Specific clinical features were associated with severe treatment resistant depression (TRD): longer duration and higher severity of the current MDD episode, moderate to high suicidal risk level and higher rates of side effects during treatments.

Among them, the severity of the illness (as assessed with the MINI) was identified as the most discriminative one.

Raising the dose of ADs versus keeping lower dose when treating non-responder MDD patients should be considered with caution in clinical practice.

The early identification of MDD patients at high risk for treatment resistance could guide clinicians in selecting optimal setting and intensity of care.