Depression not only creates enormous costs for treatment and lost work time, but also increases the risk for other costly chronic diseases such as cardiovascular disease and diabetes. The magnitude of these risks remains unclear, with existing prospective studies using small sample sizes with limited diversity and reliant on surveys. We use two billion prescription fill records to quantify depression by antidepressant fill records. We track each patient’s prescriptions longitudinally and use Cox’s time varying proportional hazard model to quantify the effect of taking antidepressants on the hazard rate of taking drugs associated with other chronic diseases quantified similarly by disease-relevant fill records. Controlling for socioeconomic variables, antidepressant use increased the hazard rate for drugs used for cardiovascular disease (1.59 fold), diabetes (1.30) and cancer (1.50). Antidepressant use also predicted substantially higher use of sedatives (3.06) and amphetamines (4.11). Antidepressant use, as a proxy for depression, is a significant risk factor for the most prevalent and costly chronic diseases, and should be treated as a disease with quantifiable and significant implications for individual health.