Treatment-resistant depression: neurobiological correlates and the effect of sleep deprivation with sleep phase advance for the augmentation of pharmacotherapy.

Objectives: To assess the neurobiology of treatment-resistant depression (TRD), and factors connected with improvement after total sleep deprivation (TSD) with sleep phase advance (SPA), for the augmentation of pharmacotherapy.Methods: The study comprised 43 patients with TRD, (15 male, 28 female), aged 48 +/- 13 years, with the illness duration 12 +/- 9 years, and the depressive episode 8 +/- 7 months. TRD was defined as a lack of significant improvement despite at least two antidepressant treatments and the augmentation with mood-stabilizers. Clinical improvement (response) was a reduction of >/=50% of points in the Hamilton Depression Rating Scale (HDRS), and the remission criterion was