Other studies have documented efficacy for different SSRIs. For example, sertraline was found to be effective in improving IELT, ejaculatory control, and sexual satisfaction [46–48]. Similarly, a recent report on the efficacy of duloxetine in treating PE showed that treatment with this SSRI increased the IELT from 38.21 16.45 seconds to 129.34 seconds 67.58 (P = 0.001 vs. control) [49].

Counseling and Sex Therapy

Other studies have documented efficacy for different SSRIs. For example, sertraline was found to be effective in improving IELT, ejaculatory control, and sexual satisfaction [46–48]. Similarly, a recent report on the efficacy of duloxetine in treating PE showed that treatment with this SSRI increased the IELT from 38.21 16.45 seconds to 129.34 seconds 67.58 (P = 0.001 vs. control) [49]. Fluvoxamine is an SSRI unrelated in its chemical structure to other SSRIs or to clomipramine.

Erectile dysfunction risk factors in non-insulin dependent diabetic Saudi patients

Of all the SSRIs, it seems to have the least effect on prolonging IELT. This information may be helpful in advising psychiatrists, as they select an antidepressant for sexually asymptomatic men for whom further prolongation of IELT would be undesired [19,50]. Escitalopram has been shown to be efficacious in the treatment of PE. It should be mentioned that as compared with other SSRIs, citalopram has not shown the greatest efficacy, and the ejaculatory-delaying effects are definitely inferior to paroxetine [51]. A meta-analysis of the effects of various SSRIs found that citalopram and fluvoxamine were the least efficacious among the SSRIs [1,21].

Sexual dysfunction in primary medical careprevalence, characteristics and detection by the general practitioner

In 2007, Safarinejad [52] published the results of his study comparing the results following 3 months of therapy with escitalopram vs. placebo. Because the SSRI activity of citalopram resides mainly in the S-enantiomer, the investigator postulated that this high selectivity of the S-enantiomer (i.e., escitalopram) may translate into higher efficacy. The study was designed to assess increases in mean geometric IELT immediately after the study (3 months), as well as at 6 months. There was an insignificant increase in the mean IELT in the placebo group, whereas the SSRI group had a 4.9-fold increase of the mean IELT. Fluvoxamine is an SSRI unrelated in its chemical structure to other SSRIs or to clomipramine. Of all the SSRIs, it seems to have the least effect on prolonging IELT. This information may be helpful in advising psychiatrists, as they select an antidepressant for sexually asymptomatic men for whom further prolongation of IELT would be undesired [19,50]. Escitalopram has been shown to be efficacious in the treatment of PE.

It should be mentioned that as compared with other SSRIs, citalopram has not shown the greatest efficacy, and the ejaculatory-delaying effects are definitely inferior to paroxetine [51]. A meta-analysis of the effects of various SSRIs found that citalopram and fluvoxamine were the least efficacious among the SSRIs [1,21]. In 2007, Safarinejad [52] published the results of his study comparing the results following 3 months of therapy with escitalopram vs. placebo. Because the SSRI activity of citalopram resides mainly in the S-enantiomer, the investigator postulated that this high selectivity of the S-enantiomer (i.e., escitalopram) may translate into higher efficacy.

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More importantly, the author showed that with a 6-month follow-up (i.e., after the medication had been withdrawn), the escitalopram group continued to demonstrate increased mean IELT (3.1-fold vs. 1.3-fold for placebo) [52]. Although escitalopram has the highest rate of bothersome side effects, such as nausea, headache, and dry mouth, the overall incidence of adverse events with all SSRIs is typically less than 5% [52]. The author cautioned that additional studies are needed before this medicine can be recommended as ideal therapy for PE. SSRIs may give rise to side effects such as fatigue, mild nausea, loose stools, or heavy perspiration.

Pelvic floor exercises

These complaints may gradually dissipate within 2–3 weeks. The side effects of clomipramine (a tricyclic antidepressant) are similar, although more pronounced, and consist of nausea, dry mouth, and fatigue. Both SSRIs and clomipramine may delay ejaculation at the expense of a diminution of libido and a moderate decrease in penile rigidity (which is reversible). Patients should be informed of these possible side effects prior to initiating therapy [1]. The abrupt reduction or discontinuation of long-term SSRI therapy can result in the “SSRI discontinuation syndrome”—a cluster of somatic and psychological symptoms including nausea and vomiting, vertigo, headache, unstable gait, lethargy, agitation, anxiety, and insomnia.

Early and Delayed Ejaculation: Psychological Considerations

These symptoms begin from 1 to 3 days after discontinuance, and may last over 1 week. The side effects can usually be reversed by the reintroduction of the SSRI [53]. Nonetheless, it is recommended that with the exception of fluoxetine, SSRIs should not be withdrawn acutely but gradually over 3–4 weeks [1]. It is also recommended that patients on SSRIs over an extended period of time undergo intermittent “wash-out periods” in order to avoid excessive levels of accumulation after multiple doses [53]. Overdose of SSRIs or (more commonly) drug– drug interactions between SSRIs and other agents that enhance the central nervous system 5-HT activity can lead to the “serotonin syndrome”—a cluster of severe, persistent symptoms including myoclonus, hyperreflexia, sweating, shivering, discoordination, and mental status changes [53]. The study was designed to assess increases in mean geometric IELT immediately after the study (3 months), as well as at 6 months. There was an insignificant increase in the mean IELT in the placebo group, whereas the SSRI group had a 4.9-fold increase of the mean IELT. More importantly, the author showed that with a 6-month follow-up (i.e., after the medication had been withdrawn), the escitalopram group continued to demonstrate increased mean IELT (3.1-fold vs.

• Premature ejaculation affects about 30% of men.
• Psychological factors often contribute to PE.
• Behavioral therapies can help manage PE.
• Topical anesthetics are alternative treatments for PE.
• SSRI antidepressants are commonly prescribed for PE.
• Combining sildenafil with PE drugs requires care.
• Lifestyle changes like exercise may improve PE.
• Stress and anxiety can trigger premature ejaculation.
• Delay techniques include the stop-start method.
• Medical treatments should be personalized for each patient.
• Education about sexual response can reduce PE.

1.3-fold for placebo) [52].

• Misusing sildenafil for PE can cause serious health risks.
• The drug's primary purpose is erectile dysfunction.
• Off-label use for PE should be supervised by a doctor.
• Performance anxiety often exacerbates PE.
• Proper medication adherence improves results.
• Natural remedies lack strong scientific support.
• Combining drugs without guidance is dangerous.
• Behavioral adjustments can sometimes eliminate PE.
• It is vital to address both physical and psychological aspects.
• Clinical trials explore sildenafil's role in PE management.
• Open communication with a healthcare professional is key.

Although escitalopram has the highest rate of bothersome side effects, such as nausea, headache, and dry mouth, the overall incidence of adverse events with all SSRIs is typically less than 5% [52]. The author cautioned that additional studies are needed before this medicine can be recommended as ideal therapy for PE. SSRIs may give rise to side effects such as fatigue, mild nausea, loose stools, or heavy perspiration. These complaints may gradually dissipate within 2–3 weeks. The side effects of clomipramine (a tricyclic antidepressant) are similar, although more pronounced, and consist of nausea, dry mouth, and fatigue.

Both SSRIs and clomipramine may delay ejaculation at the expense of a diminution of libido and a moderate decrease in penile rigidity (which is reversible).

Evaluation of ED Characteristics and Overall Satisfaction

Patients receiving long-term SSRI therapy for PE must be made aware of potential drug–drug interactions between SSRIs and other concurrent medications, and schedule their doses accordingly [53]. In men with lifelong PE,cessation of treatment results in reestablishment of the original set point within 5–7 days [1]. On-Demand Intervention (on a “Prn” Basis) Encouraging as the success of the chronic administration of SSRIs has been in the treatment of PE, side effects, such as dry mouth, headaches, and dizziness, have presented a problem [54]. Men are understandably reluctant to accept continuous, long-term headaches, sildenafil citrate tablets 150 mg dry mouth, and dizziness on a daily basis, as the price for improving IELT on significantly less frequent occasions [12,33,55,56]. In an attempt to minimize these side effects and better target the patient’s needs in a cost-effective manner, on-demand use of SSRI has been advocated [54].

Key Takeaways

There is only modest laboratory-based support for the on-demand use of SSRI. While the acute administration of SSRI leads to an abrupt lowering of 5-HT release into the synapse, it only effects a mild increase in the postsynaptic neurotransmission and stimulation of 5-HT receptors there [57–59]. Nevertheless, laboratory assessments have documented a marked increase in 5-HT in both the cerebrospinal and the extravascular fluid following a single dose of SSRI [60–62]. Examination of the time course of central and peripheral neurochemical effects of sertraline (SER) in nonhuman primates showed that the 5-HT level achieved after one oral dose of sertraline was comparable to that measured throughout a 28-day course [63]. investigated the degree of ejaculation delay induced by on-demand treatment with 20-mg paroxetine and 25-mg clomipramine in a randomized, double-blind, fixed-dose, ondemand study in 30 men with lifelong PE with an IELT of less than 1 minute.

Reasons and predictive factors for discontinuation of PDE-5 inhibitors despite successful intercourse in erectile dysfunction patients

The authors found that whereas on-demand treatment with 25-mg clomipramine led to a clinically relevant ejaculation delay, this was not the case with 20-mg paroxetine. Interestingly, when this same SSRI was taken daily for 6 weeks, the IELT increased significantly by 146 seconds [64]. Dapoxetine, an SSRI structurally related to fluoxetine, is the first SSRI developed with a short half-life, convenient for the on-demand treatment of PE [65]. Oral dapoxetine achieves peak plasma concentrations within hour, and is effectively eliminated within 24 hours. Other SSRIs may require 6–8 hours to reach peak plasma concentrations, and up to 4 weeks to achieve a steady-state [65]. Patients should be informed of these possible side effects prior to initiating therapy [1]. The abrupt reduction or discontinuation of long-term SSRI therapy can result in the “SSRI discontinuation syndrome”—a cluster of somatic and psychological symptoms including nausea and vomiting, vertigo, headache, unstable gait, lethargy, agitation, anxiety, and insomnia.

About this article

A 25-mg dose has effected delay in ejaculation, when taken as a onetime treatment 5 hours before intercourse by men with lifelong PE [1]. It has been shown to be effective in a placebo-controlled, double-blind trial, with a dose-dependent response rate. Efficacy was established, using a 10-mg dose, but the IELT increased by 249% over controls when a 25-mg dose was used, and 517% with a 50-mg dose [73,74]. Clomipramine has been studied both as a chronic-care and as an on-demand medication. have recommended a two-tiered approach, initially using a single dose of up to 25 mg, taken from 4 to 24 hours prior to intercourse. These symptoms begin from 1 to 3 days after discontinuance, and may last over 1 week. The side effects can usually be reversed by the reintroduction of the SSRI [53]. Nonetheless, it is recommended that with the exception of fluoxetine, SSRIs should not be withdrawn acutely but gradually over 3–4 weeks [1]. It is also recommended that patients on SSRIs over an extended period of time undergo intermittent “wash-out periods” in order to avoid excessive levels of accumulation after multiple doses [53]. Overdose of SSRIs or (more commonly) drug– drug interactions between SSRIs and other agents that enhance the central nervous system 5-HT activity can lead to the “serotonin syndrome”—a cluster of severe, persistent symptoms including myoclonus, hyperreflexia, sweating, shivering, discoordination, and mental status changes [53]. Patients receiving long-term SSRI therapy for PE must be made aware of potential drug–drug interactions between SSRIs and other concurrent medications, and schedule their doses accordingly [53]. In men with lifelong PE,cessation of treatment results in reestablishment of the original set point within 5–7 days [1]. On-Demand Intervention (on a “Prn” Basis) Encouraging as the success of the chronic administration of SSRIs has been in the treatment of PE, side effects, such as dry mouth, headaches, and dizziness, have presented a problem [54]. Men are understandably reluctant to accept continuous, long-term headaches, sildenafil citrate tablets 150 mg dry mouth, and dizziness on a daily basis, as the price for improving IELT on significantly less frequent occasions [12,33,55,56]. In an attempt to minimize these side effects and better target the patient’s needs in a cost-effective manner, on-demand use of SSRI has been advocated [54]. There is only modest laboratory-based support for the on-demand use of SSRI.

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While the acute administration of SSRI leads to an abrupt lowering of 5-HT release into the synapse, it only effects a mild increase in the postsynaptic neurotransmission and stimulation of 5-HT receptors there [57–59]. Nevertheless, laboratory assessments have documented a marked increase in 5-HT in both the cerebrospinal and the extravascular fluid following a single dose of SSRI [60–62]. Examination of the time course of central and peripheral neurochemical effects of sertraline (SER) in nonhuman primates showed that the 5-HT level achieved after one oral dose of sertraline was comparable to that measured throughout a 28-day course [63]. investigated the degree of ejaculation delay induced by on-demand treatment with 20-mg paroxetine and 25-mg clomipramine in a randomized, double-blind, fixed-dose, ondemand study in 30 men with lifelong PE with an IELT of less than 1 minute. The authors found that whereas on-demand treatment with 25-mg clomipramine led to a clinically relevant ejaculation delay, this was not the case with 20-mg paroxetine. Interestingly, when this same SSRI was taken daily for 6 weeks, the IELT increased significantly by 146 seconds [64]. Dapoxetine, an SSRI structurally related to fluoxetine, is the first SSRI developed with a short half-life, convenient for the on-demand treatment of PE [65]. Oral dapoxetine achieves peak plasma concentrations within hour, and is effectively eliminated within 24 hours. Other SSRIs may require 6–8 hours to reach peak plasma concentrations, and up to 4 weeks to achieve a steady-state [65]. Dapoxetine seems to have a physiological benefit, superior to paroxetine, in reducing the expulsion reflex of ejaculation [66]. While not yet FDA approved for use in the treatment of PE, the efficacy and tolerability of dapoxetine have been assessed in an integrated analysis of two, double-blind, randomized, controlled trials [67]. When taken 3 hours prior to intercourse, dapoxetine increased the IELT from 0.92 to 2.78 minutes with the 30-mg dose, and from 0.91 to 3.32 minutes with the 60-mg dose, while with placebo, the IELT only improved from 0.9 to 1.75 minutes. Dapoxetine increased the IELT 3.0– 3.7 times over baseline [67]. Nausea was the most frequently noted side effect reported in up to 20.1% of patients on the higher (60 mg) dose of dapoxetine; other commonly observed side effects in the 30- and 60-mg doses, respectively, were diarrhea (3.9%, 6.8%), headache (5.9%, 6.8%), and dizziness (3.0%, 6.2%). A two-phase or hybrid strategy has been proposed, augmenting long-term SSRIs at a low dose, with higher doses prior to intercourse, on an on-demand basis [1,53]. McMahon and Touma evaluated the efficacy of paroxetine on-demand for the treatment of PE. The authors found that the ejaculatory control achieved with paroxetine as needed is significantly better when the patients were initially treated with a daily dose of the medication and later changed to an on-demand regimen [68]. Their findings were later corroborated in a study by Salonia et al who reported that paroxetine, when initially prescribed on a longterm basis, then later switched to an on-demand basis, proved safe and effective in prolonging the IELT (from 0.33 +/– 0.04 to 4.2 +/– 0.03), and 75% of the men reported an improved satisfaction with their sexual activity [69]. Enthusiasm for treatment of PE with SSRI has recently been dampened by the release of the FDA advisory in May 2007, which warned that suicidal ideation and attempts have been associated with the initiation of these antidepressant medications, especially in young adults aged 18–24 [70].

The risk of suicide seems to be highest during the first 1 or 2 months of therapy. While a report at the 2007 American Urological Association (AUA) annual convention found that there was no associated “suicidality,” when the SSRI dapoxetine was used in the treatment of PE, the FDA advisory indicates that there is as yet insufficient evidence to exculpate any single medication from this risk. At a minimum, the circumspect clinician would carefully follow the patients for any signs of depression or suicidal ideation; it is also wise to document that the patient has been fully informed that there may be an increased risk of suicidal tendency, and also that SSRIs are not FDA approved for the treatment of PE [70–72]. Clomipramine is a tricyclic antidepressant used in the treatment of obsessive compulsive disorders. Although it is not an SSRI, clomipramine does inhibit 5-HT transport [55]. A 25-mg dose has effected delay in ejaculation, when taken as a onetime treatment 5 hours before intercourse by men with lifelong PE [1].

It has been shown to be effective in a placebo-controlled, double-blind trial, with a dose-dependent response rate. Efficacy was established, using a 10-mg dose, but the IELT increased by 249% over controls when a 25-mg dose was used, and 517% with a 50-mg dose [73,74]. Clomipramine has been studied both as a chronic-care and as an on-demand medication. have recommended a two-tiered approach, initially using a single dose of up to 25 mg, taken from 4 to 24 hours prior to intercourse.

MeSH terms

Dapoxetine seems to have a physiological benefit, superior to paroxetine, in reducing the expulsion reflex of ejaculation [66]. While not yet FDA approved for use in the treatment of PE, the efficacy and tolerability of dapoxetine have been assessed in an integrated analysis of two, double-blind, randomized, controlled trials [67]. When taken 3 hours prior to intercourse, dapoxetine increased the IELT from 0.92 to 2.78 minutes with the 30-mg dose, and from 0.91 to 3.32 minutes with the 60-mg dose, while with placebo, the IELT only improved from 0.9 to 1.75 minutes. Dapoxetine increased the IELT 3.0– 3.7 times over baseline [67]. Nausea was the most frequently noted side effect reported in up to 20.1% of patients on the higher (60 mg) dose of dapoxetine; other commonly observed side effects in the 30- and 60-mg doses, respectively, were diarrhea (3.9%, 6.8%), headache (5.9%, 6.8%), and dizziness (3.0%, 6.2%).

What you can do in the meantime

A two-phase or hybrid strategy has been proposed, augmenting long-term SSRIs at a low dose, with higher doses prior to intercourse, on an on-demand basis [1,53]. McMahon and Touma evaluated the efficacy of paroxetine on-demand for the treatment of PE. The authors found that the ejaculatory control achieved with paroxetine as needed is significantly better when the patients were initially treated with a daily dose of the medication and later changed to an on-demand regimen [68]. Their findings were later corroborated in a study by Salonia et al who reported that paroxetine, when initially prescribed on a longterm basis, then later switched to an on-demand basis, proved safe and effective in prolonging the IELT (from 0.33 +/– 0.04 to 4.2 +/– 0.03), and 75% of the men reported an improved satisfaction with their sexual activity [69]. Enthusiasm for treatment of PE with SSRI has recently been dampened by the release of the FDA advisory in May 2007, which warned that suicidal ideation and attempts have been associated with the initiation of these antidepressant medications, especially in young adults aged 18–24 [70].

Ejaculation Problems: Too Fast, Too Slow or Not at All

The risk of suicide seems to be highest during the first 1 or 2 months of therapy. While a report at the 2007 American Urological Association (AUA) annual convention found that there was no associated “suicidality,” when the SSRI dapoxetine was used in the treatment of PE, the FDA advisory indicates that there is as yet insufficient evidence to exculpate any single medication from this risk. At a minimum, the circumspect clinician would carefully follow the patients for any signs of depression or suicidal ideation; it is also wise to document that the patient has been fully informed that there may be an increased risk of suicidal tendency, and also that SSRIs are not FDA approved for the treatment of PE [70–72]. Clomipramine is a tricyclic antidepressant used in the treatment of obsessive compulsive disorders. Although it is not an SSRI, clomipramine does inhibit 5-HT transport [55].