Rectal diazepam: pitfalls of excessive use in refractory epilepsy.

INTRODUCTION: The rectal administration of diazepam (DZP) has provided a safer existence to many epilepsy patients and their carers, when prolonged or serial seizures are present. However, in patients with frequent seizures, chronic, intermittent over-administration may occur, particularly in the presence of multihandicaps. METHODS: Six patients who experienced untoward effects from excessive rectal DZP are reported. In two patients, serial plasma levels of DZP and its active metabolites were monitored. RESULTS: Three patients exhibited a pattern of cyclic reappearance of seizures, interrupted by rectal DZP, followed by sedation and gradual awakening. The intervals were approximately 4 days. The three other patients had variable and complex symptoms with serial seizures and alternating states of tension, apathy, and sleepiness. The plasma levels of DZP and desmethyl-DZP showed rapid fluctuations. CONCLUSION: When rectal DZP is prescribed, chronic and excessive administration should be avoided. Fluctuating plasma-levels may probably support a cyclic reappearance of seizures in some patients. The combination of high bolus doses and a rapid drug clearance due to enzyme inducing co-medication may probably increase the risk for rebound reactions. Toxic, withdrawal, and epileptic symptoms may be intermingled and difficult to manage. A replacement strategy in the form of a prophylactic, oral, low dose benzodiaepine regimen may facilitate the discontinuation of this prescription pattern. Adequate counselling and medically appropriate, written directions for the use of rectal DZP is mandatory.