Restless Legs Syndrome
– Diagnosis & Treatment
Restless legs syndrome (RLS) is diagnosed by a set of symptoms, so the diagnosis and treatment often get overlooked … just like fibromyalgia. RLS is a painful disease that disrupts sleep and involves abnormalities in the central nervous system. Close to one-third of fibromyalgia patients have RLS, making it important for patients to know how RLS is diagnosed and treated.1
Hallmark Symptoms
Patients often describe RLS in a variety of ways that may be perplexing to a physician. When one is winding down in the evening, there is a relentless urge to move or stretch just to escape the unpleasant sensations. The symptoms are often described as being located deep inside the legs.
Common descriptions from patients include:
- Insects/worms moving in the legs
- Twitching/grabbing sensations
- Pulling, throbbing, aching
- Electric current, soda bubbling
- Tingling, tightness, itchy bones
By bedtime, the desire to move one’s legs becomes more intense. Stretching eases the discomfort, but only for a fleeting moment. Yet it’s impossible to resist the temptation to move. Sleep is deteriorated by the uncomfortable restlessness. However, when you are in your doctor’s office the next day, the insatiable desire to move is gone and describing the symptoms is a challenge.
The urge to move and a nervous system that won’t settle down leads to disrupted sleep, making patients tired and less cognitively alert. While RLS is classified as a sleep disorder, the diagnosis doesn’t rest on a sleep study. Instead, the diagnosis is based on the urge to move your legs (or arms) PLUS all the following:2
- Related to unpleasant sensations
- Made worse by inactivity
- Partially relieved by movement
- More severe in the evening/nighttime
Eighty percent of RLS patients exhibit periodic limb movements during sleep (PLMS) but this is not required for the diagnosis. The uncontrollable limb jerking not only disrupts your sleep but also that of your bed partner.
What Causes RLS?
Iron levels in the brain are low in RLS patients but it is not completely clear how this causes sensory symptoms or PLMS. The condition was initially thought to be due to dopamine levels in the brain because treatment with dopamine boosting agents often relieves the symptoms. But RLS also involves alterations in other transmitters.3
There is an imbalance between not enough GABA and too much glutamate in the central nervous system. In turn, this impedes the nervous system’s ability to tone down sensory signals (causing pain) while motor control circuits are hyperactive (promoting movement).
GABA and glutamate changes are also found in fibromyalgia and may explain the high incidence of RLS in this condition. However, brain iron levels differ between the two diseases.
Treatments
First, your doctor needs to order two iron-related blood tests: serum ferritin and transferrin saturation. If your iron levels are low, it reduces the effectiveness of medications your doctor prescribes for RLS. So, bringing your iron levels up to the target range must be the first order of business.
The recommended method of iron treatment depends on your results, but the goal is to maintain ferritin between 100-120 ng/ml. Also, regular testing is required because a dip in iron levels can cause a worsening of symptoms.4
Serum ferritin below 75 ng/ml or transferrin saturation below 20%: Supplement with oral ferrous sulfate (325 mg/day). Take on an empty stomach with vitamin C to improve absorption. Talk to your doctor about minimizing constipation and GI issues. If these problems cannot be resolved, you may be a candidate for intravenous therapy.
Serum ferritin is between 75-100 ng/ml: Treat with intravenous iron, preferably in the form of ferric carboxymaltose. Insurance coverage for this treatment can be tricky but it won’t cause constipation.
RLS is no longer treated with medications that boost dopamine because they cause the symptoms to spread with prolonged use. Instead, three medications in the gabapentinoid class are used to raise GABA and lower glutamate. They are gabapentin encarbil (600 mg extended-release formula), gabapentin, and pregabalin. The latter two drugs may be taken in divided doses in the late afternoon and evening.
You also need to avoid medications that trigger RLS flare ups. The antihistamine, Benadryl, is the biggest offender. If your allergies act up, try the generic of Claritin or Zyrtec. Serotonin-boosting drugs can also be problematic in 5-10% of patients.
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References for RLS & Fibro
- Viola-Saltzman M, et al. J Clin Sleep Med 6(5):423-427, 2010. Free Report
- Xu Y, Guan Y, Lang B. Int J Gen Medicine 18:4041-4055, 2025. Free Report
- Ferre S, et al. Neuroscientist 25(2):113-125, 2019. Free Report
- Winkelman JW, et al. J Clin Sleep Med 21(1):137-152, 2025. Free Report