Medication

A number of medications are available that increase sphincter or pelvic muscle strength or relax the bladder, improving the ability to hold more urine. Medications are prescribed for all kinds of incontinence, but they are generally most helpful for urge incontinence.

Medications Specifically for Urge Incontinence

Anticholinergics. Anticholinergics work in the following ways:

• Inhibit the involuntary contractions of the bladder
• Increase capacity of the bladder
• Delay the initial urge to void

A major 2003 analysis reported that these drugs produce small but significant improvements. However, the medications have not been rigorously compared with behavioral methods, such as bladder training and Kegel exercises, which are very effective for most cases of urge incontinence. Anticholinergics can have distressing side effects, notably dry mouth.

Anticholinergics include:

• Propantheline (ProBanthine). This drug used to be the most commonly prescribed anticholinergic, but has been largely replaced by newer anticholinergics with fewer side effects.
• Oxybutynin (Ditropan, Oxytrol)
• Tolterodine (Detrol)
• Hyoscyamine (Levbid, Cystospaz)

Extended-release versions of oxybutynin (Ditropan XL) and tolterodine (Detrol LA) are proving to be especially effective. They improve continence and have fewer adverse effects than short-acting forms. In a major 2003 comparison study of the extended release drugs, oxybutynin was slightly better than tolterodine, but dry mouth was reported more often. A skin patch form of oxybutynin (Oxytrol) is now available. It appears to work better and have fewer side effects, such as dry mouth and constipation, than the pill form.

Oxybutynin may cause more severe central nervous side effects than previously thought, especially for children and older adults. In 2007, the FDA reviewed 202 cases of oxybutynin-related central nervous system problems. Hallucinations were reported in 27% of pediatric cases and 25% of cases involving adults age 60 and older. Eleven percent of adults age 17 – 59 years experienced hallucinations. The FDA recommends that doctors monitor patients for these symptoms.

According to one study of tolterodine, the drug also improved quality of life. A 2006 study reported that tolterodine is helpful for men with overactive bladder and urge urinary incontinence. A 2006 study, published in the Journal of the American Medical Association, suggested that a combination of tolterodine and the alpha-blocker drug tamsulosin (Flomax) may work better than either drug alone for men with lower urinary tract symptoms, including overactive bladder.

Overactive Bladder Treatments for Children

• Oxybutynin (Ditropan X) is approved for pediatric use in children ages 6 and older. The recommended dose is 5 mg once a day. A 2006 study suggested that children who have fewer episodes of daytime wetting may benefit most from this drug.
• A 2004 analysis found that tolterodine is also effective and well tolerated in children with urinary symptoms due to overactive bladder.

Side effects of anticholinergic drugs include:

• Dry eyes (a particular problem for people who wear contact lenses; patients who wear contacts may wish to start with low doses of medication and gradually build up)
• Dry mouth
• Headache
• Constipation
• Rapid heart rate
• Confusion, forgetfulness, and possible worsening of mental function, particularly in older people with dementia, such as those with Alzheimer's disease
• Hallucinations, possibly, especially for children and older adults
• Glaucoma, in rare cases

Antispasmodics. Antispasmodic drugs help relax the bladder muscle and are used for urge incontinence. Before bladder relaxants are prescribed, a thorough evaluation for obstructions in the ureter must be performed to avoid excessive urine retention.

Flavoxate (Urispas) and dicyclomine (Bentyl), the most common antispasmodics, have been used for years, although studies suggest that Urispas has very little benefit for the majority of patients with urge incontinence. The drugs also have anticholinergic properties. In May 2004, the FDA approved a new antispasmodic, trospium chloride (Sanctura), for the treatment of overactive bladder with symptoms or urge incontinence.

Possible side effects reported with use of antispasmodic drugs include:

• Weakness
• Dizziness
• Drowsiness
• Hallucinations
• Insomnia
• Dry mouth
• Impotence
• Restlessness

M3 selective receptor antagonists. In 2004, the FDA approved darifenacin (Enablex) for treatment of urge incontinence and overactive bladder. Some clinical trials suggested that darifenacin could help reduce weekly incontinence episodes by 83%. The drug’s most common side effects are dry mouth and constipation. For elderly patients, darifenacin may have less negative effects on memory than oxybutynin.

Capsaicin and Analogs. Studies have reported beneficial effects from instillation of capsaicin, a component of hot red chili peppers, into the bladder of people with hyperactive and hypersensitive bladders. Temporary adverse effects, however, can be distressing. A capsaicin analog called resiniferatoxin may be more effective than capsaicin and have fewer side effects.

Alpha-Blockers. Alpha-blockers are drugs that relax smooth muscles and improve urine flow. They are useful for men with benign prostatic hyperplasia who also have urge incontinence. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Xatral). Tamsulosin may be particularly beneficial. A 2006 study published in the Journal of the American Medical Association reported that the combination of tamsulosin and tolterodine works better than either drug alone for men with moderate-to-severe lower urinary tract symptoms, including overactive bladder. Men in the study were age 40 years and older and had symptoms related to overactive bladder and benign prostatic hyperplasia.

Medications Specifically for Stress Incontinence

Alpha-Adrenergic Agonists. Alpha-adrenergic agonists are used to strengthen the smooth muscle that opens and closes the internal sphincter. They include ephedrine and pseudoephedrine, which are common ingredients in numerous over-the-counter decongestants and appetite suppressants.

Such drugs may be helpful for patients with mild stress incontinence not caused by nerve damage, although evidence on their benefits is weak. They also can have significant side effects, particularly ephedrine. In fact, products containing a similar drug, phenylpropanolamine (PPA), have been taken off the market because of reports of a higher risk for stroke in some women who took it.

Side effects may include agitation, insomnia, and anxiety. They may have adverse effects on the heart in people with existing heart problems. People with glaucoma, diabetes, hyperthyroidism, heart disease, or high blood pressure should avoid alpha-adrenergic agonists.

Nitrovasolidators. Deficiencies in nitric oxide, a gas that keeps blood vessels open, have been associated with many disorders, including incontinence. Drugs that release nitric oxide, such as nitroflurbiprofen, are being investigated for urinary incontinence.

Tricyclic and Similar Antidepressants

Evidence indicates that both urge and stress incontinence are affected, in part, by central nervous system processes, particularly signal transmission. Investigators are particularly interested in serotonin and noradrenaline, which are chemical messengers (called neurotransmitters) that affect pathways involved with urination. (These neurotransmitters are also important for many other emotional and physical functions.) Antidepressants targeting one or both of these neurotransmitters are sometimes used for urge incontinence and may also be helpful for some people with stress incontinence.

Tricyclic Antidepressants. Tricyclic antidepressants include imipramine (Janimine, Tofranil), doxepin (Sinequan), desipramine (Norpramin), and nortriptyline (Pamelor). They provide multiple benefits for both urge and stress incontinence. They act as anticholinergic drugs and relax the bladder. They also strengthen the internal sphincter. These drugs should be used carefully. They pose some risk for adverse effects on the heart and possibly the lungs, and they have other severe side effects in older adults. These antidepressants produce side effects similar to anticholinergic drugs, and may cause drowsiness. They may also backfire and actually cause overflow incontinence in some people.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). SNRIs are specially designed antidepressants that are similar to tricyclics but do not have the same side effects. The neurotransmitters serotonin and norepinephrine are thought to play key roles in the normal action of bladder muscles and nerves. Increased neurotransmitter activity stimulates the nerve that controls the urethral sphincter. The SNRI duloxetine (Cymbalta) is approved in Europe for treatment of stress urinary incontinence. (It is approved in the U.S. for other conditions, but not stress urinary incontinence.) In 2005, the manufacturer of duloxetine withdrew its drug application after a small number of women in duloxetine urinary incontinence trials tried to commit suicide. The FDA is investigating whether duloxetine can cause suicidal behavior.

Other Drugs Used or Investigated for Incontinence

Desmopressin. Studies have reported that desmopressin (DDAVP), a drug used for bedwetting in children, may be helpful in treating adults with urinary incontinence that occurs during sleep. The drug affects sodium levels, and there is a slight risk for water intoxication with this drug.

Botulinum (Botox). Botulinum, the deadly toxin that sometimes contaminates improperly cooked foods, is also a powerful muscle-relaxant. Tiny injected amounts of a purified form (Botox) can relax the muscles and may help control overactive bladder that causes urge incontinence. It may also help relieve urinary retention that might occur after incontinence surgeries.

Other Investigational Treatments

Stem Cells. Researchers are investigating muscle stem cell injections as a treatment for stress incontinence. Several small studies have indicated promising results. In these experiments, a doctor took a biopsy of skeletal muscle tissue from a patient’s arm. Stem cells were cultured and isolated from the biopsy sample. The doctor then injected the muscle-derived stem cells into the area surrounding the patient’s urethra that is close to the damaged sphincter muscle. In research results presented at the 2007 American Urological Association annual meeting and the 2006 Radiological Association of North American Meeting, patients experienced sustained improvements in bladder control and quality of life.

Review Date: 12/21/2006
Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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