Calcium channel blockers and mental health: a comprehensive meta-analysis of psychiatric adverse events in double-blind randomized controlled trials

OBJECTIVE: L-type calcium channel blockers (CCBs) are pivotal in managing cardiovascular disorders, such as hypertension and angina pectoris. Their action on L-type calcium channels, which are not only integral to cardiovascular function but also present in the brain, prompts questions about potential effects on mental health. While previous cohort studies explored this association with mixed results, our study aims to build upon these findings by systematically investigating psychiatric adverse events (PAEs) reported in double-blind randomized controlled trials (RCTs). METHODS: A systematic search identified double-blind RCTs reporting frequencies of PAEs during CCB therapy across different indications. Separate meta-analyses were conducted for dihydropyridine (DHP) and nondihydropyridine (non-DHP) CCBs against placebo and active controls. This study was registered on INPLASY (INPLASY202480075). RESULTS: In 187 studies, encompassing 28,201 patients exposed to CCBs, several PAEs were reported, with the most common being depression, insomnia, somnolence, and agitation. Meta-analyses revealed no significant difference in PAE occurrence for CCBs vs. placebo, β-blockers, renin-angiotensin system blockers, and thiazide/thiazide-like diuretics (all P > 0.05). Restricting the analyses to cardiovascular studies, DHP CCBs were linked to lower risks of depression and insomnia compared to placebo [odds ratio (OR) 0.84, confidence interval (CI) 0.70-1.00 and OR 0.38, CI 0.15-0.99, both P = 0.05); however, these results may be artifacts and should be interpreted with caution. CONCLUSION: Concerns about negative mental health effects of CCBs appear to be unwarranted and should not deter clinicians from prescribing them when indicated. A detected signal towards positive mental health benefits in cardiovascular patients warrants further investigation.