Incidence of death in patients with intractable epilepsy during nitrazepamtreatment

Purpose: Increased risk of death has been reported in patients with intract able epilepsy (IE) taking nitrazepam (NZP). Methods: Between January 1983 and March 1994, 302 patients with IE were ent ered into a NZP compassionate-plea protocol. NZP was discontinued if there was <50% seizure reduction or significant side effects. In some patients wi th >50% reduction, it also was discontinued for lack of sufficient effect. At the end of follow-up for this study, 62 patients remained taking NZP. Pa tients took NZP from 3 days to 10 years. Results: Twenty-one of 302 patients died after institution of NZP. Fourteen of 21 of these were taking NZP at death, and in five of 21, the NZP had be en discontinued. Two patients were excluded from analysis, because it is un clear whether NZP had been discontinued before death. Sis other patients we re lost from follow-up. Of the 14 deaths with NZP, seven were sudden, six w ere of pneumonia, and one was of cystinosis. Nine had at least one contribu ting factor, such as dysphagia, gastroesophageal reflux, or recurrent aspir ations. The 294 patients took NZP for a total of 704 patient years (ptyrs), and were discontinued for a total of 856 ptyrs. Then were 1.98 deaths/100 ptyrs on NZP compared with 0.58 deaths/100 ptyrs without NZP, most of the f ormer being associated with side effects of NZP. Mortality in patients youn ger than 3.4 years was 3.98 with NZP compared with 0.26 deaths/100 ptyrs wi thout NZP (p = 0.0002). Corresponding figures in patients 3.4 years or olde r were 0.50 and 0.86 deaths/100 ptyrs, respectively. Conclusions: NZP therapy for epilepsy apparently increases the risk of deat h, especially in young patients with IE. This should be considered in antie pileptic drug (AED) management decisions.