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)

Psychosom Med. May-Jun 2005;67(3):398-406. doi: 10.1097/01.psy.0000160468.69451.7f.


Background: 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.

Objectives: 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.

Design, setting, and patients: 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.

Intervention: 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.

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

Results: 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).

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Aged
  • Antihypertensive Agents / adverse effects*
  • Atenolol / adverse effects*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / adverse effects
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / drug therapy*
  • Depressive Disorder / chemically induced*
  • Depressive Disorder / etiology
  • Female
  • Follow-Up Studies
  • Health Surveys
  • Humans
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Indoles / therapeutic use
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Treatment Outcome
  • Verapamil / adverse effects*


  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Indoles
  • Hydrochlorothiazide
  • trandolapril
  • Atenolol
  • Verapamil