Start content

Dapoxetine: The On-Demand Treatment Option

Other > premature ejaculation medicine


Experiments with knockout mice suggest that endothelial nitric oxide synthase (eNOS) gene deletion may adversely affect ejaculatory as well as erectile function.

Alternative medicine

Experiments with knockout mice suggest that endothelial nitric oxide synthase (eNOS) gene deletion may adversely affect ejaculatory as well as erectile function. Kriegsfeld and colleagues set out to study the effects of eNOS on sexual function, and discovered that male mice missing the gene for eNOS exhibited significant abnormalities in ejaculatory function. More specifically, the data from their animal study suggest that ejaculatory function may be inhibited by nitric oxide from eNOS in nongenetically altered mice, and that this effect is most likely achieved by decreasing sympathetic nervous system activity to prevent PE [85]. The authors hypothesized that administration of medications peripherally that can selectively increase eNOS may be effective in treating PE with minimal central nervous system adverse events. Patients with lifelong PE, as opposed to those with acquired or late-onset PE, are reported to have a 50% rate of concomitant ED.

What are common premature ejaculation medications?

Nevertheless, the value of PDE5 inhibitors in the treatment of PE alone has not been established. A crossover study of 31 potent men with lifelong PE found sildenafil treatment to be associated with a significantly higher IELT and higher sexual satisfaction score than any other therapy including the use of any one of a variety of SSRIs and the use of the squeezepause method [1,86]. Sildenafil was deemed “decidedly the most effective” and was recommended as a valid alternative to the use of SSRIs in the treatment of PE. Conversely, the presence of concomitant PE did not impair patient satisfaction with their improved erections, when men were treated with PDE5 inhibitors for their ED [87]. A recent review found that of five studies, three have concluded that the use of PDE5 inhibitors was helpful, even superior, in treating PE, while two placebo-controlled studies found no such improvement [88].

Definition of Premature Ejaculation

The single study, which used objective, double-blinded, placebo-controlled measures, found no improvement in PE following PDE5 inhibitors in men who did not also have associated ED [83]. In a placebo-controlled trial in 84 patients, sildenafil proved ineffective, either alone or in combination with topical therapy, in the treatment of acquired PE [2]. PDE5 inhibitors may exert a secondary benefit for patients with PE when they (i) allow for a sustained penile erection, even after ejaculation; (ii) facilitate a second intercourse after the initial ejaculation, which is often less prone to PE; and/or (iii) help the patient to overcome performance anxiety, which often exacerbates PE [83,89]. However, it is deemed unlikely that PDE5 inhibitors have a significant role in the treatment of PE—with the exception of men with acquired PE secondary to ED [1]. The use of ICI for “treatment” of PE is not supported by a large body of peer-reviewed literature, and is infrequently used in clinical practice. Kriegsfeld and colleagues set out to study the effects of eNOS on sexual function, and discovered that male mice missing the gene for eNOS exhibited significant abnormalities in ejaculatory function. More specifically, the data from their animal study suggest that ejaculatory function may be inhibited by nitric oxide from eNOS in nongenetically altered mice, and that this effect is most likely achieved by decreasing sympathetic nervous system activity to prevent PE [85]. The authors hypothesized that administration of medications peripherally that can selectively increase eNOS may be effective in treating PE with minimal central nervous system adverse events. Patients with lifelong PE, as opposed to those with acquired or late-onset PE, are reported to have a 50% rate of concomitant ED. Nevertheless, the value of PDE5 inhibitors in the treatment of PE alone has not been established. A crossover study of 31 potent men with lifelong PE found sildenafil treatment to be associated with a significantly higher IELT and higher sexual satisfaction score than any other therapy including the use of any one of a variety of SSRIs and the use of the squeezepause method [1,86]. Sildenafil was deemed “decidedly the most effective” and was recommended as a valid alternative to the use of SSRIs in the treatment of PE. Conversely, the presence of concomitant PE did not impair patient satisfaction with their improved erections, when men were treated with PDE5 inhibitors for their ED [87].

Product Dosage Quantity + Bonus Price
Cialis Generic20mg20 Pills54.72€ 52.11€
Viagra Generic50mg20 Pills40.52€ 38.59€
Kamagra Soft Tabs100mg20 Pills79.79€ 75.99€
Cialis Generic40mg20 Pills59.47€ 56.64€
Cialis Generic2.5mg10 Pills28.51€ 27.15€
Cialis Generic2.5mg30 + 4 Pills51.95€ 49.48€
Kamagra Gold100 mg360 + 6 Pills839.95€ 799.95€
Kamagra Gold100 mg120 + 6 Pills330.74€ 314.99€
Levitra Generic60mg120 + 8 Pills372.33€ 354.60€
Cialis Professional20mg30 Pills104.57€ 99.59€
Kamagra Soft Tabs100 mg32 Pills120.11€ 114.39€
Kamagra Soft Tabs100mg120 + 6 Pills311.78€ 296.93€
Viagra Soft Tabs100mg180 + 10 Pills314.95€ 299.95€

A recent review found that of five studies, three have concluded that the use of PDE5 inhibitors was helpful, even superior, in treating PE, while two placebo-controlled studies found no such improvement [88]. The single study, which used objective, double-blinded, placebo-controlled measures, found no improvement in PE following PDE5 inhibitors in men who did not also have associated ED [83]. In a placebo-controlled trial in 84 patients, sildenafil proved ineffective, either alone or in combination with topical therapy, in the treatment of acquired PE [2]. PDE5 inhibitors may exert a secondary benefit for patients with PE when they (i) allow for a sustained penile erection, even after ejaculation; (ii) facilitate a second intercourse after the initial ejaculation, which is often less prone to PE; and/or (iii) help the patient to overcome performance anxiety, which often exacerbates PE [83,89]. However, it is deemed unlikely that PDE5 inhibitors have a significant role in the treatment of PE—with the exception of men with acquired PE secondary to ED [1]. The use of ICI for “treatment” of PE is not supported by a large body of peer-reviewed literature, and is infrequently used in clinical practice. However, ICI has been used as a strategy in certain cases to allow men with PE to maintain their erections and continue satisfactory sexual intercourse despite rapid ejaculation.

In 1990, Fein reported on a small group (N = 8) of patients with PE who used vasoactive intracavernosal pharmacotherapy (mixture of phentolamine mesylate [1.0 mg/mL] and papaverine hydrochloride [30 mg/mL]) to address their PE [90]. When exploited as a temporary intervention, these artificially induced erections provided patients with confidence and encouragement, while they were awaiting results from more conventional therapies. With dosages ranging from 0.10 to 0.40 mL, the author reported that all eight patients responded successfully to this approach, while three were apparently “cured” of PE. The other five patients in the study continued to use ICIs after the completion of the study. An open-label study involving 80 potent men found that the combined use of sildenafil and paroxetine proved more efficacious than either treatment alone [69]. In treating 138 men with a progressive armamentarium of treatments, Chen et al. obtained best results when the use of sildenafil was combined with SSRIs and behavioral counseling. Sildenafil in combination with paroxetine was effective in97%of patients, compared to libido booster for women an improvement for only 47% using paroxetine alone [91]. An alternate approach combines the use of oral agents with the concomitant application of topical solutions.

Preparing for your appointment

Recent experience with the use of tramadol raises the hope that this might prove to be an agent as effective as SSRIs with less worrisome risk of side effects. For example, oral fluoxetine, when reinforced by the topical application of lidocaine ointment, effected a “cure” or an improvement in 83.3% of men, compared with 72% of those treated with fluoxetine alone [92]. Combining a psychotherapeutic with a pharmaceutical approach can provide either a stepwise or concurrent integration of psychological and medical interventions [93].

Class Summary

Clinical research in this field is hampered by the complexity, variability, and subjectivity of this complaint. The placebo effect is high and reliable, appropriately controlled studies are in the minority. Carefully devised, methodically conducted research is much needed. SSRIs have been the most promising agents to date. Minor but nettlesome side effects have long been a disincentive to chronic use of these medications. Several investigators have documented the added value of combining psychotherapy with pharmacotherapy in the treatment of ED, utilizing care models that should transfer readily to the integrated multidisciplinary management of PE [33]. Sildenafil has proven helpful as an adjunctive measure in support of a program of SSRI therapy, when combined with psychosexual counseling [91].

Advance in the understanding of PE has been hobbled by a categorical lack of solid studies on which to base clinical decision making. As a case in point, an attempt at performing a meta-analysis of all studies, which evaluate the potential for PDE5 inhibitors in the treatment of PE, found that only 2 of 14 studies assessed the patient’s reaction to his problem (“bother score”), and none took into consideration the partner’s distress. Only 1 of the 14 studies met the criteria for an evidence-based, double-blinded, placebo-controlled investigation, using validated outcome assessment tools and including objective physiological measurements [83]. The artificiality involved in studying PE under conditions necessary for objective, physiological measurement conflicts with attempts to understand, evaluate, and treat PE in its natural setting. Findings derived from studies of stopwatch timed, methodically recorded intercourse do not necessarily correlate well with performance under more spontaneous, private, and intimate circumstances.

On the brighter side, a most welcome addition to the field is the recent development and validation of a “user-friendly” questionnaire in 2007 to capture the multidimensional nature of PE and lend objectivity to diagnosing this entity [94]. A permanent cure for PE remains a distant goal. In the interim, ideal medical treatment for PE would entail the development of a medication that is effective on a rapid-acting, “on-demand” basis, without impairing the spontaneity and intimacy of the relationship. Sexual side effects (e.g., diminished libido and ED), as well as generalized side effects (e.g., nausea, insomnia, and headache), would be avoided. Novel topical therapies in the form of aerosol (i.e., TEMPE, Plethora Solutions; London, UK) and short-acting SSRI compounds that target the serotonergic system are currently undergoing clinical trials in the United States. Alza/Johnson & Johnson is soliciting an FDA approval for dapoxetine. Pfizer and Bristol-Myers Squibb also have patented agents under development [56].

This article is cited by

Despite these promising leads, it is evident that the recent FDA warning about SSRIs has resulted in a flurry of interest in alternative forms of therapy. Immunohistochemical studies have demonstrated local synthesis of oxytocin and its synthesis-associated protein, neurophysin I, in the epithelial cells of the epididymis [97]. Thus, competing against the SSRI approach, the use of oxytocin compounds as potential therapeutic agents for PE is under investigation [56]. Intervention at other points in the pathophysiologic pathway and topical therapy is also undergoing further testing and improvement [56]. Dietary deficiencies, such as low magnesium intake, may prove to play a limited role [98].

Vardenafil (Levitra®) for PE

Interest in medical therapy for PE is surging. New oral agents are now providing important relief for men afflicted with this condition. On the other hand, no agent provides a cure in lifelong PE, and no medical therapy has as yet received FDA and EMEA approval for use in the treatment of this condition [12]. Studies to date have been relatively few and often limited with respect to the number of patients enrolled and/or the study design [26]. Nevertheless, based on the level of evidence rating of those studies reviewed, both SSRIs and clomipramine have received a grade A recommendation from an expert panel at the Second International Consultation on Sexual Medicine [1]. Although specific data about these compounds are not available at the time of this writing, the Pfizer medication (UK 390957, Pfizer Inc., New York,NY, USA) has been described as a rapid-acting serotonin modulator, i.e., a short-acting SSRI [95]. The Bristol-Myers Squibb drug, BMS-505130, is a potent and selective SSRI with a short half-life with potential advantages in the treatment ofPEbecause of the relatively rapid fall in plasma concentrations [96]. Should these effective, short-acting, “ondemand” agents receive FDA and European Medicines Agency (EMEA) approval for this indication, they could dramatically alter super p force online the treatment landscape [12]. Enlivened interest on the part of the pharmaceutical industry would channel a significant increase in funding into this area, which is much in need of improved investigation, awareness promotion, and effective treatment. Despite these promising leads, it is evident that the recent FDA warning about SSRIs has resulted in a flurry of interest in alternative forms of therapy. Immunohistochemical studies have demonstrated local synthesis of oxytocin and its synthesis-associated protein, neurophysin I, in the epithelial cells of the epididymis [97]. Thus, competing against the SSRI approach, the use of oxytocin compounds as potential therapeutic agents for PE is under investigation [56].

Rights and permissions

As a case in point, an attempt at performing a meta-analysis of all studies, which evaluate the potential for PDE5 inhibitors in the treatment of PE, found that only 2 of 14 studies assessed the patient’s reaction to his problem (“bother score”), and none took into consideration the partner’s distress. Only 1 of the 14 studies met the criteria for an evidence-based, double-blinded, placebo-controlled investigation, using validated outcome assessment tools and including objective physiological measurements [83]. The artificiality involved in studying PE under conditions necessary for objective, physiological measurement conflicts with attempts to understand, evaluate, and treat PE in its natural setting. Findings derived from studies of stopwatch timed, methodically recorded intercourse do not necessarily correlate well with performance under more spontaneous, private, and intimate circumstances. On the brighter side, a most welcome addition to the field is the recent development and validation of a “user-friendly” questionnaire in 2007 to capture the multidimensional nature of PE and lend objectivity to diagnosing this entity [94].

Authors and Affiliations

A permanent cure for PE remains a distant goal. In the interim, ideal medical treatment for PE would entail the development of a medication that is effective on a rapid-acting, “on-demand” basis, without impairing the spontaneity and intimacy of the relationship. Sexual side effects (e.g., diminished libido and ED), as well as generalized side effects (e.g., nausea, insomnia, and headache), would be avoided. Novel topical therapies in the form of aerosol (i.e., TEMPE, Plethora Solutions; London, UK) and short-acting SSRI compounds that target the serotonergic system are currently undergoing clinical trials in the United States. Alza/Johnson & Johnson is soliciting an FDA approval for dapoxetine.

Benzocaine Wipes for PE

Pfizer and Bristol-Myers Squibb also have patented agents under development [56]. Although specific data about these compounds are not available at the time of this writing, the Pfizer medication (UK 390957, Pfizer Inc., New York,NY, USA) has been described as a rapid-acting serotonin modulator, i.e., a short-acting SSRI [95]. The Bristol-Myers Squibb drug, BMS-505130, is a potent and selective SSRI with a short half-life with potential advantages in the treatment ofPEbecause of the relatively rapid fall in plasma concentrations [96]. Should these effective, short-acting, “ondemand” agents receive FDA and European Medicines Agency (EMEA) approval for this indication, they could dramatically alter super p force online the treatment landscape [12]. Enlivened interest on the part of the pharmaceutical industry would channel a significant increase in funding into this area, which is much in need of improved investigation, awareness promotion, and effective treatment. Intervention at other points in the pathophysiologic pathway and topical therapy is also undergoing further testing and improvement [56]. Dietary deficiencies, such as low magnesium intake, may prove to play a limited role [98].

Side Effect Medication Type Incidence Rate Severity Level Management Strategies Notes
Nausea SSRIs, topical anesthetics 10-15% Mild to Moderate Dose adjustment, timing Usually transient
Dizziness SSRIs, topical anesthetics 8-12% Mild Standing slowly, hydration Common with beginning treatment
Headache SSRIs, topical anesthetics 5-10% Mild Analgesics, time to adjust Typically diminishes over time
Reduced Sensation Topical anesthetics 10-20% Mild Reduced dose, application timing Can affect partner satisfaction

Interest in medical therapy for PE is surging. New oral agents are now providing important relief for men afflicted with this condition. On the other hand, no agent provides a cure in lifelong PE, and no medical therapy has as yet received FDA and EMEA approval for use in the treatment of this condition [12]. Studies to date have been relatively few and often limited with respect to the number of patients enrolled and/or the study design [26]. Nevertheless, based on the level of evidence rating of those studies reviewed, both SSRIs and clomipramine have received a grade A recommendation from an expert panel at the Second International Consultation on Sexual Medicine [1].

Clinical research in this field is hampered by the complexity, variability, and subjectivity of this complaint. The placebo effect is high and reliable, appropriately controlled studies are in the minority. Carefully devised, methodically conducted research is much needed.

Expected duration

However, ICI has been used as a strategy in certain cases to allow men with PE to maintain their erections and continue satisfactory sexual intercourse despite rapid ejaculation. In 1990, Fein reported on a small group (N = 8) of patients with PE who used vasoactive intracavernosal pharmacotherapy (mixture of phentolamine mesylate [1.0 mg/mL] and papaverine hydrochloride [30 mg/mL]) to address their PE [90]. When exploited as a temporary intervention, these artificially induced erections provided patients with confidence and encouragement, while they were awaiting results from more conventional therapies. With dosages ranging from 0.10 to 0.40 mL, the author reported that all eight patients responded successfully to this approach, while three were apparently “cured” of PE. The other five patients in the study continued to use ICIs after the completion of the study.

Sertraline (Zoloft)

An open-label study involving 80 potent men found that the combined use of sildenafil and paroxetine proved more efficacious than either treatment alone [69]. In treating 138 men with a progressive armamentarium of treatments, Chen et al. obtained best results when the use of sildenafil was combined with SSRIs and behavioral counseling. Sildenafil in combination with paroxetine was effective in97%of patients, compared to libido booster for women an improvement for only 47% using paroxetine alone [91]. An alternate approach combines the use of oral agents with the concomitant application of topical solutions.

Difficulty Maintaining an Erection

For example, oral fluoxetine, when reinforced by the topical application of lidocaine ointment, effected a “cure” or an improvement in 83.3% of men, compared with 72% of those treated with fluoxetine alone [92]. Combining a psychotherapeutic with a pharmaceutical approach can provide either a stepwise or concurrent integration of psychological and medical interventions [93]. Several investigators have documented the added value of combining psychotherapy with pharmacotherapy in the treatment of ED, utilizing care models that should transfer readily to the integrated multidisciplinary management of PE [33]. Sildenafil has proven helpful as an adjunctive measure in support of a program of SSRI therapy, when combined with psychosexual counseling [91]. Advance in the understanding of PE has been hobbled by a categorical lack of solid studies on which to base clinical decision making. SSRIs have been the most promising agents to date. Minor but nettlesome side effects have long been a disincentive to chronic use of these medications.

Strategy Description Expected Outcome Time Frame Additional Notes
Mindfulness Meditation Practice focusing on the present moment to reduce anxiety Reduced performance anxiety Weeks to months Complements other treatments
Sensate Focus Exercises Partner-based touching exercises to build comfort Increased control and intimacy Several weeks Requires partner cooperation
Cognitive Behavioral Therapy Therapy addressing thoughts and anxiety related to sex Better sexual confidence Several sessions Often part of a comprehensive plan

Recent experience with the use of tramadol raises the hope that this might prove to be an agent as effective as SSRIs with less worrisome risk of side effects.

PAGE TOP