Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation

The acquired form of PE may be cured by medical or psychological treatment https://ranisarees.com/category-growth-hormone-direction-for/ of the underlying cause Waldinger and Schweitzer, 2008. To examine the efficacy and safety of dapoxetine in LPE patients as an alternative to sertraline therapy, all subjects received 30 mg dapoxetine 1–3 hours before planned intercourse and were directed to drink more than 250 mL of water. All patients were required to attempt sexual intercourse at least 4–6 times per month, and they were not taking sertraline during the trial.

For these reasons, daily administration of the SSRIs seems the likely choice for the treatment of PE. After a few weeks, as the 5-HT1A and 5-HT1B autoreceptors become desensitized, serotonin is increased in the synapse region (Waldinger 2005). With SSRI-induced blockage of the 5-HT transporters, serotonin cannot return to the presynaptic neuron, and as a consequence, serotonin levels in the synapse rise. It is the activity of the postsynaptic receptors that ultimately determines the clinical effects of daily administration of SSRIs (Waldinger 2005). Recently, Kim et al (2004) established an in vivo experimental model in which the intraluminal pressure responses of both the seminal vesicle and vas deferens could be measured simultaneously in a single animal. They stimulated the hypogastric nerve as it was more specific in action or distribution than the lesser splanchnic nerve in inducing contraction of the seminal tract by electrical stimulation.

What are the possible side effects of Priligy (Dapoxetine)?​

• Dapoxetine is not a halogenated compound, whereas others contain one or more halogen atoms.
• The drug stimuli of the SSRIs fluoxetine and paroxetine most closely resemble 5-HT2C receptor activation (Berendsen and Broekkamp 1994).
• Premature ejaculation (PE) is the most common male sexual disorder, and is estimated to affect up to 30% of men worldwide (Goldstein 2003).
• Over the past 20–30 years, clinical investigators have participated in a growing number of controlled studies that are developing our basic understanding about PE in ways that will facilitate its future treatment (Waldinger 2002).
• As a consequence, serotonin levels increase outside the cell-body and in the synapses (Waldinger 2005).

The lack of chronic serotonergic stimulation with on-demand dapoxetine precludes serotonin receptor desensitization and the downregulation of postsynaptic serotonin receptors that typically occurs with chronic SSRI use, so that on-demand dosing for PE may minimize the risk of withdrawal symptoms Waldinger, 2007. The DSM-IV-TR criteria and a baseline IELT of less than 2 min on 75% of at least four sexual intercourse events were used to enrol subjects in four of the five phase III studies Buvat et al. 2009; McMahon et al. 2010; Pryor et al. 2006. However, 58% of subjects also met the ISSM criteria for lifelong PE Porst et al. 2010. Subjects reported having had PE for an average of 15.1 years, with 64.9% of subjects classified by the investigator as having lifelong PE at screening. Demographic and baseline characteristics were similar across studies, allowing analysis of pooled phase III data. Ejaculatory latency time is probably a genetically determined biological variable which differs between populations and cultures, ranging from extremely rapid through average to slow ejaculation.

Data on their intravaginal ejaculatory latency time and premature ejaculation profile were recorded before and after the dapoxetine treatment. Clinical Global Impression of Change scores and data on Treatment-Emergent adverse events were collected after treatment. Although, many studies have been published on the use SSRIs in the treatment of PE, Waldinger et al were the first to evaluate these studies methodologically in light of evidence-based criteria (Waldinger 2003; Waldinger et al 2004b).

The most recent combination study compared sildenafil 25–100 mg plus sertraline 50 mg (48 patients) versus sertraline 50 mg alone (51 patients) and sildenafil 50 mg alone (30 patients) in 3 different groups of PE patients (Lazona and Castane 2003). The highest success rate was observed in the group receiving sertraline plus sildenafil (62.5%) followed by those receiving sertraline alone (56.8%), and lastly those who received sildenafil alone (40%). Serotonin is a very important neurotransmitter in the control of the ejaculatory reflex, with secondary involvement of cholinergic, adrenergic, oxytocinergic, and GABAergic neurons. The strongest support for serotonin’s influence on ejaculatory function derives from the observed clinical efficacy of central selective seratonin reuptake inhibitors (SSRIs) in PE (Kim and Seo 1998; Waldinger et al 1998b).

Table 1.

More specifically, a novel selective serotonin reuptake inhibitor (SSRI), dapoxetine, will be evaluated for its pharmacokinetics, efficacy, and safety record in light of available preclinical and clinical data. Premature ejaculation (PE) is the most common male sexual disorder, and is estimated to affect up to 30% of men worldwide (Goldstein 2003). PE, unlike erectile dysfunction (ED), affects men of all ages equally, from 18-year-olds to the elderly. However, both PE and ED coexist, and often PE can masquerade or be misdiagnosed as ED in many men. This is, in part, due to the lack of knowledge about PE, the absence of performing a careful history, and the non-existence of diagnostic tools for PE (Montague et al 2004). Despite its high prevalence and recognized adverse effects on men’s quality of life, only recently has attention been focused on investigating the causes of PE and developing new therapeutic strategies.

Intraseminal vesicle pressure and electromyograms of bulbospongiosus muscles were used as physiological markers of the emission and ejection phases respectively. At all doses, dapoxetine significantly reduced the proportion of rats displaying PCA-induced ejaculation in a dose-dependent manner, from 78% of rats with vehicle to 33%, 22% and 13% of rats following intravenous dapoxetine 1, 3 and 10 mg/kg, respectively. Dapoxetine significantly decreased the AUC of PCA-induced intraseminal vesicle pressure increases and bulbospongiosus muscle contractile bursts by 78% at all doses, by 91% following dapoxetine 1 and 10 mg/kg, and by 85% following dapoxetine 3 mg/kg.

After ejaculation, detumescence occurs, followed by a refractory period that lengthens with age and with repeated ejaculations. Researchers have demonstrated that the ejaculatory mechanism consists of two distinct reflexes, the glans-vasal and the urethromuscular, which are responsible for the emission and expulsion phases of ejaculation, respectively (Shafik 1998). This is consistent with the report by Yang and Bradley (1999) of an electrically distinct pathway localized to the dorsal nerve of the penis and running from the anterior urethra to the bulbocavernous muscle; this is distinct from the penile shaft afferent fibers. The cortical representation of the dorsal nerve of the penis now appears both larger and in a different location than was previously conceived (Bradley et al 1998).

Dapoxetine undergoes rapid absorption and elimination resulting in minimal accumulation and has dose-proportional pharmacokinetics, which are unaffected by multiple dosing and do not vary between ethnic groups (Figure 2) Dresser et al. 2006b; Dresser et al. 2004; Modi et al. 2006. The pharmacokinetic profile of dapoxetine suggests that it is a good candidate for on-demand treatment of PE. For example, some may experience more severe side effects, whereas others may have minimal to zero adverse effects. The manufacturer’s information leaflet contains a complete list of the possible side effects that can occur due to the usage of the drug.

At 9 months, approximately 70% of patients reported “fair”, “good”, or “very good” control over ejaculation.53 These data represent clear evidence of a significant improvement over placebo in perceived control over ejaculation in adult patients with PE taking dapoxetine 30 mg or 60 mg on-demand. Dapoxetine is a selective serotonin reuptake inhibitor, a medicine that is used for the treatment of premature ejaculation in adult men. It is best to take Dapoxetine a few hours before when sex is anticipated, about one to three hours before, rather than taking it every day, as the drug works very fast. This prospective study included LPE patients who previously attempted treatment with sertraline and who agree to receive dapoxetine therapy in our hospital from January 2020 to March 2021. Patients who received any PE therapy in the two months prior to the dapoxetine therapy were excluded.