Onset and recurrence of psychiatric disorders associated with anti-hypertensive drug classes

Abstract

The major anti-hypertensive (AHT) drug classes have been associated with differential risks of psychiatric disorders. However, existing data are limited largely to depression, and confounding variables have not always been controlled for. We sought to fill the evidence gap, using TriNetX Analytics, an electronic health records network. Amongst 58.6 million patients aged 18–90 years, patients prescribed a calcium channel blocker (CCB) were compared with those taking a diuretic, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or β-blocker. Cohorts were propensity score-matched for age, sex, race, and blood pressure. Over a 2-year exposure period, we measured the incidence and risk ratio of a first diagnosis (ICD-10 codes), or a recurrence, of psychotic, affective, and anxiety disorders, as well as substance use disorders and sleep disorders. Cohort sizes ranged from 33,734 to 322,814. CCBs were associated with a lower incidence of psychotic, affective, and anxiety disorders than β-blockers (risk ratios 0.69–0.99) and a higher incidence than ARBs (risk ratios 1.04–2.23) for both first and recurrent diagnoses. Comparisons of CCBs with ACEIs or diuretics showed smaller risk ratios that varied between disorders, and between first episode and recurrence. AHT classes were also associated with the incidence of substance use and sleep disorders. Results remained largely unchanged after more extensive cohort matching for additional potential confounders. In a secondary analysis, a comparison between ARBs and ACEIs showed lower rates of psychotic, affective, and substance use disorders with ARBs, but higher risks of anxiety and sleep disorders. In conclusion, AHT classes are differentially associated with the incidence of psychiatric disorders. ARBs show the most advantageous profile and β-blockers the least. The apparent beneficial effects of ARBs merit further study.

Brain-penetrant calcium channel blockers are associated with a reduced incidence of neuropsychiatric disorders

“…The comparison of BP-CCBs with ARBs is notable, since previous studies that have considered CCBs as a single class report advantages for ARBs on many neuropsychiatric outcomes. For example, in our previous study using the same network [17], affective and anxiety disorders were both commoner with CCBs than ARBs (risk ratios 1.27 and 1.19, respectively), whereas the present data show no difference between BP-CCBs and ARBs for affective disorders, and a lower incidence of anxiety disorders. 38% on verapamil, 66% on diltiazem.…”

“…The basic design of cohorts and selection of covariates was as described [ 17 ]. We created two types of cohort, both open to all patients aged between 18 and 90 years old.…”

“…Other studies have compared CCBs with one or more of the other antihypertensive drug classes. Results are variable, but the literature overall suggests that, for major psychiatric disorders, CCBs are associated with lower incidences than β-blockers, are broadly comparable to diuretics and ACEIs, but have a higher incidence than with ARBs [12][13][14][15][16][17][18]. A similar approximate ranking applies to delirium [19] and to neurodegenerative and movement disorders [20][21][22][23], but see also ref.…”

Renin-angiotensin System: A New Promising Therapeutic and Mechanisms for Depression and Anxiety

“…The study showed ARB users exhibited the lowest incidence of psychotic, affective, and anxiety disorders for first and recurrent diagnoses compared to CCB and β-blockers (Colbourne et al, 2021). A second analysis compared ARBs and ACEIs revealed a decreased incidence of psychosis and affective, but a greater risk of anxiety and sleep disorders (Colbourne et al, 2021). Surprisingly, a chronic high dose of captopril (40 mg/kg/d for 21 days) for mice induced depressive-like behaviors in TST and FST (Park et al, 2017).…”

“…Furthermore, 58.6 million patients aged 18-90 years were collected to study the influence of antihypertensive drugs on the onset and recurrence of psychiatric disorders. The study showed ARB users exhibited the lowest incidence of psychotic, affective, and anxiety disorders for first and recurrent diagnoses compared to CCB and β-blockers (Colbourne et al, 2021). A second analysis compared ARBs and ACEIs revealed a decreased incidence of psychosis and affective, but a greater risk of anxiety and sleep disorders (Colbourne et al, 2021).…”