Ingestion of cyclic antidepressant medications or prolongation of the electrocardiographic QRS interval are commonly considered as contraindications to the use of physostigmine as an antidote for antimuscarinic toxicity. This dictum seems to stem from a few well-publicized cases in which administration of physostigmine was temporally associated with the development of asystole. Before the report of these cases, physostigmine was more frequently used and had been considered a first-line antidote for both the neurologic and cardiac toxic effects of cyclic antidepressant overdose. This apparent inconsistency, and a resurgence of interest in physostigmine as an antidote, begs the question of the appropriateness of this drug's contraindication in all cyclic antidepressant ingestions. Review of the published clinical and experimental evidence provides little support for the clinical utility of using electrocardiographic criteria or the ingestion of cyclic antidepressants as contraindications to the use of physostigmine.
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