Studies suggest that people with major depressive disorder (MDD) often receive treatment that is not concordant with practice guidelines. To evaluate this, we (1) developed a guideline concordance algorithm for MDD pharmacotherapy (GCA-8), (2) scored it using clinical data, and (3) compared its explanation of patient-reported symptom severity to a traditional concordance measure. This study evaluated 1,403 adults (67% female, 85% non-Hispanic/Latino White, mean age 43 years) with non-psychotic MDD (per codes), from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) registry (visits from February 1, 2015, to April 13, 2021). We (1) scored 1-year concordance using the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines and deviation from 8 pharmacotherapy-related criteria and (2) examined associations between concordance and Patient Health Questionnaire depression module (PHQ-9) scores. The mean GCA-8 score was 6.37 (standard deviation [SD] = 1.30; 8.00 = perfect concordance). Among those who switched drugs (n = 671), 81% (n = 542) did not have their dose increased to the recommended maximum before switching. In our adjusted analyses, we found that a 1 SD increase in the GCA-8 was associated with a 0.78 improvement in the mean PHQ-9 score ( < .001). The comparison concordance measure was not associated with the mean PHQ-9 score (β = -0.20;  = .20;  = 0.53), and adding the GCA-8 score significantly improved the model ( = 0.54; Vuong test  = .008). By measuring naturalistic MDD pharmacotherapy guideline concordance with the GCA-8, we revealed potential treatment gaps and an inverse association between guideline concordance and MDD symptom severity.
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