When is antidepressant polypharmacy appropriate in the treatment of depression?

Depression is a serious medical condition that is often only partially improved or completely unchanged after standard treatment with antidepressant medications. Various approaches have been developed to treat this subgroup of individuals with ‘treatment-resistant’ depression; but many individuals continue to live with chronic depressive symptoms that seriously affect their quality of life and overall functioning. One relatively new strategy is ‘antidepressant polypharmacy’ – simultaneously administering two or more antidepressant medications. Given the heterogeneity of the etiology of depression, this approach could improve therapeutic outcomes by concurrently activating multiple neurological pathways with different mechanisms of action, but there is also the risk that using multiple antidepressants would increase the prevalence and severity of side effects. Further work is needed to assess the potential benefits and risks of this strategy to managing treatmentresistant depression.