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Fluoxetine Inhibits Desipramine Metabolism

TIMOTHY E. Wilens, MD; Joseph Biederman, MD; Ross J. Baldessarini, MD; Stephen P. McDermott, MD; James G. Flood, PhD
Arch Gen Psychiatry. 1992;49(9):752-752. doi:10.1001/archpsyc.1992.01820090080014
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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

REFERENCES

Nelson JC, Mazure CM, Bowers MB, Jatlow PI.  A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression . Arch Gen Psychiatry . 1991;; 48:303-307.
Bell IR, Cole JO.  Fluoxetine induces elevation of desipramine level and exacerbation of geriatric nonpsychotic depression . J Clin Psychopharmacol . 1988;;8:447-448.
Aranow RB, Hudson JL, Pope HG Jr, Grady TA, Laage TA, Bell IR, Cole JO.  Elevated antidepressant plasma levels after addition of fluoxetine . Am J Psychiatry . 1989;;146:911-913.
Fuller RW, Perry KW.  Effect of fluoxetine pretreatment on plasma and tissue concentrations of desipramine in rats . Res Commun Chem Pathol Pharmacol . 1989;;66:375-383.
Puopolo PR, Flood JG.  Detection of interference by cyclobenzaprine in liquid chromato graphic assays of tricyclic antidepressants . Clin Chem . 1987;;33:819-820.
Puopolo PR, Volpicelli SA, MacKeen Johnson D, Flood JG.  Emergency toxicology testing for basic drugs in serum using liquid chromatography with photodiode array detection . Clin Chem . 1991;;37:2124-2130.

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Nelson JC, Mazure CM, Bowers MB, Jatlow PI.  A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression . Arch Gen Psychiatry . 1991;; 48:303-307.
Bell IR, Cole JO.  Fluoxetine induces elevation of desipramine level and exacerbation of geriatric nonpsychotic depression . J Clin Psychopharmacol . 1988;;8:447-448.
Aranow RB, Hudson JL, Pope HG Jr, Grady TA, Laage TA, Bell IR, Cole JO.  Elevated antidepressant plasma levels after addition of fluoxetine . Am J Psychiatry . 1989;;146:911-913.
Fuller RW, Perry KW.  Effect of fluoxetine pretreatment on plasma and tissue concentrations of desipramine in rats . Res Commun Chem Pathol Pharmacol . 1989;;66:375-383.
Puopolo PR, Flood JG.  Detection of interference by cyclobenzaprine in liquid chromato graphic assays of tricyclic antidepressants . Clin Chem . 1987;;33:819-820.
Puopolo PR, Volpicelli SA, MacKeen Johnson D, Flood JG.  Emergency toxicology testing for basic drugs in serum using liquid chromatography with photodiode array detection . Clin Chem . 1991;;37:2124-2130.

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