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Medication

Medication Summary

The goals of pharmacotherapy are to improve overactive bladder (OAB) symptoms, reduce morbidity, and prevent complications. Anticholinergics are the first-line agents used to treat OAB. Other treatments approved for use in OAB include the beta3-receptor agonists mirabegron and vibegron and detrusor injections of onabotulinumtoxinA. Women with genital atrophy may benefit from topical estrogen therapy. In select cases of refractory OAB, tricyclic antidepressants may be helpful.

Class Summary

Anticholinergics inhibit the binding of acetylcholine to the muscarinic receptors in the detrusor, thereby suppressing involuntary bladder contractions. This results in an increase in bladder volume voided and a decrease in micturition frequency, sensation of urgency, and number of urge incontinence episodes.

Angioedema of the face, lips, tongue, and/or pharynx has been noted in several of these agents in postmarketing surveillance, including solifenacin, darifenacin, trospium chloride, and fesoterodine. Warnings are noted in the prescribing information for these agents, and if patients experience such symptoms they should seek emergency care.

Tolterodine (Detrol, Detrol LA)

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Tolterodine is a nonspecific competitive muscarinic receptor antagonist for OAB. However, it differs from other anticholinergic types in that it has selectivity for urinary bladder over salivary glands. Tolterodine exhibits a high specificity for muscarinic receptors. It has minimal activity or affinity for other neurotransmitter receptors and other potential targets, such as calcium channels.

Oxybutynin (Gelnique)

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Oxybutynin inhibits the action of acetylcholine on smooth muscle and has a direct antispasmodic effect on smooth muscles. This, in turn, increases bladder capacity and decreases uninhibited contractions. Oxybutynin is relatively M3, M1 specific. Indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

Trospium

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Trospium is a nonspecific quaternary ammonium compound that is excreted intact in the urine and thus is not dependent on the cytochrome P450 system for its metabolism. Being a quaternary amine, it is less likely to penetrate the blood-brain barrier. It antagonizes acetylcholine's effect on muscarinic receptors. Its parasympathetic effect reduces smooth-muscle tone in the bladder. Trospium is indicated to treat symptoms of OAB (eg, urinary incontinence, urgency, frequency). It is available as a single dose, and the extended release formulation should not be taken at night.

Darifenacin (Enablex)

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Darifenacin is an extended-release product that elicits competitive muscarinic receptor antagonistic activity. It reduces bladder smooth-muscle contractions. It has high affinity for the M3 receptors and less affinity for other muscarinic receptors. Darifenacin is indicated for OAB with symptoms of urge incontinence, urgency and frequency. Swallow it whole; do not chew, divide, or crush it.

Solifenacin (VESIcare)

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Solifenacin is a competitive muscarinic-receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency Also, indicated in combination with mirabegron for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Fesoterodine (Toviaz)

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Fesoterodine is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. After oral administration, fesoterodine is rapidly and extensively hydrolyzed by nonspecific esterases to its active metabolite, 5-hydroxymethyl tolterodine, which is responsible for the antimuscarinic activity of fesoterodine.

Class Summary

These agents elicit a direct inhibition of afferent nerve firing independent of the relaxing effects on bladder smooth muscle.

Mirabegron (Myrbetriq)

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Mirabegron is a beta-3 adrenergic receptor agonist that causes relaxation of the detrusor smooth muscle of the urinary bladder and increases bladder capacity. It is indicated for overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Also, indicated in combination with the muscarinic antagonist solifenacin for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Vibegron (Gemtesa)

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Vibegron is a selective beta3-adrenergic receptor agonist that increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling. It is indicated for symptoms of urge urinary incontinence, urgency, and urinary frequency associated with OAB.

Class Summary

Detrusor injections of botulinum neurotoxin type A may be considered for adults with OAB who cannot use or do not adequately respond to anticholinergic medication.

OnabotulinumtoxinA (Botox)

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OnabotulinumtoxinA is a neurotoxin derived from Clostridium botulinum. It prevents ACh release from presynaptic membrane, resulting in a temporary calming effect of muscle contractions by blocking the transmission of nerve impulses. The procedure involves multiple injections of a small amount of botox into the muscle of the bladder. The effects are not permanent and thus periodic repeat injections are often needed to maintain response. Urinary retention is a side effect of the injections and thus individuals must be willing to catheterize intermittently until the retention resolves.

Class Summary

Tricyclic antidepressants that have been used to treat OAB include imipramine and doxepin. Some agents of this type may decrease bladder contractility. They are not indicated for the first-line treatment of OAB.

Imipramine (Tofranil)

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Imipramine is useful in facilitating urine storage. It decreases bladder contractility and increases outlet resistance.

Doxepin

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Doxepin increases the concentration of serotonin and norepinephrine in the central nervous system (CNS) by inhibiting their reuptake by presynaptic neuronal membrane. These effects are associated with a decrease in symptoms of depression.

Class Summary

Hormones are used to treat OAB in association with atrophic urethritis and are not recommended as first-line therapies for OAB.

Estrogen (Premarin)

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Detrusor overactivity can be associated with atrophic urethritis; topical application of estrogen vaginal cream should be considered in women with symptomatic atrophic urethritis/vaginits.

Questions

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Zhang J, Cheng W, Cai M. Effects of electroacupuncture on overactive bladder refractory to anticholinergics: a single-blind randomised controlled trial. Acupunct Med. 2015 Jun 3. [QxMD MEDLINE Link].
Thiagamoorthy G, Cardozo L, Robinson D. Current and future pharmacotherapy for treating overactive bladder. Expert Opin Pharmacother. 2016 Jul. 17 (10):1317-25. [QxMD MEDLINE Link].
Majima T, Funahashi Y, Takai S, Goins WF, Gotoh M, Tyagi P, et al. Herpes Simplex Virus Vector-Mediated Gene Delivery of Poreless TRPV1 Channels Reduces Bladder Overactivity and Nociception in Rats. Hum Gene Ther. 2015 Nov. 26 (11):734-42. [QxMD MEDLINE Link]. [Full Text].
Robinson D, Hanna-Mitchell A, Rantell A, Thiagamoorthy G, Cardozo L. Are we justified in suggesting change to caffeine, alcohol, and carbonated drink intake in lower urinary tract disease? Report from the ICI-RS 2015. Neurourol Urodyn. 2017 Apr. 36 (4):876-881. [QxMD MEDLINE Link].
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Media Gallery

Communication between urothelium and suburothelium. ACh—acetylcholine; ATP—adenosine triphosphate; M2—muscarinic receptor subtype 2; M3—muscarinic receptor subtype 3; NO—nitric oxide; P2X1—purinergic receptor P2X, ligand-gated ion channel 1; P2X3—purinergic receptor P2X, ligand-gated ion channel 3; sGC—soluble guanyl cyclase; VR1—vanilloid receptor 1.
Overactive bladder (OAB) and quality of life (QoL). Short Form-36 (SF-36). Reprinted with permission from Blackwell.
Total community and institutional costs of overactive bladder (OAB) (in millions of dollars). UTI—urinary tract infection (UTI). Reprinted with permission from Elsevier.

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Author

Pamela I Ellsworth, MD Chief, Division of Pediatric Urology, Nemours Children's Hospital; Professor of Urology, University of Central Florida College of Medicine

Pamela I Ellsworth, MD is a member of the following medical societies: American Urological Association, Massachusetts Medical Society, Society for Fetal Urology, Society of Women in Urology

Disclosure: Nothing to disclose.

Coauthor(s)

Wellman W Cheung, MD, FACS Clinical Professor, Department of Urology and Department of Obstetrics and Gynecology, State University of New York Downstate Medical School

Wellman W Cheung, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Chinese American Medical Society, Endourological Society, American Urogynecologic Society, International Urogynaecology Association, Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction

Disclosure: Received grant/research funds from Astallas for pi.

Aneela Naureen Hussain, MD, MBBS, FAAFM Consulting Staff, Department of Family Medicine, South Texas Veterans Health Care System in San Antonio

Aneela Naureen Hussain, MD, MBBS, FAAFM is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, American Medical Women's Association, Medical Society of the State of New York, Society of Teachers of Family Medicine

Disclosure: Nothing to disclose.

Nadia Hasan Khan, MD Clinical Assistant Instructor, Staff Physician, Department of Family Practice, State University of New York Downstate Medical Center

Nadia Hasan Khan, MD is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Miriam T Vincent, MD, PhD, JD Professor and Chair, Department of Family Practice, State University of New York Downstate Medical Center

Miriam T Vincent, MD, PhD, JD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Bar Association, American Bar Association, American Academy of Family Physicians, Sigma Xi, The Scientific Research Honor Society, Society of Teachers of Family Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Edward David Kim, MD, FACS Professor of Urology, Department 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 Society for Reproductive Medicine, American Urological Association, Sexual Medicine Society of North America, Society for Male Reproduction and Urology, Society for the Study of Male Reproduction, Tennessee Medical Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Endo, Antares.

Additional Contributors

Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoscopic and Robotic Surgeons, Society of University Urologists

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Endourological Society Board of Directors; President Elect North Central Section of the American Urological Association<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cook Medical.

LiAnn N Handel, MD Resident Physician, Department of Urology, Rhode Island Hospital, The Warren Alpert Medical School of Brown University

LiAnn N Handel, MD is a member of the following medical societies: American Urological Association

Disclosure: Nothing to disclose.

Overactive Bladder Medication

Medication Summary

Anticholinergics

Class Summary

Tolterodine (Detrol, Detrol LA)

Tolterodine (Detrol, Detrol LA)

Oxybutynin (Gelnique)

Oxybutynin (Gelnique)

Trospium

Trospium

Darifenacin (Enablex)

Darifenacin (Enablex)

Solifenacin (VESIcare)

Solifenacin (VESIcare)

Fesoterodine (Toviaz)

Fesoterodine (Toviaz)

Beta3-adrenergic agonists

Class Summary

Mirabegron (Myrbetriq)

Mirabegron (Myrbetriq)

Vibegron (Gemtesa)

Vibegron (Gemtesa)

Neuromuscular Blockers, Botulinum Toxins

Class Summary

OnabotulinumtoxinA (Botox)

OnabotulinumtoxinA (Botox)

Tricyclic antidepressants

Class Summary

Imipramine (Tofranil)

Imipramine (Tofranil)

Doxepin

Doxepin

Hormones

Class Summary

Estrogen (Premarin)

Estrogen (Premarin)

Overactive Bladder Medication

Medication Summary

Anticholinergics

Class Summary

Tolterodine (Detrol, Detrol LA)

Oxybutynin (Gelnique)

Trospium

Darifenacin (Enablex)

Solifenacin (VESIcare)

Fesoterodine (Toviaz)

Beta3-adrenergic agonists

Class Summary

Mirabegron (Myrbetriq)

Vibegron (Gemtesa)

Neuromuscular Blockers, Botulinum Toxins

Class Summary

OnabotulinumtoxinA (Botox)

Tricyclic antidepressants

Class Summary

Imipramine (Tofranil)

Doxepin

Hormones

Class Summary

Estrogen (Premarin)

References

Tables

Contributor Information and Disclosures

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