title: Monotherapy With Major Antihypertensive Drug Classes and Risk of Hospital Admissions for Mood Disorders.
abstract: Major depressive and bipolar disorders predispose to atherosclerosis, and there is accruing data from animal model, epidemiological, and genomic studies that commonly used antihypertensive drugs may have a role in the pathogenesis or course of mood disorders. In this study, we propose to determine whether antihypertensive drugs have an impact on mood disorders through the analysis of patients on monotherapy with different classes of antihypertensive drugs from a large hospital database of 525 046 patients with follow-up for 5 years. There were 144 066 eligible patients fulfilling the inclusion criteria: age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days. The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641 685 person-years of follow-up). Patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had the lowest risk for mood disorder admissions, and compared with this group, those on β-blockers (hazard ratio=2.11; [95% confidence interval, 1.12-3.98]; P=0.02) and calcium antagonists (2.28 [95% confidence interval, 1.13-4.58]; P=0.02) showed higher risk, whereas those on no antihypertensives (1.63 [95% confidence interval, 0.94-2.82]; P=0.08) and thiazide diuretics (1.56 [95% confidence interval, 0.65-3.73]; P=0.32) showed no significant difference. Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and β-blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders.
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences (A.H.B., L.M., S.M., R.M.T., A.F.D., S.P.) and Institute of Health and Wellbeing (D.J.S.), University of Glasgow, United Kingdom.
authors.forename: Angela H
authors.initials: AH
authors.lastname: Boal
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences (A.H.B., L.M., S.M., R.M.T., A.F.D., S.P.) and Institute of Health and Wellbeing (D.J.S.), University of Glasgow, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences (A.H.B., L.M., S.M., R.M.T., A.F.D., S.P.) and Institute of Health and Wellbeing (D.J.S.), University of Glasgow, United Kingdom.
authors.forename: Linsay
authors.initials: L
authors.lastname: McCallum
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences (A.H.B., L.M., S.M., R.M.T., A.F.D., S.P.) and Institute of Health and Wellbeing (D.J.S.), University of Glasgow, United Kingdom.
authors.forename: Scott
authors.initials: S
authors.lastname: Muir
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences (A.H.B., L.M., S.M., R.M.T., A.F.D., S.P.) and Institute of Health and Wellbeing (D.J.S.), University of Glasgow, United Kingdom.
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences (A.H.B., L.M., S.M., R.M.T., A.F.D., S.P.) and Institute of Health and Wellbeing (D.J.S.), University of Glasgow, United Kingdom.
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.affiliation: From the Institute of Cardiovascular and Medical Sciences (A.H.B., L.M., S.M., R.M.T., A.F.D., S.P.) and Institute of Health and Wellbeing (D.J.S.), University of Glasgow, United Kingdom. sandosh.padmanabhan@glasgow.ac.uk.
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D001795:Blood Pressure Determination; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use; D016009:Chi-Square Distribution; D016208:Databases, Factual; D003865:Major Depressive Disorder / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis; D006113:United Kingdom
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D049993:Sodium Chloride Symporter Inhibitors
keywords: angiotensin-converting enzyme inhibitors; bipolar disorder; calcium channel blockers; depression; hypertension