Objective: Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy controls. A previous study by our group reported that depressed patients with elevated cholesterol levels (≧200 mg/dl) were significantly more likely to be nonresponders to fluoxetine treatment than depressed patients with nonelevated cholesterol levels. However, very little is known regarding cholesterol in patients with treatment-resistant depression (TRD). The purpose of this study was to compare cholesterol levels at baseline between depressed patients with and without TRD and to test whether cholesterol levels at baseline can predict clinical response in patients with TRD treated with open-label nortriptyline (NT). Methods: Ninety-two patients with TRD entered a 6-week open trial of NT. Baseline cholesterol levels were randomly collected for 59 of these patients. Controlling for age and gender, we compared baseline cholesterol and triglyceride levels for 35 patients with TRD who did not respond to NT with 205 non-TRD patients who responded to an 8-week open trial of fluoxetine. Furthermore, with the use of logistic regression, we tested whether baseline cholesterol levels predicted clinical response to NT in the patients with TRD. Results: Patients with TRD had higher triglyceride levels at baseline compared with depressed patients without TRD. Cholesterol defined as a dichotomous variable being elevated if equal to or greater than 200 mg/dl, predicted poor response to a 6-week open trial of NT in patients with TRD. Conclusions: The results of this study confirm the relationship between hypercholesterolemia and poor outcome in the treatment of MDD for patients with TRD.

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