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September 1992

Fluoxetine Inhibits Desipramine Metabolism

Author Affiliations

Pediatric Psychopharmacology Unit (ACC 725) Massachusetts General Hospital Boston, MA 02114
Patricia R. Puopolo
Boston, Mass

Arch Gen Psychiatry. 1992;49(9):752. doi:10.1001/archpsyc.1992.01820090080014

To the Editor.—  We read with interest the article by Nelson et al1 on the treatment of depression with fluoxetine and desipramine, particularly regarding effects of fluoxetine on serum levels of desipramine and its major active metabolite, 2-hydroxydesipramine. Fluoxetine can elevate blood concentrations and the risk of toxic effects of tricyclic antidepressants unless their dose is greatly restricted.2,3 This interaction probably reflects competition for enzymatic oxidation.4 Although ring-hydroxylation to 2-hydroxydesipramine is a major route of metabolism of desipramine, assessment of effects of fluoxetine on 2-hydroxydesipramine is very limited.2-4In a retrospective comparison of 14 adults with depression given desipramine and fluoxetine and 52 patients given desipramine alone, Nelson et al1 found serum desipramine levels to be similar in both groups despite an approximate reduction of 30% in desipramine dose with fluoxetine. In their data, we find (eg, at 4 weeks of fixed-dose treatment) lower mean

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