A 2-Year Prospective Follow-Up Study of Lower Urinary Tract Symptoms in Patients Treated With Clozapine

Abstract

Urinary incontinence and enuresis are well-known side effects of clozapine. However, clinical experience has shown that patients also suffer from diverse lower urinary tract symptoms (LUTS). The natural course of clozapine-related LUTS is unclear. Thus, a longitudinal follow-up study is needed. A total of 101 subjects who were taking clozapine initially participated. Their LUTS were evaluated using the International Prostate Symptom Score (IPSS), other questionnaires, and a medical records review. After 2 years, 87 of the original subjects could be contacted, and the status of their LUTS was re-evaluated. The average IPSS total was 7.4 +/- 5.9 at the initial evaluation. Although only 11 subjects (10.9%) reported actual incontinence, 42 subjects (41.6%) were found to have clinically significant LUTS (IPSS total score > or =8). No influencing factors could be found among the demographic and clinical variables. At the follow-up, the average IPSS total (7.9 +/- 6.0) and the percentage of subjects with clinically significant LUTS (43.7%) had both increased, although the change was not statistically significant. The prevalence of LUTS in clozapine-medicated patients was higher than in the general population of the same age. However, the prevalence of incontinence was only a quarter of that of LUTS. If clinicians focus only on incontinence, distress from LUTS will not receive appropriate attention. Furthermore, contrary to literature observations, clozapine-related LUTS did not remit easily but rather persisted even into the long-term maintenance phase. More concern should be directed at these troublesome and often neglected side effects.

Nocturnal Enuresis is an Under-recognised Side Effect of Clozapine: Results of a Systematic Review

“…-Two studies assessed the CANE point prevalence (nocturnal enuresis at the time of assessment) using a cross sectional approach (Centorrino et al 1994, Long et al 2015). -Two studies provided a 1 month prevalence using a retrospective approach (Jeong et al 2008, Yusufi et al 2007 o A Jeong et al 2008 assessment was part of a 2-year prospective follow-up study. -Four studies assessed the CANE episode prevalence (nocturnal enuresis since beginning of clozapine) using a retrospective approach (Bhirud, Shah.…”

“…Mean age ranged from 37 to 41.5 years. Jeong et al (2008) observed a higher frequency of nocturnal enuresis in women compared to men. This study was comprised of 60% males.…”

1726 Are Commonly-Used Psychoactive Medications Associated With Lower Urinary Tract Symptoms?

“…In a previous clinical study of LUTS measured using an adapted version of the IPSS scale among 101 clozapine users, women had only non-significantly higher mean scores compared to men (7.78 and 7.18, respectively). [12] Because AAPs are not currently indicated as first-line therapy for depression, it is reasonable to speculate that women using AAPs alone had more severe, potentially uncontrolled depression even after adjustment for residual depressive symptoms. However, we observed similar associations comparing joint users of SSRIs and AAPs to AAP-only users, suggesting that 'confounding by severity' did not explain the association.…”

“…We defined the presence of LUTS as a score of ≥8, corresponding to moderateto-severe symptoms. For graphical displays, LUTS severity categories were defined using the AUA-SI as follows: no symptoms (score=0), mild (1-7), moderate (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), severe (≥20). We also examined mean storage and voiding storage subscales of the AUA-SI.…”

“…[9] Urinary incontinence is a side effect of antipsychotics; [10] as is urge incontinence [11] while a recent study of clozapine (an AAP) suggested that users suffered from an excess of a broader range of LUTS than incontinence alone. [12] There is also evidence that selective serotonin reuptake inhibitor (SSRI) antidepressants could increase the risk of LUTS. [13] Prior associations between SSRIs and nocturia and risk of urinary incontinence have been documented.…”