Premature Ejaculation Medication
- Author: Aaron Benson, MD; Chief Editor: Edward David Kim, MD, FACS more...
Medication Summary
No drug is approved by the FDA for the treatment of premature ejaculation (rapid ejaculation). 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. SSRIs have been the most successful agents in delaying the too-rapid response in men who experience premature ejaculation. Desensitizing creams containing local anesthetic agents can also be useful in some men with premature ejaculation. These agents are not approved by the FDA specifically for this use, but they are believed to be of at least some efficacy and are a minimal-risk option for patients.
Premature ejaculation that relates to erectile dysfunction (ED) may resolve if ED is treated successfully. Drugs for the treatment of ED include sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis), alprostadil (Caverject, Muse), and, possibly, SSRI antidepressants (if depression is causing the ED). Details on drugs for the treatment of ED are included in the article on impotence (see Erectile Dysfunction).
If a patient does not have premature ejaculation but has depression-related ED only, the use of a drug with minimal adverse sexual effects (incidence < 1%) such as bupropion HCl (Wellbutrin) or venlafaxine HCL (Effexor) might be a consideration in an effort to avoid creating a problem with delayed ejaculation or even anorgasmia.[18] However, if the patient has significant premature ejaculation, ED, and depression, an added benefit of an antidepressant with SSRI side effects is the possibility that the premature ejaculation is also helped.[19]
Selective Serotonin Reuptake Inhibitors
Class Summary
The mechanism of action of SSRIs is linked to their inhibition of neuronal uptake of serotonin in the CNS. Various animal studies suggest that SSRIs have weak effects on norepinephrine and dopamine neuronal reuptake. They do not antagonize adrenergic (eg, alpha1-adrenergic, alpha2-adrenergic, beta-adrenergic), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT 1A, 5HT 1B, 5HT 2), or benzodiazepine receptors; therefore, they have fewer adverse anticholinergic effects than tricyclic antidepressants.
SSRIs have been observed to cause sexual side effects, the most common being delay in sexual climax for both males and females. In most cases, females require quite a bit more time to reach climax than males; therefore, delayed climax caused by an SSRI becomes an adverse effect in women. Often, the frustration and discouragement of the inability to reach orgasm induce a pattern of sexual avoidance in many females, and a corresponding decrease in libido or sexual excitement (lubrication) develops in these individuals. In males, too-rapid orgasm can cause some of the same patterns of sexual avoidance and decreased libido; thus, determining the primary problem when instituting therapy is important. Sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), citalopram (Celexa) and dapoxetine are useful SSRIs for treating premature ejaculation.
Dapoxetine is an SSRI developed specifically for the treatment of premature ejaculation. Dapoxetine may be effective at first dose (ie, on-demand) for premature ejaculation when given 1-3 hours prior to sexual intercourse, with an adverse-effect profile comparable to those of other SSRIs.[20, 21, 22] Dapoxetine is under review for approval in both the United States and Europe; thus, it is not yet available for use.
The optimal medical treatment for premature ejaculation has not been established, but, in the author's experience, single dosing prior to sexual relations can work for some males, while in others, achieving a blood level through daily use of the medication may be necessary, as in the treatment of clinical depression. Obviously, if single dosing is successful, therapy is simpler and is associated with fewer adverse effects. Therefore, this may be the preferred initial therapy. The dose may be increased in step-wise fashion until a therapeutic effect is achieved or until the maximum daily recommended dose is reached. No exact schedule of increased dosing has been determined, and the experience of the physician, response of the individual patient, adverse effects experienced by the patient, and other general medical considerations should be the guiding factors.
If one SSRI fails to help the patient, using a second choice certainly is reasonable. However, if the second choice fails, a third choice is not likely to benefit the patient. As with treatment for depression, if a patient has been on the medication for 6 weeks at maximal dose with no improvement, then the likelihood is remote that a more prolonged course of therapy with a particular drug would be successful. No reason exists for not combining medication with behavioral modification therapy, desensitizing creams, or both; additive effects or even synergy from several simultaneous treatments can occur. If all treatment fails, then the only options are for the patient to see a different health care professional, if he wishes, or for him 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.[23] These adverse effects include psychiatric and neurological sequelae, dermatologic reactions, anticholinergic effects, fluctuation in body weight, cognitive impairment, drug interactions, and sexual side effects other than delayed ejaculation (eg, ED, loss of libido). In addition, changing SSRIs should be done with caution, as a washout period is necessary to avoid overdose. SSRI discontinuation syndrome (especially with paroxetine) has been associated with dose reduction or discontinuation and may cause dizziness, nausea/vomiting, headache, gait instability, lethargy, agitation, anxiety, and insomnia.[24]
Paroxetine (Paxil)
Potent SSRI antidepressant used to treat premature ejaculation. Improvement may not be evident until at least 3 wk following initiation of treatment. If no benefit (with respect to premature ejaculation) after 6 wk or adverse effects become troublesome, medication should be discontinued in favor of an alternative treatment.
Sertraline (Zoloft)
Potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 wk following initiation of treatment. If no benefit with respect to premature ejaculation after 6 wk or if adverse effects become troublesome, discontinue in favor of alternative treatment.
Citalopram (Celexa)
Potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 wk following initiation of treatment. If no benefit (with respect to premature ejaculation) after 6 wk or if adverse effects become troublesome, discontinue in favor of alternative treatment.
Fluoxetine (Prozac)
Potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 wk following initiation of treatment. If no benefit with respect to premature ejaculation after 6 wk or if adverse effects become troublesome, discontinue in favor of alternative treatment.
Tricyclic antidepressants
Class Summary
Drugs with SSRI-like side effects (ie, delaying sexual climax) can be used to treat premature ejaculation. The tricyclic antidepressant most studied for premature ejaculation is clomipramine (Anafranil).[25, 26, 27, 28, 29] Many investigators find that clomipramine is more effective for premature ejaculation than many SSRIs.
Clomipramine (Anafranil)
Inhibits membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. These actions are believed to be responsible for its antidepressant activity. Inhibition of serotonin probably gives the SSRI-like activity that produces side effects (eg, inhibition of ejaculation).
Topical anesthetic agents
Class Summary
These agents may reduce penile sensitivity and excitability and delay ejaculation.[30, 16, 17] Condoms also reduce male sensitivity, yet no evidence shows that wearing a condom helps successfully treat premature ejaculation. Topical anesthetic cream is probably the lowest-risk medication that can be used for premature ejaculation, with no adverse systemic effects in the absence of prior hypersensitivity to the medication (patient or partner). Usually, no contraindication exists for combined therapy with topical anesthetics, antidepressants, and behavioral therapy.
Lidocaine 2.5% and prilocaine 2.5% (EMLA)
Applied to intact skin under an occlusive dressing, provides dermal analgesia. Effectiveness of this when applied to the penis is not proven; an occlusive dressing might also be difficult unless the penis is covered with a condom or cellophane. Lidocaine and prilocaine are amide-type local anesthetic agents. Both lidocaine and prilocaine stabilize neuronal membranes by inhibiting the flow of certain ions required for the initiation and conduction of nerve impulses, thus producing local anesthesia.
Phosphodiesterase (type 5) Enzyme Inhibitor
Class Summary
Some recent studies have demonstrated that sildenafil (Viagra) and other phosphodiesterase type 5 (PDE5) inhibitors in combination with SSRIs provide better results when used to treat premature ejaculation than use of SSRIs alone.[31] The reason for this is unknown, but the mechanism may be, in part, that an improved erection (firmness, duration, or both) resulting from the PDE5 inhibitor provides inhibition of ejaculation via down-regulation of receptors involved in somatosensory latency times. 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 an adjunct to treating premature ejaculation in men for whom no contraindication otherwise exists. The only PDE5 inhibitors studied recently to any degree in premature ejaculation include sildenafil (Viagra) and tadalafil (Cialis)[32, 33] ; vardenafil (Levitra) may also work, but insufficient data exist at this time to list it.
However, no studies have demonstrated superiority of PDE5 inhibitors over placebo in the treatment of premature ejaculation. The use of PDE5 inhibitors for the treatment of premature ejaculation is not approved by the FDA and is considered an off-label use.
Sildenafil (Viagra)
Sildenafil is FDA-approved for the treatment of erectile dysfunction (ED) but not specifically for premature ejaculation. If both conditions are present, sildenafil may help both problems based on recent studies. Sildenafil in combination with SSRI-type drugs helps premature ejaculation better than SSRI-type medication alone, as measured by prolongation of intravaginal ejaculatory latency time (IELT). More drug-related adverse events may occur because 2 medications are being used (sildenafil and an SSRI) rather than just one.
Tadalafil (Cialis)
PDE5 selective inhibitor. Tadalafil is FDA-approved for the treatment of ED but not specifically for premature ejaculation. Based on recent studies, tadalafil may improve both concurrently. Tadalafil in combination with SSRI-type drugs helps premature ejaculation better than SSRI-type medication alone, as measured by prolongation of IELT. More drug-related adverse events may occur because two medications are being used (sildenafil and an SSRI) rather than just one. Inhibition of PDE5 increases cGMP activity, which increases vasodilatory effects of nitric oxide. Sexual stimulation is necessary to activate response. Increased sensitivity for erections may last 36 h with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (ie, twice weekly); men can attempt sexual activity at anytime between daily doses. Available as 2.5-mg, 5-mg, 10-mg, and 20-mg tablets.
Beta-adrenergic Blocker
Class Summary
Pindolol is a nonselective beta-adrenergic antagonist that has been shown to have 5-HT1A autoreceptor antagonist properties in the dorsal raphe nuclei.[34] This 5-HT1A autoreceptor antagonist action is hypothesized to increase the synaptic content of serotonin and subsequently potentiate the action of an SSRI medication. In a recent study, Safarinejad (2008) demonstrated that a single daily high dose of pindolol in combination with paroxetine (or possibly another SSRI) delayed ejaculation in patients in whom paroxetine therapy alone failed to provide benefit.[35] However, more studies need to be performed before pindolol can be considered an ideal option for first- or second-line treatment of premature ejaculation.
Pindolol (Visken)
Nonselective beta-adrenergic antagonist used in combination with paroxetine for premature ejaculation refractory to paroxetine alone. This is an off-label use of pindolol.
Analgesic, Opioid
Class Summary
Tramadol is an analgesic with centrally acting opioid activity (weak μ-opioid effect) in addition to reuptake inhibition of 5-HT and norepinephrine. The increased synaptic content of serotonin and norepinephrine at the level of the spinal cord and peripheral sensory nerves is hypothesized to provide the mechanism of effective treatment for premature ejaculation. Safarinejad and Hosseini (2006) and Salem et al (2008) have demonstrated significant efficacy of tramadol versus placebo in terms of increased time to ejaculation, increased sexual intercourse satisfaction, and tolerability.[36, 37]
Tramadol (Ultram)
Centrally acting opioid analgesic that exerts its effect by combining opioid receptor activation with inhibition of norepinephrine and serotonin reuptake. If no benefit with respect to premature ejaculation after 6 wk or if adverse effects become troublesome, discontinue in favor of alternative treatment. Use in premature ejaculation is off-label.
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