Although current depression treatment guidelines recommend continuing antidepressant therapy for at least 4 to 9 months, many patients discontinue treatment prematurely, within 3 months. To investigate the relationship between patient-physician communication and the continuation of treatment with antidepressants and to explore the demographics, adverse effects, therapeutic response, and frequency of follow-up visits. A total of 401 telephone interviews of depressed patients being treated with selective serotonin reuptake inhibitor (SSRI) therapy between December 15, 1999, and May 31, 2000, were conducted and 137 prescribing physicians completed written surveys from Northern California Kaiser Permanente health maintenance organization outpatient clinics. Patient-physician communication about therapy duration and about adverse effects; therapy discontinuation or medication switching within 3 months after start of SSRI therapy. Ninety-nine physicians (72%) reported that they usually ask patients to continue using antidepressants for at least 6 months, but 137 patients (34%) reported that their physicians asked them to continue using antidepressants for this duration and 228 (56%) reported receiving no instructions. Patients who said they were told to take their medication for less than 6 months were 3 times more likely to discontinue therapy (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.21-8.07) compared with patients who said they were told to continue therapy longer. Patients who discussed adverse effects with their physicians were less likely to discontinue therapy than patients who did not discuss them (OR, 0.49; 95% CI, 0.25-0.95). Patients who reported discussing adverse effects with their physicians were more likely to switch medications (OR, 5.60; 95% CI, 2.31-13.60). Fewer than 3 follow-up visits for depression, adverse effects, and lack of therapeutic response to medication were also associated with patients' discontinuing therapy. Discrepancies exist between instructions that physicians report they communicate to patients and what patients remember being told. Explicit instructions about expected duration of therapy and discussions about medication adverse effects throughout treatment may reduce discontinuation of SSRI use. Our finding that patients with 3 or more follow-up visits were more likely to continue using the initially prescribed antidepressant medication suggests that frequent patient-physician contact may increase the probability that patients will continue therapy.