7,9,11,13 due to the potential drug-drug interactions and another serotonin sub-receptor and neurotransmitter receptor selectivity. ...
Article
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Purpose: DA-8031 is a novel selective serotonin reuptake inhibitor for the treatment of premature ejaculation. This study investigated the pharmacokinetics, safety and tolerability of multiple oral doses of DA-8031. In addition, a genetic analysis was explored to evaluate the effect of genetic polymorphisms on the pharmacokinetics of DA-8031. Subjects and methods: A dose block-randomized, double-blind, placebo-controlled study was conducted in 3 dose groups with 20, 30 and 40 mg of DA-8031. Healthy male subjects were randomized to DA-8031 or placebo at a 4:1 ratio in each dose group of 10 subjects by oral administration once daily for 7 consecutive days. Serial blood and urine samples were collected for the pharmacokinetic evaluation, and the pharmacokinetic-related genes were analyzed by DMETTM plus. A safety evaluation was conducted including adverse events (AEs) monitoring and 12-lead electrocardiogram (ECG). Results: The plasma DA-8031 concentration reached the maximum concentration (Cmax) in 2.2 to 3.0 h and was eliminated with a mean half-life of 25.5 to 26.7 h at steady state. The accumulation index of DA-8031 ranged 2.3 to 2.8. The systemic exposure of DA-8031 of the CYP2D6 intermediate metabolizer (IM) was significantly higher compared to the CYP2D6 poor metabolizer (PM). There were no clinically significant QTc interval changes, and all the adverse events were mild. Conclusion: After multiple oral doses of DA-8031 20, 30, and 40 mg in this study, the systemic exposure of DA-8031 increased in a more than dose-proportional manner with the increasing doses, and DA-8031 was generally well tolerated. In addition, the genetic polymorphisms of CYP2D6 have an impact on the pharmacokinetics of DA-8031.
... Dapoxetine, which is another SSRI for LPE treatment, is used on-demand. Many studies have indicated that dapoxetine increases IELT length significantly (Buvat, Tesfaye, Rothman, Rivas, & Giuliano, 2009;Pryor et al., 2006). Furthermore, oxytocin was also observed to have an effect on LPE; studies on cligosiban, which functions through the oxytocin receptor, are still being conducted (Osterloh et al., 2018). ...
Article
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The aim of our study was to compare melatonin levels of patients with lifelong premature ejaculation (LPE) (n:60) with healthy controls (n:30) and to investigate the changes of melatonin levels in the treatment with dapoxetine and sertraline. Age, body mass index, duration of marriage, weekly intercourse number, International Index of Erectile Function scores, Intravaginal Ejaculation Latency Time (IELT) and melatonin levels were recorded. LPE patients were divided into two treatment groups. The first group was included 30 patients, who received 60 mg dapoxetine for six weeks, twice a week, an hour before intercourse. The second group received 50 mg of sertraline daily, for six weeks. IELT and melatonin measures were repeated after the treatment. IELT (dapoxetine group: 41.22 ± 21.3 s, sertraline group: 48 ± 23.11 s, control group: 195.54 ± 84.14 s; p < .001) and melatonin levels (dapoxetine group: 5.75 ± 2.04 pg/mL, sertraline group: 5.49 ± 2.88 pg/mL, control group: 13.4 ± 12.09 pg/mL; p < .001) of both LPE groups were significantly lower than control group. Following the six‐week sertraline (before: 48 ± 23.11 s, after: 101.01 ± 59.55 s; p < .001) and dapoxetine (before: 41.22 ± 21.3 s, after: 97.39 ± 44.1 s; p < .001) treatments, IELT increased. The melatonin levels increased in the sertraline group (before: 5.49 ± 2.88 pg/mL, after: 10.6 ± 7.37 pg/mL; p < .001). Our results indicate that melatonin levels of LPE patients are lower than levels of healthy volunteers. Furthermore, we found a significant increase in melatonin levels following sertraline treatment.
... Es wird vermutet, dass die durch SSRI erreichte vermehrte Bindung des Botenstoffes Serotonin an 5HT2-Rezeptoren im Gehirn und Rückenmark zu einer generellen Abnahme des sexuellen Antriebs sowie zu einer verminderten Erektions-und verzögerten Ejakulationsfähigkeit führt (Pfaus, 2009;Waldinger et al., 1998). So kommt der besonders kurzwirksame SSRI Dapoxetin auch in der Behandlung der Ejaculatio praecox zum Einsatz (Buvat et al., 2009;Kaufman et al., 2009). Durch den antidepressiven Effekt sowie die allgemeine Förderung der Impulskontrolle haben sich SSRI bei Patienten mit einer paraphilen Störung und ausgeprägter sexueller Dranghaftigkeit oder einer komorbiden depressiven oder hypersexuellen (bzw. ...
Article
Die medikamentöse Behandlung der paraphilen Störung kann bei einigen Männern, die aufgrund einer Sexualstraftat verurteilt wurden oder ein hohes Risiko für die Begehung einer Sexualstraftat aufweisen, eine sinnvolle Ergänzung zur Psychotherapie darstellen. Derzeit werden folgende Pharmaka empfohlen: Selektive-Serotonin-Wiederaufnahme-Hemmer und Testosteron-senkende Pharmaka (direkte Testosteronantagonisten und GnRH-Agonisten). Obwohl aktuelle Leitlinien zur Behandlung der paraphilen Störung sowohl für erwachsene als auch für jugendliche Patienten klare Behandlungsempfehlungen geben, erfüllt der derzeitige Stand der Wissenschaft noch nicht die hohen Voraussetzungen an eine evidenzbasierte Medizin. Kürzlich wurde jedoch die erste randomisiert-kontrollierte Studie publiziert, die eine stärkere Abnahme der sexuellen Dranghaftigkeit unter GnRH-Antagonisten im Vergleich zu Placebo in einer Gruppe von Männern mit einer pädophilen Störung fand. Zumindest für den deutsch-sprachigen Raum werden vergleichbare Untersuchungen in naher Zukunft aber nicht möglich sein. Mit kleineren Einschränkungen lassen sich die Leitlinien auch auf die Behandlung der zwanghaften sexuellen Verhaltensstörung übertragen. Vor dem Einsatz der derzeit empfohlenen Pharmaka sollte eine ausführliche Aufklärung des Patienten über Nutzen und Risiken der Medikation erfolgen, nicht zuletzt auch, um dadurch die Compliance zu erhöhen. In ausgewählten Ausnahmefällen wird die medikamentöse Therapie sehr lange durchgeführt, ein Absetzen der Medikation sollte vor dem Hintergrund der umfangreichen Nebenwirkungen aber stets angestrebt werden. Findet das Absetzen unter kontrollierten und strukturierten Rahmenbedingungen statt, kann es erfolgreich verlaufen. In zukünftigen Untersuchungen sollte insbesondere die Wirkung der Testosteron-senkenden Pharmaka auf den Hirnstoffwechsel untersucht werden. Dadurch könnte es gelingen, spezifischere Therapieziele zu identifizieren, was es unter Umständen erlauben würde weniger invasive Therapiemethoden zu etablieren. Summary Pharmacological treatment is a reasonable addition to psychotherapy in some men convicted for a sexual offence or with a high risk of sexual offending. At present, the following pharmacological agents are recommended: Selective-Serotonin-Reuptake-Inhibitors (SSRI) and testosterone-lowering medications (antiandrogens and GnRH-agonists). Current guidelines concerning the pharmacological treatment of paraphilic disorders provide clear treatment recommendations; however, the current state of research is still far away from fulfilling the high requirements of an evidence-based medicine. Recently though, the first randomized-controlled trial was published showing that GnRH-antagonists led to a significantly stronger decrease in sexual preoccupation and other sexual risk variables compared to placebo in a group of pedophilic men. Conducting comparable studies in German-speaking countries will, however, not be possible in the near future. With some limitations current guidelines can also be transferred to the treatment of compulsive sexual behavior disorders. Before starting treatment all patients need to be informed about the risks and benefits of the medication. Especially testosterone-lowering medications are frequently accompanied by (severe) adverse effects. In individual cases treatment can be carried on for many years. In case therapy should be terminated this should be performed under controlled and structured circumstances. Future studies should assess the effect of testosterone-lowering medications on brain functioning and brain metabolism. These insights could guide the development of more specific and less invasive treatment methods.
... All males with PE are recommended to take a first dose, which is 30 mg, within 1-3 h before penetration of the vagina and not taking another dose within 24 h [42]. Dapoxetine previous studies reported significant improvement in the stopwatch-measured intravaginal ejaculation latency time (IELT) (as main outcome) and increased PE profile self-reported outcome measure by patients [41,43,44]. A metered-dose aerosol topical spray called Fortacin TM induces local anesthesia at the glans area of the penis [45]. ...
Article
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The incidence of premature ejaculation (PE) has been on the rise over the years. Thus, significant research efforts have been directed toward understanding the pathogenesis and hence treatment of PE. Here, we performed a comprehensive analysis of the worldwide trends in research outputs in the field of PE. This study investigated the universal findings of previous PE studies and the trending issues surrounding the condition. We employed the Web of Science Core Collection for data collection. The Excel (2016) and CiteSpace IV were used for information analysis. The information was categorized using journal names, institutions, research frontiers, citation reports, regions/countries, and authors. A sum of 886 publications concerning PE between 2008 and 2018 were identified as of July 6, 2019. The highest number of publications was identified in the Journal of Sexual Medicine published. The United States of America (USA) had the highest number of publications and H-index value. The highest co-citations were from Waldinger MD. The most common keyword was ‘drug treatment’. A steady pattern was observed for PE publications done between the period of 2008–2018. Thus, the USA is at the forefront of research on PE research. The interesting advanced research frontiers were drug treatment, circumcision, and sertraline.
... Trial data of on-demand medication intake are often observations of discrete events or episodes of when the medication was taken, including for example data on symptom severity/alleviation and information on day and time of the medication intake. Research into on-demand administration of medication have been conducted for erectile dysfunction [6][7][8], premature ejaculation in men [9,10], female sexual dysfunction [11,12], hemophilia [13], irritable bowel syndrome [14] and gastro-oesophageal reflux symptoms [15,16], amongst others. ...
Article
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Data from clinical trials investigating on-demand medication often consist of an intentionally varying number of measurements per patient. These measurements are often observations of discrete events of when the medication was taken, including for example data on symptom severity. In addition to the varying number of observations between patients, the data have another important feature: they are characterized by a hierarchical structure in which the events are nested within patients. Traditionally, the observed events of patients are aggregated into means and subsequently analyzed using, for example, a repeated measures ANOVA. This procedure has drawbacks. One drawback is that these patient means have different standard errors, first, because the variance of the underlying events differs between patients and second, because the number of events per patient differs. In this paper, we argue that such data should be analyzed by applying a multilevel analysis using the individual observed events as separate nested observations. Such a multilevel approach handles this drawback and it also enables the examination of varying drug effects across patients by estimating random effects. We show how multilevel analyses can be applied to on-demand medication data from a clinical trial investigating the efficacy of a drug for women with low sexual desire. We also explore linear and quadratic time effects that can only be performed when the individual events are considered as separate observations and we discuss several important statistical topics relevant for multilevel modeling. Taken together, the use of a multilevel approach considering events as nested observations in these types of data is advocated as it is more valid and provides more information than other (traditional) methods.
... The magnitude of placebo response in this study was higher than in the previous study we performed, although not especially high compared to many previous published studies of men with PE. 18 A greater number of study sites participated in this study (29 sites) compared to the previous study (10 sites). In the PEPIX study, the sites were chosen for their expertise in sexual medicine, whereas for the PEDRIX study both specialist and generalist centers were involved. ...
Article
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Introduction: Cligosiban is an orally administered, centrally penetrant oxytocin receptor antagonist being developed to treat premature ejaculation (PE). Aim: To determine the efficacy of 3 dose levels of cligosiban caplets to prolong intravaginal ejaculation latency time (IELT) and improve patient-reported outcomes in men with lifelong PE. Methods: Patients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts and if they met other diagnostic criteria for lifelong PE. Eligible patients (target 220 evaluable) were randomized to double-blind cligosiban 400, 800, or 1200 mg or matching placebo caplets (to be taken 1 to 6 hours prior to sexual activity). Assessments were conducted at 2, 4, and 8 weeks. Main outcome measure: Efficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, Patient's Global Impression of Severity, and the Clinical Global Impression of Change. Results: There were no clinically or statistically significant differences between cligosiban (at any dose level) and placebo for the primary endpoint (change in geometric IELT) or any of the secondary endpoints. Cligosiban was well tolerated with a side-effect profile similar to placebo. Clinical implications: This Phase IIb study failed to demonstrate the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE at doses up to 1200 mg. Strengths and limitations: This was a Phase IIb, randomized, double-blind, placebo-controlled study that was adequately powered but failed to detect a clinically meaningful or statistical difference in change in IELT between cligosiban at 3 dose levels and placebo. This is in contrast to a similarly designed proof-of-concept study where cligosiban was flexibly dosed at doses up to 800 mg and did demonstrate clinically meaningful and statistically significant changes in efficacy parameters. The reasons for this disparity are not known. Conclusions: Cligosiban was well tolerated but failed to demonstrate efficacy for the treatment of men with lifelong PE at doses up to 1200 mg. Althof S, Osterloh IH, Muirhead GJ, et al. The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX). J Sex Med 2019; 16:1188-1198.
... Sufficient evidence has been reported about the efficacy and safety of dapoxetine in treating PE (Akhvlediani & Matyukhov, 2017;Buvat, Tesfaye, Rothman, Rivas, & Giuliano, 2009;Chen, Qu, et al., 2016;Clement et al., 2012;Dresser, Desai, Gidwani, Seftel, & Modi, 2006;Feige, Pinsky, & Hellstrom, 2011). Various doses of dapoxetine can significantly prolong IELT, which is a common indicator for evaluating premature ejaculation in patients with PE (Li, Liu, Wu, Fan, & Dong, 2018). ...
Article
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To evaluate the efficacy and safety of tamsulosin combined with dapoxetine in the treatment of type IIIB chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) that is complicated by premature ejaculation (PE), a total of 251 CP/CPPS patients with PE were recruited from nine hospitals across China and were randomly divided into two groups: one received tamsulosin as a control, and the other received a combination therapy of tamsulosin and dapoxetine. Follow‐up was conducted at four time points, and indicators describing CP/CPPS and PE were compared between the two groups. In all, 223 patients were followed up at least once, and 114 patients completed all of the treatment process. The combination group showed more improvement in the symptoms of both PE and CP/CPPS, including thrust number (50.5 vs. 45), premature ejaculation profile score (11.39 vs. 6.96), intravaginal ejaculation latency time (5.95 min vs. 2.63 min) and the National Institutes of Health Chronic Prostatitis Symptom Index (7.44 vs. 11.81) in comparison with the tamsulosin group. In conclusion, for CP/CPPS patients with PE, tamsulosin combined with dapoxetine provided better therapeutic efficacy in the treatment of not only PE symptoms but also CP/CPPS indicators in comparison with tamsulosin monotherapy.
... However, it is presumed that dapoxetine works by inhibiting serotonin transporter and subsequently increasing serotonin's action at pre and postsynaptic receptors. Dapoxetine undergoes rapid (11) absorption and elimination resulting in minimal accumulation and has dose-proportional pharmacokinetics, which are unaffected by multiple dosing and do not vary between ethnic groups. The pharmacokinetic prole of dapoxetine suggests that it is a good candidate for on-demand treatment of PE. ...
Article
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Background: Premature ejaculation is a worldwide problem, characterised as the most common male sexual complaint. Selective serotonin reuptake inhibitors are widely used "off label" as pharmacotherapeutic agents in the treatment of premature ejaculation. Many pharmacological agents have been used for treatment with diverse results regarding effectiveness and safety. Objectives: To test the effectiveness and safety of on-demand usage of Dapoxetine in the treatment of premature ejaculation. Methods: Single-blind, placebo-controlled, stopwatch monitored study was conducted on 100 patients with lifelong premature ejaculation visited the outpatient clinic of urology at Ghazy Al-Hariri Teaching Hospital/Medical City Complex/Baghdad. The study covered the period from October 2010 to December 2012.Premature ejaculation was dened as intravaginal ejaculation latency time of <60 seconds in 80% or more of intercourse episodes. A total of 60 mg of dapoxetine hydrochloride was given to one group (50 patients) and placebo was supplied for the other group (50 patients). Drug or placebo was used 1-2 hours before the sexual act. Patients in both groups were followed up for 8 weeks. Our primary output was to measure the change in the intravaginal ejaculation latency time and sexual satisfaction. Results: Ninety-one (91%) completed the whole treatment schedule. The mean intravaginal ejaculation latency time after Dapoxetine and placebo increased from 57.6 and 54.2 seconds to approximately 322.5 and 92.1 seconds, respectively (P < 0.001). Sexual satisfaction was the second variable in this study and used to assess the cutoff values in denition of minimal and best clinical response to either treatment. Patients in dapoxetine group have more adverse events; however, none of these adverse events in both groups were severe enough to necessitate withdrawal from the study. Conclusion: Dapoxetine seems to provide signicantly better results in terms of intravaginal ejaculation latency time and intercourse satisfaction versus placebo. Further studies are required to draw nal conclusions on the efcacy of this drug in premature ejaculation. Key words: Premature ejaculation, dapoxetine, intravaginal ejaculation latency time. ver the past 20-30 years, premature ejaculation (PE) Otreatment paradigm, which was previously limited to behavioural psychotherapy, has expanded to include drug t r e a t m e n t. A n i m a l a n d h u m a n s e x u a l (1-3) psychopharmacological studies have demonstrated that serotonin,5-hydroxy-tryptamine (5-HT), and 5-HT receptors are involved in ejaculation and have conrmed a role for selective serotonin re-uptake inhibitors (SSRIs) in the treatment of PE. (4-6) Data from The Global Study of Sexual Attitudes and Behaviors (GSSAB), an international survey investigating the attitudes, behaviours, beliefs, and sexual satisfaction of 27,500 men and women aged 40-80 years, reported the global prevalence of PE (based on subject self-reporting) to be approximately 30% across all age groups.
... The coefficient of reliability between classes goes from 0.66 to 0.83 and its validity was confirmed by the dapoxetina and the Times of Latency of Ejaculation Intravaginal (TLEI). This instrument was validated on American and European population by Germans, Frenchman, English men, Italians and Poles (Giuliano et to., 2008) though it has been in use also in Spanish population (Bar-Or, Salottolo, Orlando, Winkler, and Group, 2012;Buvat, Tesfaye, Rothman, Rivas, and Giuliano, 2009). For the diagnosis there will be used the Premature Ejaculation Diagnostic Tool (PEDT) that measures five articles that they evaluate: impede to retard the ejaculation, ejaculation before that the patient wishes it, ejaculation with few stimulation, frustration related on having ejaculated prematurely and opinion of the couple about the ejaculation. ...
Data
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Flip zero protocol. Study protocol Trial ISM-FLI-2017-01 in english. (PDF)
... Слишком ранним считается семяизвержение, наступающее до истечения 2 мин с момента введения полового члена во влагалище, если при этом у партнерши не наступил оргазм. Некоторые авторы считают, что слишком ранним является семяизвержение, наступающее до совершения 25 фрикци онных движений [13]. ...
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The objective: to evaluate sexual health of women, whose men suffer from precocious ejaculation. Patients and methods. A gynaecological, sexological and psychological examination of 28 women of reproductive age, whose husbands were reported to have precocious ejaculation, was carried out. Results. Sexual discomfort and dissatisfaction of sexual relationships were reported by 22 (78,6%) women. Reduction of libido was established in 17 (60,7%) of the examined, primary anorgasmia – in 2 (7,1%), secondary anorgasmia – in 15 (53,6%), violation of lubrication – in 22 (78,6%), dyspareunia – in 25 (89,3%), and combination of sexual dysfunctions – in 23 (82,1%). Sexual disorders, revealed in the examined patients, were formed during 1–2 years at the background of sexual disharmonies in a couple (precocious ejaculation was established in husband’s body), accompanied in 89,3% of cases by the spectre of gynaecological pathology. Conclusions. Complex therapy in compliance with the principles of interdisciplinary approach and intergender correlations is a principle under the condition of restoration of sexual harmony in a couple. The clinical sample has demonstrated the trend of effective use of dapoxetine medicine in a complex therapy of precocious ejaculation and restoration of couple’s sexual health.
... Dapoxetine hydrochloride was currently the only SSRI approved for OD treatment for PE because of its rapid absorption and short initial half-life. Two regimens (30 mg and 60 mg OD) tested in six studies [29,40,43,50,52,61] were included in meta-analysis. Pooled evidence suggested that dapoxetine 30 mg OD and 60 mg OD both resulted in a significant increase in IELT when compared to placebo (MD 1.44; 95% CI 0.28-2.60 and MD 1.78; 95% CI 0.56-3.00, ...
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Purpose The purpose of the study was to conduct a systematic evaluation of the different general prescribed drugs for premature ejaculation (PE). Methods A systematic literature search of MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for Systematic Reviews was performed on 1 March 2018. Intravaginal ejaculation latency time (IELT) was the main outcome. Analysis was performed under multivariate random-effects network model and efficacies of drugs were ranked with surface under the cumulative ranking (SUCRA) probabilities. Results A total of 48 studies were reviewed and 40 of them were further enrolled into network meta-analysis. The majority of RCTs were of unclear methodological quality. Pooled evidence suggested that topical anaesthetic creams (TAs), tramadol, selective serotonin reuptake inhibitors (SSRIs), and phosphodiesterase type 5 inhibitors (PDE5is) are more effective at prolonging IELT comparing with placebo. TAs (90%) on demand (OD) and PDE5is plus SSRI (89.8%) had the highest SUCRA, which meant the most probable to be the most effective intervention. Conclusions We recommend the initial use of dapoxetine 30 mg OD for PE because it has been tested in largest and better designed clinical trials rather than it is more effective than the other drugs studied. TAs and tramadol 50 mg OD can be used as a viable alternative to oral treatment with SSRIs. PDE5is combined with SSRIs are more effective than SSRIs monotherapy but are also associated with more side effects. PDE5is OD can be recommended to PE patients with ED.
Chapter
Ejaculation is a complex physiological event in which multiple factors play a role. It requires a properly functioning central and peripheral nervous system and the absence of any anatomical and functional pathology. Pathologies occurring in any or more of these parameters cause ejaculation disorder. Ejaculation disorders are examined in a wide range, including premature ejaculation, delayed ejaculation, retrograde ejaculation, painful ejaculation, haemospermia, and anejaculation. Although orgasm is often a term used instead of ejaculation, it is a different physiological state and is a sense of pleasure that manifests itself with various body changes. Although orgasmic disorders are not as common as erectile dysfunction or premature ejaculation in clinical practice, they can cause serious sexual problems in men. Orgasmic disorders are mainly examined under anorgasmia and postorgasmic illness syndrome. While anorgasmia is primarily evaluated together with delayed ejaculation disease, postorgasmic illness syndrome is a different orgasmic disorder.
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Disorders of ejaculations are among the most complex complaints of patients seeking first medical help for sexual dysfunction. Among these, premature ejaculation (PE), delayed ejaculation (DE), retrograde ejaculation, and anorgasmia are the most frequently reported, and their impact on patients’ quality of life can be major. Although numerous preclinical and clinical studies have been published over the last two decades, the true pathophysiological mechanisms behind ejaculation remain unclear. In this context, this chapter aims at providing the latest evidence regarding ejaculation physiology together with detailed epidemiological data, diagnostic work-up, and treatment options upon PE, DE, retrograde ejaculation, and anorgasmia.
Article
Introduction: Premature ejaculation (PE) is a sexual dysfunction of unknown etiology affecting a substantial number of males and deteriorating sexual health and quality of life of the patient and his partner. Treatment still remains challenging; however, pharmacotherapy is considered the mainstay of therapy with behavioral and psychosexual interventions being particularly important as adjudicate procedures, within the context of a holistic approach. Areas covered: The authors review the literature on the available medications for PE, both officially registered and non-registered. Currently, only dapoxetine and an anesthetic spray containing lidocaine and prilocaine (Fortacin™) are officially approved, with the rest being used off-label. Herein, updated data regarding the efficacy and safety of the pharmaceutical agents are presented. Expert opinion: On-demand dapoxetine is reportedly efficacious and safe in treating lifelong PE and is the first medication to be approved for this purpose. Fortacin has also shown considerable efficacy and may be reliably used on-demand. Phosphodiesterase type 5 inhibitors (PDE5Is) have been found to be effective in the treatment of PE and are therefore recommended either as monotherapy or combined with other therapies (i.e. dapoxetine). Adverse events of any therapy should be taken under consideration. Physicians should encourage patients to discuss their needs and expectations and grade any improvement of their condition with treatment.
Article
Introduction Fifteen years have passed since the International Society of Sexual Medicine first established the 3-pronged criteria for premature ejaculation (PE): a short ejaculation latency, lack of ejaculatory control, and bother/distress. Although the process of establishing valid criteria for any condition or disorder is an ongoing one, a dearth of targeted research on these criteria has hindered professional societies from updating and revising them. Objectives To review and critique existing criteria used in the diagnosis of PE, to identify specific problems with them, and to recommend studies that will address shortcomings. Methods Each of the PE criteria was evaluated and compared against standard procedures for establishing validated measures. Following each analysis, targeted research to address the gaps has been recommended. Results Each PE criterion has shortcomings and each can be improved by using standard validation procedures, as noted by the targeted research outcomes. Professional societies can play an important role by encouraging broad participation in research that generates new and relevant data supporting, validating, or challenging the existing criteria. Conclusion The concepts underlying the diagnostic criteria for PE have both broad consensus and functional utility. Nevertheless, much of the research investigating PE has uncritically adopted these criteria without concomitantly recognizing their limitations. These limitations prevent determining accurate prevalence rates, interpreting research findings with confidence, and establishing efficacious treatment outcomes. Rowland DL, Althof SE, McMahon CG. The Unfinished Business of Defining Premature Ejaculation: The Need for Targeted Research. Sex Med Rev 2021;XX:XXX–XXX.
Article
Purpose: Selective serotonin re-uptake inhibitors (SSRIs) are frequently used to treat premature ejaculation (PE) in men. We performed a Cochrane review to assess the efficacy of SSRI treatment for PE. Materials and methods: We extensively searched a range of databases up to May 2020 and only included randomized controlled trials. Results: A total of 31 studies with 8,254 men were included in this analysis. We found that SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better'; risk ratio [RR], 1.92; 95% confidence interval [CI], 1.66-2.23; moderate-certainty evidence) and satisfaction with intercourse (defined as a rating of 'good' or 'very good'; RR, 1.63; 95% CI, 1.42-1.87; moderate-certainty evidence) compared to placebo. Furthermore, SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good'; RR, 2.29; 95% CI, 1.72-3.05; moderate-certainty evidence) and probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR, 1.54; 95% CI, 1.26-1.88; moderate-certainty evidence). SSRI treatment may increase IELT compared to placebo (mean difference, 3.09 minutes higher; 95% CI, 1.94 higher to 4.25 higher; low-certainty evidence). However, SSRIs may increase treatment cessations due to adverse events compared to placebo (RR, 3.80; 95% CI, 2.61-5.51; low-certainty evidence). Conclusions: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo.
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Background There are several problems with diagnostic criteria for premature ejaculation (PE) that lack objectivity, clarity and precision. They hamper accurate determination of PE prevalence estimates, investigations into the etiology of the dysfunction, impact on partners, development of validated Patient Reported Outcomes, regulatory authority oversight, and which men might benefit from specific treatment interventions. Aim We sought to review, analyze and comment on the evolution of the definitions of PE and offer suggestions for future directions for PE definitions. Our goal is to propose strategies whereby the criterion sets are useful to researchers, clinicians and governmental oversight agencies alike and bring harmony and scientific rigor among the conflicting and confusing definitions. Methods There are several premature ejaculation definitions published in the peer reviewed medical literature. The PUBMED electronic database from 1970 to 2021 was searched for published definitions. Search terms included the medical subject headings of premature ejaculation, definition and diagnosis. In chronological order, Table 1 lists the various diagnosis and criteria sets for PE. We discuss the process by which constructs, which make up diagnostic criteria sets, are operationalized and validated. Results We review definitions of PE beginning with Masters and Johnson's focus on partner orgasmic attainment and move through the nebulous and subjective criterion sets found in the early Diagnostic and Statistical Manuals and International Classification of Disease series, to the more evidenced-based definitions found in International Society of Sexual Medicine, Diagnostic and Statistical Manuals-5 and the American Urological Association (AUA) definitions. Additionally, we discuss how constructs and criteria sets have been adopted to minimize errors of inclusion and exclusion in defining disease/dysfunction. Strengths and Limitations This manuscript offers a careful chronological analysis of the published definitions of PE. This historical lens allows the reader to perceive the shifting science underlying the development of PE definitions. The manuscript is limited regarding our comments on acquired PE as evidenced-based research is incomplete. Conclusion Over the past 50 years there has been considerable forward momentum in defining PE based on well conducted scientific studies. We support the American Urological Association's modification in Intravaginal ejaculatory latency time to 2-minutes for lifelong PE, concur with the 11th revision of the International Classification of Diseases recommendation for changing the terminology from premature ejaculation to early ejaculation. We also recommend ongoing validation of definitions, moving away from the current heterosexist definition of PE based on penile-vaginal sex and urge further population based research into acquired PE to develop stronger evidenced-based criterion sets for this subtype. Althof SE, McMahon CG, Rowland DL. Advances and Missteps in Diagnosing Premature Ejaculation: Analysis and Future Directions. J Sex Med 2021;XX:XXX–XXX.
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Aims: In this study, a simple, green, and rapid capillary zone electrophoresis (CZE) method coupled with a diode array detector (DAD) was applied for the analysis of avanafil (AVA) and dapoxetine hydrochloride (DAP) as a binary mixture using vardenafil (VAR) as an internal standard (IS) in pure form and pharmaceutical formulation. Methodology: The separation was done using fused silica capillary (58.5 cm total length, 50 cm effective length, and 50 μm internal diameter) and the running background electrolyte (BGE) was 100 mM acetate buffer at pH 3.6. During the separation process, the applied voltage was 30 KV, while the temperature was 25 °C. The sample injection was applied at a pressure of 50 mbar for 10 s, and detection was carried out at 210 nm for DAP and 248 nm for AVA and VAR. Results: Analysis of the tested drugs and the internal standard was carried out in less than 6.5 min, where the migration times were 4.29, 4.90, and 6.02 min for IS, DAP and AVA respectively. The proposed method showed linearity in the concentration range 5-80 and 5-70 μg/mL with correlation coefficients 0.9996 and 0.9999 for AVA and DAP respectively. The limit of detection (LOD) was 0.523 and 0.531 for AVA and DAP respectively, while the limit of quantification (LOQ) was 1.585 and 1.608 in respective order. The Peak purity and identity in the proposed method were validated by DAD. Conclusion: The proposed CZE method was validated according to ICH guidelines and applied successfully for the estimation of AVA and DAP in their combined pharmaceutical preparation.
Article
This study was to explore whether serotonin transporter gene‐linked polymorphic region polymorphisms (5‐HTTLPR+rs25531) influence the response to dapoxetine treatment in a Chinese population with premature ejaculation (PE). 112 patients with PE re‐enrolled from our previous study received dapoxetine monotherapy. At the endpoint, patients with S’S’ had a significant increased risk of nonresponse compared with L’ carriers (p < .001). The improvement in S’S’ genotype was significantly lower in premature ejaculation profile (PEP) items of ‘control over ejaculation’ (p = .035) and ‘distress related to ejaculation’ (p = .017) than that in L’ carriers. As to clinical global impression of change (CGIC), results in S’S’ subjects showed significantly lower scores (p = .008) and a less satisfaction rate reporting at least ‘better’ (p = .020) compared with L’ carriers. Moreover, our findings suggested that patients with S’S’ were more likely to develop adverse effects (AEs) compared with L’ carriers (p = .040). This study suggests that PE patients bearing the S’S’ genotype have an inferior comprehensive efficacy and safety of dapoxetine treatment, which consist of poorer response in IELTs, less improvement in patient‐reported outcome (PRO) measures and greater incidence of AEs, than L’ carriers. Variants of triallelic 5‐HTTLPR may play a major role as a predictor of treatment response to dapoxetine.
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Objectives: Premature ejaculation (PE) is one of the most frequently seen causes of sexual dysfunction in males. The aim of this study is to investigate whether the music therapy is effective in the treatment of acquired PE and compare the intravaginal ejaculation latency time (IELT), premature ejaculation diagnostic tool (PEDT), and anxiety scores of patients with acquired PE symptoms that underwent music therapy to patients that were treated with 30 mg dapoxetine. Materials and methods: The study's inclusion criteria was as following: age range from 20-35, married, has regular sexual intercourse, non-smokers, and has no known comorbidities. All participants of the study were with acquired PE based on the International Society for Sexual Medicine criteria. Experimental group (group 1) included 60 patients that were asked to listen to relaxing music and meditate for 45 minutes before the sexual intercourse while continuing their daily routine. This group was selected randomly and prospectively from young healthy individuals. Meanwhile, control group (group 2) included 60 patients who were treated with 30 mg dapoxetine for PE and whose datas were collected from the hospital archive. The patients were evaluated before treatment and re-evaluated (PEDT, IELT, anxiety level) after 60 days. State-Trait Anxiety Inventory was used to assess state and trait anxiety. Results: In both groups, a significant difference (p<0.001) was observed in pre and post-treatment IELT, PEDT, and anxiety scores. Although group 2 showed better improvement in both IELT and PEDT scores, there was no significant difference between two groups. Conclusion: Listening to music and other similar anxiety decreasing methods can be a part of treatment plan for PE.
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Background: Premature ejaculation (PE) is a common problem among men that occurs when ejaculation happens sooner than a man or his partner would like during sex; it may cause unhappiness and relationship problems. Selective serotonin re-uptake inhibitors (SSRIs), which are most commonly used as antidepressants are being used to treat this condition. Objectives: To assess the effects of SSRIs in the treatment of PE in adult men. Search methods: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, CINAHL), clinical trial registries, conference proceedings, and other sources of grey literature, up to 1 May 2020. We applied no restrictions on publication language or status. Selection criteria: We included only randomized controlled clinical trials (parallel group and cross-over trials) in which men with PE were administered SSRIs or placebo. We also considered 'no treatment' to be an eligible comparator but did not find any relevant studies. Data collection and analysis: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were participant-perceived change with treatment, satisfaction with intercourse and study withdrawal due to adverse events. Secondary outcomes included self-perceived control over ejaculation, participant distress about PE, adverse events and intravaginal ejaculatory latency time (IELT). We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to GRADE. Main results: We identified 31 studies in which 8254 participants were randomized to receiving either SSRIs or placebo. Primary outcomes: SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better') compared to placebo (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.66 to 2.23; moderate-certainty evidence). Based on 220 participants per 1000 reporting improvement with placebo, this corresponds to 202 more men per 1000 (95% CI 145 more to 270 more) with improved symptoms with SSRIs. SSRI treatment probably improves satisfaction with intercourse compared to placebo (defined as a rating of 'good' or 'very good'; RR 1.63, 95% CI 1.42 to 1.87; moderate-certainty evidence). Based on 278 participants per 1000 reporting improved satisfaction with placebo, this corresponds to 175 more (117 more to 242 more) per 1000 men with greater satisfaction with intercourse with SSRIs. SSRI treatment may increase treatment cessations due to adverse events compared to placebo (RR 3.80, 95% CI 2.61 to 5.51; low-certainty evidence). Based 11 study withdrawals per 1000 participants with placebo, this corresponds to 30 more men per 1000 (95% CI 17 more to 49 more) ceasing treatment due to adverse events with SSRIs. Secondary outcomes: SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good') compared to placebo (RR 2.29, 95% CI 1.72 to 3.05; moderate-certainty evidence). Assuming 132 per 1000 participants perceived at least good control, this corresponds to 170 more (95 more to 270 more) reporting at least good control with SSRIs. SSRI probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR 1.54, 95% CI 1.26 to 1.88; moderate-certainty evidence). Based on 353 per 1000 participants reporting low levels of distress, this corresponds to 191 more men (92 more to 311 more) per 1000 reporting low levels of distress with SSRIs. SSRI treatment probably increases adverse events compared to placebo (RR 1.71, 95% CI 1.48 to 1.99; moderate-certainty evidence). Based on 243 adverse events per 1000 among men receiving placebo, this corresponds to 173 more (117 more to 241 more) men having an adverse event with SSRIs. SSRI treatment may increase IELT compared to placebo (mean difference (MD) 3.09 minutes longer, 95% CI 1.94 longer to 4.25 longer; low-certainty evidence). Authors' conclusions: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. Undesirable effects are a small increase in treatment withdrawals due to adverse events as well as substantially increased adverse event rates. Issues affecting the certainty of evidence of outcomes were study limitations and imprecision.
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Introduction: The use of pharmacotherapy as a first-line treatment for premature ejaculation (PE) is recommended by EAU guidelines. However, no study had analyzed multiple treatment comparisons among available on-demand therapy. Therefore, we aimed to perform a network meta-analysis (NMA) to characterize the comparative efficacy and tolerability of on-demand therapy for PE. Methods: We systematically searched randomized controlled trials (RCTs) in several databases at any period up to November 2019. NMA was performed to estimate efficacy and tolerability outcomes using intravaginal ejaculation latency time (IELT) and overall adverse effects (AEs), respectively. We ranked each outcome using the surface under the cumulative ranking curve (SUCRA) and presented the two outcomes as a clustered ranking plot. Results: A total of 19 RCTs comprising 5950 patients were included in this NMA. All active treatments showed significant improvement compared to placebo. Among the available on-demand treatment, the combination of SSRI plus PDE5i showed the highest efficacy (MD: 3.06; 95%CI 1.84-4.29) followed by tramadol 100 mg and vardenafil 10 mg (MD 2.9, 95%CI 1.63-4.16; MD 2.36, 95%CI 1.2-3.52; respectively). Based on the SUCRA, the combination of SSRI plus PDE5i had the highest score (91.7%) in efficacy, while dapoxetine 30 mg had the highest score (73.3%) in terms of tolerability. Conclusion: The combination of SSRI plus PDE5i was the treatment of choice for individuals who prioritize efficacy. For those who prioritize tolerability, dapoxetine 30 mg and vardenafil 10 mg became alternative treatments. Various on-demand therapy options require careful discussion with patient expectations of treatment effects.
Article
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To assess the comparative efficacy and safety of drug treatments for premature ejaculation. A systemic review and Bayesian network meta-analysis were executed on randomised controlled trials of drug interventions for premature ejaculation. Intravaginal ejaculation latency time and related adverse effects were outcome measures. A total of 44 RCTs with 11,008 patients were included in our NMA. In therapy <8 weeks, the ranking of drug efficacy was topical creams >selective serotonin reuptake inhibitor (SSRI)+ phosphodiesterase 5 inhibitor (PDE5i) > PDE5i > sertraline > clomipramine > paroxetine > dapoxetine 60 milligram (mg) > dapoxetine 30 mg > fluoxetine>citalopram > duloxetine>placebo. In therapy ≥ 8 weeks, the ranking of drug efficacy was SSRI + PDE5i > topical creams > paroxetine > tramadol > PDE5i > fluoxetine > dapoxetine 60 mg > dapoxetine 30 mg > clomipramine>citalopram > placebo. For total adverse events, clomipramine, dapoxetine 30 mg, dapoxetine 60 mg, paroxetine, PDE5i, SSRI + PDE5i and tramadol had a higher risk than placebo. In conclusion, in ≥8 weeks of therapy, the drug combination of SSRI + PDE5i was the most effective PE therapy. In <8 weeks of therapy, the efficacy of local anaesthetics was best. All drug treatments were ranked better than placebo. In general, drugs with better effects had more obvious side effects.
Article
Mit Dapoxetin kann eine "vorzeitige" Ejakulation hinausgezögert werden. Dass es sich dabei um ein überflüssiges und teures "Lifestyle"-Mittel handelt, versteht sich ohne weitere Erläuterung.
Chapter
Ejaculation is a complex biological event. It is based on a simple spinal reflex that is modulated by anatomical, cerebral, and learned behavioral events. As a consequence of these varied inputs, disordered ejaculation occurs and is divided into early, delayed, retrograde, and anejaculation. In addition, congenital and acquired causes of abnormal ejaculation include spinal cord injury, diabetes mellitus, congenital absence of the vas deferens, and ejaculatory duct obstruction. Common medications such as antidepressants, alpha-blockers used for enlarged prostates, and finasteride (prostate enlargement and male pattern baldness) can also contribute to disordered ejaculation. Using principles of evidence-based medicine, we review the diagnosis and management of known forms of disordered ejaculation.
Article
We conducted a systematic review and meta-analysis of published randomised controlled trials of dapoxetine for premature ejaculation. We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov and Clinical Trials.gov for studies reporting dapoxetine in men with premature ejaculation. Efficacy endpoints included intravaginal ejaculatory latency times (IELT), personal distress related to ejaculation (PDRE) and treatment-emergent adverse events (TEAEs) was used to evaluate safety. Data were analysed using a random-effects model. Electronic search identified 276 papers. The final analysis included eight papers (n = 8422 subjects). Analysis of the pooled results indicated efficacy in both IELT (weighted mean difference (WMD) = 1.67, 95% confidence interval (CI) 1.45–1.89) and PDRE (relative risk = 1.26, 95% CI 1.18–1.35). Subgroup analysis indicated efficacy (i.e. increase in IELT) for 30- and 60-mg on-demand dapoxetine (WMD 1.38 (95% CI 1.01–1.75) and 1.62 (95% CI 1.40–1.84) respectively), as well as daily use of 60 mg dapoxetine (WMD 2.18, 95% CI 1.71–2.64). The safety profile was acceptable. Based on the different effects of magnitude of the three dosing regimens, we recommend a stepwise approach, starting with 30 mg on demand, then 60 mg on demand and finally 60 mg dapoxetine daily.
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Although previous studies have investigated the safety and efficacy characteristics of oral drugs in patients with premature ejaculation (PE), the available results remained inconsistent. Hence, this article was conducted to comprehensively compare the effectiveness of oral drugs and several relevant complications in patients with PE. Relevant researches were comprehensively searching from the databases PubMed, EMBASE, and Web of Science, up to May 1st, 2018. The pooled standard mean difference (SMD) or odds ratios (ORs) with 95% Credible interval (CrI) was respectively utilized to evaluate the safety and efficacy of oral drugs in PE. A total of 25 relevant research were ultimately included in this network meta-analysis. PE oral drugs mainly included serotonin reuptake inhibitors (SSRIs) and phosphodiesterase type 5 inhibitors (PDE5i). Our results successfully shed light on the efficacy differences of oral drugs for the treatment of PE. The cumulative rank probability of IELT at 4–6 weeks from best to worst was SSRIs + PDE5i, PDE5i, and other SSRIs alone. In addition, this meta-analysis also showed fluoxetine 20 mg, dapoxetine 60 mg, PDE5i, and SSRIs + PDE5i had a higher, whereas other SSRIs alone had a relatively lower incidence rate of clinically relevant complications. In summary, our results showed that the usage of PDE5i only or in combination with SSRIs might be stronger than SSRIs alone in the efficacy of PE oral drugs. Nevertheless, it also has a problem about the side effects of PDE5i including gastrointestinal or central nervous systems complications, which prevents it as the first-line treatment drug. Despite the development of some promising new therapeutic options, SSRIs remained as the first line of therapeutic PE oral drug through a synthetical consideration at present.
Article
To evaluate the overall treatment benefits of premature ejaculation desensitisation therapy combined with 30 mg dapoxetine hydrochloride treatment on patients with primary premature ejaculation (PPE). Ninety‐nine PPE patients were randomly divided into two groups at the ratio of 2:1. Sixty‐six PPE patients received premature ejaculation desensitisation therapy accomplished by Weili Automatic Semen Collection—Penis Erection Detection and Analysis workstation (WLJY‐2008) combined with 30 mg dapoxetine hydrochloride treatment (DTCD group), and another 33 patients received 30 mg dapoxetine hydrochloride‐only treatment (DO group). Intravaginal ejaculation latency time (IELT) and premature ejaculation profile (PEP) were recorded before and during the treatment, and clinical global impression of change (CGIC) in PPE was recorded at the fourth week and the end of the treatment and the items. In both groups were significantly improved (p < 0.0001) in IELT, PEP and CGIC for premature ejaculation compared with baseline, and DTCD treatment showed a more significant improvement on PPE patients in the items compared with DO treatment (p < 0.05). Thus, premature ejaculation desensitisation combined with dapoxetine therapy may be a better choice for improving premature ejaculation with PPE.
Article
In vitro incubation of rat liver microsomes with 30 μL of 100 μmol·L⁻¹ dapoxetine and 30 μL of 10, 100, 250, 500, 1000, 2500, or 5000 μg·mL⁻¹ Wuziyanzong pill was performed at 37 °C for 60 min. Dapoxetine concentration was analyzed by high performance liquid chromatography (HPLC). The half maximal inhibitory concentration (IC50) of Wuziyanzong pill on metabolism of dapoxetine was 296.10 μg mL⁻¹ in vitro. Twelve SD rats were randomly divided into 2 groups: Control group and Wuziyanzong pill group. The two groups were administrated with 10 mL·kg⁻¹ saline (Control group) or 10 mL·kg⁻¹ Wuziyanzong pill solution (Experimental group, solution contained 200 mg mL⁻¹ Wuziyanzong pill) for 15 consecutive days. Following administration of saline or Wuziyanzong pill on the 15th day, 20 mg kg⁻¹ dapoxetine was administered to all rats. Blood was collected from the tail vein (0.3 mL) at multiple time points, and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was used to determine the concentration of dapoxetine and its main metabolites, dapoxetine-N-oxide and desmethyldapoxetine in rats. Pharmacokinetic analysis of dapoxetine showed that area under the concentration-time curve (AUC) and mean maximum plasma concentration (Cmax) of the Wuziyanzong pill group were decreased, while plasma clearance (CLz) was increased compared with control group (P < 0.01). The HPLC method for determination of dapoxetine in vitro was accurate and specific. The UHPLC-MS/MS method established for determination of dapoxetine and its major metabolites in rat plasma was rapid and specific, which met the requirements of pharmacokinetic guidelines. Wuziyanzong pill had a weak inhibitory effect on metabolism of dapoxetine in vitro, but had a very strong induction effect in vivo, suggesting the dosage of dapoxetine should be increased when administered in combination with Wuziyanzong pill.
Chapter
Direct-to-Consumer-Marketing (DTC-Marketing) stellt die wichtigste Spielart der in Kap. 12 analysierten Pull-Strategie dar. In Deutschland hat es v. a. im Bereich der Printmedien und des Fernsehens seit jeher eine gewisse Relevanz, wie v. a. journalistisch angelegte Untersuchungen gezeigt haben (Walter und Kobylinski 2010, S. 15 ff., 47 ff., 127 ff.). Durch die Verbreitung der Internetnutzung erlangt DTC-Marketing – genauer: das Online-DTC-Marketing als dessen Unterform – jedoch ein deutlich stärkeres Gewicht.
Chapter
While erectile dysfunction has received much-needed publicity, ejaculatory disorders are far more common and affect over 30% of men in the age group of 40–80 years [1–3]. Ejaculatory dysfunction encompasses a spectrum of conditions, namely, premature ejaculation (PE), delayed ejaculation (DE) and anejaculation (AE) that includes retrograde ejaculation (RE). Due to the lack of standardized definitions for these problems, the clinical diagnosis and management strategies for ejaculatory dysfunctions are somewhat arbitrary. Ejaculatory dysfunction not only affects a man’s sexual health but can also interfere with his fertility when conception is desired, thereby resulting in significant distress for both partners [4].
Article
Introduction: Various drugs are available for lifelong and acquired premature ejaculation (PE), but only dapoxetine and FortacinTM have been officially registered. On the other hand, all sorts of pharmacologically not-investigated over-the-counter-products (OTCs) are used by men with complaints of PE with normal ejaculation time durations (subjective PE). There is a need to critically review the current state of registered and nonregistered drugs for PE. Areas covered: In this review, the authors use the guideline of the International Society for Sexual Medicine (ISSM) for the treatment of PE and provide evidence-based recommendations for the pharmacotherapy of lifelong and acquired PE. This should always be accompanied by psychoeducation, counseling, and information about common and rare side effects of the various available drugs. Expert opinion: As long as subjective PE is not officially recognized as the third PE subtype, registration authorities will continue to demand drugs for subjective PE to be studied in men with lifelong PE. This is unfortunate as the method and design of studies of drugs for subjective PE differ from those of lifelong PE but also because drugs for subjective PE need to be investigated in men with subjective PE and not in men with lifelong PE.
Chapter
Premature ejaculation (PE) is the most common sexual dysfunction in men, with global prevalence estimates ranging from 20 to 40%. Men with PE report high levels of distress and interpersonal difficulty related to ejaculation, low satisfaction with intercourse, low sexual self‐confidence, and lower overall quality of life. This chapter aims to review the available evidence on topical agents, dapoxetine, off‐label selective serotonin reuptake inhibitors (SSRIs), and tramadol in the treatment of PE. It addresses a series of focused clinical questions that are addressed in a systematic fashion, including a comprehensive literature search, a rating of the quality of evidence, and an assessment of ratio of benefit and harm of a given treatment option. The clinical questions include: In patients with lifelong PE, are topical anesthetics an effective, safe, and satisfying treatment option compared with placebo for improving intravaginal ejaculatory latency time (IELT)?
Article
Introduction. Premature ejaculation (PE) is the most common male sexual dysfunction affecting men and their partners. Lack of community-based data describing this condition limits understanding of PE and its outcomes. Aim. To characterize PE in a large population of men with and without PE using patient-reported outcome (PRO) measures elicited from men and their partners. Methods. 4-week, multicenter, observational study of males (≥18 years) and their female partners in monogamous relationships (≥6 months). Screening, baseline, and follow-up visits scheduled at 2-week intervals. Clinicians diagnosed PE utilizing DSM-IV-TR criteria. Intravaginal ejaculatory latency time (IELT), measured by a stopwatch held by the partner, was recorded for each sexual intercourse experience. Subject and partner independently assessed PROs: control over ejaculation and satisfaction with sexual intercourse (0 = very poor to 4 = very good), personal distress and interpersonal difficulty (0 = not at all to 4 = extremely), and severity of PE (0 = none to 3 = severe). Results. Of the total study population (N = 1,587), 207 subjects were diagnosed with PE and 1,380 were assigned to the non-PE group. Median IELT (min) was 1.8 (range, 0–41) for PE and 7.3 (range, 0–53) for non-PE subjects (P < 0.0001). More PE vs. non-PE subjects gave ratings of “very poor” or “poor” for control over ejaculation (72% vs. 5%; P < 0.0001) and satisfaction with sexual intercourse (31% vs. 1%; P < 0.0001). More subjects in the PE vs. non-PE group gave ratings of “quite a bit” or “extremely” for personal distress (64% vs. 4%; P < 0.0001) and interpersonal difficulty (31% vs. 1%; P < 0.0001). Subject and partner assessments showed similar patterns and correlated moderately (0.36–0.57). Conclusions. PE subjects reported significantly shorter IELT. Overlap in IELT distributions was observed between the PE and non-PE groups, indicating the need for additional PRO measures to characterize PE. Shorter IELT was significantly associated with reduced ejaculatory control and sexual satisfaction and increased distress and interpersonal difficulty.
Article
To assess the utility of perceived control over ejaculation ('control') in the evaluation of treatment benefit in men with premature ejaculation (PE), and to compare effects associated with a two-category or greater increase in this variable between men receiving dapoxetine and placebo. This subanalysis used combined data from all treatment groups in an integrated analysis of two identically designed, 12-week, double-blind, randomized, placebo-controlled trials of dapoxetine. Men (2614) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text revision) criteria for PE, had a stopwatch-measured intravaginal ejaculatory latency time (IELT) of < or =2 min in > or =75% of events in a 2-week baseline period, and self-reported moderate or severe PE. Men received placebo or dapoxetine 30 or 60 mg, 1-3 h before intercourse. The stopwatch-measured IELT was recorded for each episode; the patient-reported global impression of change (PGI; 7-point scale, 'much worse' to 'much better'), control and satisfaction with sexual intercourse (5-point scales, 'very poor' to 'very good') were assessed monthly. The utility of a two-category or greater increase in control was evaluated by examining the relationship of this variable with IELT and satisfaction with sexual intercourse. Of 2341 men with baseline and endpoint assessments, 96.8% reported 'very poor' or 'poor' control at baseline, and 748 (32%) reported a two-category or greater increase in control after treatment. More than 95% of those men rated their PE as 'slightly better', 'better', or 'much better' on the PGI; 67.1% gave ratings of 'better' or 'much better.' They also had greater improvements in IELT than men with less than a two-category increase in control, with a mean (sd) change from baseline of 3.7 (4.3) vs 0.77 (1.8) min, respectively, and a greater percentage reported good or very good satisfaction with sexual intercourse than men with less than a two-category increase in control (74% vs 19%, respectively). Nausea, headache and upper respiratory tract infection were the most common adverse events reported by men with a two-category or greater increase in control (15.8%, 7.4% and 6.6%, respectively) and those without (8.5%, 5.5% and 6.5%, respectively). The proportions of men with a two-category or greater increase in control with dapoxetine 30 and 60 mg were 36.3% and 44.5%, respectively (vs 15% with placebo). A two-category or greater increase in control (5-point scale) is useful for assessing the treatment benefit in men with PE; it corresponds with improvements in the man's perception of his condition, substantially greater prolongation of IELT, and higher levels of satisfaction with sexual intercourse.
Article
Objective: To develop a contemporary, evidence-based definition of premature ejaculation (PE). Methods: There are several definitions of PE; the most commonly quoted, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders - 4th Edition - Text Revision, and other definitions of PE, are all authority-based rather than evidence-based, and have no support from controlled clinical and/or epidemiological studies. Thus in August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of PE. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critically assess the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction and personal/interpersonal distress, and to propose a new evidence-based definition of PE. Results: The Committee unanimously agreed that the constructs which are necessary to define PE are rapidity of ejaculation, perceived self-efficacy, and control and negative personal consequences from PE. The Committee proposed that lifelong PE be defined as a male sexual dysfunction characterized by ejaculation which always or nearly always occurs before or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE. Conclusion: The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the development of new tools and patient-reported outcome measures for diagnosing and assessing the efficacy of treatment interventions, and encourage ongoing research into the true prevalence of this disorder, and the efficacy of new pharmacological and psychological treatments.
Article
To evaluate the overall treatment benefit of dapoxetine for premature ejaculation (PE), with specific emphasis on improvements in personal distress and interpersonal difficulty related to ejaculation. Although these factors are key elements of numerous sets of diagnostic criteria for PE, they have rarely been evaluated as outcome measures in clinical trials. In this randomized, double-blind, placebo-controlled, phase III trial we enrolled men aged > or =18 years, from the USA and Canada, who had a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, diagnosis of PE (1238 men). Men were randomized to receive placebo or dapoxetine 60 mg as needed or once daily for 9 weeks. The once-daily treatment arm was included for analysis of withdrawal symptoms (primary endpoint; presented elsewhere). Patients completed the Premature Ejaculation Profile (PEP) on day 1 (before dosing), and on days 28 and 63 (or study endpoint), which comprised the outcome measures for perceived control over ejaculation, satisfaction with sexual intercourse, and personal distress and interpersonal difficulty related to ejaculation. The patient-reported global impression of change in PE was reported on day 63 (or study endpoint). Treatment benefit measures included the composite criteria of at least a two-category increase in perceived control over ejaculation and at least a one-category decrease in personal distress related to ejaculation from baseline at study endpoint. At baseline, approximately 5% of patients in any treatment group reported 'not at all' or 'a little bit' of personal distress related to ejaculation, which increased to 54.3% of those receiving dapoxetine (vs 35.3% with placebo; P < 0.001). Similarly, 43.0% and 40.9% of men in the placebo and dapoxetine groups, respectively, reported 'not at all' or 'a little bit' of interpersonal difficulty related to ejaculation at baseline, which increased to 76.8% and 64.2% of those with dapoxetine and placebo, respectively (P < 0.001). The percentage of men who achieved the composite criteria with dapoxetine 'as needed' was 47.6%, vs 21.7% with placebo (difference from placebo, 25.9%; P < 0.001). The distribution of responses for the PEP among men who achieved the composite criteria was similar to that reported for men without PE in a previous observational study in the USA. The most common adverse events were nausea, dizziness, headache, diarrhoea and insomnia, which were more common with dapoxetine than with placebo. Dapoxetine reduced the personal distress and interpersonal difficulty associated with PE, and was associated with patient-reported improvements in their condition. The percentage of patients who achieved a composite of a two-category or greater increase in perceived control over ejaculation and a one-category or greater decrease in personal distress related to ejaculation was substantially greater than with placebo, as were all outcome measures.
Article
To investigate the prevalence of chronic prostatitis in men with premature ejaculation. The etiology of premature ejaculation is currently considered psychological in nature. However, the possibility that urologic, hormonal, or neurologic factors may contribute to this condition should be considered in its management. We evaluated segmented urine specimens before and after prostatic massage and expressed prostatic secretion specimens from 46 patients with premature ejaculation and 30 controls by bacteriologic localization studies. The incidence of premature ejaculation in the subjects with chronic prostatitis was also evaluated. Prostatic inflammation was found in 56.5% and chronic bacterial prostatitis in 47.8% of the subjects with premature ejaculation, respectively. When compared with the controls, these novel findings were statistically significant (P <0.05). Considering the role of the prostate gland in the mechanism of ejaculation, we suggest a role for chronic prostate inflammation in the pathogenesis of some cases of premature ejaculation. Since chronic prostatitis has been found with a high frequency in men with premature ejaculation, we stress the importance of a careful examination of the prostate before any pharmacologic or psychosexual therapy for premature ejaculation.
Article
Ejaculatory disorders include premature, deficient (delayed ejaculation and anejaculation) and retrograde ejaculation. A rare symptom connected to ejaculatory disorders is male anorgasmia. In the past, ejaculatory disorders were considered as typical relational and psychological symptoms. For this reason, a number of behavioural and psycho-relational approaches have flourished from the first ideas of curing sexual problems with empirical therapy, focusing on the symptoms of sexual pathology. Such treatment includes assessment, behavioural and educational components, psychotherapy in the context of the relationship and sexual timetables. Recent advances in understanding the importance and frequency of ejaculatory disorders, insights into their organic and non-organic pathophysiology and the efficacy of a growing arsenal of pharmacological therapies lead to a new challenge which can be confronted only with the development of new, integrated therapeutic alternatives from a modern somato-psychic and holistic viewpoint.
Article
Ejaculatory disorders (disorders of emission, ejaculation and orgasm) are the most frequent sexual complaint. Conventional algorithms on ejaculatory disorders are based on an organic or psychogenic dichotomy, with the latter being traditionally considered the main etiological cause. The scope of this review is to propose a new classification of ejaculatory disorders, with special emphasis on epidemiology and subtyping of the most frequent: premature ejaculation (PE). There is growing agreement on definition, diagnosis, and treatment options. In many cases, ejaculatory disorders can be classified by psycho-neuro-uro-endocrine symptoms. Epidemiological data, new classifications and subtyping, together with new diagnostic procedures and the availability of pharmacological aids, place this topic in the mainframe of sexual medicine. This will soon demolish the barriers to seeking help perceived by patients suffering ejaculatory disorders.
Article
Thyroid hormones have a dramatic effect on human behavior. However, their role on sexual behavior and performance has seldom been investigated in men. The objective of this study was to evaluate the prevalence of sexual dysfunctions in patients with hyper- and hypothyroidism and their resolution after normalization of thyroid hormone levels. We conducted a multicenter prospective study at endocrinology and andrology clinics in university hospitals. The study included 48 adult men, 34 with hyperthyroidism and 14 with hypothyroidism. Subjects were screened for hypoactive sexual desire (HSD), erectile dysfunction (ED), premature ejaculation (PE), and delayed ejaculation (DE) on presentation and 8-16 wk after recovery from the thyroid hormone disorder. In hyperthyroid men, HSD, DE, PE, and ED prevalence was 17.6, 2.9, 50, and 14.7%, whereas in hypothyroid men, the prevalence of HSD, DE, and ED was 64.3% and of PE was 7.1%. After thyroid hormone normalization in hyperthyroid subjects, PE prevalence fell from 50 to 15%, whereas DE was improved in half of the treated hypothyroid men. Significant changes were found in the subdomains of the International Index of Erectile Function; ejaculation latency time doubled after treatment of hyperthyroidism (from 2.4 +/- 2.1 to 4.0 +/- 2.0 min), whereas for hypothyroid men it declined significantly, from 21.8 +/- 10.9 to 7.4 +/- 7.2 (P < 0.01 for both). TSH and thyroid hormone levels normalized rapidly after treatment, and changes in circulating sex steroids partially reflected the changes in SHBG levels. In summary, most patients with thyroid hormone disorders experience some sexual dysfunctions, which can be reversed by normalizing thyroid hormone levels. Despite the associated changes in sex hormone levels, the high prevalence of ejaculatory disorders and their prompt reversibility suggest a direct involvement of thyroid hormones in the physiology of ejaculation.
Article
Dapoxetine is a serotonin transporter inhibitor currently in development for the treatment of premature ejaculation. This randomized, 2-sequence, 2-treatment crossover study assessed the single- and multiple-dose pharmacokinetics of dapoxetine following once-daily administration of dapoxetine 30 mg and 60 mg to healthy male volunteers. Dapoxetine was rapidly absorbed following oral administration, with peak plasma concentrations reached approximately 1 hour after dosing; plasma concentrations after single doses of dapoxetine decreased rapidly to approximately 5% of peak concentrations by 24 hours. Elimination was biphasic, with an initial half-life of approximately 1.4 hours and a terminal half-life of approximately 20 hours. Dapoxetine showed time-invariant pharmacokinetics and dose proportionality between doses, and its pharmacokinetics was unaffected by multiple dosing. The pharmacokinetics of dapoxetine metabolites, desmethyldapoxetine and dapoxetine-N-oxide, was similarly unaffected by multiple dosing. There were no serious adverse events; the most commonly reported adverse events were diarrhea, dizziness, and nausea.
Article
No drugs are approved for treatment of premature ejaculation. Our aim was to determine the efficacy and tolerability of on-demand dapoxetine in patients with severe premature ejaculation. We determined the efficacy of dapoxetine in a prospectively predefined integrated analysis of two 12-week randomised, double-blind, placebo-controlled, phase III trials of identical design done independently, in parallel, at 121 sites in the USA. Men with moderate-to-severe premature ejaculation in stable, heterosexual relationships took placebo (n=870), 30 mg dapoxetine (874), or 60 mg dapoxetine (870) on-demand (as needed, 1-3 h before anticipated sexual activity). The primary endpoint was intravaginal ejaculatory latency time (IELT) measured by stopwatch. Safety and tolerability were assessed. All analyses were done on an intention-to-treat basis. The trials are registered at ClinicalTrials.gov, numbers NCT00211107 and NCT00211094. 672, 676, and 610 patients completed in the placebo, 30 mg dapoxetine, and 60 mg dapoxetine groups, respectively. Dapoxetine significantly prolonged IELT (p<0.0001, all doses vs placebo). Mean IELT at baseline was 0.90 (SD 0.47) minute, 0.92 (0.50) minute, and 0.91 (0.48) minute, and at study endpoint (week 12 or final visit) was 1.75 (2.21) minutes for placebo, 2.78 (3.48) minutes for 30 mg dapoxetine, and 3.32 (3.68) minutes for 60 mg dapoxetine. Both dapoxetine doses were effective on the first dose. Common adverse events (30 mg and 60 mg dapoxetine, respectively) were nausea (8.7%, 20.1%), diarrhoea (3.9%, 6.8%), headache (5.9%, 6.8%), and dizziness (3.0%, 6.2%). On-demand dapoxetine is an effective and generally well tolerated treatment for men with moderate-to-severe premature ejaculation.
Article
To characterize premature ejaculation (PE) in five European countries using intravaginal ejaculatory latency time (IELT) and the Premature Ejaculation Profile (PEP). This 8-wk, multicenter, observational study enrolled men >or=18 yr of age and their female partners. Clinicians diagnosed PE using the DSM-IV-TR criteria and at least moderate, subject-reported, ejaculation-related personal distress or interpersonal difficulty. The PEP was administered at baseline and weeks 4 and 8. Partners measured IELT; the average stopwatch-measured IELT for each 4-wk period was calculated and compared with the man's screening-estimated IELT. Relationships between individual PEP measures and IELT were assessed with path analysis. PE was diagnosed in 201 of 1115 men. Findings were similar to those in a similarly conducted US study. Mean IELT was lower in the PE versus the non-PE group (3.3 vs. 10.0min, respectively), but substantial overlap was observed. Men with PE and their partners reported significantly worse control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse, and ejaculation-related interpersonal difficulty than men without PE and their partners. Path analysis showed that perceived control over ejaculation had a significant effect on ejaculation-related personal distress and satisfaction with sexual intercourse; IELT had an effect on control over ejaculation, no direct effect on satisfaction with sexual intercourse, and a small direct effect on ejaculation-related personal distress. No major cultural differences existed between EU and US men with and without PE and their female partners. These results emphasize the importance of the PEP measures, especially perceived control over ejaculation, in characterizing PE.
Article
The intravaginal ejaculation latency time (IELT) behaves in a skewed manner and needs the appropriate statistics for correct interpretation of treatment results. To explain the rightful use of geometrical mean IELT values and the fold increase of the geometric mean IELT because of the positively skewed IELT distribution. Linking theoretical arguments to the outcome of several selective serotonin reuptake inhibitor and modern antidepressant study results. Geometric mean IELT and fold increase of geometrical mean IELT. Log-transforming each separate IELT measurement of each individual man is the basis for the calculation of the geometric mean IELT. A drug-induced positively skewed IELT distribution necessitates the calculation of the geometric mean IELTs at baseline and during drug treatment. In a positively skewed IELT distribution, the use of the "arithmetic" mean IELT risks an overestimation of the drug-induced ejaculation delay as the mean IELT is always higher than the geometric mean IELT. Strong ejaculation-delaying drugs give rise to a strong positively skewed IELT distribution, whereas weak ejaculation-delaying drugs give rise to (much) less skewed IELT distributions. Ejaculation delay is expressed in fold increase of the geometric mean IELT. Drug-induced ejaculatory performance discloses a positively skewed IELT distribution, requiring the use of the geometric mean IELT and the fold increase of the geometric mean IELT.
Article
The medical literature contains several definitions of premature ejaculation (PE). The most commonly quoted definition, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision, and other definitions of PE are all authority based rather than evidence based, and have no support from controlled clinical and/or epidemiological studies. The aim of this article is to develop a contemporary, evidence-based definition of PE. In August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of Premature Ejaculation. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critique the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction, and personal/interpersonal distress, and to propose a new evidence-based definition of PE. The committee unanimously agreed that the constructs that are necessary to define PE are rapidity of ejaculation, perceived self-efficacy and control, and negative personal consequences from PE. The committee proposed that lifelong PE be defined as ". . . a male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy." This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE. The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the development of new tools and Patient Reported Outcome measures for diagnosing and assessing the efficacy of treatment interventions and encourage ongoing research into the true prevalence of this disorder and the efficacy of new pharmacological and psychological treatments.
Article
Regulatory approval of new drug treatments for premature ejaculation (PE) demands evaluation in well-designed clinical efficacy and safety randomized clinical trials (RCTs). The objective of this article was to make recommendations for trial design and efficacy outcome measures which comprise ideal PE observational, interventional, and treatment preference trial methodology. Published data on clinical trial design, epidemiology, definitions, dimensions, and psychological impact of PE. Data on the epidemiology, definitions, dimensions, and psychological impact of PE were reviewed, critiqued, and incorporated into a series of recommendations for standardization of PE clinical trial design, outcome measures, and reporting using the principles of evidence-based medicine. PE observational trials should be prospective and should provide quantitative or qualitative data derived from objective outcome measurements and/or the results of subject interview and other trial-specific investigations for analysis. PE drug trials should employ a double-blind RCT methodology and should include placebo control, active standard drug control, and/or dose comparison trials. Application of the placebo concept to psychotherapy intervention trials is complex and fraught with both conceptual and pragmatic problems. Criteria for the ideal PE preference trial are not yet determined but are likely to be a double-blind, crossover RCT of treatment-naive subjects using randomized drug sequences of equivalent drug doses. Ejaculatory latency time (ELT) and subject/partner outcome measures of control, personal/partner/relationship distress, and other study-specific outcome measures should be used as outcome measures. There is currently no published literature which identifies a clinically significant threshold response to intervention. Data from PE observational, interventional, and preference studies are only reliable, interpretable, and capable of being generalized to patients with PE when derived from well-designed observational studies or intervention RCTs using ELT and subject/partner-reported outcome measures of perceived ejaculatory control and personal/partner/relationship distress are used as trial outcome measures.
Dapoxetine has no effects on hemodynamics or electrocardiographic assessments [abstract]
  • Modi Nb
  • Wang R B Nath
  • Rivas D S Gupta
Modi NB, Nath R, Wang B, Rivas D, Gupta S. Dapoxetine has no effects on hemodynamics or electrocardiographic assessments [abstract]. J Sex Med 2008;5:90–1.
Interview with Dr Francois Giuliano. New avenues in the pharmacological treatment of premature ejaculation
  • McKillop
McKillop C. Interview with Dr Francois Giuliano. New avenues in the pharmacological treatment of premature ejaculation. Eur Urol 2007;52:1254–7.
Dapoxetine has no effects on hemodynamics or electrocardiographic assessments [abstract]
  • Modi