Purpose: Adherence to and persistence with antidepressants are often suboptimal. However, little is known about how patient knowledge and outcome expectations may influence antidepressant adherence and persistence.

Method: Individuals who had been prescribed their first antidepressant to treat depression in the preceding 6 months were recruited to an online survey via Facebook. Knowledge, education received, and initial outcome expectations were analyzed for associations with persistence and adherence.

Results: Two hundred and twenty surveys were analyzed. A total of 117 participants had taken their antidepressant for at least 3 months; another 25 had never started or stopped after ,3 months without consulting their doctor. Differences in expectations and various educational messages among persistent and nonpersistent participants were identified. Having received the instruction "don’t stop it without checking with your doctor" was a significant independent predictor of persistence (odds ratio [OR] = 5.9, 95% confidence interval [CI] = 1.4–24.5). At the time of the survey, 82.7% of participants were taking an antidepressant and 77.9% were adherent. Significant independent predictors of adherence were a greater age (OR = 1.1, 95% CI = 1.0–1.2), knowledge (OR = 1.6, 95% CI = 1.1–2.3), being informed of common side effects (OR = 5.5, 95% CI = 1.1–29.0), and having discussed ways to solve problems (OR = 3.9, 95% CI = 1.1–14.5).

Conclusion: Improving outcome expectations and particular educational messages may increase adherence and persistence. Greater knowledge may enhance adherence. Further investigation is warranted to determine whether a focus on these simple educational messages will improve outcomes in patients who commence an antidepressant.