The aim of this study is to research the efficiency and the side effects of paroxetine, which is a selective serotonin re-uptake inhibitor (SSRI), and to compare it with amitriptyline, whose efficiency in fibromyalgia syndrome (FMS) is well known. The 40 FMS-diagnosed patients that were involved in the research were separated into two groups randomly. The patients within the first group were given paroxetine tablets (for the first weeks 20 mg/day, later 40 mg/day); those within the second group were given amitriptyline drage (for the first two weeks 10 mg/day, later 20 mg/day). The treatment continued for two months. All of the patients were evaluated by a physician, who was not aware of the therapy options, in the 2(nd), 4(th) and 8(th) weeks with regard to fatigue, morning stiffness, sleep disturbances, paraesthesia, headaches, tender point count and score, severity of global pain, Beck depression index, global efficiency and tolerance according to the patient and the physician's judgments. It is observed that paroxetine has shown good efficiency in treating the symptoms of FMS with the exception of fatigue (p < 0.5), but amitriptyline works better. The most important side effect of paroxetine is sexual dysfunction. Paroxetine therefore can be used as an alternative drug in FMS when the patients cannot use amitriptyline for any reason.