Pharmacotherapy: Major Depressive Disorder and Difficult-to-Treat Depression: Review for Nurse Practitioners

Adults worldwide are experiencing moderate-to-severe depression and anxiety, with rates rising since the coronavirus disease 2019 pandemic, especially among women. Many individuals face high levels of stress, further impacting mental health. Antidepressants and antipsychotics are commonly prescribed, yet misconceptions persist, and some health care providers may lack training in treating major depressive disorder, its subtypes, and difficult-to-treat depression, including anxious depression. Recent clinical guidelines recommend using adjunctive therapies, such as aripiprazole and brexpiprazole, earlier after a poor response to initial antidepressant treatment. This review helps nurse practitioners manage depression using a stepwise approach with updated pharmacologic evidence.