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Objectives: The present study aimed to explore psychiatrists' perceptions of duloxetine in routine clinical practice, focusing on its efficacy, tolerability, and treatment adherence in major depressive disorder (MDD) and generalized anxiety disorder (GAD). Methods: A structured questionnaire was administered to 97 psychiatrists from different regions of Spain. The survey covered demographic and professional data, prescription frequency, perceived clinical efficacy, tolerability, dosing patterns, and factors influencing adherence. Results: Overall, duloxetine was perceived as an effective treatment for both MDD and GAD, particularly in patients with somatic symptoms or comorbid anxiety. Tolerability was also positively rated, with nausea and fatigue identified as the adverse effects most commonly associated with reduced adherence. In addition, patient education and close follow-up were identified as the most effective strategies to improve adherence, whereas digital tools were considered promising but underused. Compared with other antidepressants, duloxetine was viewed as having a favorable balance between efficacy and tolerability, with similar or slightly higher adherence rates. Conclusions: These findings reflect a positive clinical appraisal of duloxetine among psychiatrists, highlighting its role as a versatile therapeutic option for affective and anxiety disorders, within the context of routine clinical practice in Spain, provided that appropriate adherence-support strategies are implemented.