帕罗西汀与达帕西汀的对比，治疗早泄的新的选择性5-羟色胺再摄取抑制剂

达帕西汀氢氯化物是一种选择性5-羟色胺再摄取抑制剂,也是第一种被批准可以按需服用治疗早泄的药物。本文目的为研究按需服用达帕西汀（30mg和H60mg）和每日服用帕罗西汀（20mg）对早泄的疗效。研究募集了150名患者进行了长达1个月的研究。患者被分成3组,每组50人。第一组按需服用达帕西汀30mg。第二组按需服用达帕西汀60mg。第三组每日服用帕罗西汀20mg。治疗结束后,我们的结果检测值相对于基准阴道内射精潜伏期（IELT）延长了。与基准IELT相比,帕罗西汀组、30mg达帕西汀组和60mg达帕西汀组的治疗后IELT分别延长了117％（P〈0．01）,117％（P〈0．01）和170％（P〈0．01）。30mg达帕西汀组和帕罗西汀组的IELT增幅相同（P〉0．05）,而60mg达帕西汀组的IELT增幅明显高于30mg达帕西汀组（P〈0．05和帕罗西汀组P〈0．01）。性交前1～3小时服用达帕西汀60mg是针对早泄的非常有效的治疗方法。然而,与当前普遍使用的帕罗西汀相比,达帕西汀30mg疗效并不显著。     

Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment �C topical versus systemic

Premature ejaculation (PE) is a common sexual dysfunction affecting 20% to 30% of men worldwide. Definitions of PE vary, but it is typically characterized by short intravaginal ejaculatory latency time (IELT) with concomitant sexual dissatisfaction and distress. PE may be lifelong or acquired, but its etiology remains unclear. Treatment of PE typically involves pharmacotherapy, particularly when lifelong. Although there are numerous reports on the off-label use of selective serotonin reuptake inhibitors (SSRIs) and other compounds, only 2 treatments have been evaluated in randomized controlled phase 3 clinical trials: PSD502 and dapoxetine (SSRI). Both significantly improved IELT and patient-reported outcome domains of ejaculatory control, sexual satisfaction, and distress as measured by the index of premature ejaculation (IPE), compared with placebo. They constitute the focus of this review. Evidence demonstrated that PSD502, dapoxetine and other SSRIs all significantly improve the symptoms of PE. Systemic use of SSRIs presents risks associated with the known pharmacology of this class. PSD502 allows for topical on-demand treatment applied applied immediately before intercourse, and is not associated with systemic adverse events.     

Treatment of premature ejaculation

Premature ejaculation (PE) is the most common male sexual disorder, and it may have a profound negative impact on a man and his partner's lives. Different organizations and societies have no consensus on the definition and classifications of PE. However, most organizations and societies include in their definitions the intravaginal ejaculation latency time (IELT), the control of ejaculation, and the distress or impact of interpersonal difficulties. Evaluation procedures have been standardized in clinical studies by the development of an objective measurement of IELT (using a stopwatch) and by the introduction of patient-reported outcome (PRO) questionnaires on ejaculation control and sexual satisfaction. The identification of four different patterns of PE—lifelong, acquired, normal variant, and premature-like ejaculatory dysfunction—is critical because of different underlying pathogeneses and consequently different management approaches. The optimal treatment for PE should be individualized, based on a patient's symptoms, expectations, and underlying variant causes. Most lifelong PE patients need pharmacotherapy (possibly in combination with psychosexual counseling) as a first-line treatment because of the underlying neurobiological etiology and the impact of PE on the couple's relationship. The management of acquired PE is etiologically specific and may include pharmacotherapy for erectile function management in men with comorbid erectile dysfunction (ED). Men with natural variable PE complain of early ejaculation in situational or coincidental conditions; the ejaculation is inconsistent and occurs irregularly. Psychoeducation and reassurance are indicated for men with this type of PE. Psychotherapy or sex counseling is the first choice of treatment for men with premature-like ejaculatory dysfunction. All pharmacotherapies such as long-term selective serotonin reuptake inhibitors (SSRIs) or on-demand topical anesthetics are off-label indications, The benefits of pharmacotherapy toward improving ejaculation times should be weighed against their safety profiles. The development of the short-acting selective serotonin reuptake inhibitor (SSRI) dapoxetine hydrochloride (30 mg and 60 mg) for oral on-demand use opened a new era of PE treatment. Other potential pharmacotherapies such as tramadol, lidocaine/prilocaine spray, and phosphodiesterase inhibitors are still under development. Their safety and efficacy profiles should be further evaluated and supported by additional clinical studies.     

Impact of physical activity on patient self‐reported outcomes of lifelong premature ejaculation patients: Results of a prospective,randomised, sham‐controlled trial

Previous studies have investigated whether physical activity increases serotonin hormone levels. Serotonin receptor dysfunction is one of the frequently accused factors of premature ejaculation (PE). Nevertheless, no studies up to date have demonstrated that the association between physical activity and premature ejaculation. We aimed to investigate the relationship between physical activity and PE and determine whether moderate physical activity might delay ejaculation time or be an alternative treatment for PE. A total of 105 patients diagnosed with PE were enrolled in this study. Of the patients, 35 were treated with dapoxetine, (30 mg) on demand (Group 1), 35 performed moderate physical activities (Group 2), and 35 performed minimal physical activity (Group 3‐sham). Demographic characteristics, metabolic equivalents (MET), premature ejaculation diagnostic tool (PEDT) and intravaginal ejaculatory latency time (IELT) were recorded. There were no significant differences among three groups in terms of age, BMI, MET, PEDT or IELT before treatment. At the end of the study, there was significant decrease in PEDT scores, and increase in IELT in groups 1 and 2 as compared to Group 3. In conclusion, a moderate physical activity longer than 30 min at least 5 times a week leads to ejaculation delay, and appears as an alternative to dapoxetine on demand for the treatment of PE.     

Comparison of the clinical efficacy and safety of the on‐demand use of paroxetine,dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation: A randomised placebo‐controlled clinical trial

The aim of the study was to compare the clinical efficacy and safety of the on‐demand use of paroxetine, dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation (PE). In a single‐blind placebo‐controlled clinical study, 150 PE patients without erectile dysfunction (ED) were included during the period of March 2015 to May 2016. Patients were randomly divided into five groups (30 patients each). On demand placebo, paroxetine (30 mg), dapoxetine (30 mg), sildenafil citrate (50 mg) and combined dapoxetine (30 mg) with sildenafil citrate (50 mg) were given for patients for 6 weeks in each group respectively. All patients were instructed to record intravaginal ejaculatory latency time (IELT) and evaluated with Premature Ejaculation Diagnostic Tool (PEDT) and the patient satisfaction score before and after treatment. The mean of IELT, satisfaction score and PEDT in all groups was significantly improved after treatment (p value = .001). Combined dapoxetine with sildenafil group had the best values of IELT, satisfaction scores and PEDT in comparison with other treatment groups (p value <.001). The combined dapoxetine with sildenafil therapy could significantly improve PE patients without ED as compared to paroxetine alone or dapoxetine alone or sildenafil alone with tolerated adverse effects.     

Effect of acute dapoxetine administration on the pudendal motoneuron reflex in anesthetized rats: comparison with paroxetine

PURPOSE: Pudendal motoneuron reflex discharges elicited by bilateral electrical stimulation of the dorsal nerves of the penis were used as an experimental model of the expulsion reflex of ejaculation to investigate the effect of acute intravenous delivery of dapoxetine, a short acting selective serotonin reuptake inhibitor, in anesthetized rats. Dapoxetine was compared with paroxetine, the selective serotonin reuptake inhibitor of reference. MATERIALS AND METHODS: Stimulating electrodes were placed bilaterally on the dorsal nerves of the penis and a recording electrode was placed on the motor branch of the pudendal nerve to monitor pudendal motoneuron reflex discharges in urethane anesthetized rats. Pudendal motoneuron reflex discharges induced by penile dorsal nerve stimulation were measured before and 60 minutes after a single intravenous injection of dapoxetine or paroxetine, each tested at 3 doses (1, 3 and 10 mg/kg) or after a single injection of vehicle. RESULTS: At all doses tested dapoxetine significantly lengthened the latency of pudendal motoneuron reflex discharges following bilateral stimulation of the dorsal nerves of the penis in comparison with vehicle, whereas only the 1 mg/kg dose of paroxetine was effective. The amplitudes of pudendal motoneuron reflex discharges were significantly decreased only in rats treated with 3 mg/kg dapoxetine compared to vehicle. CONCLUSIONS: Acute systemic delivery of selective serotonin reuptake inhibitors is capable of modulating the expulsion reflex of ejaculation in anesthetized rats with dapoxetine appearing to be more effective than paroxetine. These findings support the beneficial effect of on-demand administration of dapoxetine for premature ejaculation.     

A Novel Treatment of Premature Ejaculation

The investigation of the etiology and treatment of premature ejaculation (PE), a common and significant problem for men and their partners, has been limited by the lack of defined outcomes and differences in clinical trial designs. Currently, no medication has been approved for the treatment for PE worldwide. Recognition of serotonin as a key mediator in ejaculatory signaling has raised interest in the utility of pharmacologic intervention for treating PE. Selective serotonin reuptake inhibitors (SSRIs) have been used off-label for PE, with varied results. However, treatment with currently available SSRIs typically requires chronic dosing that increases drug accumulation and the attendant risk of adverse events. Dapoxetine is an SSRI with a short half-life (1.2 h), developed specifically for the treatment of men with PE. This agent has a unique pharmacokinetic profile characterized by rapid absorption and elimination. Dapoxetine is metabolized by multiple pathways, and no clinically relevant drug–drug interactions have been identified. Furthermore, dapoxetine pharmacokinetics do not appear to be affected by food, age, alcohol, or phosphodiesterase type 5 (PDE5) inhibitors to a relevant degree. In two placebo-controlled phase 3 trials involving >2600 men with PE, dapoxetine 60 mg given as needed over 12 wk significantly prolonged the stopwatch-assessed intravaginal ejaculatory latency time (IELT) from 0.91 min at baseline to 3.32 min (p < 0.0001), increased control over ejaculation, and increased sexual satisfaction for men and their partners compared with placebo (both p < 0.0001). These results suggest that dapoxetine may meet the medical need for on-demand therapy for PE.     

Use of paroxetine on-demand in premature ejaculation

IntroductionIt has been described varied definitions of premature ejaculation (PE), which has determined different prevalences and rates of success for the different therapies with selective serotonin re-uptake inhibitors. Our goal was evaluate the effectiveness of paroxetine like treatment of premature ejaculation administered ondemand (4-6 hours previous to intercourse) compared to the scheme of daily dose.Patients and methodA prospective study type crossover was designed with 14 patients. Grupo A: 7 patient received paroxetine 20 mg /d by three weeks followed by paroxetine 20 mg 4-6 hours before the intercourse by three weeks. Group B: the other 7 patients received the same scheme but replacing by placebo. Later to three weeks of therapy suspension, crossover was made.ResultsThe intravaginal ejaculatory latency time (IELT) pre-treatment was 0,4 minutes. In the group A the IELT average was of 4,3 minutes in the treatment with daily paroxetine; 5,8 minutes when they received paroxetine on-demanad; 0.9 with daily placebo and 0,6 with placebo on-demand (p < 0.001). For group B the IELT during the daily placebo was 0,8 minutes and with placebo on-demand it was of 1,1 . When they received daily paroxetine the IELT was 3,3 minutes and during the phase of paroxetine on-demand it was increased to 6,1 (p<0.001).ConclusionsThe treatment of premature ejaculation with paroxetine in daily dose and scheme on-demand appears similar like effective options.     

Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review

This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.     

Safety and efficacy of venlafaxine in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomised study

Venlafaxine is a serotonin-noradrenaline reuptake inhibitor antidepressant. Two hundred and twenty-two married men (mean age, 34 years) with premature ejaculation (PE) were randomly assigned to receive 75 mg of venlafaxine extended release (n = 112) (group 1) or placebo (n = 110) (group 2) for 12 weeks. Pre-treatment evaluation included history and physical examination, geometric mean intravaginal ejaculatory latency time (IELT) and International Index of Erectile Function (IIEF). The efficacy of two treatments was assessed every 2 weeks during treatment, and at the end of study, using responses to IIEF, IELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. At the end of treatment period, the geometric mean IELT in venlafaxine and placebo group demonstrated 1.7-fold (95% CI: 0.76-1.96) and 1.6-fold (95% CI: 0.87-1.84) increase respectively (P = 0.1). The mean weekly intercourse episodes increased from pre-treatment values of 1.2 and 1.18 to 2.1 and 1.9 for venlafaxine and placebo respectively (P = 0.08). Baseline mean intercourse satisfaction domain values of IIEF 12 and 12 reached to 13 and 12 at 12-week treatment in groups 1 and 2 respectively (P = 0.07). Mean number of adverse events was 32 for venlafaxine and 8 for placebo (P = 0.02). Venlafaxine is not better than placebo in treatment of PE.     

Dapoxetine and the treatment of premature ejaculation

Background

Premature ejaculation (PE) is the most common male sexual complaint. Off-label oral selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of PE. Dapoxetine is a short-acting SSRI specifically designed for on-demand use. The objective of this communication is to summarize the clinical and physiological evidence regarding the role of the serotonergic pathway and specifically dapoxetine in the treatment of PE.

Methods

A PubMed search was conducted on articles reporting data on dapoxetine for the treatment of PE. Articles describing the pathophysiology and treatment options for PE were additionally included for review.

Results

The etiology of PE is multi-factorial in nature. There are many treatment options for PE such as psychological/behavioral therapy, topical anesthetic agents, phosphodiesterase type 5 (PDE-5) inhibitors, and tramadol hydrochloride. SSRIs play a major role in PE treatment. Animal and clinical studies in addition to its pharmacokinetic document dapoxetine’s clinical efficacy and safety for on-demand treatment of PE.

Conclusions

Dapoxetine demonstrates clinical efficacy and a favorable side effect profile. Dapoxetine is currently the oral drug of choice for on-demand treatment of PE.     

Comparison of the safety and efficacy of the on-demand use of sertraline,dapoxetine, and daily use of sertraline in the treatment of patients with lifelong premature ejaculation: A prospective randomised study

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.     

Oral dapoxetine versus topical lidocaine as on-demand treatment for lifelong premature ejaculation: A randomised controlled trial

This trial aimed to assess the efficacy of on-demand oral dapoxetine versus topical lidocaine treatments for lifelong PE. Cases with lifelong PE were randomised to start treatment by oral dapoxetine 60 mg or topical lidocaine 10% spray. The intravaginal ejaculatory latency time (ILET), validated Arabic Index for PE (AIPE), Sexual Health Inventory for Men (SHIM) and frequency of intercourse/week were recorded at the baseline and after 12 weeks treatment period of the first medication before two weeks washout period and then crossing over to the other one for another 12 weeks. Results showed that both medications significantly increased both IELT and AIPE scores compared with the baseline being significantly better with topical lidocaine (63.44 s, 179.4 s versus 21.87 s, p < .05). Significant decrease of SHIM score was recorded with lidocaine but not with dapoxetine. Global Efficacy Question for the patient's assessment of the effectiveness of drugs showed that lidocaine was described as being effective by 43 cases and ineffective by 12 cases, oral dapoxetine was described as being effective by 16 cases and ineffective by 39 cases. From these accumulated data, it is concluded that topical lidocaine is more effective on-demand therapy for lifelong PE compared with oral dapoxetine.     

Effect of premature ejaculation desensitisation therapy combined with dapoxetine hydrochloride on the treatment of primary premature ejaculation

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.     

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

Background

Dapoxetine is being developed for the on-demand treatment of premature ejaculation (PE). Previous clinical trials have demonstrated its safety and efficacy.

Objective

To evaluate the long-term efficacy and safety of dapoxetine in men with PE.

Design, setting, and participants

This randomized, double-blind, parallel-group, placebo-controlled, phase 3 trial, conducted in 22 countries, enrolled men (N = 1162) ≥18 yr of age who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE for ≥6 mo, with an intravaginal ejaculatory latency time (IELT) ≤2 min in ≥75% of intercourse episodes at baseline.

Intervention

Dapoxetine 30 mg or dapoxetine 60 mg or placebo on demand (1–3 h before intercourse) for 24 wk.

Measurements

Stopwatch-measured IELT, Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change, adverse events (AEs).

Results and limitations

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.

Conclusions

Dapoxetine significantly improved all aspects of PE and was generally well tolerated in this broad population.     

Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors

Potential pharmacokinetic interactions between dapoxetine, a serotonin transporter inhibitor developed for the treatment of premature ejaculation (PE), and the phosphodiesterase-5 inhibitors tadalafil and sildenafil, agents used in the treatment of erectile dysfunction (ED), were investigated in an open-label, randomized, crossover study (n=24 men) comparing dapoxetine 60 mg, dapoxetine 60 mg+tadalafil 20 mg, and dapoxetine 60 mg+sildenafil 100 mg. Plasma concentrations of dapoxetine, tadalafil, and sildenafil were determined by liquid chromatography-tandem mass spectrometry. Tadalafil did not affect the pharmacokinetics of dapoxetine, whereas sildenafil increased the dapoxetine AUCinf by 22%; these effects were deemed not clinically important. Dapoxetine did not appear to affect the pharmacokinetics of tadalafil or sildenafil. Most adverse events were mild in nature. Thus, dapoxetine has no clinically important pharmacokinetic interactions with tadalafil or sildenafil, and the combinations are well tolerated.     

Pharmacokinetic and pharmacodynamic features of dapoxetine, a novel drug for 'on-demand' treatment of premature ejaculation

OBJECTIVE: To describe the relationship between the pharmacokinetic and pharmacodynamic properties of dapoxetine, a drug specifically developed for treating premature ejaculation (PE). METHODS: Data from various stages of the clinical development programme were analysed using validated methods for assessing ejaculatory latency. The clinical characteristics were then compared with the pharmacokinetic profile, determined from measured plasma drug concentrations. RESULTS: Pharmacodynamic and pharmacokinetic measurements confirm that 'on demand' dapoxetine has a rapid onset of action and is rapidly cleared after sexual intercourse. CONCLUSION: Dapoxetine may represent the first of a new category of selective serotonin transport inhibitors. Although dapoxetine has pharmacological similarities to other selective serotonin transport inhibitors, its efficacy after acute administration sets it apart and suggests a different mode of action. Its physicochemical and pharmacokinetic properties and its clinical efficacy make dapoxetine suitable for on-demand treatment of PE.     

Relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors treatment on premature ejaculation: decreased nitric oxide is associated with premature ejaculation

The aim of the present study was to determine the relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors (SSRI) treatment on premature ejaculation. Sixty married men (aged 20–50) with lifelong premature ejaculation and forty healthy men (aged 24–48) as control group were included in this study. The patients were evaluated by intravaginal ejaculation latency time (IELT) for premature ejaculation (PE). IELT<1 min is accepted PE. Patients with diabetes mellitus, chronic disorders or erectile dysfunction and heavy smokers were excluded. All patients were evaluated with history, physical examination, International Index of Erectile Dysfunction‐5 (IIEF‐5) score and IELT by stopwatch method. Nitric oxide levels were measured by Griess reaction, and all samples were frozen at ?80 °C. Patients were randomly categorised 4 group to receive fluoxetine 20 mg day^?1 (Group 1), paroxetine 20 mg day^?1 (Group 2), sertraline 50 mg day^?1 (Group 3) and healthy control (Group 4) for 4 weeks. Baseline and post‐treatment findings were compared between the four groups. At the end of 4 weeks, in fluoxetine, paroxetine, sertraline groups mean IELT values showed a statistically significant improvement from the baseline values (P < 0.001, P < 0.001, P = 0.03; respectively). Baseline and 1st month follow‐up mean IIEF scores were 24.5 and 23.05, 24.70 and 23.60 (P < 0.05) in group 1 and group 3 respectively; also 23.09 and 23.32 (P > 0.05) in group 2. Baseline serum NO levels were 31.8, 30.44, 30.8 and 42.84 in fluoxetine, paroxetine, sertraline and healthy control groups respectively. NO levels were statistically lower in patients with PE. After treatment of fluoxetine, paroxetine and sertraline, NO levels were increased baseline (35.8, 36.4, 38.08) (P < 0.05). Our findings indicated that PE is associated with decreased serum NO levels. After the SSRI treatment increased, NO may retard ejaculation presumably by central peripheral mechanism. Further studies are needed to confirm this suggestion and the role of NO in pathophysiology and treatment for premature ejaculation.     

按需服用达泊西汀对早泄疗效的Meta分析

目的:评价按需服用达泊西汀对早泄的疗效,为临床决策提供依据。方法:检索PubMed、Embase、BIOSIS Previews、Cochrane Library、CNKI数据库、万方资源数据库有关按需服用达泊西汀治疗早泄的研究文献,并进行Meta分析;主要评价阴道内射精潜伏时间(intravaginal ejaculatory latency time,IELT)、患者总体感觉改善情况(patient-reported global impression of change,PGI)、综合临床受益(composite PRO criteria for clinical benefit,CCCB)3项结局指标。结果:检索出相关文献159篇,剔除142篇,共有4篇文献符合纳入标准,累计患者6 081例。Meta分析结果显示:与安慰剂相比,按需服用达泊西汀在IELT[WMD=1.39,95%CI(1.23,1.55),P<0.000 01],PGI[OR=2.59,95%CI(2.21,3.04),P<0.000 01],CCCB[OR=2.59,95%CI(1.98,3.39),P<0.00001]方面差异均有显著性意义;达泊西汀60 mg与30 mg治疗组间比较,60 mg组在IELT[WMD=0.46,95%CI(0.19,0.74),P=0.0010],PGI[OR=1.32,95%CI(1.06,1.64),P=0.01]方面差异有显著性意义,在CCCB[OR=1.39,95%CI(0.90,2.15),P=0.13]方面无显著性差异。结论:本研究表明按需服用达泊西汀60 mg及30 mg均能延长早泄患者IELT,提高其PGI及改善CCCB;其中60 mg较30 mg剂量在延长早泄患者IELT及提高PGI方面效果更佳。     

The pharmacological treatment of premature ejaculation

Premature ejaculation (PE) is a common sexual dysfunction in men that is characterized by a short time to ejaculation, and a lack of control over ejaculation, and is associated with distress for men and their partners. Lack of knowledge about the aetiology of PE and lack of approved treatments might contribute to its under-diagnosis and under-treatment. The organic factors involved in PE are not well understood but serotonin (5-hydroxytryptamine, 5-HT) is important at the level of the central nervous system in the complex regulatory mechanisms involved in ejaculation. Selective serotonin reuptake inhibitor (SSRI) antidepressants (paroxetine, fluoxetine and sertraline) and the tricyclic antidepressant clomipramine increase ejaculatory control and delay ejaculation in men with PE, suggesting that pharmacological intervention might be useful for PE. These agents are intended for chronic dosing for treating psychiatric disorders because of their pharmacokinetic profile and pharmacodynamic activity, which might result in limitations when used for treating PE. Indeed, these properties might limit the utility of these drugs, whether administered on-demand or chronically, for the episodic treatment requirements of PE. Elevated synaptic 5-HT levels achieved with acute SSRI treatment might be self-limiting because of activation of presynaptic 5-HT(1A) autoreceptors, and chronic 5-HT(1A) autoreceptor desensitization might contribute to an increase in side-effects and withdrawal symptoms. Short-acting SSRIs such as dapoxetine, currently under development for the on-demand treatment of PE, might circumvent these limitations and offer better ejaculatory control and sexual satisfaction for men with PE. Phosphodiesterase-5 inhibitors have also been evaluated for treating PE, as have topical anaesthetics and the narcotic analgesic tramadol.