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Psychosom Med. 2005 May-Jun;67(3):398-406.

A Study of Antihypertensive Drugs and Depressive Symptoms (SADD-Sx) in patients treated with a calcium antagonist versus an atenolol hypertension Treatment Strategy in the International Verapamil SR-Trandolapril Study (INVEST).

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  • 1Rehabilitation Outcomes Research Center, Malcom Randall Veterans Affairs Medical Center, Department of Veterans Affairs, Gainesville, Florida, USA.



The International Verapamil/Trandolapril Study (INVEST) demonstrated comparable efficacy between verapamil SR and atenolol antihypertensive treatment strategies for clinical outcomes and blood pressure (BP) control in hypertensive patients with coronary artery disease (N = 22,576). Effects of these antihypertension strategies on mood-related issues are not well understood.


The objectives of this study were 1) to compare depressive symptoms by strategy and 2) to identify predictors of depressive symptoms in INVEST patients after 1 year of follow up.


Depressive symptoms were assessed in a subset (N = 2317) of consecutively randomized U.S. patients enrolled between April 1, 1999, and October 31, 1999. Patients were mailed surveys after randomization and after 1 year of treatment.


Patients were assigned to either a verapamil SR or atenolol strategy to achieve Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure BP goals. Trandolapril and/or hydrochlorothiazide were recommended as add-on agents.


Depressive symptoms were measured by the Center for Epidemiologic Studies-Depression (CES-D) scale.


CES-D scores improved 1.45 points (p < .001) after 1 year in patients assigned to the verapamil SR strategy, whereas a nonsignificant improvement was observed in patients assigned to the atenolol strategy (0.27 points, p = .44). Predictors of higher depressive symptoms were higher baseline CES-D score (p < .001), history of depression diagnosis (p = .03), history of stroke (p < .001), and assignment to the atenolol strategy (p < .001).


A verapamil SR strategy is a viable alternative to beta-blocker therapy for hypertensive patients with coronary artery disease, especially those at risk of depression.

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