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patient rating of control over ejaculation as fair, good, or very good, increased from 31% at baseline to 518% and 584% at study end with dapoxetine 30 and 60 mg, respectively Treatment-related side effects were uncommon, dose-dependent, included nausea, diarrhea, headache, and dizziness, and were responsible for study discontinuation in 4% (30 mg) and 10% (60 mg) of subjects Several in vitro and animal studies have demonstrated that the desensitization of 5-HT1A receptors,
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increased activation of postsynaptic 5-HT2C receptors, and the resultant higher increase in synaptic 5-HT neurotransmission seen in daily dosing of SSRI class drugs, can be acutely achieved by blockade of these receptors by administration of an on-demand SSRI and a 5-HT1A receptor antagonist [52 54] Drug combinations such as this, or single agents that target multiple receptors, may form the foundation of more effective future on-demand medication
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16 the ef cacy of these compounds in delaying ejaculation
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The use of topical local anesthetics such as lidocaine and/or prilocaine as a cream, gel or spray is well established and is moderately effective in retarding ejaculation They may be associated with signi cant penile hypo-anesthesia and possible transvaginal absorption, resulting in vaginal numbness and female anorgasmia unless a condom is used [55 57]
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Psychologic treatment of premature ejaculation
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The outcome objective of treating PE is the prolongation of ejaculatory latency, leading to a better and preferably mutually-satisfying sexual relationship between the patient and his partner As PE may result in sexual problems in the patient s partner or may lead to relationship problems, its treatment should be preceded by both a sexologic and relationship assessment
Type 5 Phosphodiesterase (PDE-5) inhibitors
Nitric oxide (NO) is becoming recognized as one of the important intracellular messengers in the brain [58] Several studies suggest that elevation of extracellular NO in the medial pre-optic area (MPOA) accelerates dopamine release and facilitates male copulatory behavior of rats, whereas a decrease of NO reduces their copulatory behavior [59 61] Several authors have reported their experience with PDE5 inhibitors alone or in combination with SSRIs as a treatment for PE [62 66] The proposed mechanisms for the effect of sildena l on ejaculatory latencies include a central effect involving increased NO and reduced sympathetic tone, smooth muscle dilatation of the vas deferens and seminal vesicles, which may oppose sympathetic vasoconstriction and delay ejaculation, reduced performance anxiety due to better erections, and down-regulation of the erectile threshold to a lower level of arousal so that increased levels of arousal are required to achieve the ejaculation threshold Most of these studies are uncontrolled and the results are confusing and dif cult to interpret The only double-blind placebocontrolled multicenter study showed no signi cant difference in the IELT of sildena l-treated subjects compared to placebo, but did demonstrate signi cant improvements in the ejaculatory control domain and the ejaculatory function global ef cacy question The latter is possibly consistent with the erectile response of sildena l [67] It is unlikely that PDE inhibitors signi cantly delay ejaculation in men with PE without erectile dysfunction However, it may well be that PDE inhibitors may be bene cial in men with erectile dysfunction and secondary PE Well-designed, placebocontrolled studies are a prerequisite to further study
Psychotherapy
A number of different psychotherapeutic approaches to PE have been described, but their ef cacy have not been evaluated in properly controlled and adequately powered trials, and the different therapeutic modalities have not been compared in formal studies It is likely that only some men seeking treatment for PE require in-depth psychotherapy In spite of hard evidence on the ef cacy of psychotherapy, behavioral retraining is still often practiced by sexologists Behavioral treatment is distinguished in the stop-start and the squeeze [11,68] The basis of behavioral retraining is the hypothesis that PE occurs because the man fails to appreciate the sensations of heightened arousal and recognize the feelings of ejaculatory inevitability