Drug Treatment for Restless Leg Syndrome
Restless legs syndrome (RLS) is a neurological disorder characterised by throbbing, pulling or other unpleasant sensations in the legs and an irresistible urge to move legs, usually during inactivity and at night-time. These sensations can range in severity from uncomfortable to irritating to painful. The discomfort is usually relieved by moving the legs(1).
This condition is associated with increased risk of nocturnal hypertension, affecting patient’s sleep, which may lead to anxiety, depression and decreased quality of life. RLS symptoms have been reported in 2.5% to 15% of the general population and it is estimated that 20% to 30% of patients with uraemia are affected by RLS (1).
Common pharmacological agents for the treatment of RLS in clinical practice include dopamine agonists, alpha-2-delta calcium channel ligands, opioids, anti-convulsants, benzodiazepines, or drugs acting on adrenergic systems such as clonidine (2).
Pramipexole is one of three non-ergoline dopamine agonists approved by the FDA for the treatment of RLS, the other two being Ropinirole and Transdermal Rotigotine. Although Pramipexole consists of both immediate and extended release formulations, only the immediate release form of the drug has been evaluated for the treatment of RLS in published trials. Therapeutic dose of Pramipexole is 0.125mg once a day (most suitable) up to 0.25mg/day (1).
At low doses, Pramipexole is usually well tolerated but common side effects may include nausea, headache, insomnia, somnolence, dizziness, orthostatic hypotension and hallucinations (3).
There are, however, some severe consequences associated with long term use of dopaminergic agonists such as Pramipexole:
• Intensification of RLS symptoms is considered the main complication of long term dopaminergic treatment. RLS symptoms may become worse; symptoms may begin earlier in the day, increased intensity of symptoms or a spreading of the symptoms to previously unaffected parts of the body. When the intensification is severe, the symptoms lose their daily rhythm, are no longer relieved by activity, and may be present continuously during the day affecting the whole body. Furthermore, severe augmentation can cause pronounced sleep disturbance and significant reduction in the quality of life (3)
• Impulse Control Disorders: This has been observed in RLS patients treated with Dopamine agonists. Some of these impulses include pathologic gambling, compulsive shopping, compulsive eating, and hypersexuality. Discontinuation of the dopamine agonist has been shown to result in resolution or improvement of the impulse control disorder (3)
• Antipsychotics may diminish the therapeutic effect of Pramipexole(3)
• Because of possible additive effects, patients are advised to take caution when taking other sedating medicinal products or alcohol in combination with Pramipexole(4)
• When given in combination with levodopa, it is recommended that the dose of levodopa is reduced and the dose of other anti-parkinsonian medicinal products is kept constant while increasing the dose of Pramipexole (4)
RLS is a lasting condition that can seriously impair the quality of life. The choice of the medication used in the treatment of RLS should be based on the severity of RLS and the effectiveness of medication for the short-term or long-term treatment of RLS. Following critical evaluation of the patient’s medications and applying sleep hygiene, dopamine agonists and other drugs have a great influence on the management of RLS and their use should be recommended where the benefits outweigh the risks (3).
1. Comella CL. Restless legs syndrome Treatment with dopaminergic agents. Neurology. 2002;58(suppl 1):S87-S92.
2. Einollahi B, Izadianmehr N. Restless Leg Syndrome: A Neglected Diagnosis. Nephro-Urology Monthly. 2014;6(5).
3. Romenets SR, Postuma RB. Treatment of restless legs syndrome. Current treatment options in neurology. 2013;15(4):396-409.
4. Pramipexole. Available from: http://www.medicines.ie/medicine/6812/SPC/Mirapexin++0.088+mg+tablets/.