At least one quarter of all patients with cancer suffer frommajor depressive disorder. Recognizing this as a major comorbidity, ASCO created guidelines for screening, assessing, and treating depression in patients with cancer . Standard response rates to antidepressants are 30%–50% regardless of what agent is selected . There is a growing recognition that pharmacoge- nomic variationmay help explain some of the low response rates and incidence of adverse effects. Data now clearly justify the clin- ical utility of using an individual patient’s pharmacogenomic pro- file to select the best treatment for depression.
CYP2C19 plays a major role in the metabolism of citalo- pram, escitalopram, and sertraline. Poor metabolizers at CYP2C19 have been shown to be at increased risk of adverse events, including QT prolongation [72, 73]. Alternatively, UMs have lower plasma concentrations and are more likely to suffer from ineffectively treated depression . CPIC recommends a 50% dose reduction in citalopram, escitalopram, and sertraline for CYP2C19 PMs and avoiding citalopram and escitalopram for CYP2C19 UMs . For CYP2C19 UMs, sertraline can be pre- scribed at the recommended starting dose, but if a patient does not respond clinically, CPIC guidelines suggest considera- tion of an alternative drug not predominantly metabolized by CYP2C19.
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