Combinación de antidepresivos vs. aumentación con antipsicóticos atípicos tras no lograr la remisión en la depresión unipolar

Introduction: achieving functional recovery as quickly as possible in the treatment of unipolar depression is a challenge that clinical practice must try to meet nowadays, since any delay in accomplishing remission of the symptoms is predictive of a larger number of recurrences and higher morbidity and mortality rates. In this topical review we aim to guide clinicians in their choice to augment with atypical antipsychotics or to combine the baseline drug with a second antidepressant, after the dose of the antidepressant initially selected has been optimized and/or the antidepressant has been changed, not achieving remission, or resulting only in a partial response after sufficient time at an appropriate dose. These decisions arise frequently in everyday clinical practice. Methodology: a systematic search in PubMed was performed under several key combinations of words, resulting in 230 reports. After applying inclusion criteria and based in title and abstract, the final number of reports selected for full revision were 113. Two main questions were answered based on these studies: 1) Is there evidence to clearly recommend combination of antidepressants vs. augmentation with antipsychotics (and the correct moment to do it) in non-responsive unipolar depression, once optimization or switching strategies have failed to obtain remission? and 2) Is it possible to identify some clinical features to guide the decision of combination of antidepressants vs. augmentation with antipsychotic agents? Results: According to our analysis, there is no data available to select one strategy from another in a clear-cut manner. Nevertheless, we suggest favoring a combination or augmentation strategy, based in a “treating to target” approach to profile the patient, considering one or two predominant clinical features that remain active as part of a major depression with partial response. Proper analysis of the symptomatic domains present, a critical view of current clinical guidelines and preferred options, considering hidden bipolarity as one of the main differential diagnoses and adopting an energetic but lucid attitude at this stage of treatment are, in our view, fundamental for achieving ad integrum patient recovery.