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).