β-Blockers were not associated with depression in adults
ACP J Club. 1992 July-Aug;117:27. doi:10.7326/ACPJC-1992-117-1-027
Bright RA, Everitt DE. β-blockers and depression. Evidence against an association. JAMA. 1992 Apr 1;267:1783-7.
To study the relationship between continuing β-blocker use and depression in adults.
Case-control study using Medicaid computerized data.
Adults who received Medicaid from 1 July 1980 to 30 December 1983 were eligible if they had been enrolled in Medicaid for ≥ 1 year, had ≥ 1 clinic visit in the past year, and were not taking bronchodilator or hypoglycemic medications. Case patients were those who had evidence of depression. 2 controls were randomly chosen for each case patient and matched for age, sex, race, and nursing home status. 4302 case patients were chosen (81%, women; 35% ≥ 65 y; 55%, white; and 12%, nursing home patients).
Assessment of risk factors
β-blocker exposures before depression were taken from computerized Medicaid-patient-specific files. Use of β-blockers—ever, in the previous year, and 7 to 90 days before the index date—were noted. β-blockers were those available during the study: propranolol, metoprolol, and nadolol. Only continuing use of β-blockers was analyzed. Benzodiazepine, antihypertensive and cardiovascular medication, estrogen replacement, and prescriptions for other drugs, and health care utilization information were also obtained.
Main outcome measures
The diagnosis and date of onset of depression were based on hospitalization with a primary or secondary discharge diagnosis related to depression, electroconvulsive therapy (ECT), or a prescription for antidepressant medication.
10% of cases and 7% of controls had prescriptions for β-blockers 7 to 90 days before the marker date; 14% of cases and 10% of controls, in the previous year; and 16% of cases and 12% of controls had ever taken β-blockers. For unadjusted data, case patients were more likely to have ever been given β-blockers before the depression marker date (odds ratio [OR] 1.51, 95% CI 1.35 to 1.67). For use of β-blockers in the previous year, the OR was 1.45 (CI 1.29 to 1.62), and for use 7 to 90 days before, the OR was 1.41 (CI 1.23 to 1.61). After controlling for confounders (benzodiazepine use, frequency of nonpsychiatric clinic visits, and multiple prescriptions), the OR was 0.98 (CI 0.87 to 1.12). The results did not change when analyzed for other potential confounding variables or depression marker used (diagnosis or ECT, only 1 vs > 1 claim for antidepressant).
After controlling for benzodiazepine use, frequency of nonpsychiatric clinic visits, and multiple prescriptions, continuing β-blocker use was not associated with depression markers in adults.
Source of funding: U.S. Food and Drug Administration.
Address for article reprint: Dr. R.A. Bright, Food and Drug Administration Center for Devices and Radiological Health, HFZ-161, 5600 Fishers Lane, Rockville, MD 20857, USA.
Although this study addresses the relation between use of β-adrenergic blockers and depression, it also shows some of the strengths and limitations of using claims databases for observational studies of adverse drug effects. Automated databases access large populations and provide information on drug exposures without recall bias. Diagnostic or procedure codes used to identify outcomes may be sensitive, but not specific, making chart review of screened cases necessary.
The use of claims data to identify depression is problematic. 2 previous studies using similar data found an association between β-blockers and antidepressant use (1, 2). These agents, however, are prescribed for conditions other than depression, and depression is managed without antidepressants. To develop a more specific marker of depression, the authors used discharge diagnoses that capture severe depression and procedure codes consistent with but not specific to depression. The association between β-blockers and depression was reduced. The association disappeared after adjustment for benzodiazepine use, frequent physician visits, and frequent prescriptions.
One must interpret with caution the conclusion that β-blockers are not associated with depression. First, the codes used undoubtedly represent a more specific marker for depression than use of antidepressant drugs but may only identify patients with severe depression. Second, benzodiazepine use, frequent physician visits, and frequent prescriptions may represent early symptoms of depression, and adjusting for these in the analysis may "overcontrol" and underestimate risk.
Whether ongoing use of β-blockers causes depression is still controversial and would be best studied prospectively. Given current knowledge, I would monitor patients and taper β-blockers for those with depressive symptoms if therapeutic alternatives were indicated.
Ronald I. Shorr, MD, MS
Vanderbilt UniversityNashville, Tennessee, USA