Nevertheless, these results do provide a basis for considering the use of antidepressant medications in combination in practice—especially the use of mirtazapine plus a reuptake blocking agent, and particularly if the first treatment has been of sufficient dose and duration but has not been of sufficient therapeutic benefit. In my view, these combinations should not be routine first-step treatments yet, as we lack large-scale trials to establish safety and efficacy in a more generally representative population. On the other hand, the results of the Blier et al. study and work by others (2, 3) support the use of an SSRI or a selective norepinephrine reuptake inhibitor combined with mirtazapine as a second or third step. The decision to use such combinations must be tempered by and weighed in conjunction with the knowledge that weight gain and sedation are expected side effects. Further efforts to evaluate the safety, efficacy, and place for antidepressant medication combinations are called for.