Major depression (MDD) presents among other symptoms with cognitive impairment and diurnal fatigue. Residual fatigue in non-remitted patients often shows neuropharmacological treatment resistance. The relationships between cognitive dysfunction, vigilance, fatigue and affective symptom intensity is poorly described in treatment-resistant MDD (TRD).

During a prospective study protocol, 17 in-patients hospitalized for TRD were compared to a healthy control group (n=17). Patients were under SNRI or SSRI and free from diurnal benzodiazepines. All subjects underwent structured psychometry (HAMD, HAD), cognitive assessment and vigilance measurements (behavioral sleep résistance task, BSRT; psychomotor vigilance test, PVT; Auditory Verbal Learning, AVLT; trail making test, TMT). Subjective fatigue and sleepiness were assessed by the Fatigue Severity and the Epworth Sleepiness Scales respectively. All measures have been performed at two time points (T1 and T2) with a 10-day interval.

T1 and T2 showed higher fatigue and sleepiness in MDD (p< 0.05). With exception for the BSRT, between group comparisons showed significant differences for all variables.Comparison for repeated measures (T1 and T2) showed improvement in depressive symptom intensity (HAMD, p< 0.0005) but cognitive and psychomotor performances only improved for the TMT (TMT-B, p=.001).

TRD presents here with psychomotor slowing, with impaired mental flexibility (executive function) and declarative memory dysfunction. Interestingly, despite subjective complaints (ESS), objective sleepiness (BSRT) had not been revealed. Furthermore affective symptom improvement was not associated to an increase in declarative memory or psychomotor performances.