Stress and Anxiety as Comorbidities, Not Causes or Mimics of RLS
Stress and anxiety do not cause RLS nor do they mimic it—they are frequently comorbid conditions that can exacerbate existing RLS symptoms, but the disorders remain clinically distinct entities requiring separate diagnostic consideration. 1
Understanding the Relationship Between RLS and Anxiety
The 2025 American Academy of Sleep Medicine guidelines explicitly recognize that RLS is often comorbid with mood and anxiety disorders, presenting treatment challenges because common anxiety treatments (serotonergic reuptake inhibitors) frequently worsen RLS symptoms. 1 This is a critical distinction: anxiety co-occurs with RLS but does not create or mimic the core sensorimotor features of the disorder.
Evidence for Comorbidity, Not Causation
Population-based studies demonstrate that patients with RLS have significantly greater anxiety and depression symptoms compared to controls, with a correlation between RLS severity and anxiety/depression severity (r = 0.21 for anxiety). 2
In cancer patients undergoing chemotherapy, those with RLS had higher levels of anxiety (adjusted OR 1.1,95% CI 1.00-1.19) compared to those without RLS, but RLS prevalence was 18.3%—driven by chemotherapy duration and female sex, not anxiety levels. 3
In Parkinson's disease patients, those with RLS had a 5.98-fold higher risk of anxiety, but RLS was identified as an independent risk factor, not a consequence of anxiety. 4
Why Anxiety Cannot Mimic RLS: Diagnostic Clarity
The International Restless Legs Study Group requires ALL five essential diagnostic criteria to be met, and anxiety does not fulfill these specific sensorimotor requirements. 5
Core RLS Features That Distinguish It From Anxiety
Urge to move with dysesthesias: RLS involves an uncomfortable urge to move the legs associated with abnormal sensations (dysesthesias), not the physiological somatic symptoms of anxiety like racing heart or tight chest. 1, 6
Relief specifically by movement: RLS symptoms are relieved by movement and return when movement stops, whereas anxiety-related restlessness may persist despite movement. 7, 5
Circadian pattern: RLS symptoms worsen in the evening/night, which is not characteristic of generalized anxiety. 1, 5
Rest/inactivity worsening: RLS worsens during both sitting AND lying down at rest—anxiety may cause restlessness but does not follow this specific pattern. 5
Recognized RLS Mimics (Anxiety Is Not Among Them)
The 2025 AASM guidelines list specific conditions that can present with RLS-like symptoms: neuropathy, akathisia, spasticity, positional discomfort, joint discomfort, nocturnal leg cramps, growing pains, and behavioral issues in children. 1 Anxiety is notably absent from this list of mimics.
The 2014 diagnostic instrument review mentions anxiety as a potential mimic that has not been specifically probed in diagnostic questionnaires, but emphasizes that validated diagnostic tools with excellent clinimetric properties successfully differentiate RLS from other conditions without anxiety causing diagnostic confusion. 8
Clinical Approach: Treating Both Conditions Separately
Avoid Medications That Worsen RLS
Tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists all exacerbate RLS symptoms and should be avoided when treating comorbid anxiety in RLS patients. 1, 9
This creates a treatment challenge requiring careful medication selection for anxiety management in RLS patients. 1
Address RLS First
Check serum ferritin levels; if ≤75 ng/mL, supplement with iron as this may improve both RLS and potentially mood symptoms. 5
Use first-line RLS treatments: alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) which do not worsen anxiety. 5
Manage Anxiety Appropriately
Consider non-serotonergic anxiolytics or cognitive-behavioral therapy for anxiety management. 6
One small case series (n=7) suggested vortioxetine, a multimodal antidepressant, may not worsen and might even improve RLS symptoms in patients with comorbid depression/anxiety, though this requires validation in randomized controlled trials. 10
Common Pitfalls to Avoid
Do not assume leg restlessness in an anxious patient is "just anxiety"—perform a careful diagnostic evaluation using the five essential RLS criteria. 5
Do not prescribe SSRIs or tricyclic antidepressants for comorbid anxiety without first considering their RLS-exacerbating effects. 1, 9
Do not confuse the physiological manifestations of anxiety (racing heart, tight chest, panic) with the specific sensorimotor urge to move and dysesthesias of RLS. 6, 1
Recognize that treating RLS effectively may reduce overall distress and potentially improve comorbid anxiety symptoms, as RLS-related sleep disruption affects roughly 90% of patients and contributes to mood disturbance. 1