Discontinuation of Clonazepam After Long‐Term Treatment

Abstract

Frequent unwanted side effects and development of tolerance are the main disadvantages of clonazepam (CZP) in long-term treatment of epileptic patients. A review of the literature shows that CZP tolerance more often appears in severe forms of childhood epilepsy (West and Lennox-Gastaut syndromes) than in other epileptic syndromes. We prospectively studied the consequences of CZP discontinuation in 40 consecutive children with difficult-to-treat epilepsies and multiple-drug therapy. The CZP was reduced stepwise in a variable daily reduction rate (0.003-0.16 mg/kg), while serum levels of the comedication were kept unchanged. In only three children (7.5%), CZP was believed to have had some antiepileptic effect; in 30 (75%) it had been ineffective, whereas in six (15%), a decrease in seizure frequency after CZP discontinuation even suggested a negative therapeutic effect. Discontinuation symptoms, mostly in the form of a transitory exacerbation of seizure frequency, occurred in 19 children (47.5%). These children had a significantly higher CZP dose and longer duration of treatment than did children without discontinuation symptoms, but there was no difference between the two groups related to the rate of CZP discontinuance.

Seizures with Clonazepam: Discontinuation and Suggestions for Safe Discontinuation Rates in Children

“…Except for the report of Specht et al (1989), reports have described only the occurrence of GTC status epilepticus. My study also showed development of a first GTC seizure and frequent attacks of non-GTC status epilepticus.…”

“…Abrupt discontinuation of clonazepam (CZP) can induce seizure exacerbation or status epilepticus (Browne, 1976), but only a few cases have been reported (Edwards and Eadie, 1973;Lund and Trolle, 1973;Edwards, 1974;Sechi et al, 1984;Sironi et al, 1984;Ghadirian et a]., 1987;Specht et al, 1989) and little is known about their clinical characteristics, including seizure symptoms, reason for rapid discontinuation of CZP, time lag from discontinuation to seizure exacerbation, and treatment. While widely recognized that abrupt CZP discontinuation should be avoided (Browne, 1978), it may occur in clinical practice because of side effects of CZP or other reasons.…”

“…Specht et al (1989) reported stepwise CZP reduction by 0.003-0.05 mglkglday in 33 children. Converting daily reduction rates to weekly rates, 1 of 5 cases reduced by G0.04 mglkgl week (0.003-0.005 mglkglday) and 12 of 28 cases reduced by >0.04 mglkglweek (0.00&0.05 mglkgl day) developed seizure exacerbation during the discontinuation period.…”

Drug Effects on the Human Electroencephalogram

“…More severe intoxication is associated with runs of high-amplitude, intermittent rhythmic delta activity superimposed on a background of nearly Drug Effects on the Human Electroencephalogram 303 continuous slow activity of less than 4 Hz. 10,20 Other Antiepileptic Drugs As a general rule, the antiepileptic drugs (AEDs) reduce epileptiform activity, 21,22 although on occasion they can exacerbate EEG abnormalities and seizures. Little reactivity is elicited by stimulation.…”

Use of Antiepileptic Drugs in Epileptology with Respect to Psychiatry

“…Of these, barbiturates and benzodiazepines are used as AEDs. Clonazepam is the most problematic drug in this respect [8] because of its high potential to produce withdrawal syndromes which cannot be safely avoided by stepwise withdrawal -as is possible with phénobarbital. As seizures are the most prominent symptoms of clonazepam withdrawal, it may be difficult to know to which of the two types of AED withdrawal syndromes the psychiatric symptomatology belongs.…”