Tolerance to desvenlafaxine in rapid metabolizing depressed patients

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.