Influence of Neuroleptics and Benzodiazepines on Metabolism of Tricyclic Antidepressants in Man

The authors tested the pharmacokinetic interaction between benzodiazepines and nortriptyline in five patients. Each patient was tested during periods of treatment with neuroleptics, diazepam, and chlordiazepoxide, and in a drug-free control period. Neuroleptics (haloperidol and perphenazine) caused changes indicating inhibition of metabolism of ¹⁴C-nortriptyline. Neither of the two benzodiazepines caused a significant change in the pharmacokinetic measurements of ¹⁴C-nortriptyline. In rats, the metabolism of ¹⁴C-nortriptyline was inhibited by pretreatment with chlordiazepoxide, but only when given in a dose of 60 mg./kg. a short time before the administration of ¹⁴C-nortriptyline.