Restless legs at night are primarily caused by a drop in dopamine activity in the brain that follows your body’s internal clock, making symptoms peak in the evening and overnight hours. About 7% of adults worldwide experience restless legs syndrome (RLS), a condition where uncomfortable sensations and an irresistible urge to move the legs intensify during periods of rest, particularly at bedtime. The underlying triggers range from low iron stores in the brain to pregnancy, kidney disease, certain medications, and genetic predisposition.
Why Symptoms Get Worse at Night
RLS has a distinct circadian pattern. The uncomfortable sensations and urge to move typically appear or intensify in the evening, peak between roughly 10 p.m. and 2 a.m., and ease by morning. This isn’t random. It’s tied to your body’s 24-hour biological rhythms, specifically to shifts in dopamine signaling, core body temperature, and melatonin release that happen as night falls.
Your brain’s dopamine system, which helps regulate movement and sensory processing, naturally dips in the evening. At the same time, your pineal gland begins releasing melatonin once darkness sets in. Melatonin can suppress dopamine release by reducing calcium flow into nerve endings, deepening the dopamine deficit that drives RLS. Research shows that the onset of melatonin secretion closely coincides with when RLS symptoms begin worsening at night. In one study, administering melatonin to RLS patients significantly worsened their motor symptoms, while suppressing melatonin with bright light exposure actually improved sensory symptoms.
Core body temperature also plays a role. RLS symptoms tend to be most intense right around the low point of your nightly temperature cycle. The combination of falling body temperature, rising melatonin, and declining dopamine creates a window where the brain’s movement-control circuits are most vulnerable to misfiring.
The Iron and Dopamine Connection
The most well-established biological cause of RLS is low iron levels in the brain, even when blood iron levels look completely normal on a standard test. Iron is essential for dopamine receptors to function properly. When iron is depleted in the parts of the brain that control movement, those receptors underperform, and the result is the crawling, tingling, or aching sensations that define RLS.
This is why clinicians check a blood marker called ferritin, which reflects your body’s iron stores. Current treatment guidelines recommend iron supplementation when ferritin falls below 75 mcg/L, with the goal of raising it above 100 mcg/L. That 75 mcg/L threshold is well within the “normal” range on most lab reports, which means many people with RLS-related iron deficiency are told their iron is fine. If you’ve had blood work and been told your levels are normal, it’s worth asking for the specific ferritin number.
Genetics and Family History
RLS runs strongly in families. A large genome-wide analysis published in Nature Genetics identified 164 genetic risk locations linked to the condition, including regions involved in glutamate signaling (a brain chemical that helps nerve cells communicate). If one or both of your parents had restless legs, your chances of developing it are significantly higher. People with a family history of RLS also tend to develop symptoms earlier in life, often before age 45.
Pregnancy
Nearly one in three pregnant women develops RLS, and the condition heavily favors the third trimester. In one study of 500 pregnant women, 29.2% met diagnostic criteria for RLS. Of those, 64.4% were in their third trimester, compared to just 4.8% in the first. Symptom severity also climbed as pregnancy progressed.
The reasons are layered. Iron and folate demands spike as the fetus grows, drawing down the mother’s reserves. Hormonal shifts, including changes in thyroid hormone levels, also appear to contribute. Higher thyroid-stimulating hormone and free T4 levels were significantly associated with third-trimester RLS in the same study. The good news: for most women, symptoms resolve within weeks of delivery.
Kidney Disease
People with advanced kidney disease have some of the highest rates of RLS. Up to 62% of patients with end-stage kidney disease on dialysis are affected, compared to the 5% to 15% rate in the general population. Failing kidneys struggle to clear waste products from the blood and often can’t produce enough of the hormone that stimulates red blood cell production, leading to anemia and poor iron availability. The combination of iron depletion, metabolic waste buildup, and disrupted mineral balance makes the condition especially persistent in this group.
Medications That Trigger or Worsen RLS
Several common medications can bring on restless legs or make existing symptoms noticeably worse. The main culprits fall into four categories:
- Antidepressants: SSRIs and SNRIs (like fluoxetine, sertraline, and venlafaxine), tricyclic antidepressants, mirtazapine, and trazodone are all associated with worsening RLS. These drugs affect serotonin and norepinephrine, which can indirectly suppress dopamine activity.
- Antihistamines: Over-the-counter allergy and sleep medications that block the H1 receptor (the active ingredient in many nighttime cold remedies and sleep aids like diphenhydramine) are a frequent and underrecognized trigger.
- Antipsychotics: Medications that block dopamine receptors directly, such as olanzapine, risperidone, and quetiapine, can provoke or intensify symptoms.
- Anti-nausea drugs: Certain anti-nausea medications that block dopamine, particularly metoclopramide, are known triggers.
If your restless legs started or worsened after beginning a new medication, that timing is worth flagging. Switching to an alternative within the same class can sometimes resolve symptoms entirely.
Caffeine, Alcohol, and Nicotine
Caffeine and alcohol have long been listed as RLS aggravators, and avoiding both in the evening is a standard recommendation. The evidence on caffeine is mostly observational, but many people with RLS report a clear connection between afternoon or evening caffeine and worse symptoms at bedtime.
Nicotine’s relationship with RLS is more complicated than you might expect. Smoking is generally discouraged, and some studies have found a higher incidence of smokers among RLS patients. But nicotine stimulates dopamine release, and a subset of patients report that smoking temporarily relieves their symptoms for 20 to 30 minutes. One Italian study found that 12% of RLS patients smoked during the night, compared to just 2% of controls, suggesting some people may be self-medicating. This doesn’t make smoking a treatment, but it illustrates how central dopamine is to the condition.
How RLS Is Identified
There is no blood test or scan that confirms RLS. Diagnosis is based on five clinical criteria established by the International Restless Legs Syndrome Study Group. You need to have an urge to move your legs (usually accompanied by uncomfortable sensations), symptoms that begin or worsen during rest, relief with movement, symptoms that are worse in the evening or night, and importantly, symptoms that can’t be better explained by another condition like leg cramps, positional discomfort, or peripheral neuropathy. That fifth criterion, ruling out mimics, was added specifically because so many other conditions can feel similar.
Blood work for ferritin, kidney function, and thyroid levels is typically part of the evaluation, since identifying a treatable underlying cause can make symptoms resolve without long-term medication. Iron supplementation alone, when ferritin is low, improves symptoms for a meaningful number of people.