Can Restless Legs Syndrome (RLS) cause depression and anxiety in patients?

RLS Likely Causes Depression and Anxiety, Not the Other Way Around

The evidence strongly suggests that RLS is the primary driver of depression and anxiety symptoms in affected patients, rather than these psychiatric conditions causing RLS. This is supported by the specific nature of depressive symptoms in RLS patients, the temporal relationship between conditions, and the distinct diagnostic criteria that separate RLS from anxiety disorders.

Evidence Supporting RLS as the Primary Cause

Depressive Symptoms Are Predominantly Somatic, Not Cognitive

• RLS patients score highest on somatic items of depression scales—particularly "reduced sleep," "loss of energy," and "work difficulties"—rather than on cognitive symptoms like guilt, worthlessness, or suicidal ideation 1
• This pattern suggests that depression in RLS patients stems from the physical burden of the disease (sleep disruption, exhaustion) rather than representing a primary psychiatric disorder 1
• The mean Beck Depression Inventory score in untreated RLS patients was 9.3, with only 17% meeting criteria for even mild depression, indicating that most patients experience somatic symptoms without full depressive syndrome 1

RLS Severity Correlates with Sleep Disruption, Which Then Drives Mood Symptoms

• RLS severity correlates significantly with impaired sleep quality (r=0.281, p=0.007) but not directly with depressive symptoms (r=0.119, p=0.237) 1
• However, anxiety and depression severity do correlate with RLS severity (r=0.21, p=0.03 for anxiety; r=0.201, p=0.04 for depression) 2
• This suggests a pathway where RLS → sleep disruption → secondary mood symptoms, rather than mood disorders causing RLS 1

Temporal and Causal Attribution Evidence

• Patient causal attributions suggest that "a considerable proportion of the excess morbidity for depression and panic disorder might be due to RLS symptomatology" 3
• The onset of RLS symptoms is unrelated to the onset, duration, or number of depressive episodes, arguing against depression causing RLS 4
• RLS symptoms follow their characteristic circadian pattern (worsening in evening/night) regardless of anxiety or depression status, indicating independent pathophysiology 5

Why Anxiety Doesn't Cause RLS: Diagnostic Distinction

RLS Has Specific Sensorimotor Criteria That Anxiety Cannot Fulfill

• 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
• RLS involves an uncomfortable urge to move the legs with abnormal sensations (dysesthesias), not the physiological somatic symptoms of anxiety like muscle tension or restlessness 5
• RLS symptoms are relieved by movement and return when movement stops, whereas anxiety-related restlessness persists despite movement 5
• RLS symptoms worsen specifically in evening/night, which is not characteristic of generalized anxiety 5

The Comorbidity Reflects Shared Consequences, Not Causation

• Meta-analysis confirms significantly higher depression (Beck Depression Inventory MD=6.58,95% CI=5.54-7.62) and anxiety (Beck Anxiety Inventory MD=9.30,95% CI=7.65-10.94) in RLS patients versus controls 6
• However, RLS patients have increased risk specifically for panic disorder (OR=4.7), generalized anxiety disorder (OR=3.5), and major depression (OR=2.6)—conditions that share sleep disruption as a common feature 3
• The American Academy of Sleep Medicine recognizes that insomnia is present in roughly 90% of RLS patients and is the primary morbidity, explaining the pathway to mood disorders 7

Clinical Implications: Treat RLS First

Avoid Psychiatric Medications That Worsen RLS

• The American Academy of Sleep Medicine recommends avoiding tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists when treating comorbid anxiety/depression in RLS patients, as they exacerbate RLS symptoms 5
• This creates a therapeutic dilemma if clinicians mistakenly assume anxiety/depression is primary and prescribe these agents, which will worsen the underlying RLS and perpetuate the cycle 5

Optimize RLS Treatment to Improve Mood

• Check serum ferritin and supplement if ≤75 ng/mL or transferrin saturation <20%, as this may improve both RLS and potentially mood symptoms 5
• Use first-line alpha-2-delta ligands (gabapentin, pregabalin) for RLS, which address the root cause without worsening mood 7
• Consider non-serotonergic anxiolytics or cognitive-behavioral therapy for residual anxiety after RLS is controlled 5

Common Pitfall to Avoid

Do not assume leg restlessness in an anxious patient is "just anxiety"—perform careful diagnostic evaluation using the five essential RLS criteria, specifically asking about urge to move (not just discomfort), relief with movement, return of symptoms when movement stops, and evening/night predominance 5, 8. Missing RLS and treating only with antidepressants/anxiolytics will worsen the patient's condition and perpetuate the psychiatric symptoms 5.