Neuropsychiatric Consequences of Lipophilic Beta-Blockers

Cojocariu, Sabina Alexandra; Maștaleru, Alexandra; Sascău, Radu Andy; Stătescu, Cristian; Mitu, Florin; Leon‐Constantin, Maria‐Magdalena

doi:10.3390/medicina57020155

Cited by 26 publications

(16 citation statements)

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“…The process of lipophilic beta-blockers that passes the blood–brain barrier may partly explain this association. It is thought to affect the synthesis and reuptake of neurotransmitters and thereby impact psychological functioning [ 13 ]. Furthermore, a study propose that β 1 -adrenoceptors play an important role in the basolateral amygdalae when looking at anxiety-like behaviour [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is thought to affect the synthesis and reuptake of neurotransmitters and thereby impact psychological functioning [ 13 ]. Furthermore, a study propose that β 1 -adrenoceptors play an important role in the basolateral amygdalae when looking at anxiety-like behaviour [ 13 ]. This suggests that beta-blocker therapy may produce an anxiolytic response.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the process of lipophilic beta-blockers (e.g. metoprolol) crossing the blood–brain barrier is thought to be associated with impaired psychological functioning [ 13 ]. Furthermore, the antiarrhythmic drug amiodarone has been linked with thyroid abnormalities in 15% of patients, and this can lead to mood, cognitive, and psychotic symptoms [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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The association between cardiac drug therapy and anxiety among cardiac patients: results from the national DenHeart survey

Rotvig

Christensen

Juel

et al. 2022

BMC Cardiovasc Disord

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Background Neuropsychiatric side effects of cardiac drugs such as nervousness, mood swings and agitation may be misinterpreted as symptoms of anxiety. Anxiety in cardiac patients is highly prevalent and associated with poor outcomes, thus an accurate identification is essential. The objectives were to: (I) describe the possible neuropsychiatric side effects of common cardiac drug therapies, (II) describe the use of cardiac drug therapy in cardiac patients with self-reported symptoms of anxiety compared to those with no symptoms of anxiety, and (III) investigate the association between the use of cardiac drug therapy and self-reported symptoms of anxiety. Methods DenHeart is a large national cross-sectional survey combined with national register data. Symptoms of anxiety were measured by the Hospital Anxiety and Depression Scale (HADS-A) on patients with ischemic heart disease, arrhythmia, heart failure and heart valve disease. Side effects were obtained from ‘product summaries’, and data on redeemed prescriptions obtained from the Danish National Prescription Registry. Multivariate logistic regression analyses explored the association between cardiac drug therapies and symptoms of anxiety (HADS-A ≥ 8). Results Among 8998 respondents 2891 (32%) reported symptoms of anxiety (HADS-A ≥ 8). Neuropsychiatric side effects were reported from digoxin, antiarrhythmics, beta-blockers, ACE-inhibitors and angiotensin receptor antagonists. Statistically significant higher odds of reporting HADS ≥ 8 was found in users of diuretics, lipid-lowering agents, nitrates, antiarrhythmics and beta-blockers compared to patients with no prescription. Conclusion Some cardiac drugs were associated with self-reported symptoms of anxiety among patients with cardiac disease. Of these drugs neuropsychiatric side effects were only reported for antiarrhythmics and beta-blockers. Increased awareness about the possible adverse effects from these drugs are important.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The association between cardiac drug therapy and anxiety among cardiac patients: results from the national DenHeart survey

Rotvig

Christensen

Juel

et al. 2022

BMC Cardiovasc Disord

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“…Although the exact pharmacological mechanisms for drug-induced nightmares are not known, several hypotheses have been made about the pathophysiology of nightmares, and REM sleep regulation (Hobson et al, 1998). In particular, the effects of β-adrenoceptor antagonists on serotonergic pathways responsible for the wake/ sleep cycle may be an explanation as some of these drugs are antagonists of 5-HT1A receptors, in addition to their ability to cross the blood-brain barrier (BBB) (Cojocariu et al, 2021). The smaller and the more liposoluble drugs are, the more they are able to cross the BBB (Cuddapah et al, 2019).…”

Section: What This Study Adds?mentioning

confidence: 99%

β-adrenoceptor antagonists and nightmares: A pharmacoepidemiological–pharmacodynamic study

et al. 2021

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Aim: To compare different β-adrenoceptor antagonists for the risk of reporting nightmare. Methods: The study involved two approaches: first, we investigated in VigiBase®, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each β-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological–pharmacodynamic analysis, we assessed whether use of β-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. Results: Of the 126,964 reports recorded with β-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19–3.61), metoprolol (1.89, 1.66–2.16), and alprenolol (1.77, 1.06–2.97). Compared to use of low lipid solubility β-adrenoceptor antagonists, use of moderate or high lipid solubility β-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47–2.00 and aROR high vs. low 1.84, 95%CI 1.53–2.22). Use of moderate or high 5-HT1A affinity of β-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of β-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04–1.43 and aROR high vs. low 2.46, 95%CI 1.93–3.13). Conclusion: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among β-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.

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“…Side-effects of β-blocker medication such as hypotension, fatigue, and bradycardia are typically acknowledged, 1 while the association between β-blocker use and the effects on patient-reported health-related quality of life (HRQoL) is less established. β-blockers have for example been linked to factors known to have a negative impact on HRQoL such as symptoms of depression, an increased prescription of anti-depressive medication, 2 and sexual dysfunction. 3 Yet, other trials have found no association between β-blocker use and depression or sexual functioning.…”

Section: Introductionmentioning

confidence: 99%

Association between β-blocker dose and quality of life after myocardial infarction: a real-world Swedish register-linked study

Humphries

Wallert

Mars

et al. 2022

European Heart Journal. Acute Cardiovascular Care

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Background β-blockers are routinely administered to patients following myocardial infarction (MI), yet their potential effect on health-related quality of life (HRQoL) is not entirely understood. We investigated the relationship between two different doses of β-blockers with HRQoL following MI. Methods and results This nationwide observational study used Swedish national registries to collate sociodemographic, clinical, medication, and HRQoL {the latter operationalized using EuroQol [European Quality of Life Five Dimensions Questionnaire (EQ-5D)]}. Estimates at 6–10 weeks and 12–14 months post-MI follow-up from pooled linear and logistic models were calculated after multiple imputation. We identified 35 612 patients with first-time MI, discharged with β-blockers, and enrolled in cardiac rehabilitation between 2006 and 2015. Upon discharge, patients were either dispensed <50% [24 082 (67.6%)] or ≥50% [11 530 (32.4%)] of the target dosage, as defined in previous trials. After adjusting for pre-defined covariates, neither the EQ-5D Index nor the Emotional Distress items were statistically different between groups. The EQ-VAS score was significantly lower in patients treated with ≥50% target β-blocker dose than those treated with <50% of the target dose [−0.87 [−1.23, −0.46], P < .001]. Results were similar at the 12-month follow-up and across sub-groups separated by sex and age. Conclusion No difference in HRQoL was found among patients taking <50% vs. ≥50% of the target β-blocker dose, except for the EQ-VAS in which higher scores were reported in those taking a lower dose. The clinical meaningfulness of this statistical significance is likely low.

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Neuropsychiatric Consequences of Lipophilic Beta-Blockers

Cited by 26 publications

References 102 publications

The association between cardiac drug therapy and anxiety among cardiac patients: results from the national DenHeart survey

The association between cardiac drug therapy and anxiety among cardiac patients: results from the national DenHeart survey

β-adrenoceptor antagonists and nightmares: A pharmacoepidemiological–pharmacodynamic study

Association between β-blocker dose and quality of life after myocardial infarction: a real-world Swedish register-linked study

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