Mirtazapine augmentation to a serotonin-reuptake inhibitor has been proposed to boost antidepressant effects and more likely to induce manic switch. Such a combined antidepressant therapy strategy should be used carefully if the patient's refractoriness is attributable to mixed depressive features. Mixed depression is more difficult to be treated by antidepressant monotherapy and related to higher risk of manic switch during treatment. We report a case with no previous history of bipolar disorder, whereas developed full-blown psychotic manic symptoms soon after switch from fluoxetine to mirtazapine. The patient's premorbid characters and clinical presentations suggested an implicit bipolarity that predisposed her to a manic switch. Her manic switch was likely to be triggered by a simulated combined effect because of complex drug interactions during shifting from fluoxetine to mirtazapine. For patients in mixed depressive states, mood stabilizers are preferable to antidepressants.