Summary: Beta-blockers, a class of drugs commonly used to treat hypertension and cardiovascular disorders, appear to reduce aggressive and violent behaviors, and can reduce suicidal behaviors.
Reductions in violence are seen in individuals using Beta adrenergic-blocking agents (β-blockers) compared with periods that they are not taking the medication, in a study published January 31st in the open access journal PLOS Medicine.
If the findings are confirmed by other studies, β-blockers could be considered as a way to manage aggression and hostility in individuals with psychiatric conditions.
β-blockers are used to treat hypertension, angina and acute cardiovascular events, heart failure and arrhythmias as well as, migraine, symptoms of hyperthyroidism and glaucoma.
They are often used for anxiety and have been suggested for clinical depression and aggression, but evidence is conflicting. They have been linked to an increased risk of suicidal behavior though evidence is inconclusive.
Seena Fazel of the University of Oxford, UK, and colleagues at the Karolinska Institute in Sweden investigated psychiatric and behavioral outcomes: hospitalizations for psychiatric disorders; suicidal behavior and deaths from suicide; and charges of violent crime.
They compared 1.4 million β-blocker users in Sweden to themselves during medicated and non-medicated periods over an eight-year period from 2006-2013.
Periods on β-blocker treatment were associated with a 13% lower risk of being charged with a violent crime by the police, which remained consistent across the analyses. Additionally, an 8% lower risk of hospitalization due to a psychiatric disorder was reported as well as an 8% increased association of being treated for suicidal behavior.
However, these associations varied depending on psychiatric diagnosis, past psychiatric problems, as well as the severity and type of the cardiac condition the β-blockers were being used to treat.
Previous research has linked severe cardiac events to an increased risk of depression and suicide, and these results might suggest that the psychological distress and other disabilities associated with serious cardiac problems, rather than the β-blocker treatment, increases the risk of serious psychiatric events. In secondary analyses, associations with hospitalization were lower for major depressive but not for anxiety disorders.
If these confirm the results of this study, β-blockers could be considered to manage aggression and violence in some individuals. Image is in the public domain
In order to understand the role of β-blockers in the management of aggression and violence, further studies including randomized controlled trials are needed. If these confirm the results of this study, β-blockers could be considered to manage aggression and violence in some individuals.
Fazel adds, “In a real-world study of 1.4 million persons, β-blockers were associated with reduced violent criminal charges in individuals with psychiatric disorders. Repurposing their use to manage aggression and violence could improve patient outcomes.”
Funding: This study was supported by the Wellcome Trust (No 202836/Z/16/Z): https://wellcome.org/grant-funding (SF), the Swedish Research Council for Health Working Life and Welfare (2015-0028): https://forte.se/en/ (PL and HL), the American Foundation for Suicide Prevention (DIG-1-037-19): https://afsp.org/research-grant-information (BMD), and Karolinska Institutet Funds (2016fobi50581): https://staff.ki.se/ki-foundations-funds-list-of-grants (YM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Associations between β-blockers and psychiatric and behavioural outcomes: A population-based cohort study of 1.4 million individuals in Sweden
β-blockers are widely used for treating cardiac conditions and are suggested for the treatment of anxiety and aggression, although research is conflicting and limited by methodological problems. In addition, β-blockers have been associated with precipitating other psychiatric disorders and suicidal behaviour, but findings are mixed. We aimed to examine associations between β-blockers and psychiatric and behavioural outcomes in a large population-based cohort in Sweden.
Methods and findings
We conducted a population-based longitudinal cohort study using Swedish nationwide high-quality healthcare, mortality, and crime registers. We included 1,400,766 individuals aged 15 years or older who had collected β-blocker prescriptions and followed them for 8 years between 2006 and 2013. We linked register data on dispensed β-blocker prescriptions with main outcomes, hospitalisations for psychiatric disorders (not including self-injurious behaviour or suicide attempts), suicidal behaviour (including deaths from suicide), and charges of violent crime.
We applied within-individual Cox proportional hazards regression to compare periods on treatment with periods off treatment within each individual in order to reduce possible confounding by indication, as this model inherently adjusts for all stable confounders (e.g., genetics and health history).
We also adjusted for age as a time-varying covariate. In further analyses, we adjusted by stated indications, prevalent users, cardiac severity, psychiatric and crime history, individual β-blockers, β-blocker selectivity and solubility, and use of other medications. In the cohort, 86.8% (n = 1,215,247) were 50 years and over, and 52.2% (n = 731,322) were women.
During the study period, 6.9% (n = 96,801) of the β-blocker users were hospitalised for a psychiatric disorder, 0.7% (n = 9,960) presented with suicidal behaviour, and 0.7% (n = 9,405) were charged with a violent crime.
There was heterogeneity in the direction of results; within-individual analyses showed that periods of β-blocker treatment were associated with reduced hazards of psychiatric hospitalisations (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.91 to 0.93, p < 0.001), charges of violent crime (HR: 0.87, 95% CI: 0.81 to 0.93, p < 0.001), and increased hazards of suicidal behaviour (HR: 1.08, 95% CI: 1.02 to 1.15, p = 0.012). After stratifying by diagnosis, reduced associations with psychiatric hospitalisations during β-blocker treatment were mainly driven by lower hospitalisation rates due to depressive (HR: 0.92, 95% CI: 0.89 to 0.96, p < 0.001) and psychotic disorders (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 hospitalisations and suicidal behaviour were inconsistent. Limitations include that the within-individual model does not account for confounders that could change during treatment, unless measured and adjusted for in the model.
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 manage aggression and violence could be investigated further.