A 67-year-old woman with bipolar disorder was admitted to our hospital. Despite the administration of medication such as lithium, valproate and carbamazepine, her depressive symptoms persisted. Ten months later, she suddenly complained of auditory hallucinations and confusion. Laboratory examination and brain computed tomography (CT) were normal. Risperidone treatment (gradually increased to 5 mg/day) resolved her psychotic features, and the risperidone was gradually decreased to 3 mg/day over a period of 1 month. Subsequently, lamotrigine treatment (25 mg every 2 days) was initiated for her prolonged depressive state in addition to risperidone (3 mg/day) and biperiden (1 mg/day). Although the patient’s general condition was normal and dehydration did not appear at the initiation of lamotrigine, 4 days later, she had severe extrapyramidal rigidity, mild hyperthermia (37.6°C), and tachycardia. Laboratory tests showed elevated creatine phosphokinase (CPK: 6155 IU/l). The possibility of infectious disease was excluded by neurological examination and normal brain CT. The patient was diagnosed with NMS. Lamotrigine, risperidone, and biperiden were immediately discontinued, and diazepam (8 mg/day) and continuous fluid infusion were initiated. Additionally, the patient was administered dantrolene (20 mg/day intravenously) for 3 days. A decrease in serum iron levels at the onset of NMS had normalized spontaneously by 5 days (from 48 to 80 μg/dl). Seven days later, after the medication for NMS, the patient’s CPK level was normal, while her extrapyramidal rigidity remained. Approximately 3 weeks later, her symptoms were completely resolved.