First-Line and Combination Therapeutics for Major Depressive Disorder

Major depressive disorder (MDD) affects one in five adults during their lifetime. Patients with MDD and their clinicians have a multitude of options to select for management of this chronic and/or recurrent condition. Selection of treatment modalities may be guided by the severity of illness. Nonpharmacologic treatments such as psychotherapy or exercise may be considered for those with mild symptom severity, with pharmacologic treatment reserved for those with moderate or higher symptom severity. Severe or very severe depression may warrant the combination of both pharmacologic and psychotherapeutic treatments. In patients who fail to improve adequately with one or more first-line treatments, augmentation with second-generation antipsychotics should be considered. There currently are no objective markers to guide the selection of one first-line treatment over other. Exciting ongoing research in the field of depression may inform new methods to personalize treatment selection and potentially lead to the development of mechanistically novel antidepressants.