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We agree with Drs. Goetz and Ingle that the use of certain antidepressants to suppress tamoxifen-induced hot flashes may be expected to improve tamoxifen persistence. Unfortunately, this question was not addressed in our study and it is not possible to draw conclusions from our results concerning the effect of concurrent antidepressant therapy on tamoxifen persistence.

Women in our study cohort were identified as having a probable recent history of depression if they received at least 1 antidepressant prescription in the year prior to the initiation of tamoxifen.1 Whether women continued with or commenced an antidepressant after the initiation of tamoxifen therapy was not recorded. For this reason, our study can only evaluate the effect of a history of depression on tamoxifen persistence.

Evaluating the effect of coprescribed antidepressant therapy on persistence in women receiving tamoxifen would have required the identification of a suitable group with which to compare these women to (eg, women with untreated side effects, of similar severity). Even with detailed diagnostic information, identifying a group such as this may not have been possible.

Results from our study indicate that women with a history of depression are 41% more likely to discontinue tamoxifen therapy. It would undoubtedly be of interest to determine what impact this has on breast cancer outcomes and whether the use of cytochrome P450 2D6 (CYP2D6)-inhibiting antidepressants places women with depression at an additional disadvantage.

However, we would suggest caution in interpreting breast cancer outcome data from observational studies of CYP2D6 inhibition that do not control for bias due to confounding. For example, women prescribed fluoxetine and paroxetine for depression or the control of side effects are likely to have an elevated risk of tamoxifen nonpersistence1, 2 and possibly a greater risk of breast cancer recurrence. It may not be appropriate to compare the outcome of these women with that of breast cancer patients without depression or side effects.

The effect of coprescribed CYP2D6 inhibitors on the outcome of breast cancer patients could be best evaluated using well-designed case-control studies. As suggested by Drs. Goetz and Ingle, the comparison of CYP2D6 inhibitors of varying potency prescribed for the same indication may be a suitable starting point.3

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Thomas I. Barron MSc Pharm*, Roisin M. Connolly MB†, John Feely MD‡, * Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, Trinity College Dublin, Dublin, Ireland, † Department of Medical Oncology, St. James's Hospital, Dublin, Ireland, ‡ Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin, Ireland.