Study objectives

To examine the association between modifiable lifestyle factors, and the risk of developing restless legs syndrome (RLS).

Methods

This is a Prospective Cohort study of population including 12,812 men participating in Health Professionals Follow-up Study and 42,728 women participating in the Nurses' Health study II. The participants were free of RLS at baseline (2002 for the HPFS and 2005 for the NHS II) and free of diabetes and arthritis through follow-up. RLS was assessed via a set of questions recommended by International Restless Legs Syndrome Study group. The Information was collected on height, weight, level of physical activity, dietary intake, and smoking status via questionnaires.

Results

During 4-6 years of follow-up, we identified 1,538 incident RLS cases. Participants with normal weight, and who were physically active, non-smoker, and had some alcohol consumption had a lower risk of developing RLS. When we combined the effects of these four factors together, we observed a dose response relationship between the increased number of healthy lifestyle factors and a low risk of RLS: after adjusting for potential confounders the pooled odds ratio was 0.67 (95% CI: 0.47-0.97) for 4 vs.0 healthy factors (p trend < 0.001). In contrast, we did not observe significant associations between caffeine consumption or diet quality as assessed by the Alternate Healthy Eating Index, and altered RLS risk in men and women.

Conclusions

Several modifiable lifestyle factors may play an important role in RLS risk.

Both restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS) may be associated with incident cardiovascular disease (CVD). However, the individual contributions of these factors to adverse CVD outcomes are unknown. During the MrOS Sleep Study, 2823 men (mean age = 76.3 years) participated in a comprehensive sleep assessment from 2000 to 2002. RLS was identified by self-report of a physician diagnosis of RLS. A periodic limb movement of sleep index (PLMI) was derived from unattended in-home polysomnography. Incident cardiovascular events were centrally adjudicated during 8.7 ± 2.6 years of follow-up. The primary outcome was all-cause CVD; secondary outcomes included incident myocardial infarction (MI) and cerebrovascular disease. Cox proportional hazards regression models were adjusted for multiple covariates, including PLMI, to examine if there were independent associations of RLS and PLMI to the outcomes. Physician-diagnosed RLS was reported by 2.2% and a PLMI ≥ 15 was found in 59.6% of men. RLS was not associated with the composite CVD outcome. RLS was significantly associated with incident MI (Hazard ratio [HR] = 2.02, 95% CI, 1.04-3.91) even after adjustment for multiple covariates. Results were only modestly attenuated when PLMI was added to the model. PLMI also was found to predict incident MI (per SD increase in PLMI, HR = 1.14, 95% CI, 1.00-1.30, p = .05), and was materially unchanged after addition of RLS. The independent risk that RLS confers for MI suggests a role for non-PLMS factors such as sleep disturbance, shared genetic factors, or PLM-independent sympathetic hyperactivity.

While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, "No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time". The panelists' assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia.

Insomnia is a significant, highly prevalent, persistent public health problem but often remains undiagnosed and untreated. Current treatment practices are not always evidence-based. When insomnia is comorbid with anxiety or depression, treatment often targets that comorbid condition with the expectation that improvement of the mental health condition will generalize to sleep symptoms. An expert panel of seven members conducted a clinical appraisal of the literature regarding the treatment of insomnia when comorbid anxiety or depression are also present. The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the panel's predetermined clinical focus statement, "Whenever chronic insomnia is associated with another condition, such as anxiety or depression, that psychiatric condition should be the only focus of treatment as the insomnia is most likely a symptom of the condition". The results from an electronic national survey of US-based practicing physicians, psychiatrists, and sleep (N = 508) revealed that >40% of physicians agree "at least somewhat" that treatment of comorbid insomnia should focus solely on the psychiatric condition. Whereas 100% of the expert panel disagreed with the statement. Thus, an important gap exists between current clinical practices and evidence-based guidelines and more awareness is needed so that insomnia is treated distinctly from comorbid anxiety and depression.

A scientific advisory panel of seven U.S. and Canadian sleep experts performed a clinical appraisal by comparing general medical opinion, assessed via a survey of practicing clinicians, regarding insomnia treatment, with the available scientific evidence. This clinical appraisal focuses on the specific statement, "Treatments for insomnia have uniformly been shown to significantly improve the associated daytime impairment seen with insomnia." The advisory panel reviewed and discussed the available body of evidence within the published medical literature to determine what discrepancies may exist between the currently published evidence base and general medical opinion. The advisory panels' evaluation of this statement was also compared with the results of a national survey of primary care physicians, psychiatrists, nurse practitioners, physician assistants, and sleep specialists in the United States. Contrary to general medical opinion, the expert advisory panel concluded that the medical literature did not support the statement. This gap highlights the need to educate the general medical community regarding insomnia treatment efficacy in pursuit of improved treatment outcomes.

Trazodone is one of the most commonly used prescription medications for insomnia; however, some recent clinical guidelines do not recommend its use for treating insomnia. This clinical appraisal critically reviews the scientific literature on trazodone as a first-line treatment for insomnia, with the focus statement "Trazodone should never be used as a first-line medication for insomnia." In addition, field surveys were sent to practicing physicians, psychiatrists, and sleep specialists to assess general support for this statement. Subsequently, a meeting with a seven-member panel of key opinion leaders was held to discuss published evidence in support and against the statement. This paper reports on the evidence review, the panel discussion, and the panel's and healthcare professionals' ratings of the statement's acceptability. While the majority of field survey responders disagreed with the statement, the majority of panel members agreed with the statement based on the limited published evidence supporting trazodone as a first-line agent as they understood the term "first-line agent".