Dr Colin Tidy, MRCGP

SSRI discontinuance syndrome (especially with paroxetine) has been associated with dose reduction or discontinuance and may cause dizziness, nausea and vomiting, headache, gait instability, lethargy, agitation, anxiety, and insomnia.

Some studies have demonstrated that combining phosphodiesterase type 5 (PDE5) inhibitors with SSRIs provides better results in the treatment of premature ejaculation than using SSRIs alone.

[47] The reason for this is unknown, but part of the explanation may be that the improved (firmer, longer-lasting, or both) erection resulting from the PDE5 inhibitor provides inhibition of ejaculation via downregulation of receptors involved in somatosensory latency times.

When to call a professional

However, numerous studies have shown that selective serotonin reuptake inhibitors (SSRIs) and drugs with SSRI-like side effects are safe and effective to treat this condition, and many physicians use these agents for this purpose. Topical desensitizing therapy with local anesthetic agents can also be useful in some men with premature ejaculation. Premature ejaculation that relates to erectile dysfunction may resolve if the erectile dysfunction is treated successfully. If a patient has depression-related erectile dysfunction but not premature ejaculation, a drug with minimal adverse sexual effects might be considered so as to avoid causing delayed ejaculation or even anorgasmia. [24] However, if the patient has premature ejaculation, erectile dysfunction, and depression, an antidepressant with SSRI side effects has the added benefit of possibly alleviating the premature ejaculation.

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In Korea and other areas of the Far East, SS (Super Secret) cream (a combination of 9 ingredients, mainly herbal) has been shown to desensitize the penis, decrease the vibratory threshold, and help men with premature ejaculation to delay their ejaculatory response significantly. [26, 27] This preparation is not yet approved by the FDA. Simple combinations of lidocaine cream or related topical anesthetic agents can also be effective. These combinations are safe as long as the patient has no history of allergy to the substance. [28, 29, 30, 31] A metered-dose lidocaine-prilocaine cutaneous spray (Fortacin) is approved in Europe. In addition, a reduction in performance anxiety may exist on a subconscious level. Regardless of the mechanism, PDE5 inhibitors have been found to be safe and effective as a therapeutic adjunct for premature ejaculation in men for whom such therapy is not otherwise contraindicated.

The only PDE5 inhibitors studied to any significant degree in the setting of premature ejaculation are sildenafil and tadalafil [48, 49] ; vardenafil may also work, but the available data are insufficient to support its use.

Pharmacologic Therapy

In males, too-rapid orgasm can cause some of the same patterns of sexual avoidance and decreased libido. Thus, it is essential to determine the primary problem when instituting therapy. SSRIs useful for treating premature ejaculation include the following: A systematic review and meta-analysis reported that although fluoxetine was more effective than placebo in treating PE, sertraline and paroxetine were more effective than fluoxetine (p < 0.05). Dapoxetine, which is generally categorized as a fast-acting SSRI, was developed specifically 10mg vardenafil online to treat this condition. It may be effective at the first dose (ie, on demand) when given 1-3 hours before sexual intercourse, and its adverse-effect profile is comparable to those of other SSRIs.

Does peyronie's disease cause premature ejaculation?

[41, 42, 43] Dapoxetine has been approved in a number of countries but not yet in the United States. In a study of men with both premature ejaculation and erectile dysfunction who were on phosphodiesterase type 5 (PDE5) therapy, dapoxetine provided treatment benefit and was generally well tolerated. [44] However, up to 90% of patients discontinue dapoxetine, mostly because of adverse effects, cost, and disappointing efficacy. The optimal medical treatment regimen for premature ejaculation has not been established. The author’s experience has been that in some males, single dosing before sexual relations can work well, whereas in others, it may be necessary to achieve and maintain a target blood level through daily use of the medication, as in the treatment of clinical depression. A single-blind randomized placebo-controlled clinical study in 100 patients concluded that tadalafil, 5 mg once daily for 6 weeks, was significantly more effective than placebo (P=0.001) and was well tolerated in the treatment of premature ejaculation.

How it works

Obviously, if single dosing is successful, therapy is simpler and has fewer adverse effects. Accordingly, this may be the preferred initial approach. If necessary, the dose may be increased in a stepwise fashion until a therapeutic effect is achieved or the maximum daily recommended dose is reached. No exact schedule for increasing the dose has been established; the experience of the physician, the response of the patient, the adverse effects experienced by the patient, and other general medical considerations should be the guiding factors. If the initial SSRI fails to help the patient, it is certainly reasonable to try a second agent.

Basic questions to ask your doctor

However, if the second choice fails, it is not likely that a third choice will offer any benefit. As with treatment for depression, if a patient has been taking the maximal dose of the medication for 6 weeks without showing any improvement, the likelihood that a more prolonged course of therapy with a particular drug would be successful is remote. There is no reason why pharmacotherapy cannot be combined with behavioral modification therapy, desensitizing creams, or both; the use of several simultaneous treatments can result in additive effects or even synergy. If all treatment fails, then the patient’s only options are as follows: To see a different health care professional, if he wishes To accept his condition as being untreatable with currently available therapeutic options Adverse effects of long-term SSRI use are a significant concern and should be considered by both the physician and the patient. [45] Such adverse effects may include the following: Sexual side effects other than delayed ejaculation (eg, erectile dysfunction or loss of libido) In addition, caution should be exercised in changing SSRIs; a washout period is necessary to avoid overdose. [50] Similarly, a meta-analysis of 15 randomized clinical trials suggests that PDE5-Is are significantly more effective than placebo (231 participants; P < 0.00001), that there is no difference between PDE5-Is and selective serotonin reuptake inhibitors (SSRIs; 405 participants, P = 0.50), and that PDE5-Is combined with an SSRI are significantly more effective than SSRIs alone (521 participants, P = 0.001). [51] The use of PDE5 inhibitors for the treatment of premature ejaculation is not approved by the FDA and is considered an off-label use.

Can premature ejaculation be prevented?

The most effective pharmacologic therapy for premature ejaculation is to administer a drug from the SSRI class. Normally, these drugs are used as antidepressants in the clinical setting. Many of these agents were found to have the side effect of significantly delaying the achievement of orgasm in both male and female patients, and it was for this reason that such agents were applied to the treatment of premature ejaculation. Some tricyclic antidepressants (TCAs) with SSRI-like activity have the same effect in orgasm that SSRIs do. The TCA that has been most frequently studied for treatment of premature ejaculation is clomipramine.

3. The squeeze technique

[33, 34, 35, 36] Many investigators find that clomipramine is more effective for premature ejaculation than many SSRIs are. Results of a multicenter, randomized, double-blind, placebo-controlled, fixed-dose clinical phase III study in 159 Korean patients suggest that 15 mg of clomipramine taken approximately 2-6 hours before sexual intercourse is effective and safe for treatment of premature ejaculation. [37] However, a systematic review and meta-analysis concluded that below a dose of 50 mg, a higher dose of clomipramine results in a longer delay of ejaculation without an increased risk of adverse events. In most cases, females require considerably more time to reach climax than males do; thus, in females taking SSRIs and SSRI-like agents, the delayed climax caused by these agents becomes an adverse effect. In many females, such an inability to reach orgasm can induce a pattern of sexual avoidance, along with a corresponding decrease in libido or sexual excitement (lubrication). A study by Safarinejad demonstrated that a single daily high dose of pindolol (a nonselective beta-adrenergic antagonist with 5-HT1A autoreceptor antagonist properties [52] ) in combination with paroxetine (or possibly another SSRI) delayed ejaculation in patients in whom paroxetine therapy alone failed to provide benefit.

• Regularly practice pelvic floor strengthening exercises.
• Use delay sprays or gels containing numbing agents.
• Implement the pause technique during intimacy.
• Engage in longer foreplay to reduce pressure.
• Avoid excessive masturbation to improve control.
• Maintain a daily routine of physical activity.
• Discuss treatment options with a urologist.
• Keep a journal of symptoms and progress.
• Try mental distraction techniques to delay climax.
• Use guided imagery or visualization methods.
• Establish a pre-sex routine to increase confidence.
• Be patient and consistent with treatment efforts.

[53] However, more studies must be performed before pindolol can be considered an ideal option for first- or second-line treatment of premature ejaculation.

• Use the start-stop technique during sex to control ejaculation.
• Practice the squeeze method to delay climax.
• Incorporate Kegel exercises to strengthen pelvic muscles.
• Try desensitizing condoms or sprays to reduce sensation.
• Engage in breathing exercises to relax and extend arousal.
• Limit alcohol intake, as it can impair sexual stamina.
• Communicate openly with your partner about concerns.
• Use topical anesthetics cautiously to avoid loss of pleasure.
• Focus on foreplay to enhance arousal control.
• Consider counseling or sex therapy for underlying issues.
• Maintain a healthy lifestyle for overall sexual health.
• Explore medication options prescribed by a doctor.

In studies by Safarinejad and Hosseini [54] and Salem et al, [55] the opioid analgesic tramadol was found to be significantly more effective than placebo in terms of increased time to ejaculation, increased sexual intercourse satisfaction, and tolerability.

• Explore prescription medications like Dapoxetine.
• Practice gradual exposure therapy techniques.
• Engage in cognitive-behavioral therapy to reduce anxiety.
• Use herbal supplements with caution and medical approval.
• Implement lifestyle changes to improve overall health.
• Avoid illicit drugs that impair sexual function.
• Incorporate regular exercise into your routine.
• Prioritize stress relief activities daily.
• Use timed masturbation to increase control.
• Restrict or delay alcohol consumption before sex.
• Focus on emotional intimacy, not just performance.
• Maintain patience and realistic expectations.

In a randomized double-blind, placebo-controlled clinical trial by Hamidi-Madani et al in 150 patients, 12 weeks of tramadol 50 mg on demand, paroxetine 20 mg on demand, and placebo all resulted in improvement, but the tramadol group experienced significantly greater benefit than the paroxetine and placebo groups (P < 0.0001).

• Start therapy early with a healthcare provider.
• Learn about psychological factors affecting performance.
• Use behavioral techniques to increase endurance.
• Consider antidepressants like SSRIs under medical supervision.
• Explore natural supplements such as L-arginine or herbal remedies.
• Practice mindfulness and stress reduction strategies.
• Avoid performance anxiety through relaxation exercises.
• Maintain a balanced diet to support sexual health.
• Limit distractions and focus on intimate connection.
• Track triggers or patterns that lead to early ejaculation.
• Use lubricants to decrease sensation and prolong intimacy.
• Seek support from sex education resources.

A systematic review and meta-analysis found that tramadol may be effective in treatment of premature ejaculation, especially when other therapies have failed, but that it remains necessary to consider the possibility of drug addiction and adverse effects before initial use or after long-term use. [57] A meta-analysis of on-demand use of tramadol noted that the available evidence was of low to moderate quality, but the drug appears to be effective in this setting, with a low rate of adverse events; the effective dose remains uncertain, but some data support the use of 50 mg.