Exploring the utility of RDoC in differentiating effectiveness amongst antidepressants: A systematic review using proposed psychometrics as the unit of analysis for the Negative Valence Systems domain

Background: RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological “constructs” that span dimensionally from normality to pathology, but its clinical utility remains controversial. Aim: To explore RDoC’s potential clinical utility by examining antidepressant effectiveness through Negative Valence Systems (NVS) domain constructs. Method: A systematic review was conducted on Web of Science, MEDLINE, EMBASE and PsycINFO for antidepressant trials that included psychometric instruments assessed by Watson, Stanton & Clark (2017) to represent NVS constructs of Acute Threat, Potential Threat and Loss. Results: 221 citations were identified; 13 were included in qualitative synthesis, none for quantitative analysis. All suffered from significant bias risks. 9 antidepressants were investigated, most within 1 construct, and most were found to be effective. Paroxetine, citalopram and fluvoxamine were found to be effective for Acute Threat, fluoxetine, desvenlafaxine and sertraline for Potential Threat, and sertraline, fluvoxamine, fluoxetine and desvenlafaxine effective for Loss. Nefazodone was found to be ineffective for acute fear. Conclusion: Preliminary evidence supports RDoC NVS constructs’ clinical utility in assessing antidepressant effectiveness, but lack of discriminant validity between Potential Threat and Loss supports their recombination into a single Distress construct. Finding of effectiveness within “normal” construct levels support the utility of a dimensional approach. Testable hypotheses were generated that can further test RDoC’s clinical utility.