Treatment Resistant-Depression (TRD), known as the failure to respond to at least two different adequate trials of antidepressant treatments (ADT) in the current episode, is a relatively frequent clinical condition, associated to a high number of relapses, hospitalizations, and an elevated use of multiple pharmacological treatments. To date, however, the association between clinical variables and non-response in TRD remains unclear.

To identify predictors of non-response in inpatients with Major Depressive Disorder (MDD) and TRD.

To investigate clinical variables as potential predictors of non-response in TRD.

Two hundred fifty-three inpatients with MDD and TRD were divided into two groups: responders and non-responders to drug therapies, according to a decrease of 50% or more of the severity of depression (measured with HAM-D 17 items) at the end of forth week of hospitalization. A general model of Cox regression (with backward stepwise method) was used to identify independent predictors of non-response to treatment.

One hundred fifty-four TRD inpatients were responders and 99 non-responders. Cox regression identified three independent clinical predictors independently associated with the group of non-responders: (1) the presence of 5 or more depressive episodes in the medical history (OR = 2.27); (2) a current comorbid anxiety disorder (OR = 1.85); (3) a history of early life adversities (ELAs) (OR = 1.60).

The findings of this study suggest that the phenomenon of non-pharmacological response in the TRD is associated with different clinical variables, which might act through separate mechanisms in determining the persistence of depressive symptomatology.