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Efficacy and safety of dapoxetine/sildenafil combination tablets in the treatment of men with premature ejaculation and concomitant erectile dysfunction—DAP-SPEED Study

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Murat Tuken
Murat Tuken
Murat Tuken
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Mehmet Gokhan Culha at Okmeydani Training and Research Hospital
Mehmet Gokhan Culha
Ege Can Serefoglu at Biruni University
Ege Can Serefoglu
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Abstract

Premature ejaculation (PE) and erectile dysfunction (ED) are the most prevalent sexual disorders in men. ED is commonly reported among patients with PE. Although recent guidelines recommend to treat ED first in men with both PE and ED, this recommendation is not based on evidence and there are limited data about the efficacy and safety of dapoxetine/sildenafil combination therapy for these patients. The aim of this study is to evaluate the clinical efficacy and safety of the dapoxetine/sildenafil combination (Dapoxil® 30/50 mg film-coated tablet) in the treatment of patients with PE and concomitant ED. In a single-center, single-arm, open-label clinical study conducted between October 2016 and September 2017, 74 patients with lifelong or acquired PE and ED were included. All patients were instructed to record their intravaginal ejaculatory latency time (IELT) with a stopwatch for 4 weeks. After the screening, they were requested to complete Premature Ejaculation Diagnostic Tool (PEDT), Premature Ejaculation Profile (PEP), and International Index of Erectile Function-Erectile Function (IIEF-EF) questionnaires before the treatment. The patients received on demand Dapoxil® 1–3 h before sexual intercourse for the next 4 weeks (2 days a week and no more than once a day). The patients were also assessed with global impression of change (GIC) question for the treatment satisfaction and the side effects were recorded. The study was completed with 53 patients (53/74, 71.62%). Mean age of the patients was 45.32 ± 10.05 years. At the end of the 4-week treatment period, the geometric mean IELT of the patients significantly increased (from 22.72 ± 15.16 to 68.25 ± 82.33 s; p < 0.001). Similarly, significant improvements were observed in the mean PEP index score (0.86 ± 0.72 vs. 2.36 ± 1.13; p < 0.001) and mean IIEF-EF domain score (13.17 ± 3.33 vs. 24.60 ± 3.96; p < 0.001). According to the GIC results, 81.13% of the patients were satisfied with the treatment. Non-serious adverse events occurred in 10 patients (18.87%) and 4 (7.55%) of these patients dropped out of the treatment. The most common adverse events were headache, palpitation, and flushing. The dapoxetine/sildenafil combination therapy significantly improves the IELT values and patient reported outcome measures of PE patients who also suffer from ED. Although several side effects were reported, these were mild and transient.
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IJIR: Your Sexual Medicine Journal (2019) 31:92–96
https://doi.org/10.1038/s41443-019-0122-2
ARTICLE
Efficacy and safety of dapoxetine/sildenafil combination tablets in
the treatment of men with premature ejaculation and concomitant
erectile dysfunction—DAP-SPEED Study
Murat Tuken1●Mehmet Gokhan Culha 2●Ege Can Serefoglu 3
Received: 22 November 2018 / Revised: 29 December 2018 / Accepted: 10 January 2019 / Published online: 31 January 2019
© Springer Nature Limited 2019
Abstract
Premature ejaculation (PE) and erectile dysfunction (ED) are the most prevalent sexual disorders in men. ED is commonly
reported among patients with PE. Although recent guidelines recommend to treat ED first in men with both PE and ED, this
recommendation is not based on evidence and there are limited data about the efficacy and safety of dapoxetine/sildenafil
combination therapy for these patients. The aim of this study is to evaluate the clinical efficacy and safety of the dapoxetine/
sildenafil combination (Dapoxil®30/50 mg film-coated tablet) in the treatment of patients with PE and concomitant ED. In a
single-center, single-arm, open-label clinical study conducted between October 2016 and September 2017, 74 patients with
lifelong or acquired PE and ED were included. All patients were instructed to record their intravaginal ejaculatory latency
time (IELT) with a stopwatch for 4 weeks. After the screening, they were requested to complete Premature Ejaculation
Diagnostic Tool (PEDT), Premature Ejaculation Profile (PEP), and International Index of Erectile Function-Erectile
Function (IIEF-EF) questionnaires before the treatment. The patients received on demand Dapoxil®1–3 h before sexual
intercourse for the next 4 weeks (2 days a week and no more than once a day). The patients were also assessed with global
impression of change (GIC) question for the treatment satisfaction and the side effects were recorded. The study was
completed with 53 patients (53/74, 71.62%). Mean age of the patients was 45.32 ± 10.05 years. At the end of the 4-week
treatment period, the geometric mean IELT of the patients significantly increased (from 22.72 ± 15.16 to 68.25 ± 82.33 s; p<
0.001). Similarly, significant improvements were observed in the mean PEP index score (0.86 ± 0.72 vs. 2.36 ± 1.13; p<
0.001) and mean IIEF-EF domain score (13.17 ± 3.33 vs. 24.60 ± 3.96; p< 0.001). According to the GIC results, 81.13% of
the patients were satisfied with the treatment. Non-serious adverse events occurred in 10 patients (18.87%) and 4 (7.55%) of
these patients dropped out of the treatment. The most common adverse events were headache, palpitation, and flushing. The
dapoxetine/sildenafil combination therapy significantly improves the IELT values and patient reported outcome measures of
PE patients who also suffer from ED. Although several side effects were reported, these were mild and transient.
Introduction
Premature ejaculation (PE) is a male sexual dysfunction
characterized by a short intravaginal ejaculatory latency
time (IELT), inability to delay or control ejaculation,
and negative personal consequences [1]. PE exerts a
psychological burden on both men and their partners,
resultinginasignificant detrimental effect on the rela-
tionship [2,3]. Over the last two decades the treatment
of PE has shifted from psychotherapy to pharmacother-
apy, where the mainly prescribed drugs are selective
serotonin reuptake inhibitors (SSRIs) and phosphodies-
terase type-5 (PDE5) inhibitors [4]. Dapoxetine is the first
medication specifically developed for the on-demand
treatment of PE [5] and its efficacy has been demon-
stratedintheseveralwell-designed meta-analyses [6,7].
However, several studies demonstrated that discontinua-
tion to the effective on-demand dapoxetine treatment is
relatively high [8,9], indicating the need for alternative
treatments.
*Ege Can Serefoglu
egecanserefoglu@hotmail.com
1University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training
& Research Hospital, Department of Urology, Istanbul, Turkey
2University of Health Sciences, Okmeydani Training & Research
Hospital, Department of Urology, Istanbul, Turkey
3Bahceci Health Group, Department of Urology, Istanbul, Turkey
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1234567890();,:
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... [12] Avrupa Üroloji Kılavuzu ise, ED sorunu olan veya olmayan PE hastalarında tek başına veya diğer tedavilerle kombinasyon halinde PDE5 inhibitörlerinin kullanımını, bu konuyla ilgili yakın zamanda yayımlanan verileri dikkate alarak desteklemektedir. [13][14][15] Bununla birlikte, zayıf çalışma tasarımı ve yayımlanmış literatürlerdeki heterojenitenin bulunmaması nedeniyle PDE5 inhibitörlerinin PE tedavisinde etkili olup olmadığına dair kanıtlar tartışmalıdır. Fosfodiesteraz tip-5 inhibitörü ile SSRI kombinasyon tedavisi genellikle PE si olan hastalarda kullanılagelmiştir. ...
... Literatürde bunu destekleyen çalışmalar mevcuttur. [14,15] Erektil disfonksiyon şikâyeti ile başvuran hastalarda çoğu zaman performans kaygısı, çeşitli korkular ve kendinden şüphe duymak gibi psikojenik faktörler de eşlik etmektedir. Bu nedenle antidepresan ve anksiyolitik etkileri olan SSRI günlük kullanımının ED tedavisinde faydalı olacağı beklenebilir. ...
... Tuken ve ark. [15] , yapmış olduğu çalışmadaki IELT skorları göz önüne alınarak %5 hata payı ve %80 güvenilirlik ile çalışmaya en az 62 hasta alınması hesaplanmıştır. ...
Erektil disfonksiyon şikâyeti ile başvurup eşlik eden prematür ejakulasyonu olan heteroseksüel hastalarda günlük tadalafil ve sertralin kombinasyon tedavisinin etkinliği ve güvenilirliği
Article
Full-text available
  • Jan 2023
Efficacy and safety of daily tadalafil and sertraline combination therapy in heterosexual patients presenting with erectile dysfunction and concomitant premature ejaculation OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of daily tadalafil 5 mg and sertraline 50 mg treatment in 3-month follow-up in patients presenting with erectile dysfunction (ED) complaints and accompanying premature ejaculation (PE) symptoms. MATERIAL and METHODS: This prospective, observational single-arm study was conducted between March and September 2021 among patients suffering from ED and concomitant Lifetime/acquired PE. The Turkish validity of the International Erectile Function-Erectile Function Index (IIEF-EF) was used for the diagnosis of ED in the patients. The patients filled the Premature Ejaculation Diagnostic Tool (PEDT) questionnaire for the diagnosis of PE. Additionally, the Premature Ejaculation Profile (PEP) score was filled. A detailed medical history was taken from all patients and a complete physical examination was performed. After a fourweek follow-up period, patients were given 5 mg tadalafil and sertraline 50 mg tablets daily. The IELT durations of the patients were recorded after 12 weeks of treatment. Premature ejaculation profile and IIEF-EF questionnaires administered to the patients at the beginning were filled again. In addition, the Global Impression of Change (GIC) questionnaire was applied in terms of treatment satisfaction. RESULTS: A total of 71 patients were included in the study. Sixty-three patients completed the study (88.73%). As a result of 3-month daily tadalafil 5 mg + sertraline 50 mg combination therapy, the geometric mean IELT, PEP index scores and subgroup scores of the patients improved and a statistically significant increase in the IIEF-EF scores (p<0.001). In addition, considering the GIC questionnaire, 81.69% (58/71) of the patients stated that they were satisfied with the treatment. CONCLUSION: In conclusion, daily administration of tadalafil and sertraline provides an effective and reliable objective and subjective improvement in the management of patients with ED and accompanying PE. Keywords: premature ejaculation, erectile dysfunction, sertraline, tadalafil, IELT
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... [16] In addition, the Sildenafil + Dapoxetine combination therapy has been reported to significantly improve the intravaginal ejaculation latency time values with mild and transient side effects. [17] Moreover, Dapoxetine has no clinically relevant pharmacokinetic interactions with Tadalafil or Sildenafil, and the drug combinations (Tadalafil + Dapoxetine or Sildenafil + Dapoxetine) are well-tolerated. [18] This manuscript discusses the effect of physiological and metabolic parameters on sexual dysfunction, particularly ED in male T2DM subjects. ...
The Efficacy of Tadalafil and Tadalafil + Dapoxetine in Managing Sexual Dysfunction in Individuals with Type-2 Diabetes Mellitus: A Clinical Study
Article
Full-text available
  • Jan 2023
Objective The present study was aimed to evaluate effect of metabolic parameters on erectile dysfunction (ED) in individuals with type-2 diabetes mellitus (T2DM) and to assess the efficacy of Tadalafil and Tadalafil + Dapoxetine combination. Materials and Methods A prospective, observational, cross-sectional, bicentric study included 216 males with T2DM who are not treated with phosphodiesterase 5 inhibitors and without chronic kidney disease. The data were obtained from demographic questionnaire, clinical laboratory reports of glycometabolic parameters namely body mass index (BMI), hemoglobin A1c (HbA1c), testosterone, vitamin B12 (VitB12), and lipid profile and analyses of the International Index of Erectile Function (IIEF) questionnaire. The effect of physical and metabolic parameters on IIEF sub-domains namely erectile function; orgasmic function; sexual desire (SD); intercourse satisfaction; and overall satisfaction was evaluated. A statistical significance was evaluated using χ ² test or t -test. Result SD is most significantly lower in subjects with imbalanced physiological and metabolic characteristics including BMI, HbA1c, testosterone, VitB12, triglyceride, high-density lipoprotein, and low-density lipoprotein. Both Tadalafil and Tadalafil + Dapoxetine significantly improved almost all IIEF parameters without any pronounced effect of either. Similarly, both the treatments improved all the IIEF parameters for subjects with high BMI except for SD. In subjects with cardiac comorbidities, the use of either treatment significantly enhanced all the IIEF scores. Conclusion The findings of this study outline the need of careful examination of sexual dysfunction in healthcare clinics for diabetic individuals. An imbalanced physiological and metabolic profile leads to ED in individuals with T2DM. Additionally, the presence of co-morbidities further elevates the odds of ED prevalence. The treatment with Tadalafil and Tadalafil + Dapoxetine drug combination shows promising results in improving the ED but a study with larger pool of subjects is needed to determine the additional benefits of Dapoxetine.
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... Selective serotonin reuptake inhibitors (SSRIs) can reduce the reuptake of 5-HT through presynaptic nerve terminals by blocking the 5-HT transporter (5-HTT) selectively [20]. Dapoxetine, a kind of short-acting SSRIs, is the sole officially licensed oral medication for the treatment of PE in several countries [21,22]. Previous studies have confirmed [23] that dapoxetine can improve quality of sexual activity in PE patients. ...
The role of tyrosine hydroxylase within dapoxetine-assisted therapy against premature ejaculation
Article
Full-text available
  • Feb 2023
  • MOL BIOL REP
Background There are several investigations that have revealed that cerebral dopamine (DA) plays a pivotal role in the occurrence of premature ejaculation (PE). Although tyrosine hydroxylase (TH) is an essential enzyme for the synthesis of DA, only few investigations have described the role of TH in regulation mechanisms for ejaculation till now. To investigate whether there is a correlation between TH expression level in the brain and different ejaculation behavior in rats. Then explore whether the TH expression in the brain will change after acute dapoxetine treatment in rats with Rapid ejaculation. Methods and results Rats (male, S-D rats, 6–8 weeks) were separated into three groups based on their ejaculation frequency: Rapid, Normal, and Sluggish. Expression level of DA in the brain was determined by enzyme-linked immune sorbent assay (ELISA) kit, TH expression level in the brain was determined by immunohistochemistry and Western Blot (WB) techniques. Among the three groups, DA and TH expression level were the highest in the Rapid ejaculation group, while the lowest was the Sluggish ejaculation group. The results also showed that TH level was positively associated with ejaculation frequency (r = 0.8038, P < 0.001) and negatively associated with ejaculation latency (r=-0.6199, P = 0.018). Furthermore, acute dapoxetine therapy in rats with Rapid ejaculation downregulated TH level in the brain. Conclusion Changes in ejaculation behavior were significantly linked with TH level. Upregulated TH in selected brain regions related with ejaculation could cause rapid ejaculation. The effect of dapoxetine in prolonging ejaculation could be related to TH downregulation within the brain.
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Choice of Drugs in Ejaculatory Dysfunction
Chapter
  • Mar 2025
Ejaculatory dysfunction is a term that describes a spectrum of debilitating diseases that impacts the quality of life of men affected. This spectrum comprises a range of symptoms and the most common subtypes encountered can be summarized as premature ejaculation (PE), delayed ejaculation (DE), anejaculation, retrograde ejaculation (RE), painful ejaculation, post-orgasmic illness syndrome (POIS), and many others. Diagnosis is challenging considering patient hesitancy for medical care seeking, high variety in presenting symptoms, and lack of consensus in diagnosing criteria. There are many treatment modalities that target each subtype of the spectrum and can broadly be categorized into psychological therapy, pharmacologic treatment, local therapies, surgical treatments, and combinations of these. In this chapter, we aim to provide background and review the current and emerging treatment modalities for each subtype of ejaculatory dysfunction.
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An overview of conventional and investigational phosphodiesterase 5 inhibitors for treating erectile dysfunction and other conditions
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  • Aug 2024
Introduction: There is a rising concern about developing innovative, efficacious PDE5I molecules that provide better safety, efficacy, and tolerability with less adverse effects. Innovative PDE5I with dual targets have also been defined in the literature. Additionally, some of PDE5I are able to selectively inhibit other enzymes such as histone deacetylase, acetylcholine esterase, and cyclooxygenase or act as nitric oxide donors. This review presents knowledge concerning the advanced trends and perspectives in using PDE5I in treatment of ED and other conditions. Areas covered: Pre-clinical and early clinical trials that investigated the safety, efficacy, and tolerability of novel PDE5I such as Udenafil, Mirodenafil, Lodenafil, Youkenafil, Celecoxib, and TPN729 in treatment of ED and other conditions. Expert opinion: Preclinical and limited early clinical studies of the new molecules of PDE5I have demonstrated encouraging results; however, safety, efficacy, and tolerability are still issues that necessitate further long-term multicenter clinical studies to ensure justification of their uses in treatment of ED and other conditions. Progress in molecular delivery techniques and tailored patient-specific management and additional therapeutic technology will dramatically improve care for ED and other conditions. The dream of ED and many other conditions becoming more effectively managed may be feasible in the near future.
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Prospective comparison of tadalafil 5 mg, dapoxetine 30 mg, and the combination of both in the treatment of premature ejaculation
Article
  • Nov 2023
Objective To compare the efficacy of tadalafil alone, dapoxetine alone, and tadalafil with dapoxetine as a combination therapy for the treatment of premature ejaculation. Patients and Methods Eligible patients attended our andrology clinic with premature ejaculation were randomly allocated into three groups: group A (92 participants) received on-demand tadalafil, 5 mg; group B (91 participants) were given on-demand dapoxetine, 30 mg; and group C (89 participants) received on-demand combination of tadalafil, 5 mg, and dapoxetine, 30 mg. We assessed the changes in the intravaginal ejaculatory latency time (IELT) and the satisfaction scores 1, 2, and 3 months after treatment. Results Highly statistically significant improvements were found in the mean IELT and satisfaction scores 1, 2, and 3 months post-treatment in all groups (P = <0.001). Post hoc analysis suggested this improvement was more pronounced in group C (P < 0.001). Conclusion Both tadalafil and dapoxetine are effective in the treatment of patients with premature ejaculation, but the combination of both drugs gives better results.
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Conservative Non-surgical Options for Erectile Dysfunction
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Full-text available
  • Nov 2022
  • Curr Urol Rep
Purpose of Review This study aimed to review recent evidence on conservative non-surgical options for erectile dysfunction (ED) in men. A narrative review of the literature was performed. A comprehensive search in the MEDLINE, Embase, and Cochrane databases was done. Papers in English language, published from May 2017 until May 2022, were included. Papers reporting basic research or animal research were excluded, as long as reviews or meta-analyses. Congress reports, clinical cases, or clinical trials protocols with no results were also excluded. Recent Findings We found a multitude of different treatment modalities for ED. We must take into account the type of patient, their comorbidities, the origin of their ED, and its severity in order to reproduce effective results using these therapies. Some of the treatments show good results with a good level of evidence (new IPDE5 formulations, intracavernous injections, shock wave therapy, hormonal theraphy, psycho-sexual theraphy). However, others (some new molecules, stem cell theraphy, platelet-rich plasma injections, oxygenation-based therapy, nutraceuticals), although some of them present promising results, require randomized studies with a larger number of patients and a longer follow-up time to be able to establish firm recommendations. Summary Regarding the conservative treatment of erectile dysfunction, in recent years, some therapies have been consolidated as effective and safe for certain types of patients. On the other hand, other treatment modalities, although promising, still lack the evidence and the necessary follow-up to be recommended in daily practice.
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The role of tyrosine hydroxylase within dapoxetine-assisted therapy against premature ejaculation
Preprint
Full-text available
  • Oct 2022
Background: There are several investigations that have revealed that cerebral dopamine (DA) plays a pivotal role in the occurrence of premature ejaculation (PE). Although tyrosine hydroxylase (TH) is an essential enzyme for the synthesis of DA, only few investigations have describedthe role of TH in regulation mechanisms for ejaculation till now. To investigate whether there is a correlation between TH expression level in the brain and different ejaculation behavior in rats. Then explore whether the TH expression in the brain will change after acute dapoxetine treatment in rats with Rapid ejaculation. Methods and Results: Male S-D rats were separated into three groups based on their ejaculation frequency: Rapid, Normal, and Sluggish. Expression level of DA in the brain was determined by enzyme-linked immune sorbent assay (ELISA) kit, TH expression level in the brain was determined by immunohistochemistry and Western Blot (WB) techniques. Among the three groups, DA and TH expression level were the highest in the Rapid ejaculation group, while the lowest was the Sluggish ejaculation group. The results also showed that TH level was positively associated with ejaculation frequency (r=0.8038, P<0.001) and negatively associated with ejaculation latency (r=-0.6199, P<0.05). Furthermore, acute dapoxetine therapy in rats with Rapid ejaculation downregulated TH level in the brain. Conclusion: Changes in ejaculation behavior were significantly linked with TH level. Upregulated TH in selected brain regions related with ejaculation could cause rapid ejaculation. The effect of dapoxetine in prolonging ejaculation could be related to TH downregulation within the brain.
View
Ejaculation and Orgasmic Disorders
Chapter
  • Nov 2022
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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Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study
Article
Full-text available
  • Apr 2017
Introduction: Although dapoxetine is the only oral pharmacologic agent approved for the treatment of premature ejaculation (PE) and is very effective, the discontinuation rate is high. Aim: To assess the discontinuation rate of patients with PE and the reasons for discontinuation in real-world practice. Methods: In total, 182 consecutive patients were enrolled. Type of PE, self-estimated intravaginal ejaculation latency time, and medical history were evaluated in all patients who also completed the erectile function domain of the International Index of Erectile Function (IIEF). Visits were scheduled 1, 3, 6, 12, and 24 months after initiation of therapy; treatment status and the reasons for discontinuation in those who did discontinue were checked. The relations of discontinuation rates were compared with various parameters and the time to discontinuation after treatment commencement. Results: Of all patients, 9.9% continued treatment to 2 years. The cumulative discontinuation rates at 1, 3, 6, 12, and 24 months were 26.4%, 61.6%, 79.1%, 87.3%, and 90.1%, respectively. Moreover, 79.1% of all patients discontinued treatment within 6 months. After 12 months, the discontinuation rate decreased sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE was not curable and that dapoxetine was required every time sexual intercourse was contemplated (25%), side effects (11.6%), perceived poor efficacy (9.8%), a search for other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs lifelong PE), with intravaginal ejaculation latency time longer than 2 minutes before treatment, on phosphodiesterase type 5 inhibitors, and with IIEF erectile function scores lower than 26 tended to discontinue early and thus exhibited high dropout rates. Conclusion: The treatment discontinuation rate of dapoxetine was very high. The main reasons for discontinuation were the cost and disappointment that treatment was required every time adequate sexual function was required. Park HJ, Park NC, Kim TN, et al. Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study. Sex Med 2017;5:e99–e105.
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An Update of the International Society of Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE)
Article
Full-text available
  • Jun 2014
Introduction: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. Aim: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. Method: A comprehensive literature review was performed. Results: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. Conclusion: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years. Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel AW, Adaikan PG, Becher E, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med 2014;2:60–90.
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Efficacy and safety of phosphodiesterase type 5 inhibitors on primary premature ejaculation in men receiving selective serotonin reuptake inhibitors therapy: A systematic review and meta-analysis
Article
Full-text available
We performed a systematic review and meta-analysis to assess whether selective serotonin reuptake inhibitors (SSRIs) and phosphodiesterase type 5 inhibitors (PDE5-Is) may have an additive therapeutic effect. A literature review was performed to identify all published randomised controlled trials (RCT) that used SSRIs combined with PDE5-Is therapy for the treatment of primary PE. The search included the following databases: EMBASE, MEDLINE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Five publications involving a total of 419 patients were used in the analysis, including 5 RCTs that compared PDE5-Is plus SSRIs with SSRIs treating primary PE. Primary efficacy endpoints: IELT (the standardised mean difference (SMD) = 1.07, 95% confidence interval (CI) = 1.00 to 1.14, P < 0.00001) indicated that utilisation of PDE5-Is and SSRIs was more effective than the SSRIs alone for a long time in patients with primary PE. Safety assessments included headache (odds ratio (OR) = 3.16, 95% CI = 1.63 to 6.11, P = 0.0006), and flushing indicated that PDE5-Is plus SSRIs were well tolerated. This meta-analysis indicates that PDE5-Is combined with SSRIs seem to provide significantly better ejaculatory latency time as compared with SSRIs alone in patients with primary PE.
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Advances in understanding and treating premature ejaculation
Article
Full-text available
  • Oct 2015
  • NAT REV UROL
Over the past several years, many advances have been made in our understanding of the epidemiology, pathophysiology, and management of premature ejaculation. Newly developed definitions of premature ejaculation are now available, and our perception of the classification, prevalence, aetiological factors, and treatment options for premature ejaculation have evolved. Despite ongoing research, there remains much to be learned about all aspects of this common sexual disorder, in particular effective clinical diagnosis and treatment options.
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Current Pharmacological Management of Premature Ejaculation: A Systematic Review and Meta-analysis
Article
  • Dec 2015
Context: Premature ejaculation (PE) is the most prevalent male sexual dysfunction. In the last few years, several pharmacologic approaches for oral or topical treatment of PE have been studied. Objective: To systematically review the literature on the outcome of pharmacologic interventions for PE on intravaginal ejaculation latency time (IELT) in comparison to placebo. Evidence acquisition: A systematic literature search of PubMed and Scopus using the term "premature ejaculation" was performed on 10 April 2015. Full-text articles on prospective randomized controlled trials (RCTs) investigating pharmacotherapy were included. The main outcome measure was IELT. Evidence synthesis: Out of 266 unique records, a total of 22 were reviewed. The majority of RCTs were of unclear methodological quality because of limited reporting of methods. Pooled evidence suggests that selective serotonin reuptake inhibitors (SSRIs), topical anesthetic creams (TAs), tramadol, and phosphodiesterase type 5 inhibitors (PDE5is) are more effective than placebo at increasing IELT (all p<0.05). However, interpretation of the current meta-analyses may be impaired as a result of frequent heterogeneity in the pooled analyses (all I(2) > 70%). Only pooled analyses for dapoxetine 30mg and 60mg were characterized by homogeneous data (both I(2)<30%) while showing a modest but statistically significant improvement in IELT compared with placebo (mean difference 1.39min, 95% confidence interval 1.23-1.54min; p<0.00001). Conclusions: Meta-analysis revealed that treatment with dapoxetine significantly improves IELT in patients with PE but with modest efficacy. The efficacy of SSRIs, TAs, tramadol, and PDE5is remains unclear owing to high heterogeneity of the available RCT data. There is a persisting need for drug research and development in the field. Patient summary: Premature ejaculation is a condition for which the cause is not well understood. Several types of treatment with medium to low efficacy are available. More research is necessary to identify the ideal treatment.
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Interplay Between Premature Ejaculation and Erectile Dysfunction: A Systematic Review and Meta-Analysis
Article
  • Nov 2015
  • J SEX MED
Introduction: The specific determinants and underlying factors linking erectile dysfunction (ED) and premature ejaculation (PE) have yet to be clearly identified. Aim: The aim of this study was to review and meta-analyze all available data regarding the link between ED and PE. Methods: An extensive Medline Embase and Cochrane search was performed including the following words: "premature ejaculation" and "erectile dysfunction". Main outcome measures: All observational trials comparing the risk of ED in relation to PE were included. Data extraction was performed independently by two of the authors (G.R, G.C.), and conflicts resolved by the third investigator (M.M.). Results: Out of 474 retrieved articles, 18 were included in the study for a total of 57,229 patients, of which 12,144 (21.2%) had PE. The presence of PE, however defined, was associated with a significant increase in ED risk (odds ratio: 3.68[2.61;5.18]; P < 0.0001). Meta-regression analysis showed that the risk of ED in PE subjects was higher in older individuals as well as in those with a lower level of education and in those who reported a stable relationship less frequently. In addition, subjects with PE and ED more often reported anxiety and depressive symptoms and a lower prevalence of organic associated morbidities, including diabetes mellitus, hypertension and dyslipidemia. All the latter associations were confirmed even after adjustment for age. Finally the risk of PE-related ED increased with the increased proportion of acquired ejaculatory problems (adj r = 0.414; P < 0.0001 after the adjustment for age). Conclusions: In conclusion, the present data showed that ED and PE are not distinctly separate entities, but should be considered from a dimensional point of view. Understanding this dimensional perspective might help sexual health care professionals in providing the most appropriate therapeutic approach to realistically increase patient related outcomes in sexual medicine.
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Efficacy of Phosphodiesterase-5 Inhibitor in Men With Premature Ejaculation: A New Systematic Review and Meta-analysis
Article
  • Aug 2015
To clarify the efficacy of phosphodiesterase-5 inhibitor (PDE5i) in men with premature ejaculation (PE). We searched the PubMed, Embase, and Cochrane Library Databases to identify all randomized controlled trials (RCTs) and compared results, including intravaginal ejaculation latency time, satisfaction, side effects, and others, after treatment with PDE5i versus placebo, PDE5i versus selective serotonin reuptake inhibitor (SSRI), or combined use of PDE5i with SSRI versus SSRI alone for treating PE. The study inclusion criteria were met by 10 studies (10 RCTs with three crossover studies) involving 775 patients. The data synthesized from these studies indicated that the efficacy of PDE5i was better than that of placebo; however, more patients had side effects while taking PDE5i. The efficacy of PDE5i was better than that of SSRIs, and no significant difference was observed in the frequency of side effects. The efficacy of the combined treatment was significantly better than that of SSRI alone; however, more patients had side effects from the combined treatment. The major limitations of this meta-analysis were that there is no universally agreed definition of PE, and the types of medications differed among the studies evaluated. PDE5i was significantly more effective than a placebo or SSRI for treating PE; however, PDE5i had more side effects than placebo. The combined treatment of PDE5i and SSRI had better efficacy but more side effects than the use of SSRI alone. Copyright © 2015 Elsevier Inc. All rights reserved.
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Selective Serotonin Reuptake Inhibitors Plus Phosphodiesterase-5 Inhibitors for Premature Ejaculation: A Systematic Review and Meta-analysis
Article
  • Aug 2015
To evaluate the efficacy and safety of combination therapy with selective serotonin reuptake inhibitors (SSRIs) and phosphodiesterase-5 (PDE-5) inhibitors for the treatment of PE. A systematic search of EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews was undertaken to identify articles that referred to the use of a combination of SSRIs and PDE-5 inhibitors for the treatment of PE. A meta-analysis of these clinical studies was performed. The post-treatment intravaginal ejaculatory latency time (IELT) and adverse events were used in this meta-analysis. Six publications involving 971 patients were included in the meta-analysis. In the analysis, we found significantly improved IELT in the combination use group compared with the use of SSRIs (mean differences (MD) 1.01, 95% confidence interval(CI) 0.61-1.41, p < 0.01) or PDE-5 inhibitors alone (MD 1.11, 95% CI 0.79-1.43, p < 0.01) for PE whether or not these patients suffered from ED. Combined treatment was more efficacious than PDE-5 inhibitors use alone on sexual satisfaction. Although the occurrence of drug-related adverse events (AEs) in the combination use group was higher than that in the use of SSRIs or PDE5 inhibitors alone group (37.5% vs. 25.63%, p < 0.01), the most common AEs were mild and tolerable. The combined use of SSRIs and PDE-5 inhibitors provided additive favorable effects in men with PE compared with SSRIs or PDE-5 inhibitors monotherapy and was generally well tolerated. Copyright © 2015 Elsevier Inc. All rights reserved.
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Efficacy of Dapoxetine for the Treatment of Premature Ejaculation: A Meta-analysis of Randomized Clinical Trials on Intravaginal Ejaculatory Latency Time, Patient-reported Outcomes, and Adverse Events
Article
  • Apr 2015
  • UROLOGY
To evaluate the efficacy of dapoxetine in the treatment of premature ejaculation (PE) with a meta-analysis method. We looked for randomized controlled trials (RCTs) from MEDLINE, EMBASE, Cochrane library, "International Standard Randomized Controlled Trial Number Register," and "ClinicalTrials.gov," which reported efficacy of dapoxetine for PE. Two reviewers searched and examined the RCTs independently. The meta-analysis was performed by RevMan5.0 software. We included 5 RCTs comparing dapoxetine with placebo. Dapoxetine was more effective than placebo for intravaginal ejaculatory latency time (weighted mean difference = 1.47; 95% confidence interval [CI] = 1.22-1.71; P <.00001). For the 4 patient-reported outcomes, dapoxetine was also more effective (for clinical global impression of change, odds ratio [OR] = 3.19; 95% CI, 2.47-4.11; P <.00001; for composite patient-reported outcomes criteria for clinical benefit, OR = 2.29; 95% CI, 1.74-3.00; P <.00001; for satisfaction with sexual intercourse, OR = 1.89; 95% CI, 1.68-2.12; P <.00001; for decrease in personal distress related to ejaculation, OR = 0.72; 95% CI, 0.57-0.90; P <.00001). Dapoxetine is effective and well tolerated for either lifelong or acquired PE. But the long-term benefits and safety remain to be investigated. Copyright © 2015 Elsevier Inc. All rights reserved.
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