OBJECTIVES: To carry-out a 6-month cost-effectiveness analysis (CEA) of the effect of Pregabalin (PGB) versus Usual Care (UC) in Duloxetine-refractory out-patients with Generalized Anxiety Disorder (GAD) treated according with usual medical practice in Mental Health Centers in Spain. METHODS: This CEA used secondary data extracted from a 6-month cohort prospective observational study (the ADAN study) designed to ascertain cost and health care resources utilization in subjects with GAD (DSM-IV criteria). Duloxetine-refractory subjects were defined as those who claimed of persistent symptoms of anxiety and showed suboptimal response (HAM-Anxiety scale≥16) after a course of standard doses of duloxetine for 6 month. At baseline, patients could switch to PGB, monotherapy or add-on, or to UC which could include ISRS/ISRN/other antidepressants, benzodiazepine, anti-epileptics different than PGB or a combination. Health outcomes included quality-adjusted life years (QALYs) gain by EQ-5D questionnaire. The perspective of CEA was that of a 3rd-payer in year 2009. Sensitivity analysis was performed by means of bootstrapping techniques (10000 re-samples were obtained) in order to obtain a cost-effectiveness acceptability curve. RESULTS: A total of 132 duloxetin-refractory subjects (mean baseline HAM-A; 25.6 pts) were identified; 103 and 29 in the PGB and UC groups, respectively. Compared with UC, PGB therapy was associated with significant QALY gain after 6 months of treatment; 0.1191±0.1163 vs 0.0810±0.0777, p=0.043, but higher healthcare costs; €1,402.1±849.1 vs €1,051.5±789.1, p=0.048. The deterministic ICER ratio was €9,210 per QALY gained with a re-sampling ICER of €11,234 (95 CI: 1,591-20,877). The 90% of re-samples fold below €20,513 threshold and 95% below €29,901.   CONCLUSIONS:   Despite the small sample and observational design, this evaluation could suggest that pregabalin may be cost-effective in comparison with usual care in duloxetine-refractory subjects with Generalized Anxiety Disorders managed in Mental Health Centers under usual medical practice in Spain.