In this study, we showed that the prevalence of MDD in patients with RLS was 9.74% whereas the incidence of MDD in non-RLS individuals was only 4.50%. Therefore, increased MDD is significantly linked to RLS.
Our meta-analysis included 12 case-control studies and revealed 2.05-fold higher MDD prevalence in RLS patients compared to non-RLS subjects. These results are consistent with those from a systematic review in 2014. Our results appear to be robust than a study which demonstrated that MDD was more prevalent in RLS group than in non-RLS group (≥ mild depression: odds ratio (OR) = 1.95, p < 0.001; ≥moderate depression: OR = 6.15, p < 0.001; and ≥ severe depression: OR = 56.54, p < 0.001), with a predominant proportion of severe depression (97%) in RLS group. A 2-to 4-fold higher risk of MDD in patients with RLS than in non-RLS subjects was also reported in epidemiological studies[9, 19–21]. Winkelman reported a positive correlation between RLS symptom frequency and depression severity. Although MDD is reported frequently in RLS patients [20, 23, 24], how MDD is associated with RLS is still unclear [25, 26]. MDD risk was increased among individuals with severe RLS symptoms compared to those facing mild to moderate symptoms. In addition, antidepressants can provoke or exacerbate RLS symptoms .
Strong association between RLS and depression could be explained by three possibilities. Firstly, RLS could cause MDD through nocturnal sleep disturbances and poor quality of life. Secondly, RLS manifestations, such as fatigue, diminished concentration and insomnia, could be misinterpreted as depressive symptoms. Thirdly, RLS and depression may share a common pathophysiology involving dopamine system. It has been reported that ropinirole, a dopamine agonist for treating RLS, improved depressive and RLS symptoms in RLS patients , whereas antidepressant treatment worsen RLS symptoms. Although no scores related to sleep was extracted for our study, two articles were rated by EES [14, 17], and one group was rated by PSQI . Several studies showed that the non-RLS group slept better than RLS group[13, 15, 16]. Our findings supported the idea that the most important cause of MDD might be chronic insomnia caused by RLS. In addition, RLS patients showed lower MMSE scores than non-RLS subjects, indicating cognitive function may be impaired in RLS cases. Cognitive impairments in RLS have been reported in several previous studies[29, 30]. Cognitive deficits in RLS patients could also result from chronic sleep disruption, comorbid MDD and a direct effect from RLS pathology itself, which requires further investigations.
Our research showed no significant difference in MDD prevalence between RLS patients under 50 years old (OR = 2.10) and those over 50 years old (OR = 2.05). Rothdach reported that men with RLS, but not women, had a higher prevalence of suffering depression. Nevertheless, in a women-only Swedish study, women with RLS had an approximately double risk of self-reported depressed mood although earlier reports achieved inconsistent conclusions. In our research, we did not consider the gender effect because we failed to extract useful data.
Our results also showed that the prevalence of MDD in RLS Asians (OR = 2.10) was not significantly different from that in Europe and American cases (OR = 2.05). No significant difference appeared in MDD rates either, between the first (8.3%) and second (9.5%) studies on RLS in Koreans. Comparing our results with those from other western studies on older adults, the prevalence rate was slightly lower in our analysis than in the study by Hogl for the group of 50–89 years (10.6%), and slightly higher than in study by Ohayon for the group over 70 years old (8.7%) .
Some limitations in this study should be noted. The risk of publication bias might exist, though we did complete a relatively comprehensive searching in various international and Chinese databases, and Egger’s tests detected no significant bias. Our selected samples, RLS 3357 individuals and 94912 non-RLS ones, might still be subjected to random errors. Since our meta-analysis covered ethnically different populations in multiple countries, heterogeneity might also affect our findings.
Despite those limitations, the present meta-analysis for the first time reliably estimated MDD prevalence among individuals with RLS, which was higher than that among non-RLS ones. Such findings should be replicated in larger, multi-sites observational studies. Our results may inspire clinicians to pay more attention to MDD in RLS and to explore effective treatments for both diseases based on their potential links in pathophysiology.