Abstract
Recurrent neuroleptic malignant syndrome (NMS) is an infrequent complication on neuroleptic rechallenge. Caroff and Mann [1] reported a 30% recurrence risk, while others report a lower risk [2,3]. We present a patient with five recurrent episodes of NMS with typical and atypical neuroleptics.
A 39-year-old man was diagnosed with schizophrenia at age 24. He was treated with oral chlorpromazine up to 300 mg/day and had six relapses before he was prescribed a depot injection of fluphenazine decanoate, 18.75 mg monthly, chlorpromazine 400 mg/day, benzhexol 6 mg/day and diazepam 10 mg/day. After about 2 years he suddenly became stuporous and stiff, with a persistent tachycardia and raised total white cell count. He was diagnosed with NMS and treated with bromocriptine. After 2 months, because he was thought disordered and hallucinated, he was given trifluoperazine which was increased to 15 mg/day. Nineteen months later he became dazed, stiff and febrile. He had a tachycardia, raised blood pressure and creatinine kinase (CK) level of 1064 U/L. Again, NMS was diagnosed and trifluoperazine discontinued. 16 days later he was started on thioridazine, as he was increasingly disturbed.
After 9 months on thioridazine he again presented with symptoms of NMS. Three weeks later he was started on promazine which was increased to 50 mg/day. But after 3 months he suffered an acute relapse of schizophrenia and was switched to clozapine. The dose was gradually titrated to 200 mg/day. Fifteen months later he presented with fever, tachycardia and profuse sweating. He was incoherent, stiff and the CK was 1840 U/L.
Two months after this he was prescribed risperidone which was increased from 1 to 4 mg/day. He remained on this dose until 2 months later when he became dazed, febrile, stiff and had a tachycardia. All other investigations, including serum ferritin levels, were normal. He was treated with bromocriptine for NMS. A month later he became increasingly disturbed, restless and thought disordered. His Positive and Negative Syndrome Scale (PANSS) score was 107 (positive subscale 23, negative subscale 37, general psychopathology 47) and benzodiazepines were insufficient to control his agitation. The patient refused ECT, with his family's support. Quetiapine was started and gradually increased. Six months later he is on Quetiapine 400 mg/day and is more settled. The recurrence of NMS here was between 2 weeks and 3 years after reintroduction of each neuroleptic. Caroff and Mann reported that 16% of patients developed signs of NMS within 24 hours of initiating neuroleptic treatment, 66% by 1 week and 90% within 30 days, and suggested that NMS is less likely to occur after 30 days [1]. Susman and Addonizio found that some of the cases were not ‘independent recurrences’, but ‘exacerbation of episodes that had begun to wane secondary to reintroducing neuroleptics’ [4]. The patient is at risk of developing NMS again. A genetic vulnerability is a possibility. Systemic risk factors, however, were present. His NMS episodes coincided with relapses of his illness in four episodes.