Abstract
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-naïve 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.
Highlights
Major depressive disorder (MDD) affects 15 million Americans over 18 years of age, and it is estimated that 13% of US adults are currently prescribed antidepressant medications [1]
To examine the recurrence of side effects after a dose increase, we identified those side effects that had onset after treatment initiation and subsequently resolved prior to a dose increase
These results provide additional information for prescribers to use in discussions with patients about the probability, duration, and dosing approaches regarding side effects occurring with escitalopram and duloxetine
Summary
Major depressive disorder (MDD) affects 15 million Americans over 18 years of age, and it is estimated that 13% of US adults are currently prescribed antidepressant medications [1].Because marketed antidepressants have relatively similar efficacy [2], the side effect profiles of the individual medications frequently become a driving factor for medication selections by physiciansBehav. Because marketed antidepressants have relatively similar efficacy [2], the side effect profiles of the individual medications frequently become a driving factor for medication selections by physicians. Between 32–60% of patients discontinue their medications within the first 3 months of treatment, with side effects frequently cited as the main contributing factor [3,4,5]. Selective serotonin-receptor inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), have emerged as the first-line medication options for treating depression, in large part because they have a more benign side effect profile and are safer in overdose than older tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors [6]. Duloxetine is an SNRI believed to exert its clinical effect by modulating the serotonin (5-HT) and norepinephrine (NE) activity in the central nervous system
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