Exploring the Role of SSRIs in Delaying Ejaculation

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, 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. 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].

How well do pills work against ejaculation too fast?

These symptoms begin from 1 to 3 days after discontinuance, and may last over 1 week. The side effects can super p force uk 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 Nonetheless, it is recommended that with the exception of fluoxetine, SSRIs should not be withdrawn acutely but gradually over 3–4 weeks [1].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]. 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].

• Topical gels can numb nerves and delay ejaculation temporarily.
• Oral pills like dapoxetine are prescription medications for PE.
• Herbal supplements claim to improve stamina and control.
• SSRIs often prescribed off-label to help delay climax.
• Some lifestyle changes, like stress reduction, may improve symptoms.

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].

A Guide to Prescription Delay Pills

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 buy blue pill 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.

Sildenafil (Viagra®) for PE

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].

Male pelvic floor muscles

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. Oral dapoxetine achieves peak plasma concentrations within hour, and is effectively eliminated within 24 hours.

• Pills that increase serotonin tend to have longer-lasting effects.
• Men should discuss all medications with their healthcare provider.
• The placebo effect can sometimes influence perceived improvements.
• Overuse of delay pills may lead to decreased natural ability.
• PE pills are one part of a holistic approach including therapy and lifestyle.

Other SSRIs may require 6–8 hours to reach peak plasma concentrations, and up to 4 weeks to achieve a steady-state [65].

• Delay pills might reduce sensation, extending intercourse time.
• The safety profile of herbal pills is less documented than pharma drugs.
• Patients should monitor for side effects and inform their doctor.
• Psychological factors like anxiety can be addressed alongside pills.
• Proper dosage and timing are key to maximizing benefits.

Dapoxetine seems to have a physiological benefit, superior to paroxetine, in reducing the expulsion reflex of ejaculation [66].

Author information

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.

Behavioral Techniques and Lifestyle Changes

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. 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%).

Expected duration

The extent of this delay varies widely depending upon the type, dose, and frequency of SSRI administration and the genetically determined ejaculatory threshold set point. The ability of SSRIs to delay ejaculation was first uncovered serendipitously during the use of these medications in the treatment of depressed men in the 1970s [40]. Fluoxetine was next shown to be helpful in the intentional treatment of PE [41]. Subsequently, a placebo-controlled trial of paroxetine proved promising [42]. A double-blind, fixed-dose trial of randomly assigned 20- or 40-mg daily doses of paroxetine in 27 patients with primary PE showed a statistically significant improvement in ejaculation time with both doses, as compared to placebo.

Other Prescription Options to Consider

Because the increase in the IELT was relatively similar in both groups, the authors concluded that daily 20-mg paroxetine “may be considered as an adequate treatment for primary premature ejaculation,” but that a higher dose may further increase the ejaculatory latency [42]. Kim and Seo compared the efficacy and safety of 4 weeks each of fluoxetine, sertraline, clomipramine, and placebo in treating PE in 36 men. As compared with an IELT increase from a baseline of 46 seconds to 2.27 minutes with placebo, therapy with the other agents resulted in increased IELT to 2.30, 4.27, and 5.75 minutes with the other agents, respectively. The SSRIs sertraline and fluoxetine were shown to be more effective than placebo in this 1998 controlled study [43]. Importantly, treatment with the SSRI sertraline was nearly as effective in delaying ejaculation as clomipramine, but had a significantly lower incidence of side effects.

Intromission time

SSRIs may cause an increase in latency time as early as 2–3 days after the initiation of oral therapy. This effect tends to plateau after 3–4 weeks, with a six- to eightfold increase in IELT [44,45]. In order of clinical response, a meta-analysis of 35 studies of daily SSRI treatment found that paroxetine was the most effective, followed by fluoxetine, then sertraline, and lastly fluvoxamine [19]. The same group also set out to assess whether the ejaculatory-delaying effects of at least some SSRIs may be applicable in men with “less-rapid” ejaculation. Following treatment with paroxetine 20 mg/day, the percentage increase in the geometric mean IELT compared with baseline in patients treated with paroxetine was 420% in patients with classic PE (less than or equal to 1 minute) and 480% in those with less rapid PE (greater than 1 minute), indicating that the paroxetine-induced percentage increase in IELT appeared to be independent of the baseline IELT, and that the findings may be extrapolated to men with less-rapid ejaculation.