Psychiatric adverse effects of anticonvulsant drugs: Incidence and therapeutic implications

Abstract

Some anticonvulsants have been reported to be associated with psychiatric adverse reactions, such as behavioural disorders, depression, mania and psychosis. However, few systematic pharmacoepidemiological studies have investigated adverse reactions to anticonvulsant drugs, which makes accurate assessment of the incidence rate of adverse drug reactions, including psychiatric adverse reactions, very difficult. Nevertheless, by reviewing clinical trials, observational studies and case reports, it can be concluded that patients exposed to vigabatrin or phenobarbital (phenobarbitone) are at the highest risk of developing psychiatric adverse drug reactions, those exposed to phenytoin probably at medium risk, while patients exposed to carbamazepine, valproic acid (sodium valproate) and benzodiazepines are at the lowest risk. Based on the available evidence, psychiatric adverse drug reactions attributable to lamotrigine and gabapentin are relatively infrequent, although further evidence is required to confirm this. Topiramate has only been marketed for 2 years and felbamate has only had limited use because of its propensity to cause serious nonpsychiatric adverse effects; with the relative lack of peer-reviewed reports it is very difficult to comment further on the risk of psychiatric adverse reactions to these drugs. Rational prescribing using: (i) monotherapy, instead of polytherapy, whenever possible; (ii) the minimal effective dosage; and (iii) escalating the dosage slowly, can reduce the risk of the patient developing psychiatric adverse drug reactions. Pre-existing psychiatric/behavioural disorders and organic brain damage are believed to predispose patients to these reactions, and such patients should be carefully monitored. The ideal treatment of a psychiatric adverse drug reaction is discontinuation of the offending drug; however, this may not be possible for all patients with epilepsy. In cases where it is necessary to continue anticonvulsant medication to obtain satisfactory seizure control, the psychiatric disorder should be treated concurrently with psychosocial interventions and psychotropic medication, as appropriate.