Over the last decades, the exact role of the serotonergic system on micturition and urinary continence in women has been investigated and discussed. Traditionally, central serotonergic pathways are considered to have a positive effect on urethral closure mechanism. However, recent clinical trials and experimental animal studies demonstrate conflicting results regarding the effect of serotonergic drugs on urethral pressure (1,2). Furthermore, observational studies suggest that exposure to selective serotonin reuptake inhibitors (SSRI) is associated with a significant increased risk of stress urinary incontinence (SUI) (3). In the light of the extensive use of SSRIs, it is relevant to investigate whether SSRI decreases urethral pressure, which potentially could worsen SUI. The aim of this study was to evaluate the effect of citalopram, a SSRI, on opening urethral pressure (OUP) in women.

We conducted a randomized, double-blind, placebo – and active controlled, double-dummy, three-way crossover study in 24 healthy female volunteers. The subjects were randomized to one of six treatment sequences according to a Latin square design balanced for period. There were three study days separated with a washout of at least eight days. On each study day, the subject received two capsules (citalopram 40 mg and placebo, reboxetine 8 mg and placebo, or two placebo). The subjects ingested the study drugs in one-hour intervals due to differences in time to maximum plasma concentrations. The primary outcome, OUP, was measured two hours after ingestion of active control drug (reboxetine) or placebo. 
Urethral pressure reflectometry (UPR) is a sensitive method for measuring urethral pressure changes during pharmacological treatment. OUP measured with UPR has demonstrated high reproducibility and correlates well with clinical severity of SUI.

Twenty-four women were screened, included and randomized, and all of them completed the study. Median age was 25 years (range 18-55) and median body mass index was 23.5 kg/m2 (range 18.6-28.7). Compared to placebo, citalopram increased OUP with 6.6 cm H20 (95% confidence interval [CI] 0.04-13.1, p=0.048) in resting condition (figure 1). In the squeezing condition, OUP increased with 7.1 cm H20 (95% CI 1.3-12.9, p=0.01) compared to placebo. The active control, reboxetine, increased OUP with 30.0 cm H20 in resting condition compared to placebo (95% CI 23.5-36.5, p<0.001), and 27.0 cm H20 (95% CI 21.2-32.8, p<0.001) in the squeezing condition.

This is the first randomized, double-blind, placebo-controlled study to investigate the effect of citalopram, a SSRI, on urethral pressure in human subjects. The study showed that citalopram caused a small placebo-corrected increase in OUP during resting conditions. The increase in OUP during squeeze was of similar magnitude. As expected, reboxetine increased OUP markedly during both resting and squeezing conditions. These results suggest that SSRIs are unlikely to induce or aggravate urinary incontinence. The substantial reboxetine-induced increase in urethral pressure suggests that reboxetine might be a rational choice for women with both SUI and indication for antidepressant treatment. However, this should be evaluated in a clinical study before implementation.

Citalopram, a SSRI, does not decrease urethral pressure in healthy women suggesting that SSRI-treatment is unlikely to cause or worsen SUI.

Klarskov N, Van Till O, Sawyer W, Cernus D, Sawyer W. Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women. Neurourol Urodyn. 2019;38(6):1700-1706. doi:10.1002/nau.24045
Klarskov N, Cerneus D, Sawyer W, Newgreen D, van Till O, Lose G. The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry. Neurourology and Urodynamics. 2018;37(1):244-249. doi:10.1002/nau.23282
Movig KLL, Leufkens HGM, Belitser SV, Lenderink AW, Egberts ACG. Selective serotonin reuptake inhibitor-induced urinary incontinence. Pharmacoepidemiology and Drug Safety. 2002;11(4):271-279. doi:10.1002/pds.705