Description of health problem

The focus of this review is the acute-phase treatment of patients with unipolar treatment-resistant depression (TRD). Patients with TRD are those with major depressive disorder (MDD) that has not responded adequately to treatment. However, there is much uncertainty regarding what constitutes the definition of TRD and whether or not, for example, a patient with a failure to respond to two antidepressants from the same class could be defined as treatment resistant. 1,2 For the purposes of this report, TRD has been defined as a failure to respond to two or more antidepressants in the current episode of depression, the definition used in the 2003 National Institute for Health and Care Excellence (NICE) clinical guideline on the treatment and management of depression in adults (CG23).(3) This definition for TRD was also reported by the authors of a large systematic review of 42 randomised trials to reflect the consensus within the literature (26 trials) 4 and in the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines(5) for biological treatment of unipolar depressive disorders. In addition, the WFSBP guidelines5 state that 'as many as 50% of non-responders to a first antidepressant trial also fail to respond to a second, different course of treatment'. However, there is a general lack of clarity or consensus around the length of treatment required prior to treatment being defined as a failure and also the impact of historical treatment failures on the definition of future episodes of TRD, i.e. whether or not TRD should be diagnosed based on antidepressant failures that have occurred in only the current episode of depression.