What Causes Restless Legs Syndrome (RLS)?

Medically Reviewed by Christopher Melinosky, MD on June 07, 2021
2 min read

The specific causes of restless legs syndrome (RLS) are not known. Disease in the blood vessels of the legs or in the nerves in the legs that control leg movement and sensation was once thought to cause RLS, but both of these suggestions have been rejected.

RLS may be related to abnormalities in brain chemicals (neurotransmitters) that help regulate muscle movements, or to abnormalities in the part of the central nervous system that controls automatic movements. Research is still being done in these areas.

RLS can sometimes be caused by an underlying medical condition (secondary RLS); however, most of the time the cause is not clear.

Many different medical conditions have been linked to RLS. The two most common conditions are iron-deficiency anemia (low blood count) and peripheral neuropathy (damage to the nerves of the arms and legs, often caused by underlying conditions such as diabetes).

Other medical conditions linked to RLS include:

  • Parkinson's disease
  • Varicose veins
  • Some tumors
  • Fibromyalgia
  • Hyper- or hypothyroidism (over- or underactive thyroid glands)
  • Pregnancy
  • Cigarette smoking
  • Vitamin and mineral deficiency, such as magnesium deficiency and vitamin B-12 deficiency
  • Severe kidney disease and uremia (kidney failure causing build up of toxins within the body)
  • Amyloidosis (build-up of a starch-like substance in the body's tissues and organs)
  • Lyme disease
  • Damage to spinal nerves
  • Rheumatoid arthritis and Sjögren syndrome
  • Certain medications or substances, such as:
  1. Alcohol
  2. Caffeine
  3. Anticonvulsant drugs (such as Dilantin)
  4. Antidepressant drugs (including amitriptyline, Paxil)
  5. Beta-blockers (drugs often used to treat high blood pressure)
  6. Antipsychotics
  7. Antihistamines
  8. Withdrawal from certain drugs, such as vasodilator drugs (for example, Apresoline), sedatives, or antidepressants (for example, Tofranil)

In many cases, RLS seems to run in families. People with a genetic link to RLS tend to get the condition earlier in life.

Find out how doctors diagnose restless legs syndrome.
Learn about restless legs syndrome treatments.
View the full table of contents for Your Guide to Sleep Disorders.