What is the role of tricyclic antidepressants (TCAs) in urinary incontinence treatment?

Updated: Jan 22, 2021
  • Author: Sandip P Vasavada, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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TCAs have historically been used to treat major depression, but their pharmacologic effects also make these drugs good choices for mixed incontinence, nocturia, and nocturnal enuresis. TCAs have also been used in the treatment of stress incontinence.

TCAs have complicated direct and indirect effects on the lower genitourinary tract. They possess both a central and peripheral anticholinergic effect, as well as being alpha-adrenergic agonists and central sedatives. The resultant clinical effect is bladder muscle relaxation and increased urethral sphincter tone. High pretreatment urethral closure pressure has served as a predictor of success.

Imipramine (Tofranil) is the most widely used TCA for urologic indications. It facilitates urine storage by decreasing bladder contractility and increasing outlet resistance. It has an alpha-adrenergic effect on the bladder neck, an antispasmodic effect on the detrusor muscle, and a local anesthetic effect on the bladder mucosa. (Note the black box warning: In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (< 24 y) taking antidepressants for major depressive disorders and other psychiatric illnesses.)

Adult dosing is 10-50 mg 1 to 3 times daily, with a range of 25-100 mg qd. Pediatric dosing is not established. Imipramine is a pregnancy category D drug.

The combination of imipramine and oxybutynin (Ditropan) produces a synergistic effect to relax the unstable bladder, allowing it to better hold urine and preventing urge incontinence.

Amitriptyline (Elavil) is a TCA with sedative properties that increases circulating levels of norepinephrine and serotonin by blocking their reuptake at nerve endings. It is ineffective for use in urge incontinence but extremely effective in decreasing symptoms of urinary frequency in women with pelvic floor muscle dysfunction. It restores serotonin levels and helps break the cycle of pelvic floor muscle spasms.

Amitriptyline is well tolerated and effective in most women with urinary frequency. Adult dosing is 10 mg qd; titrate if necessary by 10 mg/wk until a maximum dose of 150 mg is reached, urinary symptoms disappear, or adverse effects become intolerable. Pediatric dosing is not established. Amitriptyline is also a pregnancy category D drug.

In addition to anticholinergic adverse effects, serious allergic reactions have been reported with TCAs, although rarely. Cardiotoxicity rarely is problematic at the low doses used for treatment of urinary incontinence. Central effects, such as sedation and tremor, may be troublesome to some patients. On occasion, prescribing imipramine at bedtime and a musculotropic agent in the daytime may be helpful.

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