Search

Objective: Mirtazapine is known to often provoke restless legs syndrome (RLS). In this retrospective chart review study, we evaluated the socio-demographic and clinical factors related to mirtazapine-associated RLS., Methods: Computerized medical records of 181 patients treated with mirtazapine from May 2004 to October 2007 were reviewed. RLS was identified using the diagnostic criteria of the International RLS Study Group. Socio-demographic and clinical characteristics were gathered, including comorbid physical illness and concomitant medications., Results: Mirtazapine-associated RLS was observed in 14 patients (8%), and most cases had developed within a few days after starting mirtazapine. Concomitant medication with tramadol, non-opioid analgesics, antihistamine, and dopamine-blocking agents was more frequently prescribed in subjects developing mirtazapine-associated RLS. In logistic regression analysis, concomitant medication with tramadol (odds ratio: 8.61, 95% confidence interval: 1.71-43.49) and dopamine-blocking agents (odds ratio: 4.67, 95% confidence interval: 1.31-16.70) enhanced the risk of mirtazapine-associated RLS., Conclusion: The combined use of mirtazapine with tramadol or dopamine-blocking agents could potentiate the risk of RLS. Clinician should watch carefully for the development of RLS when mirtazapine is administered to patients who are taking tramadol or dopamine-blocking agents.

There is now evidence to suggest a central role for the dopaminergic system in restless legs syndrome (RLS). For example, the symptoms of RLS can be dramatically improved by levodopa and dopamine agonists, whereas central dopamine D2 receptor antagonists can induce or aggravate RLS symptoms. To our knowledge, there is no previous report regarding whether domperidone, a peripheral dopamine D2 receptor antagonist, can also induce or aggravate symptoms of RLS. Mirtazapine, the first noradrenergic and specific serotonergic antidepressant (NaSSA), has been associated with RLS in several recent publications. The authors report here a depressed patient comorbid with postprandial dyspepsia who developed RLS after mirtazapine had been added to his domperidone therapy. Our patient started to have symptoms of RLS only after he had been treated with mirtazapine, and his RLS symptoms resolved completely upon discontinuation of his mirtazapine. Such a temporal relationship between the use of mirtazapine and the symptoms of RLS in our patient did not support a potentiating effect of domperione on mirtazapine-associated RLS. However, physicians should be aware of the possibility that mirtazapine can be associated with RLS in some individuals, especially those receiving concomitant dopamine D2 receptor antagonists.

We report the case of a 78 years old female patient with primary restless legs syndrome (RLS) with an autosomal dominant pattern of inheritance. In addition, the patient also had depression. We emphasize the worsening of symptoms of RLS after the use of a selective serotonin uptake inhibitor (mirtazapine), with improvement after the drug was discontinued, and an excellent recovery with the use of low dose dopaminergic agonist (pramipexol).