Spectrum of Side Effects of Anticonvulsants in Patients with Brain Tumours

European Association of NeuroOncology Magazine 2012; 2 (1): 15-24

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Keywords: anticonvulsant,  brain tumour,  cognitive dysfunction,  drug interaction,  seizure,  toxicity

Seizures are a common manifestation in patients with brain tumours, and most patients need anticonvulsants. Apart from seizure control, the risk of side effects makes the proper choice of anticonvulsants a major concern. Toxicities not only exist as common side effects, but also appear as drug-drug interactions, neurotoxicities, and other organ dysfunctions. One reason for interactions is the use of the classical anti-epileptic drugs (AED), phenobarbital (PB), phenytoin (PHT), and carbamazepine (CBZ). Large differences in dose regimens with concomitant chemotherapy reflect the potency of these effects. Although valproic acid (VPA) can be beneficial to prevent tumour growth, it may lead to bone marrow suppression and other toxicities because of its enzyme-inhibiting properties. Another noteworthy side effect are skin reactions, like erythema multiforme, which occasionally develops during radiation. Although this side effect is rare, it can be life-threatening. Many anti-epileptic drugs can have extra toxic effects with existing organ dysfunction, like bone-marrow suppression or liver abnormalities, this applies particularly for PB, PHT, CBZ, and VPA. Existing clinical or subclinical signs of brain damage secondary to space-occupying tumoural effects or the sequelae of previous neurosurgery, radio-, and chemotherapy enhance the chances of neurotoxicity. Besides, the intake of anticonvulsants itself and their total number strongly contribute to cognitive dysfunction. As neurocognitive decline interferes with quality of life, such changes may substantially affect daily activities of patients and their family members. The multitude of co-therapies applied with brain tumours contributes to a myriad of side effects that are almost impossible to unravel, as drugs and other therapies used can have aggravating or counteracting effects on each other. Knowledge of individual anticonvulsants and anticipation of toxicity including the recognition of already existing co-morbidities all contribute to better selection and dosing of anticonvulsants, including the choice of agents that do not interact. Although this survey is not aimed at the proper drug choice, future studies need to show which anti-epileptic agents or combinations would be the best match to achieve effective seizure control together with good tolerability.