Depression and RLS

October 27, 2018 Help, Hope and Treatment By Brian B. Koo, MD This is an excerpt from the fall 2018 edition of NightWalkers, the...

October 27, 2018

Help, Hope and Treatment

By Brian B. Koo, MD

This is an excerpt from the fall 2018 edition of NightWalkers, the Foundation's quarterly magazine. To get your subscription to NightWalkers and to enjoy other benefits, become a member of the Restless Legs Syndrome Foundation today!

Individuals suspecting they may have RLS should consult a qualified healthcare provider. Literature posted by the RLS Foundation, including this blog post, is offered for informational purposes only and should not be considered a substitute for the advice of a healthcare provider. Prior to making any changes to your treatment plan, please discuss treatment options with your healthcare provider.

As anyone who has restless legs syndrome (RLS) knows, RLS can be incredibly disabling, especially when it is severe. Chronic sleeplessness and the recurring need to battle against RLS, night after night, can leave a person feeling helpless.

Helplessness and sentiments that the battle cannot be won, may then lead to hopelessness. Helplessness and hopelessness are both cardinal features of major depressive disorder, so it is no surprise that depression is quite common among those with RLS. In fact, between 40 and 60 percent of people with RLS suffer from a major depressive episode within their lifetime –more than three times the rate for people without RLS. Other anxiety and mood disorders are also common for people with RLS, including panic disorder, generalized anxiety disorder, and dysthymia, a type of near-constant, low-level depression.

If you are suffering from both RLS and depression, there is hope – both are treatable conditions. One possible key to treating your depression is to effectively treat your RLS. If your RLS symptoms are severe or uncontrolled, it is important to seek the care of a healthcare provider who is experienced in treating RLS. In short, this care includes:

  • Eliminating factors that trigger RLS, such as alcohol, caffeine and certain over-the-counter and prescribed medications (for a comprehensive list, see the handout RLS Triggers, available at
  • Checking blood iron and ferritin levels, and offering iron therapy if appropriate
  • Ensuring proper sleep hygiene
  • Assessing for sleep apnea, which is critical if there are symptoms of snoring or breathing irregularities
  • Treating RLS with medication

Of course, if depression is severe or persists even if RLS is controlled, it will be important to treat the depression with medication and/or psychotherapy. An experienced and qualified provider, preferably a psychiatrist, should provide this treatment. Simplistically, depression can be treated in three main paths: 1) healthy lifestyle, 2) psychotherapy and 3) pharmacotherapy (drug therapy).

A healthy lifestyle is essential for good mental health. This includes getting adequate aerobic exercise, eating a sensible diet, and engaging in regular social activity. Psychotherapy, whether from a psychiatrist, trained psychologist, social worker or simply someone with a good caring ear, is of utmost importance. Depression is very isolating, and sharing this experience with another person is an important step to ease the burden of isolation.

Finally, pharmacotherapy can also be extremely helpful. It should be noted, however, that pharmacotherapy will be most effective when combined with both psychotherapy and a healthy lifestyle. Medicine is by no means a silver bullet for treating depression, just as it is not a silver bullet for treating RLS.

Each of the potential therapies for depression requires active participation Brian B. Koo, MD from the patient. In addition to getting to the gym and out to social events, the patient should make the effort to find a psychotherapist, psychiatrist or someone with a good caring ear.

Choosing the right medicine to treat depression when one has RLS can be tricky, as many, if not most antidepressant medications can worsen RLS symptoms. This largely occurs through two different pharmacologic mechanisms: 1) by increasing serotonin levels and 2) by blocking histamine receptors.

Most antidepressant medications work by increasing availability of certain brain chemicals called neurotransmitters –particularly serotonin. Unfortunately, increasing serotonin worsens symptoms of RLS. One antidepressant, bupropion (Wellbutrin), works by increasing availability of the neurotransmitters dopamine and norepinephrine but not serotonin, so this antidepressant may be the first thing to try for treating depression in someone who has RLS. Of course, all medicines have side effects, and not all people with RLS will respond to bupropion or be free of side effects. It may be essential to try another antidepressant, even if it increases serotonin and has the potential to worsen RLS.

In general, histamine blockade medications, or antihistamines, are well known to make RLS worse. The prototypical medicine in this class is diphenhydramine (Benadryl). Many antidepressant medicines also have antihistamine-like qualities and should be avoided. These include mirtazapine (Remeron), doxepin (Silenor), amitriptyline (Elavil) and most other tricyclic antidepressants, with the exception of desipramine. These antidepressants are sedating; thus, a provider inexperienced in treating RLS may offer them unsuspectingly to the RLS patient, thinking that they will aid with sleep.

What I tell my patients is, if you are very depressed, even if a medicine may worsen your RLS symptoms, it is very important to treat your depression and try the medication if you’ve already explored nondrug treatments. You should not worry about whether or not the medicine will worsen your RLS. The selective serotonin reuptake inhibitors, or SSRIs, are commonly used antidepressants and can be very helpful, even for people who have RLS. The SSRIs sertraline (Zoloft) and citalopram (Celexa) may be a good start and are less activating, or stimulating, than fluoxetine (Prozac) or venlafaxine (Effexor), which may cause anxiety. In the end, individuals will have very different responses to different antidepressants, so you may need to try more than one medicine to find one that works for you.

When treating RLS with medications, another very important fact to keep in mind is that any medicine that blocks dopamine, particularly antipsychotic medications, should be avoided. Antipsychotic medications are often used by psychiatrists in addition to antidepressants, especially when a patient has insomnia, as antipsychotics are often sedating. These medications worsen RLS, so they should not be used to treat depression or sleeplessness when patients have RLS.

Both RLS and depression are treatable. Unfortunately for some, proper treatment steps are not taken because of problems with healthcare access or other issues. The most serious consequences of the undertreatment of depression are suicidal thoughts and of course, suicide itself. In a recent research study, “Suicidal Thought and Behavior in Individuals with Restless Legs Syndrome,” which was completed at Yale University and will be published in the journal Sleep Medicine, researchers found that 27.1 percent of people with RLS had either suicide plans or attempts over their lifetimes, compared to just 7.1 percent of age-, sex- and socioeconomically matched individuals without RLS (the control group).

The increased suicidal tendencies were not accounted for completely by the higher lifetime rate of depression, which was 65 percent in the RLS group and 23 percent in the control group. This suggests that there is likely something inherent to RLS that predisposes people to thoughts about and attempts at suicide. It should be noted that RLS was severe or very severe in about two-thirds of the RLS group, so this increase in suicidal thoughts and behavior may not apply to all people with RLS, especially if RLS is mild to moderate.

Most people in the RLS group who participated in the study are members of the RLS Foundation. I am very grateful to this community for your commitment to RLS research, and at the same time I have the utmost empathy for those of you who are indeed suffering with both depression and RLS.

Luckily, you have the RLS Foundation as a resource. If your RLS symptoms are not controlled, and especially if you are experiencing depression, please give real consideration to visiting the RLS Foundation Quality Care Center nearest to you. Controlling your RLS symptoms will go a long way toward improving mental health.

For those of you who are suffering with depression and suicidal thoughts, please seek psychiatric and psychotherapeutic care. If you are having thoughts of attempting suicide, please call the National Suicide Prevention Lifeline at 1-800-273-TALK (1-800-273-8255). You are not alone.


No article written for general distribution can take into account individual differences or circumstances. Readers are encouraged to share this article with their health care providers and discuss any steps taking individual circumstances into account.

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