Rectal diazepam: pitfalls of excessive use in refractory epilepsy

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.

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.

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.

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.