Does Cymbalta cause restless leg syndrome? (5+ tips)

This article will explore whether Cymbalta can cause restless leg syndrome (RLS). It will also explain the mechanism by which it can potentially contribute to the development of RLS.

Additionally, this article will explain the research findings surrounding Cymbalta-induced RLS and identify the risk factors that make individuals more susceptible to this side effect. Lastly, it will provide recommendations for managing Cymbalta-induced RLS symptoms.

Does Cymbalta cause restless leg syndrome?

Cymbalta may cause restless leg syndrome (RLS) in some people, although it is important to note that this is not a common side effect. While most people do not experience RLS while taking Cymbalta, certain risk factors may make some individuals more susceptible to this condition.

Restless leg syndrome (RLS) is a neurological disorder that leads to undesirable and irresistible movements of the extremities, especially at night. It also causes uncomfortable sensations in the affected areas.

If you are concerned about this potential side effect, it is advisable to consult with your doctor or healthcare provider.

How can Cymbalta cause restless leg syndrome?

Cymbalta is a serotonin-norepinephrine reuptake inhibitor (SNRI) that increases the availability of serotonin and norepinephrine in the brain. These neurotransmitters are part of the sympathetic nervous system.

As a result, while Cymbalta is effective in enhancing mood and managing pain, it can also increase the body’s fight and flight responses. This elevation in sympathetic activity may cause restlessness and contribute to disorders such as restless leg syndrome, passive leg movement syndrome, and hypnic jerks.

Additionally, it can lead to difficulty sleeping at night or insomnia. As a consequence, individuals may experience daytime sleepiness and tiredness [1].

What does research suggest?

There is a case report of a patient who started experiencing restless leg syndrome two weeks after initiating duloxetine treatment. The patient complained of unpleasant sensations in her extremities, prompting frequent involuntary movements, particularly at night, which significantly affected her sleep [2].

Over time, these sensations began radiating to her arms and the rest of her body, leading to frequent awakenings every 10 minutes to move and walk, as these activities were the only things that provided relief from her restless leg syndrome symptoms.

Her duloxetine administration frequency was reduced to taking it every other day instead of daily. One month later, she reported that she had completely recovered from duloxetine-induced restless leg syndrome [2].

In another case report, a hospitalized, depressed patient had been taking mirtazapine, venlafaxine, and paroxetine for three months. Subsequently, her medication regimen was modified, with venlafaxine and mirtazapine discontinued and duloxetine initiated as an alternative.

However, just two days after starting duloxetine, she began experiencing restless leg syndrome symptoms such as sudden leg movements, discomfort (especially at night), and hypnic jerks [3].

It is worth noting that despite receiving multiple treatments in the past, including duloxetine monotherapy, for her 30-year history of depression, she had not previously experienced frequent antidepressant-induced restless leg syndrome.

Hence, it was concluded that the concurrent administration of duloxetine and paroxetine led to these symptoms [3].

What factors influence Cymbalta-induced RLS?

Multiple factors can contribute to an increased occurrence of restless leg syndrome (RLS) while taking Cymbalta. These factors can be categorized into primary and secondary causes [2].

Primary Causes

The most significant factors are those that affect dopamine transmission. Individuals with genetic disorders that result in inadequate dopamine transmission are most susceptible to experiencing RLS while on Cymbalta [2].

Additionally, deficiencies of iron, especially in the brain, can impair dopamine transmission and contribute to the development of RLS, particularly in the presence of Cymbalta administration [2].

Secondary Factors

Certain metabolic disorders that impair iron metabolism, such as end-stage renal disease and pregnancy, pose a high risk of Cymbalta-related RLS [2].

Furthermore, vitamin B12 or folate deficiencies can also increase the likelihood of RLS while taking Cymbalta, with excessive alcohol intake possibly contributing to these deficiencies. Peripheral neuropathy, particularly in diabetic patients, may also predispose individuals to this side effect [2].

Other conditions that may elevate the risk of Cymbalta-related RLS include rheumatoid arthritis, spinal nerve root irritation, various spinal disorders, and Parkinson’s disease (due to dopamine insufficiency) [2].

Less common disorders like spinocerebellar ataxia 3 and Charcot-Marie-Tooth disease type 2 may also increase the susceptibility to Cymbalta-induced RLS [2].

Concurrent medications

Here are some medications that may increase the occurrence of RLS as a side effect while taking Cymbalta [2]:

  • Antidepressants are commonly associated with RLS as a side effect, including SSRIs such as fluoxetine, sertraline, and paroxetine, other SNRIs such as desvenlafaxine, and tricyclic antidepressants (TCAs) such as amitriptyline and nortriptyline.


  • First-generation antipsychotics (typical antipsychotics) like haloperidol and chlorpromazine can lead to RL.
  • Second-generation antipsychotics (atypical antipsychotics) such as risperidone and olanzapine are less likely to cause RLS.
  • First-generation antihistamines like diphenhydramine and hydroxyzine may lead to RLS as a side effect.
  • Antiemetics, including prochlorperazine and metoclopramide, can also increase the occurrence of Cynbalta-related RLS.

What to do if Cymbalta causes RLS?

First of all, you should inform your doctor about the symptoms you’re suffering from. They may consider adjusting your Cymbalta dosage or switching to an alternative medication that may have fewer side effects related to RLS. 

You may also talk to them about checking your iron, folate, or magnesium levels. Deficiencies in these nutrients could contribute to RLS, and they can offer suitable supplemention. Avoid habits that could worsen RLS symptoms, such as smoking, excessive alcohol and caffeine consumption before bed.

Taking warm baths and massaging the legs before bedtime have also been effective in preventing undesirable leg movements while sleeping. Moreover, engaging in leg and lower back training and performing certain stretches can enhance muscle coordination and decrease uncontrolled movements.

Additionally, some people find that applying heat or cold to the affected areas helps reduce discomfort. Finally, if Cymbalta-induced RLS is persistent, your doctor may prescribe certain medications.

What medications can help with Cymbalta-induced RLS?

Several medications can be used to treat Restless Leg Syndrome (RLS). The following medications have been commonly prescribed for RLS:

  • Dopamine agonists like pramipexole (Mirapex) and ropinirole (Requip) are commonly used as the first-line treatment for RLS. They work by increasing dopamine activity in the brain, which helps reduce symptoms.


  • Alpha-2 agonists like clonidine and gabapentin enacarbil are sometimes used to reduce RLS symptoms.
  • In severe cases of RLS, opioids such as codeine, oxycodone, or hydrocodone may be prescribed.
  • Benzodiazepines like Xanax, clonazepam (Klonopin), or diazepam (Valium) may be used to help relax muscles and improve sleep quality in individuals with RLS.
  • Certain anticonvulsant drugs, such as gabapentin (Neurontin) or pregabalin (Lyrica), are effective in relieving RLS symptoms, particularly if there are associated neuropathic pain symptoms.
  • Iron supplementation may be prescribed. Increasing iron levels can help improve RLS symptoms in individuals with iron deficiency.


Based on my research, I found that Cymbalta may cause restless leg syndrome (RLS) in some individuals. In my perspective, while it is not a common side effect, there are certain risk factors that can make some people more susceptible to developing RLS while taking Cymbalta. 

These factors include dopamine transmission issues, iron deficiencies, certain metabolic disorders, peripheral neuropathy, and concurrent medications that can also cause RLS. If you are concerned about this side effect, I recommend consulting with your doctor. 

They can adjust your dosage, switch you to an alternative medication, or check your nutrient levels to address the symptoms. Additionally, it is advisable to avoid smoking and excessive alcohol consumption, engage in leg and lower back training, take warm baths, and apply heat or cold to the affected areas.

Based on my knowledge, your doctor may prescribe certain medications, such as dopamine agonists or alpha-2 agonists, opioids, benzodiazepines, or iron supplements, to treat Cymbalta-induced RLS.

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Kolla BP, Mansukhani MP, Bostwick JM. The influence of antidepressants on restless legs syndrome and periodic limb movements: A systematic review. Sleep Med Rev. 2018 Apr;38:131-140. doi: 10.1016/j.smrv.2017.06.002. Epub 2017 Jun 15. PMID: 28822709.


MÜLKOĞLU, Cevriye; GENÇ, Hakan. (2021). Duloxetine-induced Restless Legs Syndrome in a Patient with Fibromyalgia Syndrome. Journal of Physical Medicine & Rehabilitation Sciences. Vol. 24 Issue 2, p183-185. 3p.


Nikolaou, Kalliopi N. MD; Michopoulos, Ioannis MD; Douzenis, Athanasios MD; Papazahos, Constantinos MD; Papageorgiou, Charalabos MD; Gournellis, Rossetos MD. Restless Legs Syndrome Associated With the Combined Use of Duloxetine Plus Paroxetine. Journal of Clinical Psychopharmacology 35(3):p 345-346, June 2015. | DOI: 10.1097/JCP.0000000000000306

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