Benadryl and restless legs

“In general,” he added, “it’s important for physicians to be up to date with their clinical recommendations for all medications and the associated side effects in the treatment of RLS. For example, there are some antidepressants that will have less negative impact on RLS compared with others.”

Dr. Lawrence Chan, Assistant Professor of Sleep Medicine at the Ohio State University Wexner Medical Center in Columbus, noted that while it’s important to increase awareness of potential worsening of RLS with serotonergic antidepressants, not using those drugs “significantly limits the treatment options for depression.”

“Bupropion is an antidepressant that is not known to worsen RLS and treating both disorders simultaneously is another option,” he said “In regards to other medications that can increase RLS symptoms, antihistamines and antipsychotics are often used off label for insomnia, so it is important to rule out RLS as an underlying cause of the sleep disturbance.”


Sleep Med 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions –

8 Triggers That Make Restless Legs Worse

  • Stress and anxiety. Rachel Salas, MD, an assistant professor of neurology at the Johns Hopkins University School of Medicine in Baltimore, says that stress and anxiety are big restless legs triggers. Stress reduction techniques like deep breathing or yoga may help.
  • Nicotine. If you need another reason to stop smoking, calming your restless legs is a good one. Talk with your doctor if you think you need help quitting.
  • Alcohol. Many people with RLS report that drinking can lead to more restless legs symptoms. Although alcohol can help people fall asleep quickly, it interferes with the quality of sleep and can make sleep apnea worse , says Alon Avidan, MD, MPH, an associate professor of neurology and director of the Sleep Disorders Clinic at UCLA. Try omitting alcohol to see whether your restless legs improve and whether you feel more rested in the morning.
  • Vigorous exercise. Getting moderate exercise during the day can help ease restlessness at night. But vigorous exercise, especially close to bedtime, can have the opposite effect in some people.
  • Medications. A number of medications can make RLS worse. In particular, anti-nausea drugs and sedating antihistamines (like Benadryl) block the brain’s dopamine receptors, causing restless legs symptoms. Antidepressants that increase serotonin and antipsychotic medications can also aggravate the condition. Let your doctor know if your restless legs symptoms worsen after you take a new medication. A change in dosage or to a different medication may do the trick.
  • Caffeine. Because caffeine is a stimulant, it can interfere with sleep if it’s consumed too close to bedtime. It’s long been on the list of restless legs triggers, but Dr. Salas says recent research shows it may not be that big of a problem. In fact, she says, it may be beneficial in some people. Try cutting out coffee, tea, colas, sports drinks, and even chocolate to see if your symptoms improve or worsen.

Other Restless Legs Triggers

Other health conditions can also cause restless legs. This is what’s called secondary restless legs syndrome:

  • Pregnancy. According to Dr. Avidan, about 20 percent of pregnant women report restless legs symptoms. This is more likely in the last three months of pregnancy, and iron deficiency is usually the culprit. If symptoms crop up when you’re expecting, your doctor will probably test the level of iron in your blood and prescribe iron supplements if it’s too low. The good news is that your restless legs symptoms will probably go away soon after you have your baby.
  • Medical conditions. Restless legs symptoms are also seen in some people with kidney failure and diabetes. Treating these conditions will often calm the restless legs.

The Restless Legs Syndrome Foundation suggests using a sleep diary to pinpoint your personal triggers and gauge the severity of your symptoms. Always tell your doctor if your symptoms get noticeably worse.

Restless Legs Syndrome Foundation Blog

October 4, 2018

Know Your Triggers

A trigger is a stimulus that causes a worsening of your RLS. Certain foods, beverages, medicines, excessive stress or exercise can be the source of a trigger. Triggers can vary from one person to another and even among members of the same family. For example, caffeine may be a trigger for one person but not another. All individuals with RLS can benefit from learning what triggers their RLS in order to avoid these substances.

Some common RLS triggers reported by individuals with RLS include:

Carbohydrates and refined sugars
Foods high in sodium
Extreme exercise
Emotional stress
Over-the-counter medications
Prescribed medications

Sleep Habits

Sleep deprivation is known to worsen RLS symptoms. Good sleep habits such as maintaining a cool, dark sleeping environment, removing electronics from the bedroom to limit exposure to blue light and adhering to a schedule of bed and wake times are key to a restful night’s sleep.


It is important to be knowledgeable about medications that are acceptable for use and those best avoided by individuals with RLS. Many prescribed and over-the-counter medications are known to aggravate RLS symptoms. The RLS Foundation Medical Alert Card lists important information about these medications on a small card that fits into your wallet so you can easily share it with your doctor, hospital and family members. Diphenhydramine (Benadryl) is an antihistamine commonly found in cold remedies and sleep aids; any over-the-counter medication containing diphenhydramine should be avoided. Decongestants like pseudoephedrine (Sudafed) can severely disrupt sleep for those with RLS. Contrary to popular belief, melatonin may worsen symptoms because of the serotonergic properties (serotonin regulates sleep, mood and appetite) found in the medication. St. John’s Wort, an herbal supplement believed to help with depressive symptoms, can cause a flare up of RLS symptoms in some individuals.

Drugs in the antipsychotic (haldol and seroquel), anti-nausea (phenergan and compazine) and antidepressant (mirtazapine) medication classes are often the culprit for a worsening case of RLS. You should never discontinue use of a medication without consulting your healthcare provider, the RLS Foundation’s Medical Bulletin contains suggestions for safe alternatives to these medications to share with your physician. If you have an upcoming surgery, it is helpful to alert your surgical team to which medications they should avoid so they are prepared.

Although certain medications may be hard to avoid, it is crucial to be vigilant about the ingredients in any of the medications you take. No one knows your RLS triggers better than you; not even your healthcare provider. When you are knowledgeable about your own triggers, you can avoid those substances before they worsen your RLS!

Q. One parent and all of my siblings have restless legs syndrome. So do I.

Benadryl, specifically its primary ingredient diphenhydramine, absolutely aggravates my RLS. I avoid it and anything else that contains it, such as the PM pain medications.

Certain nausea medications also make RLS worse. The one I recall is Phenergan.

Don’t assume your physician knows this. Several doctors I spoke with knew nothing about it. As far as I’m concerned, I’m allergic to these drugs, and list them in my records accordingly.

A. Restless legs syndrome (RLS) is characterized by an urgent feeling that you need to move your legs. Moving them alleviates sensations of crawling, itching or throbbing, but this frequently keeps people awake. You are quite right that diphenhydramine can aggravate RLS symptoms (National Institute of Neurological Disorders and Stroke). We think people who take PM pain relievers containing diphenhydramine should be alerted to this potential reaction.

Q. I was diagnosed with Barrett’s esophagus after years of daily PPI use. My then-gastroenterologist had prescribed it. However, what I thought was excess stomach acid as the cause for my indigestion, ironically, was low stomach acid. I believe this was caused by my hypothyroid condition.

My integrative cardiologist subsequently diagnosed the thyroid problem and prescribed natural desiccated thyroid (NDT). My Barrett’s esophagus cleared up and I no longer need a PPI at all. I control my digestive upsets with diet, hydrochloric acid pills, digestive enzymes and a commercial antacid if I really need it.

A. Thank you for alerting us to the link between hypothyroidism and achlorhydria. This is the medical term for low stomach acid. Although this is documented in the medical literature, we suspect that most people are unaware of the connection (World Journal of Gastroenterology, June 21, 2009).

Desiccated thyroid gland can be used to treat hypothyroidism. It supplies both T3 and T4 thyroid hormones.

Q. Thank you for writing about beta blockers making you feel like rubbish. I was diagnosed with high blood pressure eight years ago (140/80). My doctor prescribed atenolol.

It did NOTHING for my blood pressure, so after a couple of months my GP added perindopril. WOW! My blood pressure went to 120/70 in two days.

In the meantime, my heart rate that was formerly 80 or 90 BPM was now at 60 or less. Any task was so tiring! I have now passed 60 years of age and I could barely split wood.

When I realized this might be due to the atenolol, I halved the dose for two weeks, then halved it again for another two weeks. Now, a month later, my resting heart rate is back to 80. My blood pressure is 125/75 thanks to the perindopril. I can split wood, walk and even run again. For the past eight years on the beta blocker, I felt like I would pass out if I tried to run. Cheers from Australia.

A. Perindopril (Aceon) is an ACE inhibitor and is considered a first-line blood pressure treatment. Beta blockers, on the other hand, are no longer deemed the best choice for blood pressure control. They can cause fatigue and slow heart rate.

Write Joe and Teresa Graedon via their website:

Treatment for Restless Legs Syndrome Focuses on Relieving the Symptoms

March 1, 2013

Dear Mayo Clinic:

Is restless legs syndrome hereditary? Is there an effective treatment, or does a diagnosis of RLS mean I will have it for life?


Restless legs syndrome, or RLS, is not always hereditary. But it does run in some families, and several genetic links have been found for RLS. While restless legs syndrome is most often a chronic condition, treatment is available that often can effectively control its symptoms.

Restless legs syndrome is a condition characterized by an unpleasant or uncomfortable urge to move your legs. Some people describe it as a crawling, pulling or burning sensation in their thighs, calves or feet. The sensation is temporarily relieved when you get up and move around, especially by walking, or when you shift or stretch your legs. RLS symptoms typically begin after you have been sitting or lying down for some time. Symptoms also tend to get worse in the evenings and at night, and are less bothersome during the day.

In many cases of RLS, the cause is unknown. But RLS appears to be hereditary in about half the people who have it. Several specific gene variations have been associated with this disorder. Familial RLS symptoms often begin earlier in life — usually before age 40 — than they do in forms of the disease that are not hereditary.

In some cases, RLS may be related to another underlying medical condition. For example, some people with symptoms of RLS are found to have iron deficiency. In these situations, taking iron supplements may eliminate symptoms of restless legs syndrome.

Treatment for RLS usually focuses on relieving the symptoms. A variety of simple steps you can take at home may help. Taking a warm bath, massaging your legs, applying warm or cool packs, and trying relaxation techniques, such as yoga or meditation, can all be useful in calming RLS. Exercising at a moderate level on a regular basis and establishing good sleep habits can help, too. For some people, caffeine, alcohol and tobacco can trigger RLS symptoms or make them worse. You may want to try cutting back on these substances to see if your symptoms lessen.

If lifestyle changes are not enough, your doctor may prescribe medication to reduce leg restlessness. Medications that have been shown to be helpful for RLS include several that affect a chemical in your brain called dopamine. Dopamine’s job is to send messages from your brain to your body that control muscle movement. Researchers suspect that RLS may be linked to an imbalance in dopamine.

Using drugs that stimulate dopamine receptors in the brain, such as ropinirole, pramipexole or rotigotine, can help control RLS symptoms. Side effects of dopamine medications, however, may include nausea, sedation or, rarely, certain compulsive behaviors such as shopping or gambling. Caution and long-term follow-up for the use of these mediations is necessary.

Certain medications used to treat painful nerve conditions and epilepsy, such as gabapentin, also may effectively treat RLS. Other prescription drugs, including opioid analgesics, muscle relaxants and sleep medications, are sometimes used to help combat RLS symptoms as well.

Be aware that certain medications can make RLS symptoms worse, including some antidepressants and anti-nausea drugs. Review with your doctor a list of the medications you are currently taking. Your doctor may recommend substitutes, as needed, to help manage RLS.

If restless legs syndrome disrupts your daily life or hurts your overall quality of life, consider seeking specialty care. A sleep medicine physician or a neurologist can evaluate your condition and work with you to create a treatment plan that fits your situation.

— Erik St Louis, M.D., Neurology, Mayo Clinic, Rochester, Minn.

Relieving Discomfort: There are a few simple changes that people can make to help relieve some of their symptoms. Avoiding caffeine and alcohol sometimes helps people whose symptoms are aggravated by these drugs. Since bedtime is often a time when symptoms intensify, some sufferers find a bath helpful to relax the leg muscles just before retiring. Biofeedback or other relaxation techniques can also help patients who have a difficult time falling asleep.

Ropinirole is a medication shown to help control the symptoms of Parkinson’s disease. It has been proved effective in patients with moderate to severe restless legs syndrome and was recently approved by the FDA. Some patients also find relief with low doses of muscle relaxants, anti-seizure medications, painkillers, or sleeping aids. Treatment must be tailored to the patient based on individual needs and severity of symptoms. There is no cure for restless legs syndrome, but with proper diagnosis and patient care, the symptoms can, in most cases, be controlled.

A Breakthrough for Restless Legs Syndrome?

For the millions who suffer from Restless Legs Syndrome, sleep can be exceedingly difficult and disrupted. RLS is a neurological disorder and a sleep disorder, a condition that causes tingling, twitching, “creepy-crawly” feelings in the legs. These uncomfortable sensations bring about an often-urgent need to move the legs. The symptoms of RLS are most often felt when a person is lying still for a period of time, and are frequently experienced at bedtime. People with RLS commonly experience symptoms of insomnia—difficulty falling asleep and staying asleep. Medications for RLS can be successful in alleviating the twitching and tingling sensations in the lower body, but very often the insomnia symptoms remain, leaving people with RLS coping with chronic sleep problems even after the other RLS symptoms have disappeared.

This is just one of the puzzling aspects of RLS, a condition that has proved mysterious and difficult to understand, diagnose, and treat. But new research may have delivered an important breakthrough in our understanding of how RLS works in the body, and why sleep problems can stubbornly persist even after successful treatment for tingling, twitching legs.

Researchers at Johns Hopkins University School of Medicine investigated the relationship between brain chemistry and sleep among patients with RLS. They discovered abnormally high levels of a brain chemical involved in stimulating arousal. The brain chemical glutamate is an important neurotransmitter that arouses both the brain and the central nervous system. Researchers found elevated levels of glutamate present in the brains of patients with RLS. Abnormal levels of glutamate may help explain why RLS patients continue to have trouble sleeping, even after other medications have quieted the disruptive sensations in their legs.

Researchers evaluated 48 adults, including 28 patients with RLS and 20 subjects without the condition. Those with RLS had experienced symptoms of the condition for at least 6 months, on 6 or 7 nights per week. Researchers first measured glutamate levels in the brain using MRI. They then spent two days measuring participants’ sleep. They found significantly higher levels of glutamate among RLS patients than in those without the condition. Among the RLS patients in the study, those with higher levels of glutamate experienced more severely disrupted sleep.

This was a small study, and we’ll need to see follow-up research on a larger scale to confirm and further establish the role of glutamate in RLS. But these findings could represent an important step forward in our understanding of RLS. What’s more, this new information could bring about significant changes in treatment of the condition.

Previous research and treatment for RLS has focused on another of the brain’s neurotransmitters: dopamine. Dopamine plays an important role in muscle activity and body movement, and dopamine deficiency can result in involuntary muscle movement. Several drug treatments for RLS involve raising levels of dopamine, in order to soothe the involuntary twinges and intense urges to move the legs. But these drugs have not been successful in improving RLS patients’ sleep.

This new research may deliver an important piece of information to the RLS-sleep puzzle. High levels of glutamate in patients with RLS may be preventing these patients from sleeping well, a problem that is not currently being addressed by the array of dopamine-related medications being used to treat other symptoms of the condition.

As many as 10% of adults in the U.S. suffer from RLS, according to the National Sleep Foundation. RLS is a condition that very often goes undiagnosed or misdiagnosed. RLS can often be misdiagnosed as another sleep disorder or another neurological disorder, a muscular disorder. Depression is another common misdiagnosis for RLS. Research shows a strong association between depression and RLS. People with RLS appear to be at a significantly elevated risk for depression. The poor sleep experienced by so many RLS patients may play a role in their increased risk for depression. In addition to chronic sleep problems and depression, patients with RLS also appear to be at elevated risk for other serious health conditions, including hypertension and coronary heart disease. The cause of RLS is not known, but the condition does run in families, and recent research has shown evidence of a genetic link.

This latest research is an exciting breakthrough, with the potential to transform our understanding of RLS. There are many steps still to take, and questions to be explored and answered, before we know what changes are best made to the way we treat RLS. But for a condition that has often confounded experts, and caused such discomfort, disruption, and sleeplessness to so many patients, this study brings both welcome and encouraging news.

Sweet Dreams,

Michael J. Breus, PhD

The Sleep Doctor®

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