Dapoxetinos (Dapoxetine)

What is Dapoxetine?

Dapoxetine is a pharmacological agent specifically developed for the treatment of premature ejaculation (PE) in men. It belongs to the class of selective serotonin reuptake inhibitors (SSRIs), which are typically used as antidepressants. However, dapoxetine distinguishes itself by its rapid onset of action and short half-life, making it suitable for on-demand treatment. Originally developed as an antidepressant, dapoxetine's unique pharmacokinetic profile led to its repurposing for PE, an application where traditional SSRIs were not effective due to their long half-lives and delayed onset of action.

Uses

Premature ejaculation is one of the most common male sexual dysfunctions, affecting 20-30% of men globally. It is characterized by a lack of control over ejaculation, occurring sooner than desired, often within one minute of vaginal penetration. This condition can lead to significant distress, anxiety, and interpersonal difficulties. Dapoxetine is the first oral treatment specifically approved for this condition, offering a clinically significant extension of intravaginal ejaculatory latency time (IELT) and improved control over ejaculation. 

Intravaginal ejaculation latency times (IELTs) at endpoint for baseline IELT up to 1 min and up to 0.5 min for placebo, dapoxetine 30 mg (IELT fold increase: <0.5 min 3.4, <1 min 2.7) and dapoxetine 60 mg (IELT fold increase: <0.5 min 4.3, <1 min 3.4) (McMahon et al. 2010).

PE in Athletes Using Steroids

Anabolic steroid use is prevalent among athletes seeking enhanced performance and muscle mass. However, steroid use is associated with numerous side effects, including hormonal imbalances that can lead to sexual dysfunctions such as PE. The androgenic effects of steroids can disrupt the hormonal milieu, contributing to conditions like PE (Sansone et al., 2018, Armstrong et al., 2018). Dapoxetine has been shown to alleviate steroid-induced PE by modulating serotonergic pathways and enhancing the serotonin levels in the brain, which plays a crucial role in delaying ejaculation. Studies indicate that dapoxetine is effective in restoring ejaculatory control in athletes affected by steroid-induced PE, thereby improving their sexual health and overall quality of life (Corona et al., 2011).

Combination with Sialis/Viagra

When combined with erectile dysfunction medications such as Sialis or Viagra, dapoxetine can enhance sexual performance by not only prolonging the duration of the act but also improving control over ejaculation, providing a more comprehensive approach to sexual health and satisfaction.

Mechanism of Action

Dapoxetine's primary mechanism of action involves the inhibition of the serotonin transporter, which leads to an increased concentration of serotonin in the synaptic cleft. This action enhances the neurotransmitter's activity at the postsynaptic receptors, which is believed to contribute to the delay of the ejaculatory reflex. Serotonin, a key neurotransmitter, plays a significant role in the regulation of mood, emotion, and sexual function. The increased serotonergic activity in the central nervous system modulates the pathways involved in ejaculation, extending the time before ejaculation occurs (Kirkeby et al., 2010).

Upon oral administration, dapoxetine is rapidly absorbed and reaches peak plasma concentrations within 1-2 hours, making it suitable for on-demand use. The short half-life of dapoxetine, approximately 1.5 hours, ensures that the drug is quickly eliminated from the body, reducing the risk of accumulation and minimizing potential side effects associated with long-term SSRI use. This pharmacokinetic profile is particularly advantageous for patients who require intermittent treatment rather than continuous medication (Buvat et al., 2009).

Uses of Dapoxetine

Treatment of Premature Ejaculation

Dapoxetine is primarily indicated for the treatment of PE in men aged 18-64 years. Clinical trials have demonstrated its efficacy in significantly increasing IELT, improving control over ejaculation, and reducing distress associated with PE. The therapeutic effects of dapoxetine have been confirmed in several randomized, double-blind, placebo-controlled studies involving thousands of patients. These studies have shown that dapoxetine significantly extends IELT, with many men experiencing more than a three-fold increase in latency time. The treatment protocol involves taking dapoxetine 1-3 hours before anticipated sexual activity. This on-demand approach allows patients to maintain spontaneity in their sexual lives while effectively managing PE. In addition to extending IELT, dapoxetine has been shown to improve patient-reported outcomes such as perceived control over ejaculation, satisfaction with sexual intercourse, and overall sexual satisfaction (McMahon et al., 2010). When combined with erectile dysfunction medications such as Sialis or Viagra, dapoxetine can enhance sexual performance by not only prolonging the duration of the act but also improving control over ejaculation, providing a more comprehensive approach to sexual health and satisfaction.

Treatment of Depression and Other Uses

While dapoxetine is not primarily used as an antidepressant, its SSRI properties suggest potential off-label use in treating mild depressive symptoms. SSRIs function by increasing serotonin levels in the brain, which can help alleviate symptoms of depression and anxiety. However, due to its short half-life and the necessity for frequent dosing, dapoxetine is not suitable for the long-term treatment of depression, unlike other SSRIs such as fluoxetine or sertraline (Rowland, 2011). Additionally, dapoxetine's rapid onset of action may offer benefits in acute anxiety management or other conditions where immediate serotonergic effects are desired. However, these potential uses are not well-documented, and further research is needed to establish the safety and efficacy of dapoxetine in these contexts.

Dosages

Recommended Dosages

The recommended starting dose of dapoxetine is 30 mg, taken 1-3 hours before sexual activity. If the 30 mg dose is insufficient in providing the desired therapeutic effect, it can be increased to 60 mg based on individual efficacy and tolerability. The medication should not be taken more than once within a 24-hour period (Buvat et al., 2009).

Clinical guidelines emphasize the importance of individualized dosing to achieve optimal results while minimizing side effects. Patients should be monitored regularly to assess the effectiveness of the treatment and adjust the dosage as necessary (Sangkum et al., 2013).

Side Effects

Common side effects of dapoxetine include nausea, dizziness, headache, diarrhea, and insomnia. These side effects are generally mild to moderate in severity and tend to decrease with continued use. However, some patients may experience more severe side effects such as syncope (fainting), which is a notable risk associated with dapoxetine. Syncope typically occurs within the first three hours of dosing and is more likely with the higher 60 mg dose. Other potential side effects include mood changes, anxiety, and sexual dysfunction. Patients should be advised to report any adverse effects to their healthcare provider, and dose adjustments should be considered if necessary. Due to the risk of syncope and other side effects, patients are advised to avoid activities requiring full alertness, such as driving or operating heavy machinery, for at least a few hours after taking dapoxetine (Buvat et al., 2009).

Precautions

Patients with significant cardiovascular conditions, such as heart failure, conduction abnormalities, or ischemic heart disease, should avoid dapoxetine due to the increased risk of adverse cardiac events. Additionally, dapoxetine is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or those with a history of mania or severe depression. Patients should be counseled on the potential interaction between dapoxetine and alcohol, which can enhance the risk of syncope and other side effects. It is recommended to limit or avoid alcohol consumption while taking dapoxetine. Other precautions include avoiding concomitant use with potent CYP3A4 inhibitors, which can increase dapoxetine plasma levels and the risk of adverse effects (McMahon, 2012).

Storage

Dapoxetine should be stored at room temperature, between 15-30°C (59-86°F), in its original packaging to protect it from moisture and light. It should be kept out of reach of children and pets. Proper storage conditions are essential to maintain the stability and efficacy of the medication (FDA, 2020).