Summary Background β-Blockers are widely used to treat heart conditions and are suggested for the treatment of anxiety and aggression , although research is conflicting and limited by methodological issues. Additionally, β-blockers have been associated with the precipitation of other psychiatric disorders and suicidal behavior , but findings are mixed. Our objective was to examine associations between β-blockers and psychiatric and behavioral outcomes in a large population-based cohort in Sweden. Methods and findings We conducted a population-based longitudinal cohort study using high-quality, nationwide Swedish crime, mortality, and healthcare registries. We included 1,400,766 people aged 15 years and older who had received beta-blocker prescriptions and followed them for eight years between 2006 and 2013. We linked registry data on beta-blocker prescriptions dispensed to the main outcomes, hospitalizations for psychiatric disorders (not including self-assessment), harmful behavior or suicide attempts), suicidal behavior (including deaths by suicide), and violent crime charges. We applied within-individual Cox proportional hazards regression to compare treatment periods with non-treatment periods within each individual to reduce potential confounding by indication, as this model inherently adjusts for all stable confounders (p (e.g., genetics and health history). We also adjusted for age as a covariate over time. In subsequent analyses, we adjusted for established indications, frequent users, cardiac severity, psychiatric and criminal history, individual beta-blockers, beta-blocker selectivity and solubility, and use of other medications. In the cohort, 86.8% (n = 1,215,247) were 50 years or older and 52.2% (n = 731,322) were women. During the study period, 6.9% (n = 96,801) of β-blocker users were hospitalized for a psychiatric disorder, 0.7% (n = 9,960) presented suicidal behavior, and 0.7% ( n = 9,405) were accused of violent assault or crime. There was heterogeneity in the direction of the results; within-individual analyzes showed that periods of beta-blocker treatment were associated with reduced risks of psychiatric hospitalizations (hazard ratio [HR], 0.92, 95% confidence interval [CI], 0.91 to 0.93). , p < 0.001), violent crime charges (HR: 0.87, 95% CI: 0.81 to 0.93, p < 0.001), and increased risk of suicidal behavior (HR: 1.08, 95% CI: 95%: 1.02 to 1.15, p = 0.012). After stratifying by diagnosis, reduced associations with psychiatric hospitalizations during beta-blocker treatment were primarily due to lower rates of hospitalization due to depressive disorders (HR: 0.92, 95% CI: 0.89 to 0. 96, p < 0.001) and psychotic (HR: 0.89, 95% CI: 0.85 to 0.93, p < 0.001). Reduced associations with violent charges remained in most sensitivity analyses, while associations with psychiatric hospitalizations and suicidal behavior were inconsistent. Limitations include that the within-individual model does not account for confounders that could change during treatment unless they are measured and adjusted for in the model. Conclusions In this population-wide study, we found no consistent links between β-blockers and psychiatric outcomes. However, β-blockers were associated with reductions in violence , which remained in sensitivity analyses. The use of β-blockers to control aggression and violence could be further investigated. |
Age-adjusted intraindividual associations between beta-blockers and psychiatric and behavioral outcomes in the beta-blocker cohort (n = 1,400,766).
Why was this study done?
- β-blockers are primarily cardiac medications that are widely used to treat anxiety and are also suggested for the treatment of clinical depression and aggression, although research on efficacy is conflicting and limited by small samples and methodological issues.
- β-blockers have been linked to an increased risk of suicidal behavior, but the findings are inconclusive.
- More evidence is needed with large samples and appropriate designs on the actual effects on mental health and behavioral outcomes in people taking β-blockers.
What did the researchers do and find?
- We examined a population-based cohort of 1,400,766 people in Sweden who had been treated with β-blockers using a within-subject design; That is, we compared individuals to themselves during the medication and off-medication periods to account for background factors that may confound the associations.
- Periods of β-blocker treatment were associated with an 8% lower risk of being hospitalized due to a psychiatric disorder, a 13% lower risk of being charged with a violent crime by the police, and an 8% higher risk of be treated for suicide. behavior or mortality from suicide.
- Reduced associations with violent charges were consistent across sensitivity analyses, while associations with suicidal behavior and psychiatric hospitalizations varied by specific psychiatric diagnoses, prior psychiatric problems, and cardiac severity.
What do these findings mean?
This real-world study examining anxiety presentations in secondary care does not support the use of β-blockers to manage anxiety.
- Studies using other designs (e.g., randomized controlled trials) are needed to better understand the role of β-blockers in the treatment of aggression and violence.
- If the findings on violence are confirmed by studies using other designs, the use of β-blockers could be considered to control aggression and hostility in people with psychiatric conditions.
Discussion
The mechanism of action of β-blockers on aggression is uncertain; Possible explanations include mild sedation or reduced adrenergic activity centrally or peripherally, resulting in decreased catecholaminergic (i.e., "fight or flight" ) reactions to stressful situations. We found that reduced associations with violent crime charges during β-blocker treatment were consistent using alternative time periods, excluding individuals on co-prescribed medications, excluding frequent users, stratifying by different age groups, and stratifying by hospitalizations. due to heart conditions. The latter would address the possible explanation that people with serious heart conditions might be more incapacitated and therefore less likely to commit a violent crime. However, we found that associations remained diminished in both hospitalized and non-hospitalized patients. Our results were broadly consistent with evidence from small studies in individuals with psychiatric conditions and cognitive impairment, but we have substantially increased the sample size.
We also show reductions for nonviolent crimes during beta-blocker treatment and for violent crimes in 2 higher-risk groups, that is, those with a history of psychiatric problems and violent crimes, respectively. Given that evidence-based treatments for violent outcomes are very limited, this is a potentially important finding. People are currently prescribed β-blockers for aggression in psychiatric clinics and hospitals, and current work suggests some support for this. This is highlighted by the absolute rates of violent crime charges: in those with a psychiatric history in the beta-blocker cohort (n = 92,619), there were 7,502 violent crime charges during the study period committed by 2.3% ( n = 2153) from this group. Importantly, the current work is consistent with 2 small RCTs of beta blockers ( propranolol and nadolol ) on violent outcomes in psychiatric patients.
Our findings demonstrated reduced associations with violent crime charges during beta-blocker treatment. More studies using other designs (e.g., randomized controlled trials) are needed to better understand the role of β-blockers in the treatment of aggression and violence. Furthermore, the use of β-blockers to control anxiety is not supported in this real-world study of new anxiety presentations in secondary patient care. If triangulated with other designs, β-blockers could be used to control aggression and hostility in people with psychiatric conditions.
Comments
Beta Blocker Use Associated with Lower Rates of Violence
In a study published January 31 in the open-access journal PLOS Medicine , reductions in violence are seen in people who use beta-adrenergic blocking agents (beta-blockers) compared to periods when they do not take the medication. If the findings are confirmed by other studies, β-blockers could be considered a way to control aggression and hostility in people with psychiatric conditions.
β-blockers are used to treat hypertension, angina and acute cardiovascular events, heart failure and arrhythmias, as well as migraine, hyperthyroidism symptoms and glaucoma. They are often used for anxiety and have been suggested for clinical depression and aggression, but the evidence is conflicting. They have been linked to an increased risk of suicidal behavior, although the evidence is inconclusive.
Seena Fazel of the University of Oxford, United Kingdom, and colleagues at the Karolinska Institute in Sweden investigated psychiatric and behavioral outcomes: hospitalizations for psychiatric disorders; suicidal behavior and suicide deaths; and violent crime charges. They compared 1.4 million β-blocker users in Sweden during the medicated and unmedicated periods over an eight-year period from 2006-2013.
Periods of beta-blocker treatment were associated with a 13% lower risk of being charged with a violent crime by the police, which remained constant across all analyses. Additionally, an 8% lower risk of hospitalization due to a psychiatric disorder was reported, as well as an 8% increase in the association of being treated for suicidal behavior. However, these associations varied by psychiatric diagnosis, previous psychiatric problems, as well as the severity and type of cardiac condition to be treated by β-blockers.
Previous research has linked serious cardiac events to an increased risk of depression and suicide , and these results could suggest that psychological distress and other disabilities associated with serious cardiac problems, rather than β-blocker treatment, increase the risk of serious psychiatric events. . In secondary analyses, associations with hospitalization were smaller for major depressive disorders, but not for anxiety disorders.
To understand the role of β-blockers in the treatment of aggression and violence, more studies including randomized controlled trials are needed. If these confirm the results of this study, β-blockers could be considered to control aggression and violence in some people.
Fazel adds: “In a real-world study of 1.4 million people, β-blockers were associated with a reduction in violent crime charges in people with psychiatric disorders. “Recategorizing its use to control aggression and violence could improve patient outcomes.”
