OBJECTIVES: The use of innovative antidepressants has been growing as many were introduced since 1990s. However, physician prescribing patterns in innovative antidepressants is unclear. This study disentangled the impacts of sociological factors, such as physician, patient, and healthcare system factors, on the patterns and dynamics of adopting innovative antidepressants for major depressive disorder (MDD) in the US. METHODS: A retrospective 15-year cross-sectional study was conducted using the 1993-2007 National Ambulatory Medical Care Survey representing 125,605,444 MDD patients. The Heckman two-step model was used to capture physician's two-stage prescribing decision and to correct sample selection bias. First, logistic regression was applied to examine the impact of sociological factors on whether an antidepressant is prescribed. Second, multinomial logistic regression was used to capture physician choices of innovative vs. older antidepressants. RESULTS: A total of 71.22% MDD patients were prescribed an antidepressant. Physicians who were primary care physicians, non-owner of healthcare settings, practiced in Western and non-metropolitan areas, and had not seen patients before were more likely to prescribe innovative antidepressants (all p <0.001.) Patients who were younger, non-Hispanic, belong to HMOs, and took patient education were more likely to receive innovative antidepressants (all p <0.001.) Trend analyses revealed that physicians who were owners of non-solo practice, practiced in Midwestern, Northeastern and metropolitan areas were decreasing likelihood of prescribing innovative antidepressants over time. Patients who were non-white, non-black and non-Hispanic, and enrolled in Medicaid had increasing likelihood of receiving innovative antidepressants over time. CONCLUSIONS: The patterns of physician prescribing innovative antidepressants for MDD patients in the US varied with sociological factors. Patient characteristics, physicians characteristics, and healthcare system factors had impacts on physician's decision on choosing innovative antidepressants. Prescribing patterns also varied over time.