New approaches to treating resistant depression.

Persistent major depression that does not respond to adequate first- or second-line treatment is a common problem in psychiatry. This article updates evidence on recommended treatment strategies and reviews the prospects of more experimental approaches. The main pharmacological development in recent years has been the demonstration that several atypical antipsychotic drugs are effective adjunctive agents in improving symptoms in depression unresponsive to selective serotonin reuptake inhibitors, although their adverse effect burden is high. There is optimism about novel pharmacological strategies based on glutamatergic and anti-inflammatory mechanisms. It is important to combine drug and psychological treatments whenever possible. With persistent therapeutic engagement, the majority of patients remit eventually, but subsequent relapse remains a problem. Clinicians should pursue an active and collaborative treatment plan that makes use of all effective therapeutic modalities and continues into the relapse-prevention phase. LEARNING OBJECTIVES • Be aware of the concept of treatment-resistant depression as a staged condition and of the limitations of this concept • Update knowledge of the efficacy of recommended treatments for resistant depression, including new pharmacological and brain stimulation approaches • Be aware of the need for persistent therapeutic engagement and time-limited treatment trials to achieve remission and prevent relapse DECLARATION OF INTEREST P.J.C. has been a member of a Lundbeck advisory board. I.M.A. has been a member of advisory boards to Lundbeck, Servier and Alkermes. [ABSTRACT FROM AUTHOR]