In recent years, novel antidepressants and mood stabilizers for major depressive disorder and bipolar disorder have arrived on the market, and older psychiatric medications have also come to be indicated for these disorders as well. For this reason, pharmacotherapy treatment strategies for said diseases have become increasingly diverse and complex. With this fact in mind, this paper reviews the combination of medications that are the most evidence-based and logical for polypharmacy in the following cases: combined antidepressants for major depression, combined antidepressants and mood stabilizers for bipolar depression, and combined mood stabilizers in maintenance therapy for bipolar disorder. In addition, I attempt here to clearly define treatment-resistant depression and detail some of the most important considerations for avoiding cases of false treatment-resistant depression. Finally, I proffer a few personal suggestions for simplifying polypharmacy in the two disorders.
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