eMedicine Specialties > Urology > Erectile Dysfunction, Premature Ejaculation, and Sexual Disorders

Premature Ejaculation: Treatment & Medication

Author: Aaron Benson, MD, Staff Physician, Department of Surgery, Division of Urology, Southern Illinois University School of Medicine
Coauthor(s): Loren B Ost, MD, Associate Professor, Department of Surgery, Southern Illinois University School of Medicine; Urologist, SIU Physicians and Surgeons; Mark Jeffrey Noble, MD, Consulting Staff, Urologic Institute, Cleveland Clinic Foundation; Milton Lakin, MD, Head, Section of Medical Urology, Urological Institute, Cleveland Clinic
Contributor Information and Disclosures

Updated: May 5, 2009

Treatment

Medical Care

Medical treatment for premature ejaculation (rapid ejaculation) includes several options. Any serious primary medical condition (eg, angina) should be treated; for the purpose of the following discussion, the male is assumed to be healthy and premature ejaculation is assumed to be his only problem. In addition, any accompanying erection problem can be treated with various methods with excellent success (see Erectile Dysfunction); thus, only passing reference is made to treatment of erectile dysfunction (ED) that may accompany the premature ejaculation problem.

Include the female partner as much as possible in the treatment and counseling sessions in order to achieve the best outcome.

1. Relieve any underlying performance pressure on the male.

  • Assuming that premature ejaculation occurs when intercourse is attempted, the couple should be instructed that intercourse should not be attempted until premature ejaculation is treated. The male may use manual stimulation, oral sex, or other means to satisfy the female partner in the meantime.
  • If the male always experiences ejaculation with initial sexual excitement or early foreplay, this is a serious problem and probably indicates primary premature ejaculation (the history should reveal this), which then most likely requires treatment in conjunction with a mental health care professional. These more difficult cases should be screened out.

2. The couple should then be instructed on sexual therapy, such as the stop-start or squeeze-pause technique popularized by Masters and Johnson.11

  • The female partner should slowly begin stimulation of the male and should stop as soon as he senses a feeling of excessive excitement that may lead to ejaculatory inevitability.
  • Then, she should administer a firm compression of the penis just behind the glans, pressing mainly under the penis. This should be uncomfortable but not painful.
  • Stimulation then should begin again after the male has a feeling that the ejaculation is no longer imminent.
  • The process should be repeated and practiced at least 10 or more times.
  • Gradually, most males find this technique helps decrease the impending inevitable need to ejaculate.
  • After a period of practicing this method, the couple can sit facing each other, with the woman's legs crossing on top of the male's legs. She can stimulate him by manipulating his penis close to, then with friction against, her vulval area. Each time he senses excessive excitement, she can apply the squeeze and stop all stimulation until he calms down enough for the process to be repeated.
  • Finally, coitus may be attempted, with the female partner in the superior position so that she may withdraw immediately and again apply a squeeze to remove his urge to climax.
  • Most couples find this technique to be highly successful. It can also help the female partner to be more aroused and can shorten her time to climax because it constitutes a form of extended foreplay in many cases.

3. Another therapeutic modality is the use of desensitizing cream for the male.

  • In Korea and other areas of the Far East, SS cream (a combination of 9 ingredients, mainly herbal; SS stands for Super Secret) has been shown to desensitize the penis, decrease the vibratory threshold, and help men with premature ejaculation to significantly delay their ejaculatory response.12,13
  • Unfortunately, SS Cream is not yet approved by the US Food and Drug Administration (FDA), but simple combinations of lidocaine cream or related topical anesthetic agents can be used with similar effects and they are safe as long as the patient has no history of allergy to the substance.14,15

4. If the male is relatively young and can achieve another erection in a few minutes following an episode of premature ejaculation, he may find that his control is much better the second time.

  • Some therapists advise young men to masturbate (or have their partner stimulate them rapidly to climax) 1-2 hours before sexual relations are planned.
  • The interval for achieving a second climax often includes a much longer period of latency, and the male can usually exert better control in this setting.
  • In an older man, such a strategy may be less effective because the older man may have difficulty achieving a second erection after his first rapid sexual release. If this occurs, it can damage his confidence and may result in secondary impotence.

5. The most effective pharmacologic modality found to aid men with premature ejaculation is a drug from the selective serotonin reuptake inhibitors (SSRIs) class, drugs which are used normally as antidepressants in the clinical setting.

  • Some tricyclic antidepressants with SSRI-like activity yield the same result.
  • As a side effect, many of these agents have been found to cause a significant delay in reaching orgasm in both male and female patients.
  • For this reason, medications with SSRI side effects have been used in men who experience premature ejaculation.

Surgical Care

No recommended surgical treatment exists for premature ejaculation.

Consultations

  • Consultation with a sex therapist, psychologist, or psychiatrist may prove helpful if the primary care physician or urologist cannot provide successful treatment or does not have the time to explore psychological issues and implement behavioral techniques (eg, squeeze-pause). If the primary care physician or urologist is not experienced in treating premature ejaculation or is uncomfortable with treatment, then early referral should take place (to a sex therapist, psychologist, or psychiatrist). Some physicians are comfortable implementing medication therapy but not behavioral therapy. The patient should be offered all treatment options, as with any medical condition, and the physician should proceed with referral for those option(s) considered to require more specialized help than the physician can provide.
  • For men who may be experiencing a severe emotional disturbance that is an underlying factor to premature ejaculation, referral to a mental health professional is most appropriate. Diagnosis and treatment of the various psychological factors that manifest partly as premature ejaculation are beyond the scope of this discussion.

Medication

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.16 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.

Selective Serotonin Reuptake Inhibitors

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.17,18,19 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.20 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.21


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.

Adult

20 mg PO 2-12 h before sexual relations; alternatively, 20 mg/d PO, gradually titrate to response; not to exceed 40 mg/d

Pediatric

Not established

Phenobarbital and phenytoin decrease effects; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity; additive CNS depressant effects with other antidepressants, opioid analgesics, sedatives, and hypnotics; increases toxicity of MAOIs

Documented hypersensitivity; concomitant MAOIs or use within 14 d

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in recent MI or unstable heart disease; hyponatremia; although minimal adverse anticholinergic effects (compared with TCAs), use with caution in glaucoma, bladder outlet obstruction, chronic constipation, and other conditions in which adverse anticholinergic effects may exacerbate symptoms; also caution in moderate-to-severe renal or hepatic impairment, because of excessive blood level accumulation (adjust dose accordingly); does not impair motor or cognitive ability with respect to performance of complex tasks, nor does it cause somnolence, but any drug affecting the CNS may cause drowsiness, and driving and performance of other tasks requiring alertness and concentration should be avoided; seizures are rare; caution in preexisting seizure disorder; when used for premature ejaculation (off-label), patients with clinical depression should be treated by a mental health care professional; potential for depressed patients to commit suicide; priapism has been (rarely) reported


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.

Adult

50 mg PO 2-12 h before sexual relations; alternatively, 50 mg/d PO; gradually titrate to response; not to exceed 200 mg/d

Pediatric

Not established

Increases toxicity of MAOIs, diazepam, tolbutamide, and warfarin; additive CNS effects with alcohol, antidepressants, opioid analgesics, sedatives, and hypnotics; suspension contains alcohol and, therefore, is contraindicated in patients taking disulfiram (Antabuse)

Documented hypersensitivity; concomitant MAOIs or use within 14 d

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in recent MI or unstable heart disease; hyponatremia; although minimal adverse anticholinergic effects (compared with TCAs), use with caution in glaucoma, bladder outlet obstruction, chronic constipation, and other conditions in which adverse anticholinergic effects may exacerbate symptoms; caution in patients with moderate-to-severe renal or hepatic impairment, because of excessive blood level accumulation, adjust dose accordingly; does not impair motor or cognitive ability with respect to performance of complex tasks, nor does it cause somnolence, but any drug affecting the CNS may cause drowsiness, and driving and performance of other tasks requiring alertness and concentration should be avoided; seizures are rare, use with caution in preexisting seizure disorder; when used for premature ejaculation (off-label), patients with clinical depression should be treated by a mental health care professional, potential for depressed patients to commit suicide; priapism has been (rarely) reported


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.

Adult

20 mg PO daily; not to exceed 60 mg PO daily

Pediatric

Not established

Increases toxicity of MAOIs, diazepam, tolbutamide, and warfarin; additive CNS effects with alcohol, antidepressants, opioid analgesics, sedatives, and hypnotics; susp contains alcohol and is therefore contraindicated in patients taking disulfiram (Antabuse)

Documented hypersensitivity; concomitant MAOIs or use within 14 d; concomitant use of pimozide

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Suicidal ideation and behavior or worsening depression (increased risk particularly in children, adolescents, and young adults) during the first few months of therapy or following changes in dosage; abrupt withdrawal can cause serious discontinuation symptoms; increased risk of bipolar disorder or precipitation of a mixed/manic episode with antidepressant treatment only; concomitant use of NSAIDs, aspirin, or other drugs that affect coagulation may cause abnormal bleeding, particularly in the GI tract; concomitant serotonergic drug use (serotonin precursors [tryptophan]), SSRIs, serotonin-norepinephrine reuptake inhibitors) is not recommended owing to risk of serotonin syndrome; caution in diseases or conditions that produce altered metabolism or hemodynamic responses; caution in patients with hepatic impairment (reduces drug clearance), a history of mania, or a history of decreased renal clearance or seizure history; may precipitate an episode of severe renal impairment; syndrome of inappropriate secretion of antidiuretic hormone has been reported; when used for premature ejaculation (off-label), patients with clinical depression should be treated by a mental health care professional


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.

Adult

5-60 mg/d PO; most clinicians begin at 10-20 mg/d (in one dose or in two divided doses), or taken 2 h prior to intercourse as single-dose therapy; total daily dose not to exceed 80 mg/d

Pediatric

Not established

Phenobarbital and phenytoin decrease effects; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity; additive CNS depressant effects with other antidepressants, opioid analgesics, sedatives, and hypnotics; increases toxicity of MAOIs; can alter levels of antidiabetic drugs (they may need adjustment); can alter levels of warfarin, digitalis, or both; may increase benzodiazepine, phenytoin, and carbamazepine levels; increased adverse effects with tryptophan; lithium levels can increase or decrease and need monitoring; may potentiate drugs metabolized by CYP2D6, antipsychotics (eg, haloperidol, clozapine), or other antidepressants; avoid alcohol, during or within 14 d of MAOIs, or within 5 wk of thioridazine discontinuation; caution with drugs that impair hemostasis (eg, nonselective NSAIDS, aspirin, warfarin) because of increased risk of bleeding

Documented hypersensitivity; concomitant MAOIs or use within 14 d; thioridazine within 5 wk of discontinuation

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue upon unexplained allergic reaction; monitor for symptoms of mania or hypomania; caution with diseases or conditions that could affect metabolism or hemodynamic responses, diabetes, history of seizures, suicidal tendencies; altered platelet function and hyponatremia reported; monitor for clinical worsening or suicidality, especially at initiation of therapy or dose changes; avoid abrupt withdrawal; monitor for discontinuation symptoms

Tricyclic antidepressants

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).22,23,24,25,26 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).

Adult

50 mg PO 2-12 h before sexual relations; alternatively, 50 mg/d PO

Pediatric

Not established

Barbiturates, phenytoin, and carbamazepine decrease effects; increases effects of anticholinergics, sympathomimetics, alcohol, and CNS depressants; increased toxicity of MAOIs

Documented hypersensitivity; recent MI; do not use within 14 d of MAOIs administration

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in preexisting seizure disorders; recent MI or unstable heart disease; in hepatic or renal impairment, adjust dose accordingly; constipation; glaucoma; hyponatremia

Topical anesthetic agents

These agents may reduce penile sensitivity and excitability and delay ejaculation.27,14,15 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.

Adult

Apply liberally to entire penile skin 1-2 h before sexual intercourse; effect may last up to 1 h or longer after occlusive dressing or condom removed; consider removal of any remaining excess medication from penis prior to intercourse to avoid reduction in partner's vaginal sensitivity

Pediatric

Not established

Documented hypersensitivity in patient or partner

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Cautious application to skin with rash, skin eruption, or other skin irritation

Phosphodiesterase (type 5) Enzyme Inhibitor

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.28 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)29,30 ; 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.

Adult

Starting dose can range from 25-50 mg PO 1-2 h prior to sexual intercourse; best taken on empty stomach; maximum dose is 100 mg

Pediatric

Not established

Increased levels with CYP3A4 inhibitors (eg, cimetidine, ketoconazole, itraconazole, erythromycin, saquinavir) and protease inhibitors (eg, ritonavir); CYP2C9 inhibitors may decrease sildenafil clearance; CYP3A4 inducers (eg, rifampin) may decrease levels; potentiates hypotensive effects of nitrates; additional supine BP reduction with amlodipine reported; simultaneous administration with alpha-blockers may lead to symptomatic hypotension; sildenafil dose should not exceed 25 mg and should not be taken within 4 h of taking an alpha-blocker (tamsulosin HCL [Flomax] may be an exception, as it is much more specific for prostate receptors than for vascular smooth muscle receptors); avoid with other ED treatments (increased risk of priapism)

Use is contraindicated in patients who are also taking organic nitrates either intermittently or regularly

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution with MI, stroke, or life-threatening arrhythmia within last 6 months; with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); unstable angina due to cardiac failure or CAD; anatomical penile deformation; predisposition to priapism; and retinitis pigmentosa; avoid in men where sexual activity is inadvisable due to underlying cardiovascular status; decrease in supine BP reported


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.

Adult

Intermittent dosing: 10 mg PO before sexual activity; may increase to maximum recommended dose of 20 mg or decreased to 5 mg based on efficacy and adverse effects; not to exceed 1 dose per day; may be taken without regard to food

Low-dose once daily use: 2.5 mg PO qd, without regard to timing of sexual activity; may increase to 5 mg/d based on efficacy and tolerability

Concurrent administration with potent CYP 3A4 inhibitors (eg, ketoconazole, ritonavir): Not to exceed 10 mg PO q72h prn

Moderate renal impairment (CrCl 30-50 mL/min): 5 mg PO qd prn initially; may increase to 10 mg PO q48h prn

Severe renal impairment (CrCl <30 mL/min): Do not exceed 5 mg PO qd prn

Mild-to-moderate hepatic impairment: Do not exceed 10 mg PO qd prn

Pediatric

<18 years: Not established

CYP450 3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, indinavir, ritonavir) may significantly increase levels of vardenafil; vardenafil potentiates hypotensive effect of nitrates or alpha-blockers; concurrent alcohol consumption may increase orthostatic hypotension risk

Documented hypersensitivity; concurrent or intermittent use of alpha-blockers (eg, doxazosin, terazosin, prazosin) or organic nitrates in any form

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Common adverse effects include headache, flushing, rhinitis, dyspepsia, or indigestion; assess cardiovascular status before use; caution with left ventricular outflow obstruction or conditions aggravated by hypotension; caution with hepatic or renal impairment (decrease dose); may cause prolonged or painful erection; may cause back pain or myalgias; sudden vision loss caused by nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with PDE5 inhibitors following use for ED, analysis is ongoing to determine causality; sudden decreases or loss of hearing has been reported

Beta-adrenergic Blocker

Pindolol is a nonselective beta-adrenergic antagonist that has been shown to have 5-HT1A autoreceptor antagonist properties in the dorsal raphe nuclei.31 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.32 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.

Adult

7.5 mg PO qd in conjunction with paroxetine for treatment of premature ejaculation32 ; lowest dose begins at 2.5 mg PO qd

Pediatric

Not established

Clinically significant interactions can occur, particularly with verapamil, epinephrine, beta-2-adrenergic receptor agonists, clonidine, ergot alkaloids, isoprenaline, NSAIDs, quinidine, cimetidine, lidocaine, phenobarbital, or rifampicin

Bronchial asthma or chronic obstructive pulmonary disease; cardiogenic shock; documented hypersensitivity to pindolol; overt cardiac failure; second- and third-degree AV block; severe sinus bradycardia

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Anesthesia/surgery (myocardial depression); avoid abrupt withdrawal (ie, titrate when discontinuing); bronchospastic disease; congestive heart failure; diabetes mellitus; hyperthyroidism/thyrotoxicosis; liver disease; peripheral vascular disease; renal impairment

Analgesic, Opioid

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.33,34


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.

Adult

50 mg PO approximately 2 h prior to sexual intercourse; not to exceed 100 mg in 6 h and 400 mg/24 h

Pediatric

Not established

May increase toxicity of MAOIs; additive CNS depressant effects with other opioid analgesics, sedatives, antidepressants, muscle relaxants, phenothiazines, tranquilizers, and hypnotics; concomitant naloxone use in tramadol overdose may increase seizure risk

Hypersensitivity to tramadol, any other components of the product, or opioids; situations in which opioids are contraindicated, including intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids, or psychotropic drugs; may worsen CNS and respiratory depression

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Acute abdominal conditions may complicate clinical assessment of patient; abrupt discontinuation may induce withdrawal symptoms (ie, anxiety, sweating, nausea, diarrhea, tremors, insomnia); may cause abuse, misuse, and diversion in potentially addiction-prone patients; may increase risk of suicide; anaphylactoid reactions, including serious and rarely fatal reactions, have been reported, often following the first dose (increased risk in patients with a history of anaphylactoid reactions to codeine or other opioids); caution in advanced cirrhosis or factors causing reduced drug metabolism; concomitant naloxone use in tramadol overdose may increase seizure risk; caution in concomitant use of CNS depressants (alcohol, anesthetic agents, antidepressants, muscle relaxants, narcotics, phenothiazines, sedative hypnotics, tranquilizers), serotonergic drugs (SSRIs, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, MAOIs, and triptans), other opioids, neuroleptics, or other drugs that reduce seizure threshold; doses exceeding recommended range alone or in combination with CNS depressants may increase risk of seizure and overdose, which has resulted in fatalities within 1 h of administration; epilepsy, history of seizures, or other risk for seizures (eg, head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections) may occur; extended-release dose form should not be used due to lack of dosing flexibility; increased intracranial pressure or head injury may result in exaggerated carbon dioxide retention, secondary elevation of cerebrospinal fluid pressure, and miosis obscuring intracranial pathology; respiratory depression risk; suicidal ideation, suicidal, emotional disturbances or increased risk of suicide

More on Premature Ejaculation

Overview: Premature Ejaculation
Differential Diagnoses & Workup: Premature Ejaculation
Treatment & Medication: Premature Ejaculation
Follow-up: Premature Ejaculation
References
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References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: APA Press; 1994.

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Further Reading

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Keywords

premature ejaculation, PE, primary premature ejaculation, secondary premature ejaculation, sexual dysfunction, ED, erectile dysfunction, rapid ejaculation, premature ejaculator, rapid ejaculator, performance anxiety, performance pressure, impotence, erection problem, rapid sexual release, primary PE, secondary PE, anorgasmia, lifelong premature ejaculation, acquired premature ejaculation

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Contributor Information and Disclosures

Author

Aaron Benson, MD, Staff Physician, Department of Surgery, Division of Urology, Southern Illinois University School of Medicine
Aaron Benson, MD is a member of the following medical societies: American Medical Association, American Urological Association, and Illinois State Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Loren B Ost, MD, Associate Professor, Department of Surgery, Southern Illinois University School of Medicine; Urologist, SIU Physicians and Surgeons
Loren B Ost, MD is a member of the following medical societies: American Urological Association
Disclosure: Nothing to disclose.

Mark Jeffrey Noble, MD, Consulting Staff, Urologic Institute, Cleveland Clinic Foundation
Mark Jeffrey Noble, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Kansas Medical Society, Sigma Xi, Society of University Urologists, and Southwest Oncology Group
Disclosure: Nothing to disclose.

Milton Lakin, MD, Head, Section of Medical Urology, Urological Institute, Cleveland Clinic
Milton Lakin, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, and American Urological Association
Disclosure: Nothing to disclose.

Medical Editor

Leonard Gabriel Gomella, MD, FACS, The Bernard W Godwin Professor of Prostate Cancer Chairman, Department of Urology, Associate Director of Clinical Affairs, Kimmel Cancer Center, Thomas Jefferson University
Leonard Gabriel Gomella, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Laser Medicine and Surgery, American Urological Association, Sigma Xi, Society for Basic Urologic Research, Society of University Urologists, and Society of Urologic Oncology
Disclosure: GSK Consulting fee Consulting; Astra Zeneca Honoraria Speaking and teaching; Watson Pharmaceuticals Consulting fee Consulting

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center
Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, and Tennessee Medical Association
Disclosure: Lilly Consulting fee Consulting; Astellas Consulting fee Speaking and teaching; Indevus Consulting fee Speaking and teaching

 
 
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