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The American Journal of Psychiatry, VOL. 131, No. 8

Articles | August 01, 1974

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

LARS F. GRAM; KERSTIN FREDRICSON OVERØ; LARS KIRK

Am J Psychiatry 1974;131:863-866.

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Research Assistant, Psychochemistry Institute, Rigshospitalet, 9, Blegdamsvej, DK-2100 Copenhagen, Denmark

Research Assistant, Research Laboratories, H. Lundbeck & Co., Ltd., Valby Copenhagen. Denmark

Senior Registrar, Department D, St. Hans Hospital, Roskilde, Denmark

1974, The American Psychiatric Association

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Abstract

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.

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