What’s the best drug treatment for premature ejaculation?

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Clinical Inquiries

What’s the best drug treatment for premature ejaculation?

J Fam Pract. 2008 March;57(3):192-194

By

Michael G. Mercado, MD

Sandra L. Kimmer, MD, MPH

John R. Holman, MD, MPH

Gerri Wanserski, MA

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References

1. Althof SE. Prevalence, characteristics and implications of premature ejaculation/rapid ejaculation. J Urol 2006;175(3 pt 1):842-848.

2. Ahlenius S, Larsson K, Svensson L, et al. Effects of a new type of 5-HT receptor agonist on male rat sexual behavior. Pharmacol Biochem Behav 1981;15:785-792.

3. Waldinger MD, Berendsen HH, Blok BF, Olivier B, Holstege G. Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res 1998;92:111-118.

4. Waldinger MD, Olivier B. Utility of selective serotonin reuptake inhibitors in premature ejaculation. Curr Opin Investig Drugs 2004;5:743-747.

5. Waldinger MD, Hengeveld MW, Zwinderman AH. Paroxetine treatment of premature ejaculation: a double-blind, randomized, placebo-controlled study. Am J Psychiatry 1994;151:1377-1379.

6. Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B. Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis. Int J Impot Res 2004;16:369-381.

7. Busato W, Galindo CC. Topical anaesthetic use for treating premature ejaculation: a double-blind, randomized, placebo-controlled study. BJU Int 2004;93:1018-1021.

8. Atan A, Basar MM, Tuncel A, Ferhat M, Agras K, Tekdogan U. Comparison of efficacy of sildenafil-only, sildenafil plus topical EMLA cream, and topical EMLA-cream-only in treatment of premature ejaculation. Urology 2006;67:388-391.

9. Atikeler MK, Gecit I, Senol FA. Optimum usage of prilocaine-lidocaine cream in premature ejaculation. Andrologia 2002;34:356-359.

10. McMahon CG, McMahon CN, Leow LJ, Winestock CG. Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review. BJU Int 2006;98:259-272.

11. McMahon CG, Stuckey BG, Andersen M, et al. Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation. J Sex Med 2005;2:368-375.

12. Li X, Zhang SX, Cheng HM, Zhang WD. Clinical study of sildenafil in the treatment of premature ejaculation complicated by erectile dysfunction [in Chinese]. Zhonghua Nan Ke Xue 2003;9:266-269.

13. Montague DK, Jarow J, Broderick GA, et al. AUA Erectile Dysfunction Guideline Update Panel. AUA guideline on the pharmacologic management of premature ejaculation. J Urol 2004;172:290-294.

14. Richardson D, Goldmeier D, Green J, Lamba H, Harris , JR. BASHH Special Interest Group for Sexual Dysfunction. Recommendations for the management of premature ejaculation: BASHH Special Interest Group for Sexual Dysfunction. Int J STD AIDS 2006;17:1-6.

EVIDENCE-BASED ANSWER

Antidepressants—specifically clomipramine, fluoxetine, paroxetine, and sertraline—are best and have been shown to improve symptoms of premature ejaculation (strength of recommendation [SOR]: A, meta-analysis of randomized controlled trials [RCTs]). The topical application of prilocaine-lidocaine cream (trade name EMLA) improves intravaginal ejaculatory latency time (IELT), but penile numbness and loss of erection may occur (SOR: B, based on several small RCTs).

There is no evidence that phosphodiesterase type 5 (PDE5) inhibitors—such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)—decrease instances of premature ejaculation in otherwise healthy men. There is limited evidence, however, that PDE5 inhibitors reduce symptoms of premature ejaculation for men with concomitant erectile dysfunction (SOR: B, systematic review of RCTs of variable quality).

Clinical commentary

Overcome any reluctance to discuss premature ejaculation
Vincent Lo, MD
San Joaquin Family Medicine Residency, French Camp, Calif

Family physicians should be comfortable diagnosing and treating premature ejaculation because of their unique and long-term relationship with the patient. But that’s not always the case. Premature ejaculation is underdiagnosed and undertreated because of a reluctance to discuss it, by both patient and physician.

A thorough medical history, including pertinent sexual history and physical examination, can often establish the diagnosis of premature ejaculation. Effective treatments can improve sexual satisfaction and quality of life for both the men and their partners.

Evidence summary

Premature ejaculation is the most common male sexual dysfunction, but there is no universally accepted definition or validated screening instrument. The pathophysiology and etiology remain incompletely understood.¹ Based on surveys, prevalence rates for premature ejaculation are approximately 20% to 30%.¹

FAST TRACK

SSRIs significantly delay ejaculation compared with placebo

Studies in male rats have demonstrated that serotonin with various 5-HT receptor subtypes are involved in the ejaculatory process.² Based on these studies, it’s been suggested that lifelong premature ejaculation is a neurobiological phenomenon related to decreased central serotonergic neurotransmission, 5-HT_2c receptor hyposensitivity, or 5-HT_1a receptor hypersensitivity.³

Antidepressants delay ejaculation

The introduction of selective serotonin reuptake inhibitors (SSRIs) revolutionized the treatment of premature ejaculation.⁴ In 1994, the first study of SSRIs in men with premature ejaculation demonstrated a delaying effect with paroxetine (Paxil).⁵ Since that time, SSRIs have been repeatedly investigated for their propensity to delay ejaculation. Certain SSRIs and the tricyclic antidepressant clomipramine (Anafranil) have become the agents of choice for the treatment of premature ejaculation.⁶

A meta-analysis⁶ of 35 treatment studies with serotonergic antidepressants from 1943 to 2003 shows that, despite major differences in design and drug dosing, clomipramine, fluoxetine (Prozac), paroxetine, and sertraline (Zoloft) significantly delay ejaculation compared with placebo. The percentage increase in IELT was the primary outcome measured. The rank order of efficacy was:

paroxetine (1492% IELT increase; 95% confidence interval [CI], 918–2425)
sertraline (790% IELT increase; 95% CI, 532–1173)
clomipramine (512% IELT increase; 95% CI, 234–1122)
fluoxetine (295% IELT increase; 95% CI, 172–506).⁶

Of the 35 studies used in the previous meta-analysis, 8 studies (N=263) were prospective, double-blind, real-time stopwatch studies that were separately analyzed in a subsequent meta-analysis. These 8 studies evaluated clomipramine, fluoxetine, paroxetine, sertraline, citalopram (Celexa), fluvoxamine (Luvox), mirtazapine (Remeron), and nefazodone (Serzone) against placebo. Paroxetine (783% IELT increase, 95% CI, 499–1228), clomipramine (360% IELT increase, 95% CI, 200–435), sertraline (313%, 95% CI, 161–608), and fluoxetine (295%, 95% CI, 200–435) exerted a significant delay in the IELT compared with placebo.⁶

FAST TRACK

Topical prilocaine/lidocaine cream (EMLA) improves intravaginal ejaculatory latency time

EMLA cream: “Improvement” and “cure” seen

EMLA cream, a topical anesthetic, has been evaluated as a treatment option for premature ejaculation. One double-blinded RCT⁷ (N=29) showed significant improvement in the IELT (measured by stopwatch by the subject’s partner) from baseline compared with placebo (8.45 min vs 1.95 min; P<.001) at 2 months.

Evidence-based answers from the Family Physicians Inquiries Network