Relapse after switching antidepressants because of tamoxifen use: a report of 2 cases.

To the Editor: A paper has been presented stating that antidepressants that inhibit the hepatic isoenzyme cytochrome P450 2D6 may reduce tamoxifen concentrations in female breast cancer patients and that this could lead to higher recurrence of cancer.1 The cancer center in my region has therefore asked its patients undergoing treatment with tamoxifen to switch antidepressants to one less likely to inhibit P450 2D6. Although this may provide medical advantages for some women at risk, caution would be prudent given some patients' hesitancy in changing an antidepressant that already is working or if a woman is particularly committed to her current medicine.2 Switching raises the possibility that patients in remission from their major depression may have a recurrence. I report here what I believe may be the first published reports of depression relapse in such patients. Case 1. Ms A, a 47-year-old woman with a history of major depressive disorder, recurrent (DSM-IV criteria), had been stable on fluoxetine monotherapy 60 mg/day for several years. She attempted to wean herself from medicine in the past only to relapse. She developed breast cancer in 2009 and was told by her oncologist to switch antidepressants since she was also put on tamoxifen treatment. She slowly weaned herself from fluoxetine and started escitalopram 10 mg/day, and her depression returned. She became so severely mentally ill that she made plans to commit suicide and her sister flew in from out of town to care for her. Five weeks after the switch, it was decided with her family to switch her back to fluoxetine 60 mg/day, and her depression remitted within 3 weeks. Case 2. Ms B, a 51-year-old woman, was in remission for her major depressive disorder, recurrent (DSM-IV criteria), on duloxetine 60 mg/day, but starting in late 2009 was slowly cross-titrated to desvenlafaxine 50 mg/day for 1 month and then 100 mg/day for 1 month several months after developing breast cancer and starting tamoxifen. The dose of desvenlafaxine was increased because her depression returned to the extent that her son said he no longer wanted her to come home until she was back on duloxetine. She could not work as a consequence of ongoing crying spells and concentration difficulty. Three months after switching from duloxetine to desvenlafaxine, she went back to duloxetine 60 mg/day, which again was effective. These cases describe potential consequences associated with discontinuation of effective antidepressants even if being replaced with one with a similar mechanism of action. These patients might have also relapsed on their original antidepressant from their cancer diagnosis or treatment, although both were diagnosed and treated several months to years earlier and were psychiatrically stable until switching. Although recurrence of breast cancer is a serious consideration, one must not overlook the consequences of recurrent depression. Patients may feel that relapse of depression is as serious as relapse from cancer, so a cautious approach is advisable. Clinicians and patients should be aware that switching someone who is responding well to their antidepressant does not predict successful outcome when switching to a similar one. The psychiatrist should consider discussing alternative treatment options with the oncologist. Perhaps the dose of tamoxifen could be adjusted upward. Patients should be given an explanation of risk if being advised to discontinue effective psychiatric treatment.