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

Abstract

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-stabilisers. Clinical improvement (response) was a reduction of ≥50% of points in the Hamilton Depression Rating Scale (HDRS), and the remission criterion was ≤7 points in HDRS, lasting until the 14th day after TSD + SPA. Results TRD severity was associated with greater activity of the hypothalamic-pituitary-adrenal axis, the pro-inflammatory status of the immune system and lower reactivity of the hypothalamic-pituitary-thyroid axis. The response was achieved by 18 of 42 subjects, and connected with the later onset and shorter duration of the disease. In responders, there was a decrease in cortisol and interferon-gamma. In all subjects, a decrease in thyroid hormones was observed. Conclusions TRD can improve after augmentation of pharmacotherapy by TSD + SPA and some biological changes may be compatible with a decrease in allostatic load.