Pharmacological interventions in the treatment of various cognitive, behavioural and neurological problems after brain injury often may involve combinations of medications from various drug classes. This carries the implication of potentially new or previously undereported drug interactions. A case report is presented in which a commonly used anticonvulsant drug, valproic acid, and a commonly used antidepressant, desipramine, interacted in such a manner as to cause potentially toxic serum concentrations of desipramine. This case demonstrates the important point that it is not simply the addition of one drug to another that may cause interaction, but the withdrawal of a particular drug which may then adversely impact the remaining drug regimen.