Predictors of response to augmentation treatment in patients with treatment resistant depression: a systematic review

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Background: Treatment resistant depression (TRD) is an important contributor to the global burden of depression. Antidepressant augmentation is a recommended treatment strategy for TRD patients, but outcomes remain poor. Identifying factors that are predictive of response to augmentation treatments may improve outcomes.
Aims: This review aimed to synthesise the existing literature examining predictors of response to augmentation treatments, in patients who had insufficiently responded to initial treatment.
Methods: A systematic search was conducted identifying 2241 unique manuscripts. 24 examining predictors of outcome to pharmacological or psychological augmentation treatment were included.
Results: Atypical antipsychotics were the most frequently assessed treatment class (9 studies), closely followed by mood stabilisers (8 studies). Only 1 eligible psychological augmentation study was identified. Early response to treatment (week 2) was the best supported predictor of subsequent treatment outcome, reported by 6 studies. Many predictor variables were only assessed by 1 report, and others such as pre-treatment severity yielded contradictory results, both within and across treatment classes.
Conclusions: This review highlights the importance of early response as a predictor of pharmacological augmentation outcome, with implications for both the monitoring and treatment of resistant unipolar patients. Further replication is needed across specific interventions to assess fully the generalisability of this finding. However, the clear lack of consistent evidence for other predictive factors both within and across treatments, and the scarce examination of psychological augmentation, demonstrates the need for much more research of a high quality if response prediction is to improve outcomes for TRD patients.
Original languageEnglish
JournalJournal of Psychopharmacology
Publication statusPublished - 17 Sept 2019


  • Depression
  • Prognostic factors
  • drug augmentation
  • review


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