Residual symptoms are a common hindrance to daily life for patients with major depressive disorder. Even after antidepressant treatment has led patients to meet remission criteria, almost all patients have at least 1 symptom that remains unresolved. These symptoms can increase the risk for relapse, a chronic course, and suicide attempts. Residual symptoms are lingering symptoms that do not resolve with treatment of the depressive episode, and they should be distinguished from symptoms of comorbid psychiatric or medical conditions and medication side effects. By understanding how various antidepressants affect the 3 monoamine systems of serotonin, norepinephrine, and dopamine, clinicians can select treatments based on the most effective mechanism of action. Dual-action agents show promise for alleviating depressive symptoms that do not resolve with single-action agents. Medications that increase norepinephrine or dopamine neurotransmission may improve several common residual symptoms left after treatment with serotonin-specific agents. Treatment strategies like adjunctive therapies and dosing options are given for common residual symptoms, including sleep difficulties, sexual dysfunction, and pain. For patients to truly regain their quality of life, clinicians must target residual symptoms.
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