Abstract
Neuroleptic malignant syndrome (NMS) has rarely been associated with discontinuation of atypical antipsychotics [1]. We describe a case of NMS precipitated by a single dose of parenteral haloperidol in a patient who had abruptly discontinued clozapine.
Mr A, a 26-year-old Indian man, was diagnosed with schizophrenia of 6 years duration. Initially, he was treated with haloperidol (up to 10mg/day) for 6 months, which was discontinued due to extra pyramidal symptoms. He had sequential trials with other antipsychotics, but 3 years ago, due to lack of improvement in symptoms, he was 948 CORRESPONDENCE started on clozapine (titrated to 300 mg/day). Mr A's current hospitalization was precipitated by his abruptly stopping the clozapine. On the first day of admission and 36 hours after the last dose of clozapine, he received a single dose of intramuscular 10 mg haloperidol. Within hours of receiving the injection, he developed severe cogwheel rigidity. Creatine phospokinase (CPK) level done on the second day of admission was 900 IU/L (normal range: 0–200) and on the same day he began to exhibit delirious behaviour. Subsequent serial CPK levels were 6000 IU/L and 13 000 IU/L over the next 2 days, respectively. He had perspiration and fever, but it was never more than 38°C. His pulse rate and blood pressure were stable. Laboratory investigations showed only leukocytosis count (14×109/L; normal range: 4.5–11.0). A diagnosis of NMS was made according to the DSM-IV criteria (marked and persistent CPK elevation beyond 72 hours is less likely to be due to a single intramuscular injection alone; [2]). Bromocriptine, 10 mg/day, was started on the fourth day of admission with good response within 2 days. Subsequent CPK levels were 429 IU/L and 160 IU/L on the sixth and the 10th day, respectively. Within a week, Mr A showed complete recovery from NMS, but was in florid psychosis for which he was treated with lorazepam (6 mg/day) for 5 days. Bromocriptine was continued for 2weeks and then stopped. Subsequently, he received a course of eight treatments with electro-convulsive therapy resulting in resolution of psychosis. A successful rechallenge with clozapine at 25 mg/day was made and the dose was gradually increased to 250 mg/day without recurrence of NMS or psychotic symptoms.
There are a couple of interesting facets to this presentation. First, the patient didn't develop NMS when he was being treated with haloperidol alone (although bioavailability of parenteral haloperidol is higher), but developed it with a single dose of parenteral haloperidol once he had stopped the clozapine. Cholinergic rebound occurring after abrupt discontinuation of clozapine has been reported and a case also describes NMS as a presenting syndrome of clozapine discontinuation [1]. Moreover, it is known that NMS is a manifestation of a hypodopaminergic state. Taking these observations together, it can be hypothesized that the dopamine–acetylcholine imbalance secondary to the abrupt discontinuation of clozapine may have predisposed this patient for NMS on re-exposure to haloperidol, a potent dopamine antagonist. Second, absence of hyperthermia, as in our case, has been reported in cases of NMS due to clozapine [3]. In line with this, investigators have shown no correlation between the degree of rigidity and hyperthermia [4]. In conclusion, the possibility of emergence of NMS has to be borne in mind in patients who abruptly discontinue clozapine.