In this case report the development of incontinence within one week after beginning sertraline and resolution after medication change leads to consideration of a causative relationship between sertraline and UI.
Sertraline is one of the agents used as first choice for treatment of many psychopathologies led by depression due to relatively reliable side effect profile in children and adolescents. Serotonin plays a very important role in control of the bladder through central and peripheral mechanisms. Increased activity in the serotonergic system inhibits the parasympathetic pathway, easing storage of urine 10. Through this mechanism pathway and specifically SSRIs are stated to have antienuretic effect on central presynaptic 5-HT1A and peripheral 5-HT3 receptors 11. This antienuretic effect is reported for fluoxetine, sertraline, paroxetine and fluvoxamine 12-16. However, in addition to the antienuretic effect of SSRIs, some cases are observed where, contrary to expected, SSRI use caused incontinence 7.
When cases reported with the SSRIs like sertraline, citalopram, paroxetine and fluvoxamine are examined, the mechanism for the enuretic effect has still not been fully explained. Continence is provided through the α-adrenergic pathway of the bladder sphincter, with acetylcholine released by the cholinergic nerves innervating the detrusor muscle known to affect emptying contractions. Additionally, serotonin ensures modulation through three different serotonin receptor regions (5-HT4, 5-HT7 and 5-HT1A) at nerve endings innervating the bladder muscle 16. Patients treated with 5-HT4 agonists (for example, cisapride) for gastrointestinal system motor functions were observed to have increased frequency of miction 17. Based on these findings, activation of neuronal 5-HT4 receptors in the detrusor muscle was predicted to mediate incontinence 18. Additionally, activation of dopamine receptors occurring through potential dopamine reuptake inhibition with sertraline may suppress urethral sphincter activity and as a result is considered to reduce urethral resistance causing urine leakage symptoms.
Interestingly, urinary incontinence with sertraline use did not continue after fluoxetine use. Pharmacologically, sertraline is known to have some α-adrenergic blockage and dopamine reuptake inhibitor properties that fluoxetine does not have. Additionally, fluoxetine had 5-HT2C agonist effect that sertraline does not have 10. In reality, adrenergic blockage shown with sertraline but not with fluoxetine may cause urinary incontinence by reducing the bladder internal sphincter tonus. These properties may explain why incontinence was only observed with sertraline use.
In the literature, a ten-year old case with OCD and social phobia diagnosis was reported to develop incontinence 2 times per week while using 50 mg/day sertraline for 2 months. Increasing the dose led to increased frequency during the day and night on the third day and sertraline treatment was stopped due to reduced functionality. UI then ended; however, fluoxetine treatment was begun due to continuation of complaints 8. An eight-year old male case with social phobia and major depression diagnosis began sertraline treatment of 25 mg/day and nocturnal enuresis began after the dose was raised to 50 mg/day. After stopping sertraline treatment after a total of 5 weeks, enuresis resolved within 1 week 7. Similarly, in our case, incontinence reduced 1 week after stopping sertraline treatment and was completely resolved within ten days. However, in spite of low dose (25 mg/day) sertraline use by our patient, incontinence occurred within the first week and did not occur in dose-linked manner.
Another notable aspect of our case is the history of primary enuresis nocturna and father’s enuresis history in the family. A small number of studies have found previous enuresis history is a risk factor for urinary incontinence, while a study in the adult period found 31.4% of patients with UI had enuresis history in the childhood period 19. Another study investigating 1333 female patients with mean age of 48 years found women with history of enuresis in the childhood period reported more frequent urge symptoms and urinary leakage 20. In our case, the enuresis history may have created a tendency toward urinary incontinence.
In conclusion, UI is an important problem affecting the patient, their family and surroundings. Considering the effects on quality of life of patients in the presence of UI, we think it is beneficial to report our case in terms of clinicians being aware of this side effect in order to increase treatment compliance of patients.
