Reviewed by Sahil Chopra, MD.

Research by Savit Malhotra and Theresa Do.

Introduction

So far in our Crash Course on Restless Legs Syndrome (RLS), we have learned about multiple treatment options for managing symptoms. We started with dopaminergic medications and understanding why they are no longer the first-line treatment for RLS. We then introduced gabapentinoids, which have become the rising first-line treatments, and in our last article, we told the cautionary tale of opioids for RLS. This week, we will be continuing our conversation on medications available to help with RLS by discussing benzodiazepines and why the American Academy of Sleep Medicine (AASM) often advises against using these medications. Though there are some use cases, the current AASM guidelines for RLS state that there is a very low certainty of evidence supporting their use. In this week’s article, we will break down what the current literature says and how benzodiazepines fit into the current treatment regimen. 

Understanding Benzodiazepines

Benzodiazepines (also known as “benzos”), a class of depressants, are a type of medication used for amnestic, anxiolytic, hypnotic, and sedative effects.[1] Alprazolam, lorazepam, clonazepam, diazepam, and temazepam are among the most commonly used and prescribed benzodiazepines, and while they each work differently in terms of speed, duration, and potency, their underlying mechanisms are similar.[2,3] Benzodiazepines bind to benzodiazepine receptors in the central nervous system. These receptors consist of a chloride channel called the GABA-A receptor, and in the presence of GABA (an inhibitory neurotransmitter) these channels open to allow chloride ions to enter the neurons. Benzodiazepines increase the effect of GABA, leading to increased influx of chloride ions, which causes hyperpolarization.[4] Hyperpolarization (which is when a neuron becomes more negative in charge) reduces how frequently the neurons can become excited, which leads to CNS depression.[5] Simply put, benzodiazepines slow down neural activity, which is what gives them their sedative and relaxing effects.

Oftentimes, clinicians recommend against the long-term use of benzodiazepines. One reason is due to their addictive nature, which can lead to a person developing weakness, blurred vision, drowsiness, poor judgment, mood changes, and risk-taking behaviors.[6] Studies have also found that chronic benzodiazepine use can cause a decline in cognitive function and can lead to dementia/dementia-like diseases.[7] Even for conditions like insomnia, clinicians advise against the long-term use of benzodiazepines, regardless of how effective they are for sleep. Studies have found that taking benzodiazepines for longer than 3-4 weeks can cause withdrawal symptoms if usage is abruptly stopped, with many recommending that the medication be prescribed for only 1-2 weeks.[8] 

Aside from the risk of addiction, benzodiazepines also come with a host of adverse effects. For example, those who are taking benzodiazepines may exhibit aggressive behavior, an increased risk of falls, amnesia, and (for those who are pregnant) potential neonatal morbidity.[7,9]

Role of Benzodiazepines in RLS 

In general, benzodiazepines are used to produce a calming and sedative effect. They help relax the body and muscles, which is why they can be prescribed in the short-term (less than 4 weeks) for sleep disorders such as insomnia.[1, 10] However, as of 2025, the AASM does not recommend benzodiazepines as a main treatment for RLS due to their lack of clinical benefits and safety concerns.[11] Even through the previous decade, there has been “insufficient evidence” to support benzodiazepines as a treatment for RLS, despite their use in other sleep conditions.[12] Their effects seem more to improve sleep continuity, rather than core RLS symptoms such as limb sensations. This can lead to patients having a false sense of treatment success and potentially undermining their RLS severity. Importantly, benzodiazepines do not address the underlying neurobiological mechanisms of RLS, such as dopaminergic dysfunction or iron deficiency (to be addressed in a future article). 

One major concern of benzodiazepines for the treatment of RLS is that patients who are routinely taking benzodiazepines can develop a dependence for the medication.[1] Dependence is defined as a state where a patient’s body gets used to taking the medication and requires continued use to function normally.[13] This physical dependence can develop even with short-term use (as little as 2-4 weeks for some benzodiazepines like alprazolam), though risk increases significantly with longer duration and higher doses.[14] Within dependence, a patient may also experience tolerance of the medication’s effects (e.g., needing a higher dosage or amount of the drug to elicit the same effects) and withdrawal when not taking the medication (e.g., having physical symptoms without the drug). Withdrawal can also cause feelings such as anxiety and insomnia around sleep.[15] Some people experience withdrawal symptoms that can persist for weeks to months after stopping benzodiazepines, which can significantly impact quality of life.[14] This poses an addictive risk, as patients can find themselves relying on the medication to feel “okay”. Furthermore, benzodiazepines carry risks of next-day sedation, cognitive impairment, and increased fall risks, particularly in older adults.[16,17] Given these considerable risks of dependence, withdrawal, and other side effects, benzodiazepines are generally reserved as a last-line treatment for RLS when other, safer medications have failed.

Conclusion

Benzodiazepines have historically been used to manage sleep disturbances, but their role in RLS is now considered limited and there is "insufficient" evidence about their efficacy and safety. While these medications may improve sleep onset and continuity, they do not address the core symptoms and pathophysiology of RLS. Therefore, patients may only feel a temporary relief in their sleep while their RLS symptoms continue to persist. Moving forward, we will discuss alternative treatments, such as oral iron and iron infusions, which specifically target the iron mechanisms of RLS.

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