The selective estrogen receptor modulator, tamoxifen, is extensively used for the endocrine treatment of all stages of hormone receptor-positive breast cancer. Tamoxifen is a mainly inactive prodrug, necessitating metabolism by the cytochrome P450 (CYP450) pathway, predominantly the Cytochrome P450 2D6 (CYP2D6), into the active metabolites 4-hydroxytamoxifen and, in particular, endoxifen to achieve its therapeutic effect. As several women treated with tamoxifen may experience depressive symptoms or may have a previous or actual major depressive episode with ongoing antidepressant treatment or need for a new-onset therapy, the coprescription of an antidepressant drug may be particularly problematic as several antidepressants are potent CYP2D6-inhibiting drugs. We herein report a case of a patient with major depression and concurrent tamoxifen therapy successfully treated with agomelatine monotherapy.

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