DESIGN: Open-label, randomized, intention-to-treat trial with enrollment occurring April through November 1999.

SETTING: Thirty-seven primary care clinics within a research network.

PATIENTS: Five hundred seventy-three depressed patients started on one of three selective serotonin reuptake inhibitors (SSRIs) by their primary care physician and who completed a baseline interview.

INTERVENTIONS: Patients were randomized to receive fluoxetine, paroxetine, or sertraline.

MEASUREMENTS AND MAIN RESULTS: Outcomes assessed included physical symptoms, depression, and multiple domains of HRQoL. Prevalence of physical symptoms was determined at baseline and after 1, 3, 6, and 9 months of treatment. Stepwise linear regression models were used to determine the independent effects of physical symptoms and depression on HRQoL domains.

Of the 14 physical symptoms assessed, 13 were present in at least a third to half of the patients at baseline. Each symptom showed the greatest improvement during the initial month of treatment. In contrast, depression continued to show gradual improvement over a 9-month period. Physical symptoms had a predominant effect on pain (explaining 17% to 18% of the variance), physical functioning (13%), and overall health perceptions (13% to 15%). Depression had the greatest impact on mental (26% to 45%), social (14% to 32%), and work functioning (9% to 32%).

CONCLUSIONS: Physical symptoms are prevalent in depressed patients and initially improve in the first month of SSRI treatment. Unlike depression, however, improvement in physical symptoms typically plateaus with minimal resolution in subsequent months.