Medication Summary
No drug is specifically approved by the US Food and Drug Administration (FDA) for the treatment of premature (early) ejaculation. However, various agents have been safely and effectively used for this purpose. Selective serotonin reuptake inhibitors (SSRIs) and antidepressants with SSRI-like effects have been the most successful. Desensitizing creams containing local anesthetics can also be useful in some cases; though not FDA-approved, they are believed to be of at least some efficacy and carry minimal risk.
Premature ejaculation that relates to erectile dysfunction may resolve if the erectile difficulty is treated successfully. Drugs for the treatment of erectile dysfunction include sildenafil, vardenafil, tadalafil, alprostadil, and, possibly, an SSRI (if depression is causing the erectile dysfunction).
Selective Serotonin Reuptake Inhibitors
Class Summary
The mechanism of action of SSRIs is linked to their inhibition of neuronal uptake of serotonin (5-HT) in the central nervous system (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, or beta-adrenergic), cholinergic, GABAergic, dopaminergic, histaminergic, serotonergic (5-HT1A, 5-HT1B, or 5-HT2), or benzodiazepine receptors; therefore, they have fewer adverse anticholinergic effects than tricyclic antidepressants (TCAs) do.
Adverse effects of long-term SSRI use are a significant concern and should be considered by both the physician and the patient. These adverse effects include psychiatric and neurologic sequelae, dermatologic reactions, anticholinergic effects, fluctuation in body weight, cognitive impairment, drug interactions, and sexual side effects other than delayed ejaculation (eg, erectile dysfunction or loss of libido.
Paroxetine (Paxil, Pexeva)
Paroxetine is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.
Sertraline (Zoloft)
Sertraline is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.
Citalopram (Celexa)
Citalopram is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.
Fluoxetine (Prozac)
Fluoxetine is a potent SSRI used to treat premature ejaculation. Improvement may not be evident until at least 3 weeks after the initiation of treatment. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment.
Tricyclic antidepressants
Class Summary
Drugs with SSRI-like side effects (eg, delaying sexual climax), such as certain TCAs, can be used to treat premature ejaculation. The TCA most studied for treatment of premature ejaculation is clomipramine, which may be more effective than many SSRIs for this purpose.
Clomipramine (Anafranil)
Clomipramine inhibits the 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 rise to the SSRI-like activity that produces side effects (eg, inhibition of ejaculation).
Topical anesthetic agents
Class Summary
Topical anesthetics may reduce penile sensitivity and excitability and delay ejaculation. Topical anesthetic cream is probably the lowest-risk medication that can be used for premature ejaculation; it has no adverse systemic effects, in the absence of prior hypersensitivity to the medication on the part of the patient or his partner. As a rule, there is no contraindication for combined therapy with topical anesthetics, antidepressants, and behavioral therapy.
Lidocaine 2.5% and prilocaine 2.5% (EMLA)
Lidocaine and prilocaine are amide-type local anesthetic agents. Both agents stabilize neuronal membranes by inhibiting the flow of certain ions required for the initiation and conduction of nerve impulses, thus producing local anesthesia. Lidocaine and prilocaine are applied to intact skin under an occlusive dressing, providing dermal analgesia. The effectiveness of this approach when it is applied to the penis is unproved; an occlusive dressing might also be difficult unless the penis is covered with a condom or cellophane.
Phosphodiesterase Type 5 Inhibitors
Class Summary
In some studies, sildenafil and other phosphodiesterase type 5 (PDE5) inhibitors in combination with SSRIs has yield better results in treating premature ejaculation than SSRIs alone. The mechanism of this effect is unknown. Regardless of the mechanism, PDE5 inhibitors are safe and effective treatment adjuncts for premature ejaculation if not otherwise contraindicated. The only PDE5 inhibitors studied to any degree in this setting are sildenafil and tadalafil; vardenafil may also work, but more data are needed.
Sildenafil (Viagra)
Sildenafil is FDA-approved for the treatment of erectile dysfunction but not specifically for the treatment of premature ejaculation. If both conditions are present, sildenafil may help them both. Sildenafil in combination with an SSRI-type drug alleviates premature ejaculation better than an SSRI-type drug alone, as measured by prolongation of intravaginal ejaculatory latency time (IELT). More drug-related adverse events may occur because 2 medications are being used rather than just 1.
Tadalafil (Cialis)
Tadalafil is FDA-approved for the treatment of erectile dysfunction but not specifically for the treatment of premature ejaculation. Studies suggest that it may improve both conditions concurrently. Tadalafil in combination with an SSRI-type drug alleviates premature ejaculation better than an SSRI-type drug alone, as measured by prolongation of IELT. More drug-related adverse events may occur because 2 medications are being used rather than just 1.
Inhibition of PDE5 increases cyclic guanosine monophosphate (cGMP) activity, which increases the vasodilatory effects of nitric oxide. Sexual stimulation is necessary to activate response. Increased sensitivity for erections may last 36 hours with intermittent dosing. For more frequent sexual activity (eg, twice weekly), a daily low-dose regimen may be recommended; men can attempt sexual activity at any time between daily doses. Tadalafil is 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. It is hypothesized that this 5-HT1A autoreceptor antagonism increases the synaptic content of 5-HT and subsequently potentiates the action of an SSRI medication. More studies are required before pindolol can be considered an ideal option for first- or second-line treatment of premature ejaculation.
Pindolol
Pindolol is a 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 inhibition of reuptake of 5-HT and norepinephrine. It is hypothesized that the increased synaptic content of serotonin and norepinephrine at the level of the spinal cord and peripheral sensory nerves provides the mechanism for effective treatment of premature ejaculation.
Tramadol (Ultram, Rybix ODT, ConZip, Ryzolt)
Tramadol is a centrally acting opioid analgesic that exerts its effect by combining opioid receptor activation with inhibition of norepinephrine and serotonin reuptake. If there is no beneficial effect on premature ejaculation after 6 weeks or if adverse effects become troublesome, it should be discontinued in favor of an alternative treatment. Treatment of premature ejaculation is an off-label use of tramadol.
