Depressed patients often complain of sleep disturbance. Routine antidepressive strategies sometimes fail to deal with this intractable issue. Indeed, the supplementation of sleep promoting antidepressants (eg, trazodone, mirtazapine, and agomelatine) is prevalent in clinical practice. However, the combination of different antidepressants may increase the affective lability. Herein, we document a patient with unipolar depression who was compliant with sertraline treatment and who dramatically switched to mania after adding trazodone as a sleeping aid. This case extended our understanding of the potential manic-switching risk when trazodone is used to promote sleep.