A pediatric neurologist and his associates at the Children’s Mercy Hospital, Kansas City, report 6 deaths among 80 patients with intractable epilepsy treated with nitrazepam. The patients who died were 13-39 mos of age (mean 28 mos) and had received nitrazepam for 2 to 19 months (mean 8 mos) in a dosage of 0.9-2.7 mg/kg/d (mean 1.4). Up to 2 additional but unnamed antiepileptic drugs were used concurrently but no patient received other benzodiazepines. The dosage of nitrazepam in the 6 fatal cases was significantly higher and approximately double that in 22 survivors of the same age range (mean 0.7 mg/kg/d). Patients in both groups had multiple seizures, including generalized tonic-clonic, myoclonic and focal types but none had infantile spasms or absence attacks. Perinatal asphyxia, Prader-Willi syndrome, pertussis vaccine-related encephalopathy, and nonketotic hyperglycinemia were the etiological diagnoses in 4 of the 6 fatal cases. Three of the 6 had known factors contributing to death: congestive heart failure, aspiration of gastric contents, and unexplained hyperthermia, shock, and respiratory failure. Three patients died unexpectedly and autopsies in 2 were unrevealing. The cause of death was undertermined but a nitrazepam-induced swallowing disturbance and aspiration was suspected. The authors recommend that the use of nitrazepam in young children should be restricted to those resistant to other antiepileptic drugs, the dose should not exceed 0.8 mg/kg/d, and children with prior swallowing difficulties should be observed closely. 
COMMENT: Nitrazepam (Mogadon) is considered the most effective benzodiazepine for control of infantile spasms and other myoclonic seizures. It is not usually recommended for the treatment of generalized tonic-clonic seizures, as employed in this study, which might explain the necessity for the larger doses in the affected infants.
In a study at Children’s Memorial Hospital, Chicago , the side effects of nitrazepam in a trial involving 36 infants and children with myoclonic seizures included drowsiness (50%), ataxia (20%), hypotonia (20%), and muscular weakness (9%). Anorexia and vomiting developed in 2% and skin rash in 2%. the most serious adverse effects of nitrazepam in our study were symptoms suggesting autonomic dysfunction, previously unreported. Excessive drooling of saliva occurred in 9 (25%) infants and pulmonary congestion with wheezing developed in 4 (11%) debilitated infants with diplegia and severe retardation. Miosis of the pupils was also noted. The pulmonary symptoms required withdrawal of the drug or reduction of the dose to less effective levels and possible fatalities were avoided. The nitrazepam-induced drooling and aspiration in some cases have recently been explained by a delay of cricopharnygeal relaxation . The tolerance that develops to nitrazepam and the autonomic and sedative side-effects of larger doses seriously detract from the usefulness of this agent in long-term theraphy of infantile spasms. In debilitated infants, perhaps nitrazepam should be contraindicated.