Having a good night’s sleep is essential for our well-being. Restless legs syndrome (RLS), a neurological disorder, can disrupt sleep patterns and may significantly impact quality of life. It is known to be the fourth leading cause of insomnia, with up to 85% of individuals with RLS finding it difficult to fall or stay asleep. By understanding the condition and adopting safe medication practices, patients can better manage symptoms and their sleep quality.

What is Restless Legs Syndrome (RLS)?

RLS is characterized by an uncomfortable urge to move the legs, particularly when resting or sitting still. Symptoms typically worsen in the evening or at night but tend to improve with movement, such as walking or stretching. While RLS can occur at any age, it is most commonly diagnosed between the ages of 40 and 60, with symptoms often beginning earlier if RLS is associated with a family history. Risk factors may include pregnancy, anemia (low iron levels), Parkinson’s disease, and end-stage kidney disease. RLS is associated with a higher risk of depression and anxiety, and treating these conditions in RLS patients requires caution, as certain antidepressants may worsen RLS symptoms.

Drug-Induced RLS

As previously mentioned, there are medical conditions like anemia and Parkinson’s disease that are known risk factors for RLS. However, more attention should be given to drug-induced RLS, as there is emerging evidence supporting that there might be an association between certain drug classes and RLS, such as antidepressants, antipsychotics, and antiepileptics.

Although the exact causes of drug-induced RLS are unclear, some theories suggest that decreased iron levels in the substantia nigra, a region of the brain associated with RLS, may play a role. Emerging theories also indicate that neurotransmitters like dopamine and serotonin may be involved. Medications that increase serotonin levels have also been shown to raise the risk or severity of RLS. Furthermore, an imbalance between dopamine and thyroid hormone levels has been suggested as another contributing factor to RLS. These theories help explain why antidepressants, antipsychotics, and antiepileptics may trigger or worsen RLS, as they all impact the pathways in the brain that are related to dopamine, serotonin, or thyroid hormones.

Management of RLS

Management of RLS may involve non-medication approaches and medication-use measures that are customized to the patient’s needs and symptoms. Non-medication interventions may include:

• Reducing caffeine, nicotine, and alcohol intake

• Practicing good sleep habits and getting adequate rest

• Exercising regularly

• Massaging, stretching, or using heating or vibrating pads on affected areas

For medication management of RLS, dopamine receptor agonists (e.g., pramipexole, ropinirole, rotigotine) could be considered to reduced RLS symptoms and improve sleep quality. Gabapentin or pregabalin are typically recommended for initial treatment to help patients with severe sleep disturbance or insomnia associated with RLS. If iron deficiency is causing RLS, then iron supplements may help. If RLS is associated with medication use (i.e., drug-induced), and is affecting the patient’s quality of life, then consulting the prescriber or primary care provider about switching medications may be necessary.

Safe Medication Practices for RLS

The International Restless Legs Syndrome Study Group (IRLSSG) developed an evidence-based best practice guide for long-term medication management of RLS, available at https://pubmed.ncbi.nlm.nih.gov/23859128/. In general, medications for RLS are effective for durations ranging from one to five years. When starting a medication for RLS, beginning with a low dose can help minimize side effects. It is important for patients to follow the prescribed dose and avoid adjusting doses on their own. Open communication and regular check-ins with the healthcare team can help manage potential side effects and make optimal lifestyle adjustments. The “5 Questions to Ask About Your Medications” (https://www.ismp-canada.org/medrec/5questions.htm) resource can facilitate meaningful discussions between the patient and healthcare providers to optimize medication therapy management.

By Samir Kanji, Laura Brady, and Certina Ho

Samir Kanji and Laura Brady are PharmD Students at the Leslie Dan Faculty of Pharmacy, University of Toronto; and Certina Ho is an Assistant Professor at the Department of Psychiatry and Leslie Dan Faculty of Pharmacy, University of Toronto.