General treatment of PE (premature ejaculation) 5.1 Medication 5.1.1 Selective 5-hydroxytryptamine reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) (1) Dapoxetine There is level 1a evidence confirming the efficacy and dose safety of dapoxetine administered on demand for the treatment of primary and secondary premature ejaculation, and no evidence of increased suicidal or withdrawal syndrome with dapoxetine Risk. One study found that 30 mg and 60 mg of dapoxetine taken before intercourse increased IELT by 2.5 and 3 times, respectively, compared to the placebo group, and increased ejaculatory control, decreased pain, and increased satisfaction. Dapoxetine has been marketed in China under the trade name Bilevel, which is used as an on-demand treatment for premature ejaculation and has equal therapeutic efficacy for primary and secondary premature ejaculation. Treatment-related side effects are rare and mainly seen as dose-dependent, including nausea, diarrhea, headache, dizziness, etc. (2) Non-indicated treatment of premature ejaculation with SSRIs and TCAs A recent meta-analysis of all studies of this class of drug therapy showed that paroxetine appeared to exert the strongest ejaculatory delay with an approximately 8.8-fold increase in IELT above baseline. SSRIs may cause significant decreases in sperm concentration, motility, and morphology, and tapering over 3-4 weeks to avoid withdrawal syndrome is contraindicated in Bipolar depressed patients. In studies of antidepressants for the treatment of patients with depression and/or anxiety disorders with PE, this class of drugs was found to mildly increase the risk of suicidal ideation or suicide attempts in younger affected individuals. In contrast, no similar phenomenon was found for patients with PE without depression. The new Guidelines state that SSRIs need to be prescribed with caution for patients with PE who are no older than 18 years of age or who have comorbid depression and especially suicidal ideation. 5.1.2 Local anesthetics Lidocaine, proparacaine in cream, gel or spray form are commonly used. pSD502, a lidocaine/proparacaine spray, has been reported to increase IELT by 6.3-fold and improve ejaculatory control and sexual satisfaction. However, decreased penile sensation during sex has been reported and transferred to the partner, and it is recommended that condoms or washing off the active anesthetic may be used to prevent penile anesthesia and possible resulting vaginal absorption. 5.1.3 Phosphodiesterase type 5 (PDE5) inhibitors Although some evidence suggests that PDE5 inhibitors are safe and effective when used on demand or given in daily doses in patients with primary premature ejaculation with normal erectile function, PDE5 inhibitors are not recommended for patients with lifelong premature ejaculation with normal erectile function. 5.1.4 Other medications Tramadol is not recommended for the treatment of PE. animal studies have shown that the central control of oxytocin antagonist inhibits the ejaculatory impulse, however, in a study in humans, oxytocin antagonist did not clinically and statistically improve IELT. penile injections of blood-activating drugs are not recommended for the treatment of PE. Modulation of the dorsal penile nerve is an invasive and irreversible procedure intended to increase IELT, and it is recommended that the safety of this treatment be confirmed prior to its use. 5.3 Psychological and behavioral therapies For primary premature ejaculation, marital counseling, guidance, and/or therapeutic relationships may be a useful adjunct to medical interventions if premature ejaculation is causing psychological and interpersonal concerns. For secondary premature ejaculation, helping patients improve ejaculatory control through behavioral training, seeking restrictive patterns of sexual behavior, and addressing intercourse issues may all be relevant for patients with secondary premature ejaculation. Once the patient’s confidence and sense of control improves, it may be possible to reduce or discontinue medical interventions. The new Guidelines thus introduce the concept of combination therapy, which refers to the combination and emphasis on psychosocial treatment while the patient takes and successfully obtains multiple effective medical treatments. The combination of PDE5 inhibitors and SSRIs has the potential to effectively treat secondary premature ejaculation with ED and is more effective than primary premature ejaculation with moderate ED. There is reliable evidence to support the use of drugs for ED to treat PE in combination with ED, but the combination of drugs for PE and ED is not recommended.