Duloxetine (DLX) is approved for treatment of Major Depressive Disorder (MDD).

Aims of this study were to assess the clinical outcome of DLX in the treatment of MDD, with efficacy measures based on clinician and patient assessment, and to evaluate the predicitve value of DLX plasma levels on clinical response.

45 out-patients affected by MDD were included in the study and prescribed 30-120 mg/day of DLX for 12 weeks.

Patients were evaluated at T0, after 2 (T1), 4 (T2), and 12 weeks (T3), by using HAMD21, HAMA, CGI-S, and the self-rating scales BDI and VAS. Plasma samples were collected at T2.

Responders (50% reduction in HAMD21) were 60% and remitters (HAMD21 ≤7) were 56%. HAMD21 showed a significant improvement at T1, T2, T3 vs T0. HAMA and CGI-S showed a significant improvement at T2, T3 vs T0.

15 (33%) patients discontinued the treatment.

Blood pressure, heart rate, and body weight did not show relevant changes.

DLX plasma levels ranged from 5 ng/ml to 135 ng/ml (mean 53.56 ± 39.45 SD). The incidence of side effects irritability and anxiety was found to be significantly correlated with the highest DLX level/dose (mean 1.6 ng/ml/mg ± 0.29 SD) (p=0.02).

We observed a curvilinear relationship between HAMD21 percentage of amelioration at T2 and DLX plasma levels/dose (mg/kg) (y=22.74+0.78x-0.0038x2, R2=0.134; p=0.23).

Good medium-term clinical response, but plasma levels showed an increased of adverse events at higher values, reducing the advantages of dose escalation.