Incidence of neurodegenerative and cerebrovascular diseases associated with antihypertensive drug classes

Harrison, Paul J.; Colbourne, Lucy; Luciano, Sierra

doi:10.1192/bjp.2020.249

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…For example, the effect on first diagnosis rules out the possibility that results are confounded by differential prescribing of AHTs to patients with a known psychiatric disorder, whilst the effect on recurrence suggests that the mechanism of the AHT effects applies equally to the processes maintaining psychiatric disorders as to their initial triggering. We previously reported, in this electronic health records network and over the same 2-year exposure period, that AHT classes are associated with a differential incidence of delirium 19 and of neurodegenerative and cerebrovascular diseases 21 . In those studies, ACEIs and ARBs were grouped together as renin-angiotensin system (RAS) agents.…”

Section: Discussionmentioning

confidence: 98%

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

2021

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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.

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Section: Discussionmentioning

confidence: 98%

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

2021

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“…The role of RASis in degenerative neurological disorders remains unclear (Table 1, Ref. [137][138][139][140][141][142][143][144][145][146]), although an early proof-of-concept double-blind placebocontrolled study shows perindopril, an ACE inhibitor, enhances the effect of levodopa without inducing dyskinesia [137]. Multiple review articles discuss the theoretical benefit of RASis for neurodegenerative diseases, but to date these drugs are not routinely used clinically for these disorders [40,78,82,147,148].…”

Section: Therapeutic Potential Of Rasis and Future Perspectivesmentioning

confidence: 99%

The renin-angiotensin system in central nervous system tumors and degenerative diseases

Haron

Kilmister

Davis

et al. 2021

Front Biosci (Landmark Ed)

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“…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 – 18 ]. A similar approximate ranking applies to delirium [ 19 ] and to neurodegenerative and movement disorders [ 20 – 23 ], but see also ref. [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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

Colbourne

Harrison

2022

Mol Psychiatry

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Calcium channel blockers (CCBs) differ in their ability to penetrate into the brain. Pharmacoepidemiological studies suggest that CCBs as a class may have beneficial effects on the risks and outcomes of some psychiatric and neurological disorders. It is plausible but unknown whether this effect relates to their brain penetrance. To address this, we used the TriNetX electronic health records network to identify people prescribed a brain-penetrant CCB (BP-CCB), or those given amlodipine, a CCB with low brain penetrability. We created cohorts of patients who, prior to first CCB exposure, either had to have, or could not have had, a recorded ICD-10 diagnosis in any of the following categories: psychotic disorder; affective disorder (including bipolar disorder and major depressive disorder); anxiety disorder; substance use disorder; sleep disorder; delirium; dementia, or movement disorder. Cohort pairs were propensity score matched for age, sex, race, blood pressure, body mass index, and a range of other variables. The outcomes were the incidence of these disorders measured over a two-year exposure period. Matched cohort sizes ranged from 17,896 to 49,987. In people with no prior history of psychiatric or neurodegenerative disorder, there was a significantly lower incidence of most disorders with BP-CCBs compared to amlodipine, with risk ratios ranging from 0.64 to 0.88 and an overall risk ratio of 0.88, i.e. a risk reduction of 12%. In people who did have a prior psychiatric or neurodegenerative diagnosis, differences were much smaller, but again showed lower risks for several disorders with BP-CCBs compared to amlodipine. The differences were somewhat more marked in women and in people less than 60 years old. Results were similar when comparing BP-CCBs with verapamil and diltiazem. We also compared BP-CCBs with angiotensin receptor blockers, and found an overall risk ratio of 0.94 in favour of BP-CCBs, but with differential effects across disorders including a higher risk of psychotic disorder and dementia, but a lower risk for anxiety and sleep disorders. In some analyses, there was evidence of residual confounding even after the extensive matching, in that negative control outcomes showed a reduced incidence with BP-CCBs relative to the comparator cohort. In summary, CCBs that readily penetrate the brain are associated with a lower incidence of neuropsychiatric disorders, especially first diagnoses, compared to CCBs which do not. This may reflect their blockade of neuronal voltage-gated calcium channels. The findings encourage repurposing trials using existing BP-CCBs, and suggest that novel BP-CCBs with enhanced and more selective central actions might have greater therapeutic potential for psychiatric and neurodegenerative disorders.

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Incidence of neurodegenerative and cerebrovascular diseases associated with antihypertensive drug classes

Cited by 3 publications

References 11 publications

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

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

The renin-angiotensin system in central nervous system tumors and degenerative diseases

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

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