The existing data on the effect of antipsychotic agents on seizure thresholds are inadequate, but it appears that high-potency agents such as haloperidol are generally safe in this regard. All antipsychotic agents may produce neuroleptic malignant syndrome, an uncommon idiosyncratic reaction that does not appear to be dose related. The syndrome is characterized by rigidity, high fever, delirium, and marked autonomic instability. There are no pathognomonic laboratory abnormalities, but the rigidity may be severe enough to produce myonecrosis with marked elevations of muscle enzymes. Renal failure may occur from myoglobinuria and dehydration.
Treatment requires drug discontinuance and meticulous supportive care.
The dopamine agonist bromocriptine and the direct-acting muscle relaxant dantrolene have both proved helpful in the treatment of neuroleptic malignant syndrome. Patients who resume treatment with antipsychotics after recovering from neuroleptic malignant syndrome have a high incidence of recurrence of the syndrome. Risk factors for the syndrome appear to include dehydration and intercurrent illness. Tardive dyskinesia may occur in 20 percent of patients who receive antipsychotic drugs for more than a year. All antipsychotic drugs except clozapine have been implicated.