Paroxetine (Paxil®) for Premature Ejaculation
Paroxetine (Paxil®) is an antidepressant, a selective serotonin reuptake inhibitor (SSRI). Paroxetine has been approved by the U.S. FDA as a safe and effective treatment for:
- Generalized Anxiety Disorder (GAD)
- Social Anxiety Disorder
- Panic Disorder
- Obsessive Compulsive Disorder (OCD)
- Posttraumatic Stress Disorder (PTSD)
- Hot flashes
Efficacy for Premature ejaculation
Premature ejaculation (PE, rapid ejaculation) is ejaculation occurring on or shortly after vaginal penetration and before the person wishes it. Premature ejaculation usually has a physiological basis.
Currently no medications are FDA-approved for Premature ejaculation. However, paroxetine is recommended for the management of PE by American Urological Association7 and International Society of Sexual Medicine6 guidelines.
Paroxetine been shown to cause ejaculation-delaying side effects in multiple clinical trials13. These findings have led to the use of paroxetine in the treatment of premature ejaculation in men. Several clinical trials have successfully tested paroxetine effectiveness for prolonging intravaginal ejaculatory latency time (IELT)9. Premature ejaculation not responding to paroxetine therapy can be managed with combination of paroxetine and pindolol14.
Head-to-head comparisons between paroxetine and other medications provide imortant data on relative efficacy and safety of different treatments:
- Paroxetine in combination with sildenafil (Viagra) provides significantly greater intercourse satisfaction in men with premature ejaculation8 than paroxetine alone. This combination may be particularly effective for men with erectile dysfunction and secondary PE.
- Tramadol "on-demand" is better than paroxetine "on-demand" for prolonging the ejaculatory latency time 5. However, paroxetine daily therapy is more effective than tramadol "on-demand" 10.
- Daily use of paroxetine is more effective than daily use of dapoxetine in prolonging ejaculatory latency time and promoting intercourse satisfaction in men with premature ejaculation 11. Also, paroxetine is better tolerated than dapoxetine 17.
- Paroxetine is more effective than acupuncture 15.
Dosage for Premature ejaculation
Paroxetine can be taken either on a daily basis or “on demand” before sexual activity7.
“On demand” regimen: 20 mg 4 hours before intercourse.
Daily regimen: 10-40 mg daily. Unlike episodic therapy, daily use allows spontaneous sexual activity.
Duration of therapy: treatment most likely will be needed on a continuing basis.
- Improves intravaginal ejaculatory latency time and sexual satisfaction 11
- Recommended by the AUA7 and ISSM6 guidelines
- Strong ejaculation-retarding properties -- treatment failure is rare 16.
- Slow onset of action (5 hours) makes paroxetine inconvenient for “on-demand” use
- Adverse effects on sperm 3
- Patients are often reluctant to treat PE with antidepressant paroxetine 12
- Most withdrawal issues of the SSRI's, may cause severe discontinuation syndrome 1
- Highest rate of sexual side effects 2
- Potential for weight gain higher than with other SSRIs4
- Potential for drug interactions.
Paroxetine alternatives for PE:
- SSRIs -- fluoxetine, sertraline7
- Tricyclic antidepressant clomipramine (Anafranil®)
- Topical local anaesthetics (lidocaine, prilocaine)
- Condoms containing a local anaesthetic
- PDE-5 inhibitors -- sildenafil (Viagra®)
- Absorption: Completely absorbed via oral administration. Food does not reduce its absorption.
- Metabolism: Paroxetine undergoes extensive first-pass metabolism in the liver. At least 85% of paroxetine is oxidized to a catechol intermediate that undergoes subsequent methylation and conjugation to clinically inactive glucuronide and sulfate metabolites. Metabolism is accomplished in part by cytochrome P450 2D6 (CYP2D6). Saturation of this enzyme at clinical doses contributes the nonlinear kinetics observed with increasing dose and duration of paroxetine treatment. The elderly are more susceptible to the saturation of hepatic metabolic capacity, leading to increased plasma concentrations of paroxetine at lower-than-usual doses.
- Elimination half-life: 24 hours
- Excretion: Urinary excretion of unchanged paroxetine is generally less than 2% of dose whilst that of metabolites is about 64% of dose. About 36% of the dose is excreted in faeces, probably via the bile, of which unchanged paroxetine represents less than 1% of the dose. Thus paroxetine is eliminated almost entirely by metabolism.
Mechanism of action
Paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake. Paroxetine inhibits the reuptake of serotonin at the neuronal membrane, enhances serotonergic neurotransmission by reducing turnover of the neurotransmitter, therefore it prolongs its activity at synaptic receptor sites and potentiates 5-HT in the CNS. Paroxetine is potent in its ability to inhibit 5-HT reuptake. Paroxetine very weakly inhibits reuptake of norepinephrine and dopamine.
Reviews, Discussions, Forums
- 1. Stahl MM, Lindquist M, Pettersson M, Edwards IR, Sanderson JH, Taylor NF, Fletcher AP, Schou JS. Withdrawal reactions with selective serotonin re-uptake inhibitors as reported to the WHO system. Eur J Clin Pharmacol. 1997;53(3-4):163-9. PubMed
- 2. Montejo AI, Llorca G, Izquierdo JA, Ledesma A, Bousono M, Calcedo A, Carrasco JL, et al. Sexual dysfunction secondary to SSRIs. Actas luso-espanolas de neurologia, psiquiatria ciencias afines. 1996 Nov-Dec;24(6):311-21.
- 3. Tanrikut C, Feldman AS, Altemus M, Paduch DA, Schlegel PN. Adverse effect of paroxetine on sperm. Fertil Steril. 2010;94:1021–1026. PubMed
- 4. Fava M. Weight gain and antidepressants. J Clin Psychiatry.
2000;61 Suppl 11:37-41. PubMed
- 5. Tarek A. Gameel, Ahmad M. Tawfik, Mohamed O. Abou-Farha, Mohamed G. Bastawisy, Mohamed A. El-Bendary, Abd El-Naser El-Gamasy. On-demand use of tramadol, sildenafil, paroxetine and local anaesthetics for the management of premature ejaculation: A randomised placebo-controlled clinical trial. Arab Journal of Urology Volume 11, Issue 4, Dec. 2013
- 6. International Society for Sexual Medicine. Pharmacologic Treatment of Premature Ejaculation .Updated 2014 ISSM
- 7. American Urological Association Guideline on Premature Ejaculation AUA
- 8. Salonia A., Maga T., Colombo R., Scattoni V., Briganti A., and Cestari A. A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. J Urol, 168: 2486, 2002. PubMed
- 9. McMahon CG, Touma K. Treatment of premature ejaculation with paroxetine hydrochloride. Int J Impot Res. 1999 Oct;11(5):241-245; discussion 246. PubMed
- 10. Alghobary M, El-Bayoumy Y, Mostafa Y, Mahmoud el-HM, Amr M. Evaluation of tramadol on demand vs. daily paroxetine as a long-term treatment of lifelong premature ejaculation. J Sex Med. 2010 Aug;7(8):2860-7. PubMed
- 11. Safarinejad MR. Comparison of dapoxetine versus paroxetine in patients with premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study. Clin Neuropharmacol. 2006 Sep-Oct;29(5):243-52. PubMed
- 12. Salonia A, Rocchini L, Sacca' A, et al. Acceptance of and discontinuation rate from paroxetine treatment in patients with lifelong premature ejaculation. J Sex Med. 2009 Oct;6(10):2868-77. PubMed
- 13. Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B. Effect of SSRI antidepressants on ejaculation. J Clin Psychopharmacol. 1998 Aug;18(4):274-81. PubMed
- 14. Safarinejad MR. Once-daily high-dose pindolol for paroxetine-refractory premature ejaculation: a double-blind, placebo-controlled and randomized study. J Clin Psychopharmacol. 2008 Feb;28(1):39-44. PubMed
- 15. Sunay D, Sunay M, Aydoğmuş Y, Bağbancı S, Arslan H, Karabulut A, Emir L. Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial. Eur Urol. 2011 May;59(5):765-71. PubMed
- 16. Janssen PK, Touw D, Schweitzer DH, Waldinger MD. Nonresponders to daily paroxetine and another SSRI in men with lifelong premature ejaculation: a pharmacokinetic dose-escalation study for a rare phenomenon. Korean J Urol. 2014 Sep;55(9):599-607. PubMed
- 17. Jern P, Johansson A, Piha J, Westberg L, Santtila P. Antidepressant treatment of premature ejaculation: discontinuation rates and prevalence of side effects for dapoxetine and paroxetine in a naturalistic setting. Int J Impot Res. 2015 Mar-Apr;27(2):75-80. PubMed
- Generic name: Paroxetine
- Trade names: Paxil, Paxtine, Brisdelle
- Pharmacologic category: Selective serotonin reuptake inhibitor
- FDA approved: December 29, 1992
- Manufacturer: GlaxoSmithKline
- Habit forming? No
- Pregnancy risk factor: D