Mild myoclonus is reasonably common with various cyclic antidepressants. However, antidepressants rarely cause severe myoclonus, and no risk or predisposing factors have been reported in the literature. We report a case of exceptionally severe myoclonus developing at therapeutic doses and modest serum levels of imipramine. The patient went on to experience dystonia and catatonia. Both of these were in typical settings (after haloperidol and with psychotic bipolar depression, respectively) and responded to typical treatment. On further investigation, the patient was found to have left-sided schizencephaly and a corresponding history of very mild developmental delay. We suggest that the onset of one movement disorder after drug therapy (eg, myoclonus) may predict the development of other movement disorders (e.g., catatonia). We further propose that severe tricyclic-induced myoclonus should prompt the physician to rule out a coexisting structural lesion of the central nervous system.