A New Way to Treat Overactive Bladder

The first new drug to treat overactive bladder in decades

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An estimated 33 million Americans live with overactive or "leaky" bladders: an uncomfortable and potentially embarrassing condition which is hard to treat. For more than three decades, there have been no new drugs to treat this condition. However in 2012, the FDA approved mirabegron (Myrbetriq) to treat overactive bladder.  

Overactive bladder or urge incontinence refers to overactivity of the detrusor muscle.

The detrusor muscle is part of the bladder wall, and when it's overactive, it contracts too much, and leakage of urine ensues.  

Overactive bladder is the most common form of urinary incontinence. Women with this condition feel an intense urge to urinate followed by uncontrollable leakage. Men experience similar symptoms, but leakage can be compromised by benign prostatic hypertrophy or urethral obstruction. 

Before the introduction of mirabegron, overactive bladder was treated using pelvic floor (Kegel) exercises and biofeedback; lifestyle modification, such as weight loss or caffeine avoidance; onabotulinumtoxinA or Botox injection into the detrusor muscle; and antimuscarinic drugs such as tolterodine (Detrol), oxybutynin (Urotrol) and solifenacin.

Antimuscarinic drugs have numerous adverse effects which make them intolerable to many people who take them. These adverse effects include dry mouth, constipation, blurred vision and cognitive disturbance.

(This toxidrome is often associated with the saying,  "Blind as a bat, mad as a hatter, red as a beet, hot as Hades, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone.")

Mirabegron is much more specific in its actions than antimuscarinic drugs usually used to treat overactive bladder.

MIrabegron also doesn't oppose the sympathetic nervous system as pervasively as antimuscarinic drugs do. Specifically, mirabegron is a beta-3 adrenergic agonist which specifically targets the receptors in the detrusor muscle (97 percent of beta-3 mRNA produced by the body is produced in the detrusor muscle). 

Unlike antimuscarinic drugs, mirabegron doesn't interfere with beta-1 and beta-2 receptors in other parts of the body. In other words, whereas antimuscarinic drugs have the precision of a machete and effect various organ systems, mirabegron is more akin to a surgeon's scalpel and affects mostly the bladder.

During Phase II and Phase III clinical trials, mirabegron was tested in more than 10,500 participants. In these studies, participants showed a decrease in the volume of urine voided, number of urgency episodes, number of incontinence episodes and number of nocturia episodes (nighttime incontinence)

Although mirabegron has proven much more tolerable than antimuscarinic drugs, during clinical trials, some people still experienced adverse effects including:

  • increased blood pressure
  • urinary tract infection
  • abdominal pain
  • elevated heart rate
  • elevated blood pressure
  • cold-like symptoms

Although increases in heart rate and blood pressure secondary to the use of mirabergron are modest, some experts worry about the cardiac effects of mirabergron. Specifically to date, there has been little research on mirabegron's use in adults older than 70 years old; thus, some physicians don't prescribe this drug to older patients with heart and kidney problems. Furthermore, it's still unclear whether mirabegron is effective when used with antimuscarinic drugs.

In addition to being more tolerable than antimuscarinic drugs in clinical trials, mirabegron has also proven to improve quality of life measures among people with overactive bladder. Overall, mirabegron appears to be a promising new way to treat overactive bladder especially among people who can't tolerate antimuscarinic drugs. Nevertheless, more research needs to be done before we exactly understand its nuances of treatment with mirabegron.

Selected Sources

Article titled "Mirabegron in Overactive Bladder: A Review of Efficacy, Safety, and Tolerability" by CR Chapple published in Neurourology and Urodynamics in 2013.  Accessed on 8/28/2015.

Harper G, Johnston C, Landefeld C. Geriatric Disorders. In: Papadakis MA, McPhee SJ, Rabow MW. eds. Current Medical Diagnosis & Treatment 2015. New York, NY: McGraw-Hill; 2014. Accessed August 28, 2015.

Article titled "Patient-Reported Outcomes With the b3-Adrenoceptor Agonist Mirabegron in a Phase III Trial in Patients With Overactive Bladder" by V Khullar and co-authors published in Neurourology and Urodynamics in 2015.  Accessed on 8/28/2015.






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