Dose-Dependent Urinary Incontinence with Sertraline Use in Obsessive-Compulsive Disorder

Case History

Ms. K is a 34-year-old female, gravida 1, para 1 (G1P1001) with a psychiatric history of major depressive disorder, previously managed with bupropion in her early 20s. Following delivery of her child, she developed symptoms of generalized anxiety disorder with panic attacks. Ms. K subsequently developed intrusive thoughts related to the health and well-being of her child, that morphed into intrusive, unwanted thoughts about aggression and harm towards her baby and began avoiding contact with her infant due to fear and guilt. Bupropion was restarted by her primary care clinician, due to her past response, but was only mildly helpful. She was referred to Psychiatry and diagnosed with obsessive compulsive disorder (OCD). Patient Health Questionnaire-9 (PHQ-9) screening score was 11 and Generalized Anxiety Disorder-7 (GAD-7) screening score was 13 at her initial visit. Bupropion was discontinued in favor of sertraline and addition of cognitive behavioral therapy (CBT) with an exposure response prevention (ERP) approach was also recommended.

Symptomatology

Depressive symptoms and anxiety began to improve. At 3-month follow-up PHQ-9 and GAD-7 scores had both decreased to 1. Of note, GAD-7 screens for anxiety but not obsessive-compulsive disorder symptoms. Due to ongoing intrusive thoughts of harming her child and a dose dependent response to the medication, sertraline was uptitrated to 300 mg daily over the course of 6 months. She started experiencing urinary urgency and associated urinary urge incontinence at the 300 mg dose. She had no previous episodes of urinary urge or stress incontinence, pelvic floor dysfunction, or prior history of obstetric complications.

Given significant improvement and remission of her psychiatric symptoms, (PHQ-9 and GAD-7 scores of 0 at 6 months and no further intrusive, obsessive thoughts) she maintained this high dose of sertraline for one year and then followed up in the Perinatal Psychiatry Clinic in the context of preconception planning and wanting to consider tapering sertraline due to urinary side effects. She noted that she was working from home in the context of the COVID-19 pandemic and the benefit of sertraline outweighed the inconvenience of the side effect, and therefore she had opted to continue the medication. However, with return to working in the office and considering another pregnancy, she wanted to reevaluate her treatment plan. At the 300 mg dose of sertraline, she reported experiencing incontinence half of the days. She described acute onset uncontrollable urge to urinate with associated loss of bladder control. Often she was unable to make it to the bathroom prior to urination. This was a full volume void. This generally occurred in the morning. If she forgot her dose of sertraline or was delayed in taking the medication, she did not have any urinary urgency or incontinence. Additionally, a possible contributing factor to her urinary urgency included her report of drinking a total of six cups of coffee per day. This was her baseline caffeine consumption and did not change with her use of sertraline or her postpartum course. Sertraline was decreased to 250 mg. After one month on this dose, she was still experiencing urinary urgency, but her urge incontinence has resolved. Sertraline was gradually reduced to 150 mg. At this dose, she reports low level OCD symptoms with brief intrusive thoughts about harm, no compulsions, and no avoidance. She continues to report slight morning urinary urgency, though remains free of further incontinence, and is working to decrease her caffeine consumption to one cup of caffeinated coffee and two to three cups of decaffeinated coffee. No other interventions were implemented, including pelvic floor exercises, nor detection of any genitourinary comorbidities.

Diagnosis

This patient’s symptoms were consistent with new onset urinary urgency and urge incontinence in the setting of sertraline use. Worsening of this condition with escalating doses is indicative of dose-dependent SSRI-induced urinary incontinence, with possible contributions from high caffeine consumption and postpartum status. Caffeine is a known bladder irritant that may be associated with urinary urgency.¹ However, previous data indicates that long-term caffeine intake has no associated risk with progression of urinary incontinence.² In this setting, use of high-dose sertraline is felt to be the primary driver behind her urinary incontinence.

Treatment

Given stability of psychiatric symptoms and the patient’s request to decrease psychotropic medication use in preparation for a planned pregnancy, sertraline dosing was decreased from 300 mg daily to 150 mg daily in a stepwise fashion. As her daily dose decreased, symptoms of urinary urgency and incontinence improved. While she continued to experience abrupt urges to urinate at the decreased dose, adequate timing to reach the restroom prior to voiding was present and she no longer experienced urine leakage. Ongoing engagement with non-pharmacologic treatment, specifically cognitive behavioral approaches was encouraged throughout her treatment course.

Discussion

Previous association between urinary incontinence and the use of selective serotonin reuptake inhibitors (SSRIs) has been noted at a rate of approximately 14 cases per 1000 patients per year.³ When compared to other SSRIs, the relative risk of urinary incontinence with sertraline use is 1.72 (95% CI 1.10-2.78).³ Despite this finding, symptoms consistent with both urinary incontinence and overactive bladder are lower in SSRIs compared to their counterpart, the serotonin norepinephrine reuptake inhibitors (SNRI).^4,5

Urinary incontinence with venlafaxine use has been implicated in several previous publications^6–8 with some patients having resolution of their incontinence by switching to an alternative treatment, such as sertraline.⁵

Potentiation of cholinergic neuromuscular transmission within the detrusor muscle of the bladder through serotonin-induced activation,⁹ modulation of bladder sphincter tone,¹⁰ or interaction with downstream dopaminergic effects¹¹ have all been proposed mechanisms for antidepressant-induced urinary incontinence. However, the exact mechanism behind this phenomenon remains unknown.

The prudent clinician should be aware of and screen for other contributing factors that may be precipitating urinary incontinence including, but not limited to: past obstetric complications, gynecologic anomalies such as pelvic organ prolapse urinary tract foreign body, urolithiasis, urologic malignancy, urinary tract infection, diabetes mellitus or diabetes insipidus, or pharmacologic contributors including diuretics, alpha-adrenergic agonists, and angiotensin-converting enzyme blockers.¹²

The use of SSRIs is common for multiple psychiatric conditions. Clinicians should be aware of the increased risk of urinary incontinence with use of these agents, particularly at higher doses which have been shown to be more effective for management of OCD.^13,14 Current literature is limited, but the incidence is estimated to occur in three of every 200 people treated per year.³ The current case indicates that the risk of SSRI-induced urinary incontinence may occur in a dose-dependent fashion- increasing with higher doses and resolving with dose reduction. Rather than discontinuing an effective medication, clinicians may consider a trial of a lower dose or interventions targeted at the urinary symptoms themselves. This may include behavioral modification (timed voiding, dietary modification), pelvic floor muscle training, and possible pharmacologic interventions.¹⁵