Temporal Profiles and Dose-Responsiveness of Side Effects with Escitalopram and Duloxetine in Treatment-Naive Depressed Adults

Side effect profiles of antidepressants are relevant to treatment selection and adherence among patients with major depressive disorder (MDD), but several clinically-relevant characteristics of side effects are poorly understood. We aimed to compare the side effect profiles of escitalopram and duloxetine, including frequencies, time to onset, duration, dose responsiveness, and impact on treatment outcomes. Side effects occurring in 211 treatment-naive patients with MDD randomized to 12 weeks of treatment with flexibly-dosed escitalopram (10-20 mg/day) or duloxetine (30-60 mg/day) as part of the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study were evaluated. Escitalopram- and duloxetine-treated patients experienced a similar mean number of overall side effects and did not differ in terms of the specific side effects observed or their temporal profile. Experiencing any side effect during the first 2 weeks of treatment was associated with increased likelihood of trial completion (86.7% vs. 73.7%, p = 0.045). Duloxetine-treated patients who experienced dry mouth were significantly more likely to achieve remission than those who did not (73.7% vs. 44.8%, p = 0.026). Side effects that resolved prior to a dose increase were unlikely to recur after the increase, but only about 45% of intolerable side effects that required a dose reduction resolved within 30 days of the reduction. At the doses used in this study, escitalopram and duloxetine have similar side effect profiles. Understanding characteristics of side effects beyond simple frequency rates may help prescribers make more informed medication decisions and support conversations with patients to improve treatment adherence.