Psychiatry 2007 [FEBRUARY] 16 E xperienced clinicians are increasingly aware of the limitations of antidepressant monotherapies to completely treat the acute symptoms of major depressive disorder (MDD) and to sustain the benefits over time. In fact, many patients with MDD who are treated with SSRIs achieve only partial treatment responses and may suffer from residual symptoms contributing to a poorer outcome. 1 Consequently, the “old school” teaching of reluctant polypharmacy is being recast as a more strategic new approach incorporating augmentation or combination antidepressant treatments. In this interview, Dr. Maurizio Fava reviews the importance of treating residual symptoms and describes some of his preferred strategies. DO RESIDUAL SYMPTOMS MATTER? Dr. Fava: They matter a lot. Partial treatment responders may suffer from persistent psychological, behavioral, and somatic symptoms, including sadness, anhedonia, guilt, fatigue, insomnia, decreased appetite, decreased motivation, cognitive deficits, and even pain. 1 Furthermore, these patients are highly susceptible to relapse. Depressed patients with residual symptoms have poorer prognoses and tend to function worse over time. In one study of long-term outcome, 76 percent of treated patients with persistent, residual symptoms relapsed within 10 months, in contrast to only 25 percent of patients without residual symptoms. 2 So, in my opinion, achieving full symptom remission is the ultimate objective in the treatment of depressed patients. HOW DO YOU DEFINE SYMPTOM REMISSION? Dr. Fava: One way to determine a remission status is to use a rating instrument, such as the Hamilton rating scale for depression. Using the 17-item version of this scale, total scores <8 have been traditionally used to define symptom remission. This means that some residual symptoms may remain, but most of these patients are much improved and able to function. Augmentation and Combination Strategies to Treat the Residual Symptoms of Major Depressive Disorder by Maurizio Fava, MD; and Steven D. Targum, MD Psychiatric Research Applied to Clinical Practice This month’s installment features an interview with Maurizio Fava, MD, Vice-Chair, Department of Psychiatry, Massachusetts General Hospital and Professor of Psychiatry, Harvard Medical School, Boston, Massachusetts.