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Beta-Blockers and Depression After Myocardial Infarction. A Multicenter Prospective Study
Abstract
The purpose of this research was to explore the prospective relationship between the use of beta-blockers and depression in myocardial infarction (MI) patients.
Beta-blocker use has been reported to be associated with the development of depression, but the methodological quality of studies in this field is weak.
In a multicenter study, MI patients (n = 127 non-beta-blocker users and n = 254 beta-blocker users) were assessed for depressive symptoms (using the Beck Depression Inventory [BDI] at baseline and t = 3, 6, and 12 months post-MI) and International Classification of Diseases-10 depressive disorder (Composite International Diagnostic Interview). Patients were matched using the frequency matching procedure according to age, gender, hospital of admission, presence of baseline depressive symptoms, and left ventricular function.
No significant differences were found between non-beta-blocker users and beta-blocker users on the presence of depressive symptoms (p > 0.10 at any of the time points) or depressive disorder (p = 0.86). Controlling for confounders did not alter these findings. A trend toward increasing BDI scores was seen in patients with long-term use of beta-blockers and patients with higher beta-blocker dose.
In post-MI patients, prescription of beta-blockers is not associated with an increase in depressive symptoms or depressive disorders in the first year after MI. However, long-term and high-dosage effects cannot be ruled out.
... [9] Previous studies had linked b-blockers use with an increased risk of depression, but more recent studies have found no significant association between the two. [10] Antiplatelet drugs, such as aspirin, may reduce the risk of depression by reducing inflammation, [11] but this remains controversial. CCBs modulate nerve cell signaling by regulating calcium channels, but whether this effect is beneficial or harmful in depression remains unclear. ...
... England/25 RCT HADS Simvastatin (À) Pravastatin (À) Haghighi et al 2014 [30] Atorvastatin Switzerland/60 RCT HDRS Atorvastatin (À) van Melle et al 2006 [10] b-blockers Multinational/381 Multicenter study ...
... No significant differences were found between non-b-blocker users and b-blocker users in the presence of depressive symptoms. [10] Additionally, the results of Sorgi et al, [39] Rosenberg et al, [40] and Pérez-Stable et al [41] also support this view. There are also some studies suggesting that the use of b-blockers increased the risk of depression. ...
Objective:
Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.
Data sources:
The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science.
Study selection:
Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article.
Results:
We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient.
Conclusions:
Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with β-blockers, diuretics, and nitrates.
... In another publication which was the result of multi- center studies, Beck Depression Inventory was used to estimate the occurrence of the symptoms of depression in patients after myocardial infarction. In 254 patients taking beta blockers and 127 patients not treated with them, the study did not reveal a statistically significant difference between these two groups with regard to the occurrence of depression after 3, 6 and 12 months after myocardial infarction [90]. Similar results were obtained in a publication by Ranchord et al., also concerning patients after myocardial infarction; the article did not confirm an increase in depression symptoms after 1, 6 and 12 months of beta-blocker therapy [91]. ...
... Należy zwróć uwagę, iż liczba prób była niewielka, a przedziały ufności były dość szerokie. W kolejnej publikacji będącej wynikiem wieloośrodkowych badań, u pacjentów po zawale mięśnia sercowego oceniono wystąpienie objawów depresji, przy użyciu Kwestionariusza Depresji Becka [90]. U 254 pacjentów przyjmujących beta-blokery i 127 pacjentów nie leczonych beta-blokerami badanie nie wykazało statystycznie istotnej różnicy pomiędzy tymi grupami w zakresie występowania depresji po 3, 6 i 12 miesiącach od zawału mięśnia sercowego [90]. ...
... W kolejnej publikacji będącej wynikiem wieloośrodkowych badań, u pacjentów po zawale mięśnia sercowego oceniono wystąpienie objawów depresji, przy użyciu Kwestionariusza Depresji Becka [90]. U 254 pacjentów przyjmujących beta-blokery i 127 pacjentów nie leczonych beta-blokerami badanie nie wykazało statystycznie istotnej różnicy pomiędzy tymi grupami w zakresie występowania depresji po 3, 6 i 12 miesiącach od zawału mięśnia sercowego [90]. Podobne wyniki uzyskano w publikacji Ranchord'a i współ., również dotyczącej pacjentów po zawale mięśnia sercowego, która nie potwierdziła zwiększenia objawów depresji po 1, 6 i 12 miesiącach terapii beta-blokerami [91]. ...
Introduction: Beta blockers are mainly used in treating cardiovascular diseases. However, it has been observed that these drugs have also an anxiolytic potential. Over the years, a number of clinical trials have been conducted aimed at determining the effectiveness of beta blockers in treating anxiety disorders.
The aim of the article: The main objective of the article is to present the significance and position of adrenolytic drugs in the pharmacotherapy of anxiety disorders on the basis of available literature. Moreover, the authors also decided to take into account the data from current research results, considering the problem of side effects of using adrenolytic drugs - especially the controversial reports on their effect on the development of affective disorders.
Method: An analysis was conducted of articles from Medline/PubMed database, selected on the basis of the following key words: anxiety disorders, beta blockers, adrenolytic drugs, as well as on the basis of their dates of publication: 1960-2017. In order to conduct a reliable and complete review of literature, the authors decided to include works from quite an extended period of time. The articles included in the review were published in Polish and English.
Results: The review of articles concerning the treatment of anxiety disorders clearly suggests that propranolol is effective in reducing the frequency of panic attacks and the tendency for avoidance behavior in patients with agoraphobia. Other studies report on potential benefits in terms of early interventional prevention and treating posttraumatic stress disorder with propranolol. However, there is lack of randomized clinical trials concerning the therapeutic effect of other adrenolytic drugs in treating anxiety disorders. Early research works reported that (mainly lipophilic) beta blockers may have a depressogenic effect; however, the latest studies have not confirmed it.
The contemporary research on the therapeutic potential of beta blockers in treating anxiety disorders is insufficient. What seems to be most promising, however, are reports concerning the desirable effects of using adrenolytic drugs in treating posttraumatic stress disorder, which implicates the necessity of conducting further research verifying the validity of their application.
... An association between treatment with β-blockers and depression in AMI patients was shown in two randomized controlled trials (RCTs) 8,9 but not in another RCT. 10 However, these RCTs did not use validated measures of depression. Subsequent studies that used standardized measures of depression found no association between β-blocker use and depression in AMI patients, [11][12][13] but these studies also had design limitations, including not adjusting for baseline depression, 11,12 socioeconomic status, or other psychosocial factors (e.g., social support) [11][12][13] -all of which may confound the association of β-blocker use and depression. Furthermore, all prior studies in AMI patients using standardized measures of depression have included patients who were already on β-blocker treatment prior to AMI and none have assessed the association between de novo initiation of β-blocker therapy and depression. ...
... An association between treatment with β-blockers and depression in AMI patients was shown in two randomized controlled trials (RCTs) 8,9 but not in another RCT. 10 However, these RCTs did not use validated measures of depression. Subsequent studies that used standardized measures of depression found no association between β-blocker use and depression in AMI patients, [11][12][13] but these studies also had design limitations, including not adjusting for baseline depression, 11,12 socioeconomic status, or other psychosocial factors (e.g., social support) [11][12][13] -all of which may confound the association of β-blocker use and depression. Furthermore, all prior studies in AMI patients using standardized measures of depression have included patients who were already on β-blocker treatment prior to AMI and none have assessed the association between de novo initiation of β-blocker therapy and depression. ...
... Two prospective observational studies using standardized diagnostic measures/interviews for depression also did not find an association between β-blocker use and depression after AMI. 12,13 However, the first study lacked adequate adjustment for baseline depression as assessment for depression did not occur until 8 to 10 days after AMI. 12 Although the second study did adjust for baseline depression as well as for many other potential confounding clinical factors, 13 neither of these studies adjusted for other potential confounders of depressive symptoms, such as socioeconomic and psychosocial factors. We were able to improve upon the limitations of these prior investigations by adjusting for a number of important patient characteristics, including several key socioeconomic and psychosocial variables with the potential to confound the relationship with depression, such as education level, financial difficulties, marital status, insurance type, and social support. ...
Introduction:
Although β-blockers reduce mortality after acute myocardial infarction (AMI), early reports linking β-blocker use with subsequent depression have potentially limited their use in vulnerable patients. We sought to provide empirical evidence to support or refute this concern by examining the association between β-blocker initiation and change in depressive symptoms in AMI patients.
Methods:
Using data from 2 US multicenter, prospective registries of AMI patients, we examined 1-, 6-, and 12-month changes in depressive symptoms after the index hospitalization among patients who were β-blocker-naïve on admission. Depressive symptoms were assessed using the validated 8-item Patient Health Questionnaire (PHQ-8), which rates depressive symptoms from 0 to 24, with higher scores indicating more depressive symptoms. A propensity-matched repeated-measures linear regression model was used to compare change in depressive symptoms among patients who were and were not initiated on a β-blocker after AMI.
Results:
Of 3,470 AMI patients who were β-blocker-naïve on admission, 3,190 (91.9%) were initiated on a β-blocker and 280 (8.1%) were not. Baseline PHQ-8 scores were higher in patients not initiated on a β-blocker (mean 5.78 ± 5.45 vs 4.88 ± 5.11, P = .005). PHQ-8 scores were progressively lower at 1, 6, and 12 months in both the β-blocker (mean decrease at 12 months 1.16, P < .0001) and no-β-blocker groups (mean decrease 1.71, P < .0001). After propensity matching 201 untreated patients with 567 treated patients, initiation of β-blocker therapy was not associated with a difference in mean change in PHQ-8 scores at 1, 6, or 12 months after AMI (absolute mean difference with β-blocker initiation at 12 months of 0.08, 95% CI -0.81 to 0.96, P = .86).
Conclusions:
Initiation of β-blocker therapy after AMI was not associated with an increase in depressive symptoms. Restricting β-blocker use because of concerns about depression appears unwarranted and may lead to undertreatment of AMI patients.
... The use of beta-blocker therapy commonly used in CHD treatment protocols has been widely thought to be associated with increased risk for depression (van Melle et al., 2006). The MIND-IT ( Van den Brink et al., 2002) and Depression and Myocardial Infarction (DepreMI) (Spijkerman et al., 2005) However, there was a significant relationship between increasing depression screening scores and high dose beta blockade at six months (7.2 vs. 5.6, P = 0.03) and 12 months (7.4 vs. 5.8, P = 0.05) which suggests that the use of a lowest dose of beta-blocker therapy to improve cardiac function should be prescribed in order to minimize or prevent worsening depressive symptoms in at-risk CHD patients. ...
... trial data were used byvan Melle et al. (2006) to address this important clinical issue. Results of the vanMelle et al. (2006) investigation showed that there was no significant difference in depression scores between beta-blocker users and non-users in a large sample of matched post-MI patients (n=381; 127 non-users and 254 users) evaluated at 3, 6, and 12 months post-MI. ...
... trial data were used byvan Melle et al. (2006) to address this important clinical issue. Results of the vanMelle et al. (2006) investigation showed that there was no significant difference in depression scores between beta-blocker users and non-users in a large sample of matched post-MI patients (n=381; 127 non-users and 254 users) evaluated at 3, 6, and 12 months post-MI. ...
... CONCLUSIONS: Our findings show that primary care hypertension patients who use a lipophilic beta-blocker are more likely to have higher depression scores than those who do not use a lipophilic beta-blocker. instruments, have not found a clear association between beta-blockers and depression [7][8][9] or did even find a reduced risk of depression with betablocker use. 10 However, these studies focused on patients with established heart disease, including patients treated with percutaneous coronary intervention (PCI), with angina pectoris, 10 with an implantable cardioverter defibrillator (ICD), 7 or patients who recently had an MI. 9 The results of the study of van Melle et al showed no association between betablocker use at discharge and symptoms of depression at 3, 6, and 12 months, but they found a significant association between beta-blocker use and symptoms of depression before admission to the hospital. This association remained significant even after controlling for confounders such as hypertension and previous MI. ...
... instruments, have not found a clear association between beta-blockers and depression [7][8][9] or did even find a reduced risk of depression with betablocker use. 10 However, these studies focused on patients with established heart disease, including patients treated with percutaneous coronary intervention (PCI), with angina pectoris, 10 with an implantable cardioverter defibrillator (ICD), 7 or patients who recently had an MI. 9 The results of the study of van Melle et al showed no association between betablocker use at discharge and symptoms of depression at 3, 6, and 12 months, but they found a significant association between beta-blocker use and symptoms of depression before admission to the hospital. This association remained significant even after controlling for confounders such as hypertension and previous MI. ...
... This association remained significant even after controlling for confounders such as hypertension and previous MI. 9 To our knowledge, only the study of Luijendijk et al selected elderly people with and without cardiac disease and/or hypertension. 8 This study found an association between highly lipid-soluble beta-blockers and depression in the first 90 days of use; however, the effect disappeared after 90 days. ...
Background and objectives:
Previous findings regarding a possible association between beta-blocker use and depression are mixed. To our knowledge there have been no studies investigating the association of beta-blockers with depression in primary care hypertension patients without previous myocardial infarction. The aim of this study was to determine the relation between lipophilic beta-blocker use and depression in elderly primary care patients with hypertension.
Methods:
This was a cross-sectional study in primary care practices located in the South of The Netherlands. Primary care hypertension patients without previous myocardial infarction or heart failure (n=573), aged between 60 and 85 years (mean age=70±6.6), were included. All patients underwent a structured interview that included a self-report questionnaire to assess depression (PHQ-9), which was divided in four groups (PHQ-9 score of 0, 1--3, 4--8, 9 or higher).
Results:
A PHQ-9 score of 0 was more prevalent in non-beta-blocker users versus lipophilic beta-blocker users (46% versus 35%), a PHQ-9 score of 4--8 was less prevalent in non-beta-blocker users as compared with lipophilic beta-blocker users (14% versus 25%). A chi-squared test showed that lipophilic beta-blocker users as compared to non-beta-blockers users were more likely to be in a higher depression category. Ordinal regression showed a significant relationship between use of lipophilic beta-blockers and depression (OR=1.60, 95% CI=1.08--2.36) when adjusting for potential confounders.
Conclusions:
Our findings show that primary care hypertension patients who use a lipophilic beta-blocker are more likely to have higher depression scores than those who do not use a lipophilic beta-blocker.
... 5 Impending gangrene of extremities and exacerbation of Raynaud's phenomenon are also stated in the literature as the complications of PPL overdose. 6 To the best of our knowledge, this is the first time that TMJ dislocation is demon- strated as a complication of PPL intoxication. ...
... Bilateral TMJ dislocation in poisoned patients can result due to dystonic reactions to various drugs (metoclo- pramide and antipsychotics), extreme opening of mouth during yawning (similar to opioid withdrawal syndrome), attempts at tracheal intubations process, and vomiting after some acute drug toxicity or chemical poisoning. 5,6 None of these risk factors were present in the two cases presented here. As well, neither patient had recent facial trauma secondary to loss of consciousness. ...
... There was no pain and no spasm of masticator muscles on palpation of the TMJ, conflicting with mechanisms of TMJ dislocation declared by earlier studies. [5][6][7] PPL has a topical anesthetic effect that may explain the absence of pain in these patients. Although PPL can increase release of the neurotransmitter acetylcholine at the neuro- mascular junction of skeletal muscle, we could not definitely verify dislocation of TMJ as a complication of severe acute PPL overdose. ...
Temporomandibular joint (TMJ) dislocation has not previously been reported as a complication of beta-blocker toxicity. We are reporting two cases of TMJ dislocation resulted from acute severe intoxication with pure propranolol (PPL) for the first time. Bilateral TMJ dislocation happened in two patients who were admitted to intensive care unit with diagnosis of severe acute PPL toxicity. Clinical diagnosis of TMJ dislocation was obtained by physical examination. Successful reduction was performed for both patients without subsequent recurrence in two weeks following hospital discharge. Both of our subjects had no previous history of lower jaw dislocation. There was not any risk factor for dislocation such as convulsion during admission period, recent face trauma, or oral manipulation by the medical team. This study showed that TMJ dislocation may occur after severe acute PPL toxicity probably due to spastic contraction of the lateral pterygoid muscle. This is against previously mentioned hypothesis that stated masseteric muscles contraction as the main cause of a bilateral dislocated TMJ.
... Clinical Medicine Insights: Endocrinology and Diabetes for measuring depression, were observed in patients using a higher dosage of beta-blockers or with long-term use. 14,17 To our knowledge, no studies have been performed in dialysis patients. ...
... Lipophilic beta-blockers are able to pass the blood-brainbarrier and may therefore cause central nervous system sideeffects, such as depressive symptoms and sleeping problems. 14,15 Exclusion of Atenolol and Sotalol users, which display hydrophilic properties and are therefore suggested to be unable to cross the blood-brain-barrier, increased the risk of depressive symptoms in our analysis. ...
Background
Depression is associated with lower quality of life and increased risk of mortality. The prevalence of depression in chronic dialysis patients, as well as in patients with diabetes, is more than 20%. It is debated whether use of beta-blockers increases the risk of depression. Therefore, we examined in chronic dialysis patients with and without diabetes, the association between beta-blockers and depressive symptoms.
Methods
Data were collected from the DIVERS-I study, a multicentre prospective cohort among chronic dialysis patients in the Netherlands. Depressive symptoms were assessed with the Beck Depression Inventory (BDI-II). We defined depressive symptoms as a BDI-II score ⩾16. The cross-sectional association at baseline between depressive symptoms and beta-blocker use in chronic dialysis patients, was studied by multivariable logistic regression adjusted for potential confounders.
Results
We included 684 chronic dialysis patients, of whom 43% had diabetes mellitus, and 57% used a beta-blocker of which 97% were lipophilic. After multivariable adjustment, the OR (95% CI) for depressive symptoms in patients with compared to without diabetes was 1.41 (1.00-1.98), and in beta-blocker users compared to non-users 1.12 (0.80-1.56), respectively. Dialysis patients with diabetes and beta-blocker use compared to those without diabetes and not using beta-blockers had an OR of 1.73 (1.12-2.69) for depressive symptoms. The association was stronger in dialysis patients with diabetes and lipophilic beta-blocker use with an OR of 1.77 (1.14-2.74).
Conclusions
We found a possible association between lipophilic beta-blocker use and depressive symptoms in chronic dialysis patients with diabetes.
... However, most studies supporting this concern had small sample sizes were not prospective in design, or did not use direct, validated measures of depression. 72 A recent prospective study of post-MI patients taking β-blockers compared with matched patients not taking β-blockers found that the groups did not significantly differ with regard to depressive symptoms as measured by the validated BDI after 1 year of follow-up. 72 A prospective study of patients undergoing implantable cardioverter-defibrillator placement did not find an association between β-blocker use and depressive symptoms. ...
... 72 A recent prospective study of post-MI patients taking β-blockers compared with matched patients not taking β-blockers found that the groups did not significantly differ with regard to depressive symptoms as measured by the validated BDI after 1 year of follow-up. 72 A prospective study of patients undergoing implantable cardioverter-defibrillator placement did not find an association between β-blocker use and depressive symptoms. 73 Furthermore, a prospective study among post-cardiac catheterization patients found that β-blockers were associated with fewer depressive symptoms in a doseresponse relationship. ...
... Depression and anxiety are associated with heart failure (Glassman et al. 1983), and its prevalence can range from 15 % to 36 % (Konstam et al. 2005). Patients who have undergone coronary artery bypass surgery or experienced a recent myocardial infarction are well known to suffer more major depressive episodes and anxiety which is also linked to subsequent events including death (Frasure-Smith et al. 1993; van Melle et al. 2006). Thus, with anecdotal and case reports and even with small uncontrolled studies, it is easy to see why particular medications that are cardiac specific might be inappropriately thought to produce neuropsychiatric disorders such as depression. ...
... A prospective study of the prevalence of depression 3 or 4 months post-myocardial infarction did not find that β-blockers reach significance as a predictor (Schleifer et al. 1991). These findings were confirmed in a multicenter prospective trial of nearly 400 post-myocardial infarction patients prescribed either beta-blockers or other drugs and followed for 12 months (van Melle et al. 2006). A study from the Harvard community health plan population who followed a large number of patients starting a range of pharmaceutical treatments for at least 6 months found that the rates of depression (major and minor) in those prescribed beta-blockers after adjustment for age and sex were similar to those who were prescribed other drugs (Gerstman et al. 1996). ...
Cardiac medications including β-blockers, cardiac glycosides, and antiarrhythmics have long been known to have CNS effects including alterations in mood, emotion state anxiety, and depression. While the predominant effects come from those with higher lipophilicity and when used at high doses, the evidence is actually quite mixed. At cardiac therapeutic doses, lipophilic β-blockers like propranolol have actually few CNS effects on mood. The effectiveness of β-blockers is established for relieving performance anxiety, but the actions involve more a peripheral relief of somatic symptoms rather than a central effect. By contrast the reduction in consolidation of aversive and stressful memory by propranolol appears to involve altering the functioning of the amygdala and hippocampus directly. While evidence suggests that β-blockers reduce aggressive behaviors associated with various psychological conditions such as schizophrenia, they are now used relatively rarely. Cardiac glycosides such as digoxin have been implicated in causing a variety of mental dysfunctions including depression, yet quality prospective trials are lacking and evidence is largely anecdotal. The difficulty is that the patients likely to receive either β-blockers or digoxin are often suffering heart failure which in itself causes mood alterations such as depression. The current review analyzes the evidence of mood-altering side effects for the various pharmacological agents used to treat cardiac disease.
... This finding indicates that depression may be related to underlying disease, rather than to the use of β-blockers. In a multicenter study of patients with MI, no difference was seen in the incidence of depression between β-blocker and non-β-blocker users [148]. Therefore, it is reasonable to prescribe β-blockers to patients with MI and depression. ...
Depression is common among patients with acute coronary syndrome (ACS). Although multiple studies have confirmed that depression is an independent risk factor for poor outcomes in ACS, general awareness of this issue is still limited. Ongoing research has described detailed aspects of depression in ACS, with various mechanistic hypotheses put forward to explain the complexity of this comorbidity. Several investigations have explored management strategies in this subgroup of patients, including screening for depression, antidepressant treatment, and cardiac rehabilitation. However, evidence of long-term improvement in clinical outcomes is still scarce, and a more comprehensive understanding of the underlying mechanisms that link depression with ACS is required to further improve disease management.
... One of these reports stated how the research team found no significant difference in depressive symptom assessment between non-β-blocker users and βblocker users. 10 Those findings would suggest that βblockers might not be able to affect serotonin inhibitors as strongly as previously believed. A multitude of contrasting opinions can potentially explain the resistance that many overlooking bodies, such as the FDA, feel about using β-blockers in a role for mental health treatment. ...
Beta-blockers (β-blockers) are pharmacotherapeutics that have been used to treat patients with cardiovascular symptoms since their discovery in the 1960s. They work by targeting B1 and B2 receptors which are involved the stress response, which consequently lead to reduced activation of the “flight-or-fight mechanism”. It has also been noticed that β-blockers can be beneficial in treating anxiety disorders and other mental health complications. Currently, the only approved drugs for anxiety and other mental health conditions include benzodiazepines and selective serotonin reuptake inhibitors. Historically, there has been strong resistance to the use of β-blockers in mental health treatment because of the prevalence of depressive symptoms during treatment. Recently, a growing number of studies have seen that there is no strong relationship between β-blockers and depression in patients. Although there are still other adverse effects related to the usage of β-blockers, investigating the relationship between depressive symptoms and β-blockers may suggest a potential therapeutic option in mental health treatments. This review explores the history of β-blockers, their mechanism of action, developments in their use as a mental health treatment and current approved pharmacotherapeutics for mental health.
... However, there is contrasting evidence; β-blockers have been associated with decreases in depression and anxiety in other observational investigations [9,10,[14][15][16][17][18][19] and a randomised controlled trial [20]. In addition, there are several observational studies [2,3,[21][22][23][24][25] and randomised controlled trials [26][27][28][29][30] showing no associations with psychiatric events. ...
Background:
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.
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 manage aggression and violence could be investigated further.
... Some of these studies were based on small sample sizes, were cross-sectional in design with unclear temporal relationship between exposure and outcome, or relied solely on the use of antidepressants as a proxy for a depression diagnosis [13,16]. In contrast, other observational studies did not report such an association [17,18]. The large Danish populationbased register study by Kessing et al. even found possible protective effects of propranolol, atenolol, bisoprolol, and carvedilol on the risk of depression [18]. ...
Introduction:
Depression is a commonly cited adverse effect of β-blockers but the evidence for a causal relationship is limited.
Objective:
We aimed to explore whether β-blockers are associated with an increased risk of new-onset depression.
Methods:
We conducted a case-control study using the UK population-based Clinical Practice Research Datalink (CPRD) GOLD. We identified patients aged 18-80 years with an incident depression diagnosis between 2000 and 2016, and matched controls, and estimated the risk (odds ratio [OR]) of depression in association with use of β-blockers. We also conducted analyses of exposure, categorised by number and timing of prescriptions and by indication for β-blocker use.
Results:
The study encompassed 118,705 patients with incident depression and the same number of matched controls. The odds of developing depression were increased for current short-term use of any β-blocker (adjusted OR [aOR] 1.91, 95% confidence interval [CI] 1.72-2.12), whereas current long-term use was not associated with the risk of depression compared with never use. The elevated risk of depression among short-term users was mostly confined to propranolol users with a neuropsychiatric disorder (aOR 6.33, 95% CI 5.16-7.76), while propranolol users with a cardiovascular indication were only at marginally increased risk of depression (aOR 1.44, 95% CI 1.14-1.82).
Conclusions:
This study suggests that the association between use of β-blockers and depression may not be causal but rather a result of protopathic bias. Propranolol is often prescribed to treat neuropsychiatric symptoms, suggesting that the onset of depression may be related to the underlying indication rather than to an effect of a β-blocker therapy.
... Unfortunately, the level of physical activity was not available in this sample, so this possibility could not be explored. Also, research indicates that beta-blockers are associated with less depressive symptoms in patients with cardiac disorders [30,31]. This might explain the slight 'protective' effect on chest pain that was found in case of depression. ...
Objective:
To examine if chest pain increases the risk of depression and anxiety, or, on the other hand, depression and anxiety increase the risk of chest pain onset in patients with coronary heart disease (CHD).
Design:
Prospective clinical study.
Setting:
16 general practices in the Greater London Primary Care Research Network.
Participants:
803 participants with a confirmed diagnosis of CHD at baseline on the Quality and Outcomes Framework (QOF) CHD registers.
Main outcome measures:
Rose Angina Questionnaire, HADS depression and anxiety subscales and PHQ-9 were assessed at seven time points, each 6 months apart. Multi-Level Analysis (MLA) and Structural Equation Modelling (SEM) were applied.
Results:
Chest pain predicts both more severe anxiety and depression symptoms at all time points until 30 months after baseline. However, although anxiety predicted chest pain in the short term with a strong association, this association did not last after 18 months. Depression had only a small, negative association with chest pain.
Conclusions:
In persons with CHD, chest pain increases the risk of both anxiety and depression to a great extent. However, anxiety and depression have only limited effects on the risk for chest pain. This evidence suggests that anxiety and depression tend to be consequences rather than causes of cardiac chest pain. Intervention studies that support persons with CHD by providing this information should be devised and evaluated, thus deconstructing potentially catastrophic cognitions and strengthening emotional coping.
... Lastly, in this study respondent's age, sex, place of residence, B-blocker medication, marital status, comorbid diabetes mellitus and hypertension, living condition and lipid profile were not significantly associated with depression among CVD patients in the final model. The finding was in line with the study done in USA, Netherland, Japan, Denmark, Brazil, Pakistan [12,20,27,30,32,38,53,[57][58][59]. ...
Background
Depression and heart disease are an important public-health problem. Depression is one of the most prevalent and disabling psychiatric disorders with more than three times increased risk among patients with cardiovascular disorders.
Objective
To identify the prevalence and associated factors of depressive disorder among adult patients with cardiovascular disease.
Methods
Institution based cross-sectional study design was used to conduct this study on 293 study participants attending an outpatient cardiac clinic at Jimma University Teaching Hospital. All eligible patients were recruited into the study consecutively. Depression was assessed using patient health questionnaire-9. The patient health questionnaire-9 had a total score of 27, from which 0–4: no/minimal depression, 5–9: mild depression, 10–14: moderately depression, 15–19: moderately severe depression and 20–27 severe depression. The data was feed into Epi-data version 3.1 and lastly exported to SPSS version 21 for analysis. Bivariate analysis was used to analyze the statistical association of covariates of interest with depressive disorder among patients with cardiovascular disease. Then, logistic regression analysis was used as a final model to control confounders. The strength of association was measured by a 95% confidence interval.
Results
A total of 293 adult patients diagnosed with the cardiovascular disease were included in the study with 97% (n = 284) of response rate, 47.2% (n = 134) males and 52.8% (n = 150) females, making female to a male ratio around 1.1:1. The prevalence of depression was 52.8% (n = 150/284). Out of the subjects with depression 52.67% (n = 79), 36.0% (n = 54) and 11.33% (n = 17) were mild, moderate and severe depression, respectively. Variables such as employed, unemployed, physical activity, current cigarette user and poor social support were independently associated with depression in the final model.
Conclusions
In this study, depression was found to be highly prevalent psychiatric comorbidity in adult cardiovascular disease patients.
... Através da ação do medicamento, o coração trabalha com menos carga e consequentemente a ação da adrenalina e dos hormônios do estresse também diminuem, dando a sensação de cansaço e fadiga para os pacientes. No entanto, não há um consenso na literatura no que se refere aos betabloqueadores agravarem ou potencializarem os sintomas de depressão(PENA et al., 2011;PINHO et al., 2003;VAN MELLE et al., 2006).A associação de um quadro cardíaco e sintomas depressivos aumentam a taxa de reinfarto, de morbidade, bem como mortalidade(THOMBS et al., 2006). Esses pacientes tem uma menor probabilidade de retomar as atividades laborais, tem menos tolerância na prática de atividade física, menos adesão ao tratamento médico, declínio cognitivo emenor qualidade de vida (O'NEIL; SANDERSON; OLDENBURG, 2010). ...
Cardiovascular diseases are among the leading causes of disability and death. One of the forms of treatment for them is the percutaneous coronary intervention (PCI). After a diagnosis or cardiac procedure, patients have psychological symptoms that often go unnoticed and interfere with their health condition. The aim of this article was to evaluate the intensity of anxiety and depression symptoms in adult and elderly patients hospitalized after PCI. The design of the study was cross-sectional, analytical, correlational and comparative. Participants were 266 patients who had undergone PCI. Their average age was 64.5 years (SD =8.9 years) and most of them were men (68%) with a diagnosis of acute myocardial infarction (AMI) (64.3%). The research instruments used were the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory - Second Edition (BDI-II). Data collection was performed during the patients' hospitalization and statistical analysis was carried out by means of the Chi-SquareTest, the Kolmogorov -Smirnov Test and ANOVA. The level of significance used wasp < .05. Results showed that the majority of patients presented severe symptoms of anxiety (29.7%) and minimum intensity depressive symptoms (51.9%). The study highlights the importance of assessing and treating psychological symptoms after PCI as these interfere with the patient's adherence to treatment and with their quality of life.
... Studies have found that β blockers have to be lipophilic and able to cross the blood-brain barrier to exert neuropsychological side effects. 31 Metoprolol, a moderately lipophilic β blocker commonly prescribed for CHF, also prevents a part of pressor response to psychological stress. 32 Studies suggest that depression is associated with a poor prognosis of survival in CHF patients, and antidepressant treatment has shown only modest or no improvements in outcomes. ...
Background
Metoprolol treatment is well established for chronic heart failure (CHF) patients, but the central nervous system side effects are often a potential drawback.
Objective
To investigate the impact of metoprolol treatment on change in mental status of CHF patients with clinical psychological disorders (such as depression, anxiety, and burnout syndrome).
Methods
From February 2013 to April 2016, CHF patients with clinical mental disorders received metoprolol (23.75 or 47.5 mg, qd PO, dose escalated with 23.75 mg each time until target heart rate [HR] <70 bpm was achieved) at the Second Affiliated Hospital of Kunming Medical University. Mental status was assessed by means of the Hospital Anxiety and Depression Scale (HADS) and the Copenhagen Burnout Inventory (CBI) scale. The primary outcome assessed was change in mental status of patients post-metoprolol treatment and the association with reduction in HR achieved by metoprolol.
Results
A total of 154 patients (median age: 66.39 years; males: n=101) were divided into eight groups on the basis of their mental status. HR decreased significantly from baseline values in all the groups to <70 bpm in the 12th month, P≤0.0001. The HADS depression and CBI scores significantly increased from baseline throughout the study frame (P≤0.0001 for all groups), but a significant decrease in the HADS anxiety score was observed in patients with anxiety (P≤0.0001 for all groups). Regression analysis revealed no significant correlation in any of the groups between the HR reduction and the change in the HADS/CBI scores, except for a change in the CBI scores of CHF patients with depression (P=0.01), which was HR dependent.
Conclusion
Metoprolol treatment worsens the depressive and high burnout symptoms, but affords anxiolytic benefits independent of HR reduction in CHF patients with clinical mental disorders. Hence, physicians need to be vigilant while prescribing metoprolol in CHF patients who present with mental disorders.
... The lack of an established treatment to prevent the onset of depression thus represents a knowledge gap in the context of trauma care. blockers have, however, demonstrated promising effects on the reduction of depressive thoughts in patients following physiological stress caused by cancer and ischemic cardiac disease [16][17] . It is, therefore, reasonable to suggest a potential therapeutic role of -blockers in the context of trauma care and the prevention of post-traumatic depression. ...
Introduction:
Depressive symptoms occur in approximately half of trauma patients, negatively impacting on functional outcome and quality of life following severe head injury. Pontine noradrenaline has been shown to increase upon trauma and associated β-adrenergic receptor activation appears to consolidate memory formation of traumatic events. Blocking adrenergic activity reduces physiological stress responses during recall of traumatic memories and impairs memory, implying a potential therapeutic role of β-blockers. This study examines the effect of pre-admission β-blockade on post-traumatic depression.
Methods:
All adult trauma patients (≥18 years) with severe, isolated traumatic brain injury (intracranial Abbreviated Injury Scale score (AIS) ≥3 and extracranial AIS <3) were recruited from the trauma registry of an urban university hospital between 2007 and 2011. Exclusion criteria were in-hospital deaths and prescription of antidepressants up to one year prior to admission. Pre- and post-admission β-blocker and antidepressant therapy data was requested from the national drugs registry. Post-traumatic depression was defined as the prescription of antidepressants within one year of trauma. Patients with and without pre-admission β-blockers were matched 1:1 by age, gender, Glasgow Coma Scale, Injury Severity Score and head AIS. Analysis was carried out using McNemar's and Student's t-test for categorical and continuous data, respectively.
Results:
A total of 545 patients met the study criteria. Of these, 15% (n=80) were prescribed β-blockers. After propensity matching, 80 matched pairs were analyzed. 33% (n=26) of non β-blocked patients developed post-traumatic depression, compared to only 18% (n=14) in the β-blocked group (p=0.04). There were no significant differences in ICU (mean days: 5.8 (SD 10.5) vs. 5.6 (SD 7.2), p=0.85) or hospital length of stay (mean days: 21 (SD 21) vs. 21 (SD 20), p=0.94) between cohorts.
Conclusion:
β-blockade appears to act prophylactically and significantly reduces the risk of post-traumatic depression in patients suffering from isolated severe traumatic brain injuries. Further prospective randomized studies are warranted to validate this finding.
... Beta-blockers can cause fatigue and erectile dysfunction but have not been shown to precipitate depression. In a prospectively conducted study, van Melle et al. ( 2006 ) demonstrated a similar prevalence of depression in post-infarct patients independent whether or not they were prescribed beta-blockers. Similarly, statins have also been implicated in depression but two systematic analyses of the literature have refuted this assertion (Macedo et al. 2014 ;Parsaik et al. 2014 ). ...
The human body is organised into a number of bodily systems that each serve a key function. Since diseases tend to predominantly afflict one of these physiological-based systems, the practice of medicine has evolved into the management of diseased-based systems. Consequently, cardiac disease is primarily under the care of cardiologists and psychological disorders under psychiatrists. This specialty-based approach has given clinicians the opportunity to focus their skills on one system and therefore more thoroughly address and treat the disease process.
... Bei Behandlung mit Antidepressiva waren die selektiven Serotonin-Wiederaufnahmehemmer (SSRI) besser als die nicht-selektiven [16]. Auf der anderen Seite hatte die Behandlung von Herzinfarktpatienten mit Betablockern keine Auswirkungen auf Depressionssymptome [17]. ...
... However, rigorously conducted, placebo-controlled, studies have since disproven the conventional wisdom that beta-blockers worsen overall depressive symptoms. 18 While this does not preclude the possibility that certain individuals are susceptible to rare depressogenic side-effects of beta-blockers, this class of drug should not be denied to depressed patients for this reason. Instead, careful attention should be paid to ensuring that depressed patients are using all available evidence-based risk-reducing pharmacologic treatments since these patients are at elevated risk for cardiac events. ...
Among patients with cardiovascular disease (CVD), depression is highly prevalent and is associated with worse cardiovascular prognosis and lower quality of life. Treatments for depression in CVD patients produce modest, but clinically significant reductions in depressive symptoms and show promise for improving cardiovascular prognosis. While tricyclics should generally be avoided, antidepressants from multiple other classes appear to be safe in cardiac patients. A strategy of engaging patients in choosing medications or psychotherapy and then intensifying treatment to therapeutic goal appears to be more effective at reducing depression than single mode interventions. Recommendations for screening all CVD patients for depression may be premature given increased costs associated with screening and gaps in knowledge about the risk-benefit ratio of depression treatment in mild and moderately depressed patients.
... A score of 2 on one item would require the presence of symptoms 1 week later. [4]). However, Barnett Meyers, M.D., indicated that treatment was seldom discontinued in patients with these Abnormal Involuntary Movement Scale ratings, raising some questions about whether clinicians considered the rating clinically meaningful (personal communication with Barnett Meyers, M.D., October 7, 2009). ...
... Bei Behandlung mit Antidepressiva waren die selektiven Serotonin-Wiederaufnahmehemmer (SSRI) besser als die nicht-selektiven [16]. Auf der anderen Seite hatte die Behandlung von Herzinfarktpatienten mit Betablockern keine Auswirkungen auf Depressionssymptome [17]. ...
Psychosozialer Streß in der Familie und am Arbeitsplatz hat in den Industrieländern gravierende Folgen für Gesundheit, Gesundheitssysteme und Ökonomie. Bei Männern wird vor allem durch Streß am Arbeitsplatz das Risiko erhöht, an Herz-Kreislauf-Störungen, insbesondere an Arteriosklerose zu erkranken. Dieser Einfluß von psychosozialem Streß und Depressionen, die oft als Folge davon auftreten, ist in vielen Studien, zum Beispiel in der Interheart-Studie (2004), eindeutig belegt. In dem Netzwerk der Faktoren, die Arteriosklerose begünstigen, spielen streß-induzierte Veränderungen von neuronalen, hormonellen und molekularen Prozessen eine wichtige Rolle. Hier sollen vor allem die Wirkungen von Streßhormonen, Blutdruck, inflammatorischen Zytokinen und oxidativem Streß auf die Gefäßwand und die Plaquebildung in ihren mole-kularen Wirkungsmechanismen dargestellt werden. Ein vertieftes Verständnis dieser Prozesse auf den verschiedenen Ebenen ist von zentraler Bedeutung im Hinblick auf Prävention und Therapie von Herz-Kreislauf-Erkrankungen, deren Ansätze kurz skizziert werden. In industrial countries, psychosocial stress mainly at work and in the family causes health risks. These risks represent major threats to the national health systems and economies. A significantly elevated risk concerns heart and vascular diseases, particularly atherosclerosis whose depend-ence on stress is well-documented, for example in the recent Interheart Study (2004). Within the network of factors which enhance atheroscle-rosis, stress-induced changes of neuronal, hormonal and molecular processes play important roles. A focus is laid, therefore, on the effects of stress hormones, blood pressure, inflammatory cytokines and oxidative stress on the vascular system. Insights into these processes are of particu-lar importance with respect to prevention and therapy of atherosclerosis. New approaches are briefly summarized. Blickpunkt DER MANN 2007; 5 (1): 12–8.
... β -Blockers are commonly used to treat MI patients. Even though β -blocker use has been reported to be associated with development of depression in MI patients, this effect has not been supported (158) . β -Blockers are also used to treat the adrenergic symptoms, such as palpitations, of panic disorder which is also treated with SSRIs (159) . ...
Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to treat depression and a broad range of other comorbidities. The increased use of SSRIs in patients with various comorbidities treated with different drugs engenders the risk of pharmacokinetic drug interactions via cytochrome P450 (CYP450) enzymes inhibition. In the present review, we provide an overview of documented clinically significant drug interactions between SSRIs and other drugs co-prescribed in psychiatric patients for the same or other diseases. We further discuss the significance of drug interactions in the era of pharmacogenomics to underline the need for using information on both genotype and drug interactions towards implementing better clinical outcomes through personalized medicine.
... The first positive study found that beta-blockers in general are related to depression [4]. This study was followed by numerous negative studies [6e16,18e20, 22,23,25]. For propranolol (or lipophilic beta-blockers), although the first small study reported a nonsignificant risk [5], a cycle seemed to have sparked off with two large studies published shortly after. ...
... In our study, β-blockers did not predict either anxiety or depressive symptoms as also reported in some recent studies [21] [37]. Aspirin use was associated with lesser scores on both HAM-A and HAM-D. ...
The study was conducted to assess the occurrence of anxiety and depression in patients with recent myocardial infarction (MI) and also to assess the relationship of these symptoms with other relevant factors and clinical outcome.
A total of 103 patients with recent MI attending the cardiology outpatient department (OPD) of a tertiary care centre in India were included. The patients were evaluated using Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Mini International Neuropsychiatric Interview (MINI), and pertinent demographic and clinical parameters were recorded. The patients were followed up at 12 weeks telephonically to ascertain outcome.
Significant anxiety and depressive symptoms were present in 48.5% and 25.2% of the sample. Anxiety or depressive disorder diagnosis was present in 25.2% of the sample. Aspirin use predicted lower anxiety and depressive symptom scores. A multivariate linear regression showed that female sex, history of angina and use of aspirin independently predicted scores on HAM-A. Diagnosis of psychiatric disorder, use of aspirin and increased body mass index also independently predicted scores on HAM-D.
There is a need to screen for anxiety and depressive symptoms in patients with MI, so that appropriate intervention can be incorporated in the management plan.
Perimenopausal depression, occurring shortly before or after menopause, is characterized by symptoms such as emotional depression, anxiety, and stress, often accompanied by endocrine dysfunction, particularly hypogonadism and senescence. Current treatments for perimenopausal depression primarily provide symptomatic relief but often come with undesirable side effects. The development of agents targeting the specific pathologies of perimenopausal depression has been relatively slow. The erratic fluctuations in estrogen and progesterone levels during the perimenopausal stage expose women to the risk of developing perimenopausal-associated depression. These hormonal changes trigger the production of proinflammatory mediators and induce oxidative stress, leading to progressive neuronal damage. This review serves as a comprehensive overview of the underlying mechanisms contributing to perimenopausal depression. It aims to shed light on the complex relationship between perimenopausal hormones, neurotransmitters, brain-derived neurotrophic factors, chronic inflammation, oxidative stress, and perimenopausal depression. By summarizing the intricate interplay between hormonal fluctuations, neurotransmitter activity, brain-derived neurotrophic factors, chronic inflammation, oxidative stress, and perimenopausal depression, this review aims to stimulate further research in this field. The hope is that an increased understanding of these mechanisms will pave the way for the development of more effective therapeutic targets, ultimately reducing the risk of depression during the menopausal stage for the betterment of psychological wellbeing.
Myocardial infarction (MI) can have significant physical and mental consequences. Depression is a prevalent psychiatric condition after MI which can reduce the quality of life and increase the mortality rates of patients. However, the connection between MI and depression has remained under-appreciated. This review examines the potential connection between depression and MI by overviewing the possible pathophysiologic mechanisms including dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, coagulation system dysfunction, inflammation, environmental factors, as well as, genetic factors. Furthermore, depression can be an adverse event of medications used for MI treatment including beta-blockers, statins, or anti-platelet agents. The need for early detection and management of depression in patients with MI is, therefore, crucial for improving their overall prognosis. Adherence to treatments and regular follow-up visits can ensure the best response to treatment.
Objective:
This study examined whether antihypertensive medications and other patient characteristics are associated with severe depressive symptoms in a patient with hypertension.
Methods:
Patients with a diagnosis of hypertension were recruited from the internal medicine outpatient clinics of a hospital in Amman, Jordan, into this cross-sectional study. Depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9); anxiety by the General Anxiety Disorder-7; sleep quality by the Insomnia Severity Index; and psychological stress by the Perceived Stress Scale. Multivariable binary logistic regression was used to examine the association between the different classes of antihypertensive medication and depressive symptoms.
Results:
Of the 431 participants, 282 (65.4%) were men; 240 (55.7%) reported having type 2 diabetes; 359 (83.3%) had dyslipidemia; 142 (32.9%) were on beta-blockers; 197 (45.2%) were on ACE inhibitors or angiotensin receptor blockers; 203 (47.1%) were on metformin; and 133 (30.9%) were taking sulfonylurea. Severe depressive symptoms, indicated by scoring above the cut-off of 14 on the PHQ-9, was present in 165 (38.3%) patients. Severe depression was associated with younger age (<55 years) (OR = 3.15, 95% CI = 1.829-5.41, P < 0.001), unemployment (OR = 2.15, 95% CI = 1.15-4.00, P = 0.01), diabetes (OR = 1.81, 95% CI = 1.09-3.02, P = 0.02), severe anxiety (OR = 6.40, 95% CI = 3.64-11.28, P < 0.001), and severe insomnia (OR = 4.73, 95% CI = 2.85-7.82, P < 0.001).
Conclusion:
Severe depressive symptoms were not associated with antihypertensive medications or other drugs used by hypertensive patients. Instead, age, diabetes, anxiety, and insomnia were the primary correlates of depression.
This study aimed to investigate the association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease (CVD). This meta-analysis was registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD42020197839) and conducted in accordance with the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. The PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were systematically searched to identify all available studies on this topic. Random-effects multivariate meta-regression was performed to investigate the sources of study heterogeneity. Review Manager version 5.3 and Stata 12.0 were used for data analyses. This meta-analysis included 54 studies with a total number of 212651 patients. Overall, in patients with CVD, aspirin (odds ratio [OR]:0.91, 95% confidence interval [CI]:0.86-0.96, P=0.02) was associated with a lower risk of depression, while calcium channel blockers (CCB) (OR:1.21, 95%CI:1.05-1.38, P=0.008), diuretics (OR:1.34, 95%CI:1.14-1.58, P=0.0005), and nitrate esters (OR:1.32, 95%CI:1.08-1.61, P=0.006) were associated with a higher risk of depression, additionally, statin (OR:0.79, 95%CI:0.71-0.88, P<0.0001) was associated with a lower risk of anxiety, but diuretics (OR:1.39, 95%CI:1.26-1.52, P<0.00001) was associated with a higher risk of anxiety. Subgroup analysis presented that, in patients with hypertension, β-blockers were associated with a higher risk of depression (OR:1.45, 95%CI:1.26-1.67, P<0.00001); in patients with coronary artery disease (CAD), statin (OR:0.77, 95%CI:0.59-0.99, P=0.04), and aspirin (OR:0.85, 95%CI:0.75-0.97, P=0.02) were associated with a lower risk of depression, while CCB (OR:1.32, 95%CI:1.15-1.51, P<0.0001) and diuretics (OR:1.36, 95%CI:1.12-1.64, P=0.002) were associated with a higher risk of depression, additionally, diuretics was associated with a higher risk of anxiety (OR:1.41, 95%CI:1.28-1.55, P<0.00001); in patients with heart failure, nitrate esters (OR:1.93, 95%CI:1.19-3.13, P=0.007), and diuretics (OR:1.58, 95%CI: 1.02-2.43, P=0.04) were associated with a higher risk of depression. The use of cardiovascular drugs should be considered when evaluating depression or anxiety in patients with CVD to improve the care and treatment of these patients.
Objectives. In geriatric patients, cardiovascular diseases and type 2 diabetes are considered the most common chronic health problems. Moreover, increasing the prevalence of depression, which significantly reduces the quality of life and increases disability in this group, has also been observed. This paper aims to review the literature on the relationship between drugs from selected pharmacological groups used in the treatment of diabetes and cardiovascular diseases and depression, both with respect to their depressive and antidepressant effects. Literature review. The increased risk of the prevalence and the severity of depression is associated with strongly lipophilic beta-blockers and insulin therapy. In contrast, drugs that block the RAA system reduce the risk of developing and worsening symptoms of depression and improve cognitive function in elderly patients. Literature reports indicate the antidepressant effect of commonly used antidiabetic drugs such as metformin and incretin drugs (GLP-1 analogues and DPP-4 inhibitors). The potential anti-depressive effect of intranasal insulin administration requires further research. Conclusions. Based on the review, it should be stated that due to the frequent occurrence of mood disorders in elderly patients, the selection of drugs used in the therapy of somatic diseases should allow for the risk of causing or worsening symptoms of depression. However, the possibility of their beneficial effect on mood disorders should also be considered.
Depression resulted as an important factor associated with the myocardial infarction (MI) prognosis. Patients with MI also have a higher risk for developing depression. Although the issue of depression after MI has become a matter of clinical concern, the molecular mechanism underlying depression after MI remains unclear, whereby several strategies suggested have not got ideal effects, such as selective serotonin reuptake inhibitors. In this review, we summarized and discussed the occurrence mechanism of depression after MI, such as 5-hydroxytryptamine (5-HT) dysfunction, altered hypothalamus-pituitary-adrenal (HPA) axis function, gut microbiota imbalance, exosomal signal transduction, and inflammation. In addition, we offered a succinct overview of treatment, as well as some promising molecules especially from natural products for the treatment of depression after MI.
Beta blockers reduce mortality and morbidity in patients with heart failure. Early reports linking β-blockers with depression may have limited their use in heart failure patients with co-morbid depression. Although more recent studies have challenged the association between β-blocker therapy and depression, patient and physicians remain concerned. The goal of this study is to evaluate the utilization and outcomes of β-blocker therapy in heart failure patients with depression. This is a retrospective cohort study of patients at a multicenter integrated healthcare system with a diagnosis of heart failure from 2008 to 2014. Among 6,915 patients with heart failure with left ventricular ejection fraction of <50%, 1,252 (18.1%) had a diagnosis of depression. Patients with depression were more likely to be women and had a higher prevalence of cardiovascular risk factors. Depression was associated with decreased odds of β-blocker treatment (adjusted odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62 to 0.95; p = 0.016). During a mean follow-up of 2.6 years, 439 (35.1%) patients with depression died compared with 1,549 (27.4%) patients without depression. Depressed patients not treated with β-blocker had higher mortality compared with nondepressed patients (adjusted hazard ratio [HR], 1.4, 95% CI 1.09 to 1.7, p = 0.005). When treated with β-blockers, their risk of mortality was attenuated (HR 1.1, 95% CI 0.97 to 1.2, p = 0.14). In conclusion, β-blocker therapy remains underutilized in heart failure patients with depression, and its underutilization contributes to the reduced survival rate observed in this cohort.
Background:
Bereavement is associated with an increased risk of cardiovascular disease; however, no reports exist of interventions to reduce risk. In a randomized, double-blind, placebo-controlled trial of 85 recently bereaved participants, we determined whether β-blocker (metoprolol 25 mg) and aspirin (100 mg) reduce cardiovascular risk markers and anxiety, without adversely affecting bereavement intensity.
Methods:
Participants were spouses (n = 73) or parents (n = 12) of deceased from 5 hospitals in Sydney, Australia, 55 females, 30 males, aged 66.1 ± 9.4 years. After assessment within 2 weeks of bereavement, subjects were randomized to 6 weeks of daily treatment or placebo, and the effect evaluated using ANCOVA, adjusted for baseline values (primary analysis).
Results:
Participants on metoprolol and aspirin had lower levels of home systolic pressure (P = .03), 24-hour average heart rate (P < .001) and anxiety (P = .01) platelet response to arachidonic acid (P < .001) and depression symptoms (P = .046) than placebo with no difference in standard deviation of NN intervals index (SDNNi), von Willebrand Factor antigen, platelet-granulocyte aggregates or bereavement intensity. No significant adverse safety impact was observed.
Conclusions:
In early bereavement, low dose metoprolol and aspirin for 6 weeks reduces physiological and psychological surrogate measures of cardiovascular risk. Although further research is needed, results suggest a potential preventive benefit of this approach during heightened cardiovascular risk associated with early bereavement.
Cardiac medications including β-blockers, cardiac glycosides, and antiarrhythmics have long been known to have CNS effects including alterations in mood, emotion state anxiety, and depression. While the predominant effects come from those with higher lipophilicity and when used at high doses, the evidence is actually quite mixed. At cardiac therapeutic doses, lipophilic β-blockers like propranolol have actually few CNS effects on mood. The effectiveness of β-blockers is established for relieving performance anxiety, but the actions involve more a peripheral relief of somatic symptoms rather than a central effect. By contrast the reduction in consolidation of aversive and stressful memory by propranolol appears to involve altering the functioning of the amygdala and hippocampus directly. While evidence suggests that β-blockers reduce aggressive behaviors associated with various psychological conditions such as schizophrenia, they are now used relatively rarely. Cardiac glycosides such as digoxin have been implicated in causing a variety of mental dysfunctions including depression, yet quality prospective trials are lacking and evidence is largely anecdotal. The difficulty is that the patients likely to receive either β-blockers or digoxin are often suffering heart failure which in itself causes mood alterations such as depression. The current review analyzes the evidence of mood-altering side effects for the various pharmacological agents used to treat cardiac disease.
Heart failure (HF) affects approximately 5.1 million adults in the USA, with expectations of a rise to nearly 8 million adults by 2030. Patients with HF are at increased risk for morbidity/mortality, and comorbidities can further complicate care for these patients. Diabetes mellitus, chronic pain, arrhythmias, and depression are diagnoses that often coexist with HF. Medications commonly used to treat these comorbidities may induce or worsen HF symptoms, so determining appropriate drug therapy is important. Healthcare providers must understand the relationship between these medications and HF in order to improve prescribing practices to increase patient safety and reduce morbidity and mortality. This manuscript discusses the association between certain medications used to treat the aforementioned diagnoses and their relationship to HF. The purpose of this article is to provide guidance on which pharmacologic options require special consideration, increased monitoring, or complete avoidance in HF patients with diabetes mellitus, chronic pain, arrhythmias, and/or depression.
To perform a detailed, qualitative review of existing literature on the co-occurrence of bipolar disorder and metabolic syndrome, the impact of metabolic dysregulation on patients with bipolar disorder, and treatment considerations, with a focus on bipolar depression.
Searches of the PubMed database (October 23, 2012) and Cochrane Library (September 20, 2013) were conducted for English-language articles published from January 1980 onward containing the keywords bipolar AND metabolic, weight, obesity, diabetes, dyslipidemia, OR hypertension in the title or abstract. The searches yielded 1,817 citations from which case reports, conference abstracts, and pediatric studies were excluded.
Abstracts and titles were evaluated for relevance to the stated objectives. Full texts of 176 articles were obtained for further evaluation; additional articles were identified from reference lists.
Metabolic risk factors are highly prevalent yet undertreated in patients with bipolar disorder. Putative factors accounting for the link between bipolar disorder and metabolic syndrome include behavioral/phenomenological features, shared neurobiologic abnormalities, and adverse effects of psychotropic medications. A comprehensive assessment of metabolic risk and regular monitoring of body mass index, waist circumference, lipid profile, and plasma glucose are important for patients with bipolar disorder. Management strategies for the bipolar patient with metabolic risk factors include use of bipolar disorder medications with better metabolic profiles, lifestyle interventions, and adjunctive pharmacotherapy for dyslipidemia, hypertension, and/or hyperglycemia.
Adequate management of metabolic syndrome may improve clinical outcomes in patients with bipolar disorder, as well as prevent adverse cardiovascular events and the development of diabetes.
The aim of this article is to provide an overview on depression as a risk factor for the onset and follow-up of cardiovascular disease (CVD). In brief, the current state of psychobiological mechanisms bridging the gap between affective states and somatic consequences are presented. Four meta-analyses dealing with depression as a CVD risk factor in apparently healthy populations with >100,000 participants included, extracted an adjusted effect estimator of 1.60–1.90. Depressed subjects present with an unhealthier lifestyle (nutrition, smoking, physical activity). Three major psychobiological pathways directly acting on the circulatory system are under discussion: (1) hyperregulation of the autonomic nervous system (e.g., increased mean heart rate, increased heart rate responses, impaired heart rate variability), (2) overshooting stress responses of the endocrine system with impaired feedback mechanisms (e.g., for cortisol release), and (3) the immune system with dysregulated release of acute phase proteins and proinflammatory cytokines, all involved in a bidirectional crosstalk with the patient’s affective state and leading to platelet activation and flow mediated endothelial (dys-)function. Nonadherence and adverse side effects of medications also contribute to the lethal properties of depression in CVD.
BACKGROUNDDepression is associated with adverse prognosis in cardiac patients, warranting the availability of brief and valid instruments
to identify depressed patients in clinical practice.
OBJECTIVESWe examined whether the two-item Patient Health Questionnaire (PHQ-2) was associated with adverse events in percutaneous coronary
intervention (PCI) patients treated with paclitaxel-eluting stenting (using the continuous score and various cutoffs), overall
and by gender.
DESIGNProspective follow-up study.
PARTICIPANTSConsecutive PCI patients (n = 796) seen at a university medical centre.
MEASUREMENTSPHQ-2 at baseline. The study endpoint was an adverse event, defined as a combination of death or non-fatal myocardial infarction
(MI) at follow-up (mean of 1.4years).
RESULTSAt follow-up, 47 patients had experienced an adverse event. Using the continuous score of the PHQ-2 and the recommended cutoff
≥3, depressive symptoms were not associated with adverse events (ps > 0.05). Using a cutoff ≥2, depressive symptoms were significantly associated with adverse events (HR: 1.89; 95% CI: 1.06–3.35)
and remained significant in adjusted analysis (HR: 1.90; 95% CI: 1.05–3.44). Depressive symptoms were associated with an increased
risk of adverse events in men (HR: 2.69; 95% CI: 1.36–5.32) but not in women (HR: 0.76; 95% CI: 0.24–2.43); these results
remained in adjusted analysis.
CONCLUSIONSDepression screening with a two-item scale and a cutoff score of ≥2 was independently associated with adverse events at follow-up.
The PHQ-2 is a brief and valid measure that can easily be used post PCI to identify patients at risk for adverse health outcomes.
Objective:
There is a reciprocal association between major depressive disorder (MDD) and coronary heart disease (CHD). These conditions are linked by a causal network of mechanisms. This causal network should be quantitatively studied and it is hypothesised that the investigation of vagal function represents a promising starting point. Heart rate variability (HRV) has been used to investigate cardiac vagal control in the context of MDD and CHD. This review aims to examine the relationship of HRV to both MDD and CHD in the context of vagal function and to make recommendations for clinical practice and research.
Methods:
The search terms 'heart rate variability', 'depression' and 'heart disease' were entered into an electronic multiple database search engine. Abstracts were screened for their relevance and articles were individually selected and collated.
Results:
Decreased HRV is found in both MDD and CHD. Both diseases are theorized to disrupt autonomic control feedback loops on the heart and are linked to vagal function. Existing theories link vagal function to both mood and emotion as well as cardiac function. However, several factors can potentially confound HRV measures and would thus impact on a complete understanding of vagal mechanisms in the link between MDD and CHD.
Conclusions:
The quantitative investigation of vagal function using HRV represents a reasonable starting point in the study of the relationship between MDD and CHD. Many psychotropic and cardiac medications have effects on HRV, which may have clinical importance. Future studies of HRV in MDD and CHD should consider antidepressant medication, as well as anxiety, as potential confounders.
Vascular risk factors (VRFs) have been associated with stroke and cognitive impairment, however, the role of VRFs in predicting post-stroke depression (PSD) has not been assessed. The objective of the current study was to determine whether VRFs are associated with the risk of PSD in an acute stroke population.
In this observational study, patients meeting World Health Organization MONICA Project and National Institute of Neurological Disorders and Stroke criteria for stroke were eligible. Patients were assessed for depression, cognition, and stroke severity, and VRF and demographic information were obtained.
A total of 102 patients were recruited within 4 months post-stroke. Using a score of ≥16 on the Center for Epidemiological Studies Depression scale to determine depressive symptoms, 38 patients (age 72.1 ± 15.6, 44.7% male) screened positive for depressive symptoms and 64 (age 70.1 ± 13.6, 51.6% male) screened negative. Analysis of VRFs showed that only hypertension (P = .044) independently predicted the presence of depressive symptoms (χ(2) = 4.742, P = .029, Nagelkerke R (2) = .062).
Hypertension was associated with post-stroke depressive symptoms, while there was no relationship between PSD and other VRFs. Hypertension may have a greater impact than other VRFs on mood following stroke and may have a role in prevention and treatment of PSD.
Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose-response relationship between beta blocker dose and depressive symptoms.
Patients treated with PCI (N=685) completed the depression scale of the Hospital Anxiety and Depression Scale 1 and 12 months post PCI. Information about type and dose of beta blocker use was extracted from medical records.
Of all patients, 68% (466/685) were on beta blocker therapy at baseline. In adjusted analysis, beta blocker use at 1 month post PCI (OR: 0.82; 95% CI: 0.53-1.26) was not significantly associated with depressive symptoms. At 12 months post PCI, there was a significant relationship between beta blocker use and depressive symptoms (OR: 0.51; 95% CI: 0.31-0.84), with beta blocker therapy associated with a 49% risk reduction in depressive symptoms. There was a dose-response relationship between beta blocker dose and depressive symptoms 12 months post PCI, with the risk reduction in depressive symptoms in relation to a low dose being 36% (OR: 0.64; 95% CI: 0.37-1.10) and 58% (OR: 0.42; 95% CI: 0.24-0.76) in relation to a high dose.
Patients treated with beta blocker therapy were less likely to experience depressive symptoms 12 months post PCI, with there being a dose-response relationship with a higher dose providing a more pronounced protective effect.
Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD.
Between 2003 and 2010, 448 consecutively implanted ICD patients were enrolled in the prospective Mood and personality as precipitants of arrhythmia in patients with an Implantable cardioverter Defibrillator: A prospective Study (MIDAS), of which 429 completed the Hospital Anxiety and Depression Scale (HADS) and the ICD Patient Concerns questionnaire (ICDC) at baseline. Eighty per cent of all patients received beta-blocker therapy. In univariate analysis, beta-blocker therapy was not significantly associated with symptoms of anxiety, depression, and ICD concerns (β = -0.030, β = 0.007, and β = -0.045, respectively; all P's >0.36). Type of beta-blocker showed a trend towards significance for mean levels of ICD concerns (P = 0.09). No association was found between dosage and emotional distress (all P's >0.21). After adjustment for relevant clinical and demographic variables, the association of beta-blocker therapy and symptoms of anxiety, depression, and ICD concerns remained non-significant (β = 0.009, β = 0.037, and β = 0.019, respectively; all P's >0.47).
In patients receiving an ICD, beta-blocker therapy was not associated with symptoms of anxiety, depression, and ICD concerns. Research is warranted that further elucidates the link between beta-blocker therapy and emotional distress in this vulnerable patient group.
To measure the previously reported beta blocker induced adverse changes in mood state and anxiety measures, and to determine if prolonged aerobic exercise attenuates such mood modifications.
After 4 days of drug treatment with comparable doses of propranolol (40 and 80 mg), metoprolol (50 and 100 mg), or placebo, mood (POMS) and anxiety states (STAI) were assessed in healthy volunteers, before and after 1 h of treadmill walking exercise at 50% maximum oxygen uptake.
Compared to placebo, resting "tension", "depression", and "total mood disturbance" were significantly higher on propranolol 80 mg, but all were reduced with exercise. "Fatigue" and "confusion" were also higher on propranolol, and were unaffected by exercise. "Fatigue" was also higher than placebo after exercise on metoprolol 100 mg. "Anxiety" was unaffected by drug treatment or exercise.
The evidence that beta blockers, and particularly propranolol, have adverse effects on mood was confirmed. It would be preferable to prescribe a beta blocker which does not adversely alter mood states. However, exercise significantly reduced the measures of "tension" and "depression" which were adversely increased by propranolol. Exercise prescription may therefore not only be compatible with beta blockade, but a highly desirable adjuvant therapy.
To assess the association of depression following myocardial infarction (MI) and cardiovascular prognosis.
The authors performed a meta-analysis of references derived from MEDLINE, EMBASE, and PSYCINFO (1975-2003) combined with crossreferencing without language restrictions. The authors selected prospective studies that determined the association of depression with the cardiovascular outcome of MI patients, defined as mortality and cardiovascular events within 2 years from index MI. Depression had to be assessed within 3 months after MI using established psychiatric instruments. A quality assessment was performed.
Twenty-two papers met the selection criteria. These studies described follow up (on average, 13.7 months) of 6367 MI patients (16 cohorts). Post-MI depression was significantly associated with all-cause mortality (odds ratio [OR], fixed 2.38; 95% confidence interval [CI], 1.76-3.22; p <.00001) and cardiac mortality (OR fixed, 2.59; 95% CI, 1.77-3.77; p <.00001). Depressive MI patients were also at risk for new cardiovascular events (OR random, 1.95; 95% CI, 1.33-2.85; p = .0006). Secondary analyses showed no significant effects of follow-up duration (0-6 months or longer) or assessment of depression (self-report questionnaire vs. interview). However, the year of data collection (before or after 1992) tended to influence the effect of depression on mortality (p = .08), with stronger associations found in the earlier studies (OR, 3.22; 95% CI, 2.14-4.86) compared with the later studies (OR, 2.01; 95% CI, 1.45-2.78).
Post-MI depression is associated with a 2- to 2.5-fold increased risk of impaired cardiovascular outcome. The association of depression with cardiac mortality or all-cause mortality was more pronounced in the older studies (OR, 3.22 before 1992) than in the more recent studies (OR, 2.01 after 1992).
Depression following myocardial infarction (MI) can be a first-ever episode for some, whereas for others, it may represent a recurrent episode or one that was present at the onset of the infarction. We investigated if there are differences in pre- and post-MI characteristics between these subtypes.
Four hundred sixty-eight patients admitted for an MI were assessed for the presence of an ICD-10 depressive disorder following MI. A comparison was made between first-ever and ongoing or recurrent depression on demographic and cardiac data, personality, and depression characteristics.
Depressive disorder during the first post-MI year was present in 25.4% of the MI patients (n = 119), and almost half were ongoing or recurrent (n = 53, 44.5%). Recurrent and ongoing depression was related to high neuroticism (Z = 2.77, P < .01), whereas first-ever depression was associated with MI severity (poor left ventricular ejection fraction: Z = 1.64, P = .05; PTCA or CABG during hospitalization: Z = 1.88, P = .03; arrhythmic events: Z = 1.49, P = .06).
Our results suggest that in the first-ever post-MI depression cases, depression may be triggered by the severity of the MI, whereas ongoing and recurrent depression is more related to personality. Future research should address the question whether these subtypes of depression differ in cardiovascular prognosis and response to psychiatric treatment.
The β-Blocker Heart Attack Trial (BHAT) was a National Heart, Lung, and Blood Institute-sponsored, multicenter, randomized, double-blind, and placebo-controlled trial designed to test whether the regular administration of propranolol hydrochloride to men and women who had experienced at least one myocardial infarction would result in a significant reduction in total mortality during a two- to four-year period. During a 27-month interval, 3,837 persons between the ages of 30 and 69 years were randomized to either propranolol (1,916 persons) or placebo (1,921 persons), five to 21 days after the infarction. Depending on serum drug levels, the prescribed maintenance dose of propranolol hydrochloride was either 180 or 240 mg/day. The trial was stopped nine months ahead of schedule. Total mortality during the average 25-month follow-up period was 7.2% in the propranolol group and 9.8% in the placebo group. Arteriosclerotic heart disease (ASHD) mortality was 6.2% in the propranolol group and 8.5% in the placebo group. Sudden cardiac death, a subset of ASHD mortality, was 3.3% among the propranolol patients and 4.6% among the placebo patients. Serious side effects were uncommon. Hypotension, gastrointestinal problems, tiredness, bronchospasm, and cold hands and feet occurred more frequently in the propranolol group. Based on the BHAT results, the use of propranolol in patients with no contraindications to β-blockade who have had a recent myocardial infarction is recommended for at least three years. (JAMA 1982;247:1707-1714).
• Using records of the Saskatchewan Prescription Drug Plan, we determined the incidence of antidepressant use (a marker for depressive symptoms) in patients who received β-blockers or other treatments for chronic diseases (diuretics, antihypertensives, and hypoglycemics) during 1984, but not in the previous 6 months. Antidepressants initiated within 12 months after the study drug were counted. Of the 3218 new β-blocker users, 6.4% received concurrent prescriptions (ie, within 34 days) for an antidepressant and β-blocker. Only 2.8% of the reference group (no study drug use) received an antidepressant. A greater proportion of patients prescribed propranolol (9.5%) received an antidepressant than those prescribed other "lipophilic" (3.9%) or "hydrophilic" (2.5%) β-blockers. Incidence ratios for propranolol revealed the overall risk antidepressant use was 4.8 (95% confidence interval [Cl], 4.1 to 5.5) times that of the reference group and 2.1 (95% Cl, 1.7 to 2.5) times that of all other study drug users. For propranolol, relative risk of antidepressant use (drug/reference group) varied with age and was greatest in the 20- to 39-year-old group (17.2; 95% Cl, 13.7 to 21.5).
(Arch Intern Med. 1990;150:2286-2290)
The difficulties inherent in obtaining consistent and adequate diagnoses for the purposes of research and therapy have been pointed out by a number of authors. Pasamanick12 in a recent article viewed the low interclinician agreement on diagnosis as an indictment of the present state of psychiatry and called for "the development of objective, measurable and verifiable criteria of classification based not on personal or parochial considerations, but on behavioral and other objectively measurable manifestations."Attempts by other investigators to subject clinical observations and judgments to objective measurement have resulted in a wide variety of psychiatric rating scales.4,15 These have been well summarized in a review article by Lorr11 on "Rating Scales and Check Lists for the Evaluation of Psychopathology." In the area of psychological testing, a variety of paper-and-pencil tests have been devised for the purpose of measuring specific
Little information exists on the epidemiology of central nervous system side effects in patients taking antihypertensive medications. We examined prevalence rates of tricyclic antidepressant (TCA) use among a random sample (N=143,253) of Medicaid recipients. The TCA use was compared for patients taking any of seven antihypertensive agents and for those prescribed insulin or oral hypoglycemic agents. Use of TCA was significantly higher in patients taking β-blockers (23% over two years) than for patients taking hydralazine or hypoglycemics (both 15%) or methyldopa or reserpine (both 10%). Prevalence rate ratios revealed a risk of being prescribed a TCA of 1.5 (95% confidence interval, 1.4 to 1.7) for patients receiving β-blockers relative to patients receiving hydralazine or hypoglycemics. β-Blocker use may be an important cause of iatrogenic depression among hypertensive patients.(JAMA 1986;255:357-360)
Objective.
—To evaluate the relationship between β-blockers and depression.Design.
—Case-control study.Setting.
—New Jersey Medicaid recipients during July 1980 to December 1983.Participants.
—New depression case patients (N = 4302) were identified from Medicaid claims for depression markers (antidepressant drugs, in-hospital depression diagnosis, or electroconvulsive therapy). Control patients were randomly selected and matched on the basis of Medicaid enrollment on the case patients' date for first depression marker (index date), birth year, sex, race, and nursing home residency status.Main Exposure Measure.
—β-Blocker use as evidenced by prescription claims in the year before the index date.Results.
—Case patients overall were more likely to have taken β-blockers (simple, matched odds ratio [OR] of 1.45; 95% confidence interval [CI], 1.29 to 1.62). Controlling for confounders (benzodiazepine use, frequent outpatient visits, and frequent use of medications other than β-blockers) resulted in a null effect (OR=0.98; 95% CI, 0.87 to 1.12). The ORs were consistently lower for case patients with a depression diagnosis or electroconvulsive therapy than for cases with only antidepressant use as a marker. These results did not vary by age, sex, race, nursing home status, or use of other selected specific medications.Conclusions.
—Ongoing β-blocker use was not causally related to markers of depression. The difference between this study and those it contradicts is that this one identified certain confounding variables that accounted for the apparent relationship.(JAMA. 1992;267:1783-1787)
To evaluate the relationship between beta-blockers and depression.
Case-control study.
New Jersey Medicaid recipients during July 1980 to December 1983.
New depression case patients (N = 4302) were identified from Medicaid claims for depression markers (antidepressant drugs, in-hospital depression diagnosis, or electroconvulsive therapy). Control patients were randomly selected and matched on the basis of Medicaid enrollment on the case patients' date for first depression marker (index date), birth year, sex, race, and nursing home residency status. MAIN EXPOSURE MEASURE: beta-Blocker use as evidenced by prescription claims in the year before the index date.
Case patients overall were more likely to have taken beta-blockers (simple, matched odds ratio [OR] of 1.45; 95% confidence interval [CI], 1.29 to 1.62). Controlling for confounders (benzodiazepine use, frequent outpatient visits, and frequent use of medications other than beta-blockers) resulted in a null effect (OR = 0.98; 95% CI, 0.87 to 1.12). The ORs were consistently lower for case patients with a depression diagnosis or electroconvulsive therapy than for cases with only antidepressant use as a marker. These results did not vary by age, sex, race, nursing home status, or use of other selected specific medications.
Ongoing beta-blocker use was not causally related to markers of depression. The difference between this study and those it contradicts is that this one identified certain confounding variables that accounted for the apparent relationship.
Depressive symptoms were rated during a double-blind placebo-controlled trial of nadolol for chronic aggression. Depressive symptoms were not significantly different in nadolol and placebo groups during any phase of the drug trial.
Depression is frequently seen in patients following myocardial infarction (MI), many of whom are receiving digitalis glycosides, beta-blockers, or other agents that may exert central nervous system (CNS) effects. In a prospective study of the clinical significance of post-MI depression, 335 patients were assessed using a standardized diagnostic interview for depression at 8 to 10 days, and 190 were reinterviewed at 3 to 4 months. Patients prescribed digitalis, beta-blockers, or other cardioactive medications at hospital discharge were identified. Logistic regression analyses were performed to determine the contribution of these agents to depression at 3 to 4 months, controlling for medical and sociodemographic factors as well as for baseline depression. Treatment with digitalis predicted depression at 3 to 4 months (p less than 0.05); no other medications, including beta-blockers, predicted depression (p greater than 0.10). Digitalis may have CNS effects that contribute to depression post-MI and this finding should be considered in the differential diagnosis of depression in cardiac patients.
Using records of the Saskatchewan Prescription Drug Plan, we determined the incidence of antidepressant use (a marker for depressive symptoms) in patients who received beta-blockers or other treatments for chronic diseases (diuretics, antihypertensives, and hypoglycemics) during 1984, but not in the previous 6 months. Antidepressants initiated within 12 months after the study drug were counted. Of the 3218 new beta-blocker users, 6.4% received concurrent prescriptions (ie, within 34 days) for an antidepressant and beta-blocker. Only 2.8% of the reference group (no study drug use) received an antidepressant. A greater proportion of patients prescribed propranolol (9.5%) received an antidepressant than those prescribed other "lipophilic" (3.9%) or "hydrophilic" (2.5%) beta-blockers. Incidence ratios for propranolol revealed the overall risk antidepressant use was 4.8 (95% confidence interval [CI], 4.1 to 5.5) times that of the reference group and 2.1 (95% CI, 1.7 to 2.5) times that of all other study drug users. For propranolol, relative risk of antidepressant use (drug/reference group) varied with age and was greatest in the 20- to 39-year-old group (17.2; 95% CI, 13.7 to 21.5).
This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.
Little information exists on the epidemiology of central nervous system side effects in patients taking antihypertensive medications. We examined prevalence rates of tricyclic antidepressant (TCA) use among a random sample (N = 143,253) of Medicaid recipients. The TCA use was compared for patients taking any of seven antihypertensive agents and for those prescribed insulin or oral hypoglycemic agents. Use of TCA was significantly higher in patients taking beta-blockers (23% over two years) than for patients taking hydralazine or hypoglycemics (both 15%) or methyldopa or reserpine (both 10%). Prevalence rate ratios revealed a risk of being prescribed a TCA of 1.5 (95% confidence interval, 1.4 to 1.7) for patients receiving beta-blockers relative to patients receiving hydralazine or hypoglycemics. beta-Blocker use may be an important cause of iatrogenic depression among hypertensive patients.
Depression is believed to be a common side effect in patients receiving beta-blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy-seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty-one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta-blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications.
A single-blind study was conducted in 52 hypertensive patients, aged 25 to 68 years, to compare the side effects of an equally effective antihypertensive regimen of propranolol and atenolol. All patients had a history of side effects with beta-blocker therapy. Patients were treated with propranolol 40 to 160 mg bid for 8 weeks, followed by atenolol 50 to 100 mg given once daily for 8 weeks, and then rechallenged with the required dosage of propranolol for 8 weeks. Mean systolic and diastolic blood pressures were controlled during all three treatment phases. Side effects showed a definite trend toward improvement during the atenolol treatment phase. CNS side effects, in particular, showed significantly (P less than .05) reduced severity scores and overall incidence rates during the atenolol treatment phase. In conclusion, this study showed that at equally effective antihypertensive dosages the hydrophilic beta blocker atenolol produced significantly fewer CNS side effects than the lipophilic beta blocker propranolol.
A randomised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years. The principal antihypertensive agents were atenolol and bendrofluazide. There was a reduction in the rate of fatal stroke in the treatment group to 30% of that in the control group (95% confidence interval 11-84%, p less than 0.025). The rate of all strokes (fatal and non-fatal) in the treatment group was 58% of that in the control group (95% confidence interval 35-96%, p less than 0.03). The incidence of myocardial infarction and total mortality was unaffected by treatment. Questionnaires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment.
Depressive symptoms were measured in 34 white male patients receiving propranolol treatment for cardiovascular illness. The Hamilton Rating Scale for Depression and the Hudson Generalized Contentment Scale were used to measure depressive symptoms. Patients with a positive personal or family history of depression had significantly higher depression scores than those with a negative history. Although there was no correlation between propranolol dosage and depressive symptoms for the population as a whole, among patients with a negative history there was a highly significant positive correlation between propranolol dosage and depression scores.
In a multicentre double-blind randomised study, the effect of sotalol 320 mg once daily was compared with that of placebo in patients surviving an acute myocardial infarction. Treatment was started 5--14 days after infarction in 1456 patients (60% being randomised to sotalol, and 40% to placebo) who represented 45% of those evaluated for entry. Patients were followed for 12 months. The mortality rate was 7.3% (64 patients) in the sotalol group and 8.9% (52 patients) in the placebo group. The mortality was 18% lower in the sotalol than in the placebo group, but this difference was not statistically significant. The rate of definite myocardial reinfarction was 41% lower in the sotalol group than in the placebo group (p less than 0.05). Although the differences in mortality were not significant, this trial supports the evidence that, in the year after myocardial infarction, beta adrenoceptor blocking drugs reduce mortality by 20--25%.
We carried out a double-blind, randomized study, based at The Academic Department of Cardiology in Newcastle upon Tyne, to compare the effect of sotalol 320 mg once daily with that of placebo in patients from 20 hospitals who survived an acute myocardial infarction. Treatment was started 5-14 days after infarction in 1456 patients; 60% were randomized to sotalol and 40% to placebo. This represented 45% of those evaluated for entry. All patients were followed for 12 months and the analysis was done on an "intention-to-treat" principle. Sixty-four patients (7.3%) in the sotalol group died, compared with 52 (8.9%) in the placebo group. Although the mortality rate was 18% lower in the sotalol group, the difference was not statistically significant. There was a significant reduction in confirmed reinfarction, but not in all suspected reinfarctions.
We studied the occurrence of depression in new users of propranolol (n = 704), other beta-blockers (n = 587), angiotensin-converting enzyme inhibitors (n = 976), calcium channel blockers (n = 742), and diuretics (n = 773) in the Harvard Community Health Plan population. The period of the study was from April 1988 to June 1991. All study subjects were followed for new or newly recurrent depression for up to 6 months after receiving their first study prescription. Case status was confirmed by blinded medical record review. We found 10 cases of depression that met DSM-III-R criteria ("major depression") and an additional 18 cases that had one or more symptoms consistent with depression ("minor depression"). Rates of major depression in users of beta-blockers and users of non-beta-blocker study drugs were 5.8 per 1000 person-years of exposure and 9.6 per 1000 person-years, respectively. None of the cases of major depression was propranolol associated. Rates of major or minor depression (combined) in users of beta-blockers and users of non-beta-blockers were 20.2 per 1000 person-years and 25.2 per 1000 person-years, respectively. The age- and sex-adjusted relative risk of major or minor depression associated with the use of beta-blockers compared to non-beta-blockers was 0.8 (95% CI, 0.3-1.9). The relative risk associated with propranolol compared to non-beta-blockers was also 0.8 (95% CI, 0.1-2.7). Therefore, depression occurred no more frequently in beta-blocker users than in other members of the study base.
Many cardiovascular drugs have been implicated as causes of depression. With the exception of beta-blockers, few have been studied in formal epidemiologic designs. I present a new approach to such analyses that effectively controls for confounders that are stable over time. I analyzed the exposure histories of 11,244 incident antidepressant users, using the Odense University PharmacoEpidemiologic Database. All persons starting both beta-blockers and antidepressants during a predefined period were identified. If beta-blockers do not cause depression, this particular population should show equal numbers of persons starting either drug first. A depression-provoking effect of beta-blockers would generate an excess of persons starting beta-blockers first, that is a nonsymmetrical distribution of prescription orders. Confounders causing the two drugs to be co-prescribed would rarely be expected to affect the symmetry. The initial screening showed nonsymmetrical prescription orders for a wide range of cardiovascular drugs. After adjustment for an increasing incidence of antidepressant prescribing, I found a depression-provoking effect only for angiotensin-converting enzyme (ACE) inhibitors (rate ratio = 1.29; 95% confidence interval = 1.08-1.56) and calcium channel blockers (rate ratio = 1.31; 95% confidence interval = 1.14-1.51). This prescription sequence symmetry analysis may be useful as a screening tool.
To assess the effectiveness of beta blockers in short term treatment for acute myocardial infarction and in longer term secondary prevention; to examine predictive factors that may influence outcome and therefore choice of drug; and to examine the clinical importance of the results in the light of current treatment.
Systematic review of randomised controlled trials.
Randomised controlled trials.
Patients with acute or past myocardial infarction. Intervention: beta Blockers compared with control.
All cause mortality and non-fatal reinfarction.
Overall, 5477 of 54 234 patients (10.1%) randomised to beta blockers or control died. We identified a 23% reduction in the odds of death in long term trials (95% confidence interval 15% to 31%), but only a 4% reduction in the odds of death in short term trials (-8% to 15%). Meta regression in long term trials did not identify a significant reduction in effectiveness in drugs with cardioselectivity but did identify a near significant trend towards decreased benefit in drugs with intrinsic sympathomimetic activity. Most evidence is available for propranolol, timolol, and metoprolol. In long term trials, the number needed to treat for 2 years to avoid a death is 42, which compares favourably with other treatments for patients with acute or past myocardial infarction.
beta Blockers are effective in long term secondary prevention after myocardial infarction, but they are underused in such cases and lead to avoidable mortality and morbidity.
This study evaluated screening abilities of self-report questionnaires for depression in first myocardial infarction (MI) patients. One month post-MI, 206 patients with first MI were screened for major and minor depression using the 90-item Symptom Check List (SCL-90), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), and the 17-item Hamilton Depression Rating Scale (Ham-D). The Structured Clinical Interview for DSM-IV criteria was used as the gold standard. Sensitivity and specificity for different cutoff points, using relative operating characteristics curves, were assessed. The internal consistency for all scales was good. When screening for major and minor depression, the optimal cutoff scores are lower than those for screening major depression only. The SCL-90, BDI, HADS, and Ham-D proved to have acceptable abilities for screening post-MI major and minor depression.
Patients with a depressive disorder after myocardial infarction (MI) have a significantly increased risk of major cardiac events. The Myocardial INfarction and Depression-Intervention Trial (MIND-IT) investigates whether antidepressive treatment can improve the cardiac prognosis for these patients. The rationale and outline of the study are described.
In this multicenter randomized clinical trial, 2140 patients admitted for MI are screened for depressive symptoms with a questionnaire 0, 3, 6, 9, and 12 months after MI. Patients with symptoms undergo a standardized psychiatric interview. Those with a post-MI depressive episode are randomized to intervention (ie, antidepressive treatment; n = 190) or care-as-usual (CAU; n = 130). In the intervention arm, the research diagnosis is to be confirmed by a psychiatrist. First-choice treatment consists of placebo-controlled treatment with mirtazapine. In case of refusal or nonresponse, alternative open treatment with citalopram is offered. In the CAU arm, the patient is not informed about the research diagnosis. Psychiatric treatment outside the study is recorded, but no treatment is offered. Both arms are followed for end points (cardiac death or hospital admission for MI, unstable angina, heart failure, or ventricular tachyarrhythmia) during an average period of 27 months. Analysis is on an intention-to-treat basis.
The MIND-IT study will show whether treatment of post-MI depression can improve cardiac prognosis.
To review the clinical benefits of beta-blockers as secondary prevention following a myocardial infarction (MI) and to address the reasons that clinicians are reluctant to use beta-blockers in specific patient populations.
MEDLINE was searched for articles published from January 1966 to October 2002. Relevant studies were identified by systematic searches of the literature for all reported studies of associations between beta-blocker underuse and secondary prevention of MI. Additional studies were identified by a hand search of references of original or review articles.
English-language human studies were selected and analyzed.
Associations were observed in studies of beta-blocker use as secondary prevention of MI. A lower rate of beta-blocker treatment occurred in older patients and in patients with comorbid conditions such as diabetes, heart failure, chronic obstructive pulmonary disease, asthma, and peripheral arterial disease. In addition, underuse was attributed to the perception of high rates of adverse events associated with beta-blockers. beta-Blocker use as secondary prevention of an MI can lead to a 19-48% decrease in mortality and up to a 28% decrease in reinfarction rates. Nonetheless, beta-blockers are significantly underused in many patient populations due to concomitant disease states. Due to their normal physiologic deterioration, the elderly are at an increased risk of low cardiac output and bradycardia when given a beta-blocker; therefore, they should be started on a low dose that is then slowly titrated. In diabetic patients, beta-blockers can impair glucose control leading to hypoglycemia; therefore, post-MI diabetic patients must routinely monitor their blood glucose levels. In patients with decompensated heart failure, beta-blocker use can lead to further cardiac depression, but lower oral starting doses with slow titration can reduce this risk. beta-Blockers can induce bronchospasm in patients with chronic obstructive pulmonary disease or asthma, but cardioselective beta-blockers and appropriate use of medications such as albuterol can minimize these effects. Finally, in patients with peripheral arterial disease, with the exception of hypertensive patients with Reynaud's phenomenon, beta-blockers can be used safely. The only absolute contraindications to beta-blockers are severe bradycardia, preexisting sick sinus syndrome, second- and third-degree atrioventricular block, severe left ventricular dysfunction, active peripheral vascular disease with rest ischemia, or reactive airway disease so severe that airway support is required.
Overall, the cardiovascular benefits of beta-blockers as secondary prevention of MI significantly outweigh the risks associated with their use.
Depression following myocardial infarction (MI) is associated with complicated cardiac rehabilitation, non-compliance and poor prognosis. Whether depression following MI can be predicted from variables routinely assessed during hospitalization for MI is unknown.
Using data from the Myocardial INfarction and Depression-Intervention Trial (MIND-IT), we identified 2,177 MI patients (mean age 63 years; 23% female). Patients were randomly divided into a derivation and a validation sample. In the derivation sample, we analyzed variables potentially associated with the development of post-MI depressive disorder, which were tested in the validation sample.
In the year following MI, 18.5% suffered from depressive disorder (ICD-10 criteria). In a multivariate model, factors associated with depression were younger age (OR 1.94; CI 1.38-2.74), hypercholesterolemia (OR 1.68; CI 1.08-2.61), the use of calcium channel blockers at discharge (OR 1.80; CI 1.20-2.71), and left ventricular ejection fraction (LVEF) (OR 4.14 for patients with LVEF <30%; CI (2.42-7.10). The derived predictors were tested in the validation sample. The final model yielded two clinical predictors, i.e., younger age and severe LV-dysfunction, which correctly predicted post-discharge depression status in 82.9% of the MI patients. The model yielded a high negative predictive value (89%). A positive depression questionnaire (BDI) during hospitalization increased the positive predictive value of 23% to 52%.
During hospitalization for MI and using a two-step strategy with common clinical variables, i.e., younger age, severe LV-dysfunction and BDI score during hospitalization, it is possible to identify MI patients with a high risk for subsequent development of depression.
Digitalis and beta-blocking agents: effects on depression following myocardial in-farction 2214van Melle et al. Beta-Blockers and Post-MI Depression JACC
- Sj Schleifer
- Wr Slater
- Mm Macarihinson
Schleifer SJ, Slater WR, Macarihinson MM, et al. Digitalis and beta-blocking agents: effects on depression following myocardial in-farction. Am Heart J 1991;121:1397–402. 2214van Melle et al. Beta-Blockers and Post-MI Depression JACC Vol. 48, No. 11, 2006 December 5, 2006:2209–14
Beta-Blockers and Post-MI Depression Reprint requests and correspondence: Dr
- Van Melle
JACC Vol. 48, No. 11, 2006 van Melle et al. December 5, 2006:2209–14 Beta-Blockers and Post-MI Depression Reprint requests and correspondence: Dr. Joost P. van Melle, Department of Cardiology, Thoraxcenter, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, the Netherlands. E-mail: j.p.van.melle@med.umcg.nl. REFERENCES