OBJECTIVES Major Depressive Disorders (MDD) guidelines recommend using antidepressants with dual mechanism-of-action (venlafaxine, duloxetine) when resistant to a prior course of Selective-Serotonin-Reuptake-Inhibitors (SSRI). Dose to use should be close to the DDD recommended by WHO. Routine clinical practice may be frequently far from guidelines. The aim was to ascertain the average maintenance daily dose (DD) of venlafaxine and duloxetine in the monotherapy of patients with MDD who showed resistance to a previous SSRI in routine medical practice in Spain. METHODS Retrospective analysis extracting consecutively electronic medical records (EMR) of the BSA, a provider which health plan coverage includes near 120,000 inhabitants in Badalona (Spain). EMR of male/female patients, >18 years, included in the chronic prescription follow up program, with a MDD ICD-9-CM code (296.2x/296.3x), and who were resistant to a previous SSRI course, were extracted for analysis. Resistant was defined as persistence of symptoms (score >17 in the Hamilton-Depression scale and/or reduction lower than 30% of the baseline score). Maintenance DD was considered the dose repeated (refills) at least two time consecutively during the study period (years 2012-2013). RESULTS Three-sixty-eight EMR [81% women, 60.3 (15.2) years] were extracted; 160 of duloxetine and 208 of venlafaxine. Average maintenance DD were 65mg/day and 117 mg/day for duloxetine and venlafaxine, respectively. Demographics, number of comorbidities or previous SSRI were not related with average dose. 86% of duloxetine EMR were prescribed the WHO DDD for this drug (60mg), while only 42% of venlafaxine received its WHO DDD (100mg), p<0.001. Number of DDD per day were significantly higher with venlafaxine; 1.17 (1.10-1.23) vs. 1.09 (1.05-1.12), p=0.049.     CONCLUSIONS Routine medical practice average maintenance DD of venlafaxine and duloxetine in SSRI resistant subjects with MDD are different in terms of both their recommended doses in labelling or guidelines and in number of DDD per day.