Evaluation of dapoxetine hydrochloride in treatment of primary premature ejaculation

Abdallah M Attia; Sherif M Abo-elmaaty

doi:10.4103/1110-2098.192410

ORIGINAL ARTICLE

Year : 2016 | Volume : 29 | Issue : 2 | Page : 393-395

Evaluation of dapoxetine hydrochloride in treatment of primary premature ejaculation

Abdallah M Attia, Sherif M Abo-elmaaty
Department of Dermatology, Andrology & STIs, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission	14-May-2014
Date of Acceptance	09-Jun-2014
Date of Web Publication	18-Oct-2016

Correspondence Address:
Sherif M Abo-elmaaty
Department of Dermatology, Andrology & STIs, Kafr El-sheekh Hospital, Kafr El-sheekh, 33511
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/1110-2098.192410

Abstract

Objective:
The aim of the study was to evaluate the role of dapoxetine in treatment of primary premature ejaculation (PE).
Background:
PE is regarded as the most common male sexual disorder. To date, there is no accurate and objective diagnostic test or specific treatment for PE. Dapoxetine hydrochloride is recently developed for treatment of primary PE. It is a short-acting selective serotonin reuptake inhibitor. Although it was refused by the food and drug administration (FDA) in 2005, it is now available in many countries, including Egypt, for treatment of PE. Its efficacy and side effects are not fully studied and few studies exist in this regard with controversial results.
Materials and methods:
This was a double-blind, placebo-controlled, cross-over study. It included 24 patients with primary PE, selected according to the International Society of Sexual Medicine definition of primary PE with intravaginal ejaculatory latency time (IELT) less than 1 min. The patients received dapoxetine 60 mg and placebo for 6 weeks, each with 2 weeks in between as a washout period. The drug and placebo were received on demand 1–3 h before the sexual activity. Efficacy and tolerability were evaluated by IELT and Arabic index of premature ejaculation (AIPE) mean score changes, and the side effects were reported upon at baseline and at 1, 3, and 6 weeks.
Results:
Dapoxetine significantly increased IELT by first, third, and sixth week and the geometric mean by 5.15 ± 0.17 folds, and with dapoxetine (60 mg) the AIPE became normal in 88.9% of patients by the sixth week, whereas placebo failed to give any change.
Conclusion:
Dapoxetine is a promise drug for PE as on-demand treatment. Dapoxetine significantly improved the IELT and AIPE, and it is well tolerated.

Keywords: dapoxetine, premature ejaculation, sexual disorders

How to cite this article:
Attia AM, Abo-elmaaty SM. Evaluation of dapoxetine hydrochloride in treatment of primary premature ejaculation. Menoufia Med J 2016;29:393-5

How to cite this URL:
Attia AM, Abo-elmaaty SM. Evaluation of dapoxetine hydrochloride in treatment of primary premature ejaculation. Menoufia Med J [serial online] 2016 [cited 2023 Dec 4];29:393-5. Available from: http://www.mmj.eg.net/text.asp?2016/29/2/393/192410

Introduction

Premature ejaculation (PE) is a sexual dysfunction with high prevalence. According to some reports, it is present in about 20–30% of the male population ^[1]. It is now classified into four types: primary (lifelong), secondary (acquired), natural variable, and premature-like ejaculatory dysfunction ^[2]. There were no objective parameters to measure primary PE until Waldinger in 1994 introduced the intravaginal ejaculatory latency time (IELT) as an objective parameter that measures the time from vaginal penetration to ejaculation ^[3]. Primary PE is now finally defined by the International Society of Sexual Medicine (ISSM) as ejaculation that always or nearly always occurs within or less than 1 min of IELT, in all or nearly all sexual acts, and causes negative personal consequences for one or both partners ^[4]. The exact etiology of primary PE is still unknown. There are diverse ranges of biogenic and psychological theories but all of them are not evidence based ^[5]. Genetic predisposition and disturbances in serotonin and its receptors involved in ejaculation (5-HT 1A and 2C) are supposed for the primary type. Chronic prostatitis, neuropathy, and disseminated sclerosis are the suspected causes for the secondary type. Sexual abstinence is believed to be the cause of the natural variable PE. Overestimation and psychic disorders are believed to be the causes for the premature-like ejaculatory dysfunction ^[6]. Until now, no specific treatment has been approved for management of primary PE. Drugs used for this aim were founded for treatment of other diseases, and delay of ejaculation is one of their side effects ^[7]. Dapoxetine HCl is a novel short-acting selective serotonin reuptake inhibitor (SSRI), which was founded only for this purpose — treatment of PE ^[8]. It is stated that it is used only on demand and acts through selectively modulating the 5-HT receptors involved in ejaculation (5-HT 1A and 2C) as well as by elevating the brain serotonin level. Although dapoxetine is not approved yet by FDA, it seems to be effective and promising in treatment of primary PE ^[9]. This study aimed to evaluate the efficacy and the probable side effects of dapoxetine in treatment of patients with primary PE, in a double-blind placebo-controlled cross-over study.

Materials and Methods

This study was conducted in the Andrology Unit, Dermatology, Andrology and STIs Department, Faculty of Medicine, Menoufia University during the period from January to August 2013. It was a randomized, prospective, double-blind placebo-controlled cross-over study. It included 24 patients with primary PE, selected according to the ISSM definition of primary PE with IELT less than 1 min. All patients are in stable marriage (X = 3.9 ± 3.5 years) and their mean age was 29.3 ± 5 years, with no urological, medical, or other sexual problems, and they did not receive any medical treatment or treatment for their PE in the previous 15 days before inclusion. The patients received dapoxetine 60 mg and placebo for 6 weeks, each with 2 weeks in between as a washout period. The drug and placebo were received on demand 1–3 h before the sexual activity. During the whole phases, the patients were instructed to perform sexual intercourse twice/week, not to perform more than one intercourse in each session, and not to pause or to perform intermittent act. Exclusion criteria included:

erectile dysfunction,
organic secondary PE,
sexual frequency less than 2/week,
sexual dysfunction of the partner,
history of medical or psychiatric illnesses,
current use of SSRIs, tricyclic antidepressant, or PDE5Is,
current use of other forms of treatment of PE, and
PE not in agreement with the ISSM definition.

Data management

The Wilcoxon test was performed for continuous quantitative parametric variables and the Mann–Whitney U-test for nonparametric variables. Partial correlation coefficient for testing association between variables was also applied. A P-value of less than 0.05 was considered statistically significant.

Analyses were conducted with SPSS v. 13 software (SPSS Inc., Chicago, Illinois, USA) and Epi Info version 3.3, released by Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA, in October 2004.

Results

In 66.7% of the patients, IELT was elevated from less than 1 min to at least 5 min by the sixth week of dapoxetine 60 mg use, whereas placebo showed no change. Dapoxetine significantly increased IELT by first, third, and sixth week and the geometric mean by 5.15 ± 0.17 folds, whereas placebo failed to show any change compared with baseline values. Dapoxetine 60 mg when compared with placebo significantly increased the geometric mean IELT and the geometric mean fold ([Figure 1]). With dapoxetine (60 mg), the Arabic index of premature ejaculation (AIPE) became normal in 88.9% of patients by the sixth week, whereas placebo failed to give any change. Compared with baseline, dapoxetine (60 mg) significantly increased the AIPE score, whereas placebo did not. Compared with placebo, dapoxetine increased the AIPE score significantly ([Figure 2]). No severe adverse effects were reported (for both dapoxetine and placebo), and only with dapoxetine one patient was withdrawn because of severe nausea. No sexual side effects were reported with either dapoxetine or placebo, with no change in the degree of erection, desire, or ejaculate volume. The reported side effects by dapoxetine were mostly mild, moderate, and disappeared on continuation. These were in the order of frequency: nausea (22.4%), dizziness (22.4%), headache (11.2%), diarrhea (11.2%), fatigue (5.6%), and somnolence (5.6%) ([Figure 3]). Only one patient was withdrawn because of severe nausea due to dapoxetine.

Figure 1: Intravaginal ejaculatory latency time (IELTs) changes/min by placebo and dapoxetine (60 mg) after 1, 3, and 6 weeks of treatment compared with baseline

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Figure 2: Arabic index of premature ejaculation (AIPE) score changes by dapoxetine (60 mg) compared with placebo by the end of treatment

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Figure 3: Side effects reported by dapoxetine compared with placebo

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Discussion

Although the condition is highly undertreated, SSRIs that were developed to treat depression and other psychiatric disorders are used increasingly as off-label treatment for PE, on the basis of their side effect of delay ejaculation. However, these compounds were not developed to treat PE, are long acting, and are associated with drawbacks. SSRIs adverse effects include psychiatric and neurological issues, anticholinergic side effects, changes in the body weight, cognitive impairment, and sexual side effects (e.g. erectile dysfunctions and loss of libido). SSRIs have longer half-lives and generally take longer time to reach peak concentrations [10). Dapoxetine is a short-acting SSRI developed specifically for the treatment of PE. The drug's mechanism of action is thought to be related to inhibition of neuronal reuptake of serotonin and subsequent potentiation of serotonin activity. In contrast to conventional SSRIs approved for depression, which take 2 weeks or longer to reach steady-state concentration, dapoxetine has a unique pharmacokinetic profile with a short time to maximum serum concentration (about 1 h) and rapid elimination (initial half-life 1–2 h). By 24 h, plasma concentration is less than 5% of peak values. These attributes make dapoxetine suitable for on-demand treatment of PE ^[1]. In this study, efficacy and tolerability were evaluated by IELT and AIPE mean score changes, and the side effects were reported upon at baseline and at 1, 3, and 6 weeks, except AIPE, which was assessed at baseline and at the end point of the study (sixth weeks). As the arithmetic mean may overestimate the results of the drug, we depended upon the geometric mean IELT and geometric mean fold increase in IELT as recommended ^[0]. The results showed that 18 (75%) of 24 included patients completed the study until its end, whereas six (25%) did not (four were lost during follow-up, one because of lack of efficacy and one because of severe nausea he felt with dapoxetine). In 12 (66.7%) of 18 patients who completed the study, dapoxetine increased the IELT from less than 1 min at baseline to at least 5 min by the end of the study, whereas placebo showed no change in the IELT. The reported side effects by dapoxetine were mostly mild to moderate and disappeared on continuation. These were in the order of frequency: nausea (22.4%), dizziness (22.4%), headache (11.2%), diarrhea (11.2%), fatigue (5.6%), and somnolence (5.6%).

Conclusion

In this study, we demonstrate that dapoxetine is a promise drug for PE as on-demand treatment. Dapoxetine significantly improved the IELT and AIPE, and it is well tolerable and caused mild side effects.

Conflicts of interest

There are no conflicts of interest.[11]

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