Dr. Bob's Psychopharmacology Tips

Imipramine / phenytoin interactions

Date: Thu, 04 Jan 96 14:17:41 PST
From: William Wilson <wilsonw@ohsu.edu>
Subject: Imipramine / phenytoin interactions

A seventyish woman comes to me having been on imipramine 75 mg/d for many years, along with a very low dose antipsychotic. She had found this combination to stabilize her chronic anxiety, depression, and mood lability.

About 6 months ago she had a grand mal seizure, which was evaluated by a competent neurologist who put her on Dilantin. She says "the Dilantin took away the effects of the imipramine." I don't have any blood level data.

She is now doing well on desipramine and risperidone, along with the Dilantin. But she keeps telling me the story of the imipramine /dilantin effect.

I am aware that tricyclics can lead to increases in Dilantin levels (references below) but have not found anything about Dilantin decreasing imipramine levels.

Houghton GW, Richens A. Inhibition of phenytoin metabolism by other drugs used in epilepsy. International Journal of Clinical Pharmacology & Biopharmacy. 12 (1-2): 210-6, 1975 Jul.

Pond SM, Graham GG, Birkett DJ, Wade DN. Effects of tricyclic antidepressants on drug metabolism. Clinical Pharmacology & Therapeutics. 18 (2): 191-9, 1975 Aug.

Perucca E, Richens A. Interaction between phenytoin and imipramine. British Journal of Clinical Pharmacology. 4 (4): 485-6, 1977 Aug.

From: Eduardo Dunayevich <dunayev@penn.com>
Date: Thu, 4 Jan 1996 22:26:10 -0500
Subject: Imipramine / phenytoin interactions

Ketter TA, Flockhart DA, Post RM, Denicoff K, Pazzaglia PJ, Marangell LB, George MS, Callahan AM. The emerging role of cytochrome P450 3A in psychopharmacology. Journal of Clinical Psychopharmacology. 15 (6): 387-98, 1995 Dec:

describes cytochrome P450 3A3/4 as induced by phenytoin and responsible for the demethylation of tertiary amine TCAs.

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