Is Mirabegron (beta-3 adrenergic agonist) effective for treating Premature Ejaculation Disorder (PEDs)?

Mirabegron for Premature Ejaculation Disorder

Mirabegron is not recommended for treating premature ejaculation disorder (PE) as there is no evidence supporting its efficacy for this condition. Current guidelines from the European Association of Urology (EAU) and American Urological Association (AUA) do not include mirabegron among recommended treatments for PE 1, 2.

First-Line Treatments for Premature Ejaculation

The following treatments have demonstrated efficacy for PE:

Pharmacological Options:

1. Selective Serotonin Reuptake Inhibitors (SSRIs):

   • Daily use: paroxetine (10-40 mg/day), sertraline (25-200 mg/day), fluoxetine (5-20 mg/day) 1, 2
   • On-demand use: paroxetine (20 mg 3-4 hours pre-intercourse), sertraline (50 mg 4-8 hours pre-intercourse) 1, 2

2. Dapoxetine (specifically approved for PE in many countries except USA):

   • Available in 30 mg and 60 mg doses
   • Shows 2.5-3.0 fold increases in IELT (Intravaginal Ejaculatory Latency Time)
   • Up to 4.3-fold increase in patients with baseline IELT <30 seconds 1

3. Topical Anesthetics:

   • Lidocaine/prilocaine cream or spray
   • Applied 20-30 minutes before intercourse
   • Can increase IELT up to 6.3-fold over 3 months 1, 2

4. Tramadol:

   • Shows up to 2.5-fold IELT increase
   • Use with caution due to addiction potential 1

Other Considerations:

• PDE5 inhibitors may not significantly improve IELT but can enhance confidence and sexual satisfaction 1
• Combination of PDE5 inhibitors with SSRIs shows superior results to SSRI monotherapy 1
• α1-adrenoceptor antagonists (alfuzosin, terazosin) have shown modest efficacy but are not first-line treatments 1, 2

Why Not Mirabegron?

Mirabegron is a β3-adrenoceptor agonist approved for treating overactive bladder 1. However:

1. No clinical evidence supports its use for PE in any of the current guidelines 1, 2
2. The mechanism of action (stimulation of β3-adrenergic receptors in the bladder) has no established relationship to ejaculatory control
3. Network meta-analyses of PE treatments do not include mirabegron among effective options 3
4. Even for its approved indication (overactive bladder), mirabegron shows limited long-term persistence (39.4% at 12 months) 4

Treatment Algorithm for PE

1. Rule out erectile dysfunction (ED) - If ED is present, treat it first or concurrently, as PE may improve once ED is effectively managed 2

2. First-line treatment options:

   • For lifelong PE: Pharmacotherapy is recommended as first-line 1

     • Approved options: dapoxetine (on-demand) or lidocaine/prilocaine spray
     • Off-label options: daily SSRIs or on-demand tramadol

   • For acquired PE: Address underlying causes first, then follow same treatment approach as lifelong PE

3. If first-line treatment fails:

   • Consider combination therapy (e.g., SSRI + PDE5 inhibitor) 1
   • Consider α1-adrenoceptor antagonists 1, 2

Important Caveats

• Most medications used for PE (except dapoxetine in some countries) are used off-label 1
• SSRIs should be started at the lowest effective dose to minimize side effects 1
• Common side effects of SSRIs include dry mouth, nausea, drowsiness, and reduced libido 1, 2
• Topical anesthetics may cause genital numbness and potentially transfer to partner 1
• Treatment discontinuation rates for dapoxetine increase over time (up to 90% at 2 years), mainly due to cost (29.9%) and disappointment with the on-demand nature (25%) 1

In conclusion, while various treatment options exist for PE with demonstrated efficacy, mirabegron is not among them and should not be considered for this indication based on current evidence.