Use of antidepressants and risks of restless legs syndrome in patients with irritable bowel syndrome: A population-based cohort study.

Yung-Chu Hsu,Solomon Chih-Cheng Chen,Hsin-Yi Yang,Herng-Sheng Lee,Wan-Ting Huang,Rachel A Annunziato

doi:10.1371/journal.pone.0220641

Abstract

Previous research has suggested an association between antidepressants use and clinical restless legs syndrome (RLS) in patients, but there has never been a single study investigating the risk of RLS in irritable bowel syndrome (IBS) patients treated with antidepressants. Hence, we aimed to explore the association between IBS and RLS and to examine the risk of RLS in IBS patients treated with antidepressants. With the use of the National Health Insurance Research Database of Taiwan, 27,437 adults aged ≥ 20 years with newly diagnosed IBS (ICD-9-CM Code 564.1) and gender- and age-matched 54,874 controls without IBS were enrolled between 2000 and 2012. All patients were followed-up until RLS diagnosis, withdrawal from the National Health Insurance program, or end of 2013. We used the Cox proportional hazards model to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of RLS. RLS was more prevalent in IBS patients than in the non-IBS group (7.57 versus 3.36 per 10,000 person-years), with an increased risk of RLS (adjusted HR [aHR], 1.91; 95% CI, 1.52–2.40). Multivariate Cox proportional hazards analysis identified older age (age, 51–65 years; aHR, 1.67; 95% CI, 1.09–2.56; and age > 65; aHR, 1.59; 95% CI, 1.02–2.48), hypothyroidism (aHR, 4.24; 95% CI, 1.92–9.37), CAD (aHR, 1.70; 95% CI, 1.17–2.48), and depression (aHR, 3.15; 95% CI, 2.14–4.64) as independent RLS risk factors in IBS patients. In addition, the male SSRIs users were associated with significantly higher risk of RLS (aHR, 3.05 95% CI, 1.34–6.92). Our study showed that the IBS group has higher risk of RLS. Moreover, SSRIs use may increase the risk of RLS in male IBS patients.

Highlights

Irritable bowel syndrome (IBS) is a chronic, relapsing gastrointestinal disorder characterized by recurrent abdominal discomfort or pain, bloating, abnormal stool form and frequency, straining at defecation, and urgency [1]
Multivariate Cox proportional hazards analysis identified older age, hypothyroidism, CAD, and depression as independent restless legs syndrome (RLS) risk factors in IBS patients
A multivariate Cox proportional hazards analysis identified that patients aged > 65 years, hypothyroidism, CAD, and depression were associated with significantly higher risk of RLS compared with patients without these conditions (Table 2)

Summary

Introduction

Irritable bowel syndrome (IBS) is a chronic, relapsing gastrointestinal disorder characterized by recurrent abdominal discomfort or pain, bloating, abnormal stool form and frequency, straining at defecation, and urgency [1]. The global pooled prevalence of IBS has been estimated to be ranging from 9%–23%, with a female predominance [2]. The pathophysiology of IBS is poorly understood and multiple factors are involved in the pathogenesis of IBS, including genetic susceptibility, visceral hyperalgesia, altered gastrointestinal motility, and neurological and psychological factors [3, 4]. A couple of studies have suggested that sleep disorders, restless legs syndrome (RLS), are possible comorbidities in IBS patients [6, 7]. According to the previous studies, nearly 25%–30% of IBS patients experience RLS [6,7,8]

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