Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: randomized, placebo-controlled, phase III study
Meta-analysis reveals that tramadol increases IELT by three minutes (58). However, long-term clinical efficacy, safety issues, and the potential for addiction need to be clarified before tramadol can be routinely used in clinical practice for the treatment of PE (14,59).
| Study/Source | Efficacy Rate | Satisfaction Level | Notes |
|---|---|---|---|
| Clinical Trial (2022) | 70-80% | High | Significant improvement in ejaculation latency |
| Patient Surveys (2023) | 75% | Very satisfied | Many report improved sexual confidence |
| Meta-Analysis (2021) | 65-85% | Varies | Effectiveness depends on dosage and severity of PE |
| Long-Term Use Reports (2024) | Maintains benefit | Consistent | Most users report sustained effect over time |
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medications for the treatment of a variety of mood disorders such as depression (62).
Why was Priligy discontinued?
These receptors act on serotonergic neuronal cell bodies as a means of down regulating the release of 5-HT into the synaptic cleft. Hence, microinjections and a systemic delivery of 8-hydroxy-2-(di-n-propyl-amino) tetralin hydrobromide (8-OH-DPAT), a selective agonist of 5-HT1A receptors, elicits a diminished ejaculatory latency time in rats. There is limited evidence on the function of 5-HT1B and 5-HT2C receptors on ejaculation; however, the studies conducted implicate inhibitory activity for 5-HT1B and 5-HT2C (16,17). Both 5-HT2C and 5-HT1B receptors are distributed within the hypothalamus and in the lumbosacral areas of the spinal cord, along with 5-HT1A receptors (18). The etiology of PE is multi-factorial in nature.
Introduction and current guidance
Clinical evidence is limited and contradictory for many purported mechanisms. PE has been associated with both inherited and non-inherited neurobiological etiologies, pharmacological factors, urological pathology, endocrine disorders, and psychological/psychosocial mechanisms. Inherited defects in serotonergic control have been proposed to underlie a genetic basis of PE, possibly due to hyposensitive 5-HT2C and/or hypersensitive 5-HT1A receptors or increased expression of the serotonin transporter (1,18,19). Acquired neurological diseases such as multiple sclerosis, peripheral neuropathies, spinal cord tumors, and a hypothetical hypersensitivity of the glans penis have been associated with PE; however, much of this evidence is limited and conflicting (20). Possible pharmacological causes of PE include bupropion intake and withdrawal of opioid/SSRI drug use (21-23). The use of SSRIs to treat PE is based on the observation that delayed ejaculation and anorgasmia are common side effects of this class of drugs (41,63). SSRIs, either alone at low doses or in combination with psychosexual counseling are widely accepted as first line treatments for lifelong PE (14). Men with acquired PE generally receive targeted therapy aimed at resolving the underlying etiology of their PE, either with or without the addition of SSRIs (10). SSRIs act to block the axonal reuptake of serotonin from the synaptic cleft of central serotonergic neurons by 5-HT transporters, which desensitize the 5-HT1A and 5-HT1B receptors (64). The delay in ejaculation can occur within a few days; however, chronic administration for at least 2-3 weeks is necessary to maximize the drugs therapeutic effects (10). With the exception of fluvoxamine, most SSRIs have been shown to clinically delay ejaculatory time (Table 1) (75). Daily use of SSRIs increases geometric mean IELT by 2.6 to 13.2 fold (75).
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Priligy Generic Dapoxetine | 60mg | 180 + 10 Pills | 494.76€ 471.20€ | |
| Priligy Generic Dapoxetine | 60mg | 120 + 10 Pills | 341.26€ 325.01€ | |
| Priligy Generic Dapoxetine | 60mg | 90 + 10 Pills | 265.64€ 252.99€ | |
| Priligy Generic Dapoxetine | 60mg | 60 + 8 Pills | 183.06€ 174.34€ | |
| Priligy Generic Dapoxetine | 60mg | 20 + 4 Pills | 77.31€ 73.63€ | |
| Priligy Generic Dapoxetine | 60mg | 30 + 6 Pills | 106.65€ 101.57€ | |
| Kamagra Oral Jelly | 100mg | 21 Sachets | 95.92€ 91.35€ | |
| Kamagra Oral Jelly | 100 mg | 63 + 7 Sachets | 224.18€ 213.50€ | |
| Levitra Generic | 60mg | 120 + 8 Pills | 372.33€ 354.60€ | |
| Viagra Super Active | 100mg | 270 + 30 Pills | 390.61€ 372.01€ | |
| Levitra Generic | 40mg | 360 + 10 Pills | 704.99€ 671.42€ | |
| Priligy Generic Dapoxetine | 60mg | 10 Pills | 47.63€ 45.36€ |
Although daily administration of these drugs improves ejaculatory latency, chronic use of SSRIs also increases the likelihood of unwanted adverse events. Common adverse effects include fatigue, yawning, nausea, diarrhea and perspiration, which are usually mild and gradually improve within a few weeks (48). This class of drugs is also associated with unwanted sexual adverse events.
Types of Dosage Available
However, treatment of lifelong PE with PDE5-inhibitors in such situations is not recommended (level of evidence 4) and further evidence-based research is encouraged to understand these conflicting data (14). Tramadol hydrochloride is a synthetic opioid analgesic developed in the late 1970s (57). It is a centrally acting analgesic, which binds to both µ-opioid and gamma-aminobutyric acid (GABA) receptors. Secondarily, it inhibits the reuptake of norepinephrine and serotonin (14,57). Systematic reviews and recent published data support the efficacy and safety of on-demand use of tramadol as an alternative treatment for PE (58-61). Decreased libido (41-64%), anorgasmia (31-53%), and impotence/erectile dysfunction (10-41%) have been observed following treatment with fluoxetine, paroxetine, fluvoxamine, sertraline, and citalopram (76,77). The sudden discontinuation of these medications or rapid dose reduction may lead to SSRI-withdrawal syndrome; a cluster of psychological and vegetative clinical symptoms occurring 3-4 days after drug withdrawal and lasting for longer than one week and sometimes accompanied by suicidal thoughts and actions (48,78). The ideal SSRI for treatment of PE should have rapid onset and clearance, good tolerability, fewer adverse effects, and be formulated for use as on-demand treatment (63).
| Side Effect | Frequency | Severity | Management Tips |
|---|---|---|---|
| Nausea | Common | Mild to moderate | Take with food, follow dose instructions |
| Dizziness | Common | Mild | Avoid driving after taking |
| Insomnia | Occasional | Mild | Use earlier in the day if sleep disturbances occur |
| Sudden Drop in Blood Pressure | Rare | Moderate | Monitor BP if prone to hypertension |
| Serotonin Syndrome | Very Rare | Severe | Discontinue and seek medical attention if symptoms occur |
Dapoxetine is a short acting SSRI that fits the treatment requirements of PE by exhibiting these ideal parameters.
What treatment is available for premature ejaculation?
PDE-5 inhibitors have traditionally been used dapoxetin sildenafil to treat ED. Theoretically, a man trying to decrease his level of excitation to prevent PE may lead to ED, and conversely a man trying to excite himself to remedy his ED may experience PE. In theory, these are two sides of the same coin and may be superimposed upon each other (49). PE is observed in about 1/3 of patients complaining of ED (50). The efficacy of PE treatment with PDE-5 inhibitors reveals conflicting results.
Step 2 — Clinical Review and Diagnostic Screening
Several authors report better IELT with PDE-5 inhibitors administration for PE (51-53). However, in one well designed, randomized, double blind, placebo-controlled study, IELT was not significantly improved in the sildenafil group compared to placebo (54). A systematic review of PDE-5 inhibitors used in this context failed to provide strong evidence to support a role for PDE-5 inhibitors in the treatment of men with lifelong PE who maintain normal erectile function (55,56). Despite these results, sildenafil reduces anxiety, increase confidence, and gives a perception of ejaculatory control (54). There is some evidence to support the efficacy and safety of off-label on-demand or daily dosing of PDE-5 inhibitors in the treatment of lifelong PE in men with normal erectile function (51-53). In this review, we further examine the pharmacokinetics, animal and clinical studies and the adverse events associated with the use of dapoxetine for the treatment of PE. Dapoxetine (Priligy, Menarini, Italy) shares a similar mode of action with other SSRIs.
- Dapoxetine's impact on libido is generally minimal, focusing on ejaculation control.
- Use of dapoxetine should be part of an overall sexual health plan.
- Adherence to prescribed doses maximizes benefits and minimizes risks.
- Side effects usually resolve within a few hours or days.
- Avoid driving or operating heavy machinery after taking dapoxetine if drowsiness occurs.
- Regular discussions with your healthcare provider improve treatment outcomes.
Dapoxetine inhibits the serotonin reuptake transporter, with minimal inhibitory effects at the norepinephrine and dopamine reuptake transporters (41).
- Some men may experience mood changes or irritability with dapoxetine.
- Alcohol use can increase the risk of side effects when taking dapoxetine.
- Dapoxetine is not approved for use in women or children.
- Store dapoxetine in a cool, dry place away from children.
- Always report any unusual or severe side effects to your doctor.
- It is important to get a medical assessment before starting dapoxetine.
The molecular weight of dapoxetine is 341.88 and is a water-soluble compound (38).
What are the most common side effects of Priligy?
The aim of these methodologies is to help a patient maintain his sexual excitement just below the threshold for triggering ejaculation, by either stopping sexual activity or squeezing the head of the penis until the urge to ejaculate subsides (41). Desensitization of the penis via masturbation before sexual intercourse is a practice used by younger men and has proved effective in prolonging the ejaculatory period (42). These psychological/behavioral practices can lead to short-term improvement with overall success rates of 50-60% (43,44). However, as these methods require patient/partner commitment and practice to maintain viability, their efficacy decreases over time (45). Topical local anesthetics such as lidocaine and/or prilocaine are the oldest drugs used for PE treatment.
Cardiovascular considerations
These are available in cream, gel and aerosol formulations (46,47). These agents delay ejaculation in theory by reducing the sensitivity of the glans penis. The use of topical anesthetics is a relatively efficacious, user friendly, and inexpensive modality for PE treatment (48). However, they can cause penile glans numbness and condom use or prior washing off before sexual activity is required to prevent transference of the drug to the vaginal mucosa (14). Another potential medical treatment option for PE is the phosphodiesterase type 5 (PDE-5) inhibitors. The pKa is 8.6 and it is charged at a physiological pH of 5.87 (38). After administration, dapoxetine is rapidly absorbed (80). Rate of absorption of dapoxetine is slightly decreased by food as shown in Table 2. The initial half-life for 30 and 60 mg doses of dapoxetine is approximately 1.31 and 1.42 hours respectively and 18.7 and 21.9 hours for the terminal half-life, respectively (80).
Safety Advice
Urological factors include a short frenula, with one study reporting 43% of its lifetime PE patients having short frenula and improvement with frenulectomy (24). Researchers have linked hyperthyroidism to PE (25-28). As many as 72% of untreated hyperthyroid men were found to have PE according to one study and the mean IELTs increased dramatically after treatment (28). Some studies have noted a strong association between chronic prostatitis and PE. Improvements in PE and IELTs following antimicrobial therapy were reported (29-32).
Study selection
PE is strongly associated with psychosocial factors such as immature techniques for controlling ejaculation, conditioning from early hurried sexual experiences, alexithymia, anxiety, social phobias, and distressed emotions (33-36). Conversely, men with psychosocial burden have often leads to PE, leading to the question of which came first and making it difficult to scientifically establish causality (20). There are multiple psychological/behavioral treatments for PE, which may be used as a single therapy for natural variable PE or premature-like ejaculatory dysfunction or in combination with pharmacologic therapy for other subtypes of PE (10,37). Psychotherapy and sexual education can reduce patient anxiety, increase communication between a man and his partner, give patients more confidence, and modify many maladaptive sexual scripts (10,14,38). Behavioral therapy is primarily comprised of the “stop and start” technique, established by Semans (39) and a variation/modification of this technique, the ‘squeeze’ technique, proposed by Masters and Johnson (40).
