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Tolerance to desvenlafaxine in rapid metabolizing depressed patients

Parker, Gordon B.a,b; Brotchie, Heather L.a,b; Hyett, Matthewb

International Clinical Psychopharmacology: March 2011 - Volume 26 - Issue 2 - p 84–87
doi: 10.1097/YIC.0b013e328341e333
Original Articles

The terms ‘tolerance’ and ‘poop out’ are commonly applied to describe the progressive loss of effectiveness of a previously effective antidepressant and where the individual may be a rapid metabolizer of those drugs as a consequence of possessing certain polymorphisms of P450 (CYP) liver enzymes, especially CYP2D6 and CYP2C19. As the antidepressant desvenlafaxine is not metabolized by those enzymes, it might be hypothesized that it would be less likely to be associated with tolerance or poop out, even for patients whose genotyping pattern is indicative of rapid metabolizing. In this study, we report on five patients who had a historical pattern suggestive of tolerance to other antidepressant drugs, whose genotyping test indicated that they were CYP2C19 rapid metabolizers, and who experienced ‘poop out’ again when commenced on desvenlafaxine. Although desvenlafaxine is theoretically an option in patients with a history of tolerance to antidepressants, these case reports indicate that this drug may not necessarily overcome the problem of tolerance in rapid metabolizing patients.

aSchool of Psychiatry, University of New South Wales

bBlack Dog Institute, Prince of Wales Hospital, Randwick, Sydney, New South Wales, Australia

Correspondence to Gordon B. Parker, Black Dog Institute, Prince of Wales Hospital, Randwick 2031, Sydney, New South Wales, Australia Tel: +61 2 93824372; fax: +61 2 93824343; e-mail:

Received June 2, 2010

Accepted October 25, 2010

© 2011 Lippincott Williams & Wilkins, Inc.