Treatment-resistant depression: definition and treatment approaches.

Little systematic attention has been directed toward the subject of treatment-resistant depression. Although these patients constitute a distinct minority, their treatment consumes a major portion of the clinician's time. Thus, the authors address the problems of defining and treating the estimated 750,000 patients with treatment-resistant depression. Several major factors concerning treatment-resistant depression appear evident: (1) although there is an emerging consensus of what constitutes "adequate" treatment, the majority of patients receive suboptimal drug regimens; (2) misdiagnosis of depression subtypes can lead to suboptimal treatment and "pseudo-resistance" to drug therapy; (3) treatment strategies for resistant depression should use systematic algorithms to avoid confusion and limit "therapeutic nihilism" in the patient and physician; and (4) the patient's risk/benefit ratio for each successive treatment application must be considered with the potential benefit weighed against the increasing risk of illness morbidity and likelihood of adverse events and/or suicide.