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From the Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Address correspondence and reprint requests to Dan V. Iosifescu, MD, Massachusetts General Hospital, 50 Staniford Street, suite 401, Boston, MA 02114. E-mail: diosifescu{at}partners.org
Objective: An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the "vascular depression" hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD).
Method: We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male 
45, female 55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0–6) by the number of risk factors present. Treatment outcome was measured as response (50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17
7).
Results: In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission.
Conclusion: Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of "vascular depression" in younger subjects.
Key Words: major depressive disorder • treatment outcome • cardiovascular risk factors
Abbreviations: MDD = major depressive disorder; Ham-D-17 = the 17-item Hamilton Rating Scale for Depression.
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