Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy

Abstract

A B S T R A C T Phenobarbital and phenytoin have good antiepileptic effect, but clinically significant untoward effects occur during their long-term use. Phenobarbital may cause hyperactivity, behavioral problems, sedation, and even dementia; these effects are dose related to some extent. Side effects of phenytoin include sedation, a cerebellar syndrome, phenytoin encephalopathy, psychosis, locomotor dysfunction, hyperkinesia, megaloblastic anemia, decreased serum folate level, decreased bone mineral content, liver disease, IgA deficiency, gingival hyperplasia, and a lupus-like hypersensitivity syndrome. Especially susceptible to the neurotoxic effects of phenytoin are epileptic children with severe brain damage who are on multiple drugs. In those children, balance disturbance may develop and be followed by gradual loss of locomotion. Among 131 mentally retarded epileptic patients, phenytoin intoxication occurred in 73 (56 YG), of whom 18 experienced persistent loss of locomotion. There is experimental evidence that the toxic action of phenytoin lies at the cellular level, predominantly in the cerebellum. Many experts avoid the long-term use of phenytoin because of its insidious and potentially dangerous side effects. Phenobarbital (PB) and phenytoin (PHT) are classic antiepileptic drugs, but insidous and severe untoward effects have been associated with their use. These effects may include impaired mental capacity, disturbed body balance, and even loss of locomotion, which may jeopardize the effective control of epileptic seizures. Therefore, physicians are confused as to whether these drugs should be used at all; if so, then they want to know how the drug therapy should be arranged. This report surveys the clinical neurotoxicity and other side effects of PB and PHT during long-term treatment of epilepsy, including their possible mechanisms and significance in clinical practice, and offers quidelines for the management of affected patients.

Epilepsy and brain injury: A case report of a dramatic neuropsychiatric vicious circle

“…Topiramate is useful in both focal and generalized epilepsy [36], reducing seizure frequency and impulsivity and having a mood-stabilizing effect [37]. Phenobarbital may cause dose-related hyperactivity and behavioural disorders [38] and its discontinuation may result in decreased impulsiveness and hyperactivity [39]. Drug-resistant epilepsy with post-ictal aggression, like the one described here, has also been described in a case series of patients with frontal and temporal dysfunction [40].…”

Phenytoin‐induced choreoathetosis after serial seizures due to traumatic brain injury and chronic alcoholism

“…From the literature, it is well known that PHT can induce hyperkinesias such as chorea . Side effects of PHT other than hyperkinesia include gingival hyperplasia, irreversible hypertrichosis, encephalopathy, sedation, a cerebellar syndrome, psychosis, locomotor dysfunction, megaloblastic anemia, decreased serum folate levels, osteoporosis, liver disease, IgA deficiency, a lupus‐like hypersensitivity syndrome, and lethal Stevens–Johnson syndrome . The cause of PHT‐induced hyperkinesias is unclear but it has been speculated that it could be a toxic effect since PTH is well known to be mitochondrion‐toxic .…”

Pathological long‐bone fractures in residents with cerebral palsy in a long‐term care facility in South Africa

“…The most commonly prescribed drugs were carbamazapine and phenobarbitone. Both drugs are hepatic-enzyme inducing agents which result in increased catabolism of vitamin D (Sherk et al 1977, Liavainen and Savolainen 1983, Sheth et al 1995. We tried to address the problem by 3 months of administration of vitamin D. This resulted in an improvement in serum Ca and a decrease in serum ALP levels in both groups, despite the ACT being unchanged.…”