Characterising anxiety in major depressive disorder and its use in predicting antidepressant treatment outcome: An iSPOT-D report

Objective: Major depressive disorder commonly co-occurs with one or more anxiety disorders or with clinically significant levels of anxiety symptoms. Although evidence suggests that anxious forms of depression are prognostic of poorer antidepressant outcomes, there is no clear definition of anxious depression, and inferences about clinical outcomes are thus limited. Our objective was to compare and evaluate definitions of anxious depression and anxiety-related scales according to clinical and antidepressant outcome criteria. Method: A total of 1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic, major depressive disorder were assessed at baseline on clinical features. Participants were then randomised to one of three antidepressants and reassessed at 8 weeks regarding remission and response of the 17-item Hamilton Rating Scale Depression (HRSD 17 ) and the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR 16 ). Anxious depression was defined as major depressive disorder with one or more anxiety disorders or major depressive disorder with a HRSD 17 anxiety/somatisation factor score ⩾7. Anxiety-related scales included the HRSD 17 anxiety/somatisation factor and the 42-item Depression Anxiety Stress Scales (DASS 42 ) anxiety and stress subscales. Results: Anxious depression definitions showed poor agreement (κ = 0.15) and the HRSD 17 anxiety/somatisation factor was weakly correlated with both DASS 42 anxiety ( r = 0.24) and stress subscales ( r = 0.20). Anxious depression definitions were also associated with few impairments on clinical features and did not predict poorer antidepressant treatment outcome. However, higher DASS 42 anxiety predicted poorer HRSD 17 and QIDS-SR 16 remission, and item-level analysis found higher scores on items 9 (situational anxiety) and 23 (somatic anxiety) of the DASS 42 predicted poorer treatment outcome, even after adjusting for covariates and multiple comparisons. Conclusion: Common definitions of anxious depression show poor agreement and do not predict poorer treatment outcome. Anxiety symptoms may be better characterised dimensionally using DASS 42 when predicting treatment outcome.