Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment.

The authors conducted a systematic review for randomized controlled trials (RCT), relevant open-label trials, meta-analyses and ongoing trials of pharmacological and psychotherapeutic approaches to treatment-resistant depression (TRD). Results showed that switching to a different antidepressant is a useful option following nonresponse to a first-line agent.

Even though widely used in clinical practice, there is limited evidence to support antidepressant combination for TRD. Notwithstanding evidence for lithium or T3 augmentation to be successful in TRD, most studies were carried out when participants were treated with tricyclic antidepressants (TCA).

Of the available strategies to augment the response to new-generation antidepressants, the use of some atypical antipsychotics is best supported by evidence. Several novel therapeutic options are currently discussed. Evidence also showed that cognitive therapy (CT) is an effective strategy for TRD.

Overall findings supported the a need for additional large-scale RCT of TRD. The development of new antidepressants targeting novel pathways opens a promising perspective for the management of TRD.

Article: The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives, Carvalho A.F., Berk M., Hyphantis T.N., McIntyre R.S., Psychotherapy and Psychosomatics, DOI:10.1159/000357500, published March 2014.