Evaluation of insomnia should include a complete medical and psychiatric history and assessment of sleep-related behaviors and symptoms. Therapies for persistent insomnia include cognitive behavioral therapy (considered the first-line treatment) and hypnotic medications.
Both basic and clinical data suggest a potential significant role for GABA in the etiology and maintenance of primary insomnia (PI). Proton magnetic resonance spectroscopy (1H-MRS) can non-invasively determine GABA levels in human brain. Our objective was to assess GABA levels in unmedicated individuals with PI, using 1H-MRS. Matched-groups, cross-sectional study conducted at two university-based hospitals. Sixteen non-medicated individuals (8 women) with PI (mean age = 37.3 +/− 8.1) and 16 (7 women) well-screened normal sleepers (mean age = 37.6 +/− 4.5). PI was established with an unstructured clinical interview, a Structured Clinical Interview for DSM-IV (SCID), sleep diary, actigraphy and polysomnography (PSG). 1H-MRS data were collected on a Varian 4 Tesla magnetic resonance imaging/spectroscopy scanner. Global brain GABA levels were averaged from samples in the basal ganglia, thalamus, and temporal, parietal, and occipital white-matter and cortex. Average brain GABA levels were nearly 30% lower in patients with PI (.18 +/− .06) compared to controls (.25 +/− .11). GABA levels were negatively correlated with wake after sleep onset (WASO) on two independent PSGs (r = −0.71, p = 0.0024 and −0.70, p = 0.0048). Our preliminary finding of a global reduction in GABA in non-medicated individuals with PI is the first demonstration of a neurochemical difference in the brains of those with PI compared to normal sleeping controls. 1H-MRS is a valuable tool to assess GABA in vivo, and may provide a means to shed further light on the neurobiology of insomnia.
Restless legs syndrome (RLS) is a common disorder. The population prevalence is 1.5% to 2.7% in a subgroup of patients having more severe RLS with symptoms occurring 2 or more times a week and causing at least moderate distress. It is important for primary care physicians to be familiar with the disorder and its management. Much has changed in the management of RLS since our previous revised algorithm was published in 2013. This updated algorithm was written by members of the Scientific and Medical Advisory Board of the RLS Foundation based on scientific evidence and expert opinion. A literature search was performed using PubMed identifying all articles on RLS from 2012 to 2020. The management of RLS is considered under the following headings: General Considerations; Intermittent RLS; Chronic Persistent RLS; Refractory RLS; Special Circumstances; and Alternative, Investigative, and Potential Future Therapies. Nonpharmacologic approaches, including mental alerting activities, avoidance of substances or medications that may exacerbate RLS, and oral and intravenous iron supplementation, are outlined. The choice of an alpha2-delta ligand as first-line therapy for chronic persistent RLS with dopamine agonists as a second-line option is explained. We discuss the available drugs, the factors determining which to use, and their adverse effects. We define refractory RLS and describe management approaches, including combination therapy and the use of high-potency opioids. Treatment of RLS in pregnancy and childhood is discussed.
Sleep disturbance is the primary clinical morbidity of restless legs syndrome (RLS). To date, sleep disturbance in RLS has been measured in (1) clinical samples with polysomnography (PSG) or (2) population-based samples by self-report. The objective of this study was to analyze sleep by PSG in a population-based sample with symptoms of RLS. Cross-sectional observational study Community-based 3433 older men and women None RLS was evaluated using an 8-item self-administered questionnaire based on NIH diagnostic criteria and required symptoms occurring ≥ five times per month and associated with at least moderate distress. Health-related quality of life (HRQOL) was determined using the SF-36. Unattended, in-home PSG was performed. Data were assessed using general linear models with adjustment for demographic, health-related variables, and apnea-hypopnea index (AHI). Subjects with RLS had longer adjusted mean sleep latency (39.8 vs 26.4 min, P < 0.0001) and higher arousal index (20.1 vs 18.0, P = 0.0145) than those without RLS. Sleep latency increased progressively as the frequency of RLS symptoms increased from 5–15 days per month to 6–7 days per week. No differences in sleep stage percentages were observed between participants with and without RLS. Subjects with RLS also reported poorer HRQOL in all physical domains as well as in the Mental Health and Vitality domains. These novel PSG data from a nonclinical, community-based sample of individuals with RLS document sleep disturbance in the home even in individuals with intermittent symptoms.