To describe the frequency of drug combinations (substrate-substrate or substrate-inhibitor) with the potential to interfere with the CYP2D6 metabolic pathway in patients receiving antidepressant medication for major depressive disorder.

We carried out an observational study using outpatient medical records. We included adult subjects who initiated antidepressant medication during 2008–2010. Patients were assigned to three study groups: no combination, substrate-substrate, and substrate-inhibitor. Follow-up period was 12 months. Main measures: demographics, comorbidity and medication persistence. Statistical analysis included a logistic regression model, P < 0.05.

Five thousand six hundred and thirty patients were recruited (61.9 years, 76.9% female), 24.4% (CI: 23.8 – 26.0%) received some kind of drug combination (substrate-substrate: 15.4%, substrate-inhibitor: 9.0%). Variables significantly associated with drugs combinations that may act on the CYP2D6 metabolic pathway were: dementia (OR = 4.2), neuropathy (OR = 4.2) and stroke (OR = 1.9), P < 0.001. Medication persistence at 12 months was longer in patients with no combination (55.3%) than in patients receiving substrate-substrate (50.5%) or substrate-inhibitor (45.0%) combinations, P < 0.001.

Twenty-five percent of major depressive disorder patients received a combination of drugs with the potential to interfere with CYP2D6 metabolic pathway. These combinations increased with comorbidity and resulted in shorter medication persistence of antidepressant treatment.